|
1
|
Chen AL, Robbins M, Masters S, Boudiab E, Finn D, Peshel E, Thomas G, Studzinski D, Truscott S, Watterworth C, Novotny N, Ivascu F, Iacco A. Examining the role of thromboelastography in patients with COVID-19. Perfusion 2025:2676591251340967. [PMID: 40366108 DOI: 10.1177/02676591251340967] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/15/2025]
Abstract
BackgroundCOVID-19 causes a severe respiratory distress syndrome. Systemic inflammation and hypercoagulability are common. These findings are often evaluated with non-specific markers, including CRP, D-dimer, and fibrinogen. We sought to evaluate thromboelastography (TEG) to better understand this complex coagulopathy.MethodsWe conducted a prospective observational study analyzing TEG results in hospitalized patients with COVID-19. TEG was performed on admission and at pre-set intervals. Based on the TEG findings, patients were deemed "hypercoagulable" or "not hypercoagulable." Clinical outcomes were recorded.Results88 patients were evaluated. 78/88 (89%) were hypercoagulable. 10% of the hypercoagulable group (8/78) died compared to none in the non-hypercoagulable group (0/10), with thrombotic events occurring in 9% (8/88), a higher requirement for O2 support in 19% (17/88), and prolonged length of stay exceeding 4 days for 74% (65/88). No statistical significant differences were observed between the groups for any of the four adverse events. Patients with complete fibrinolysis shutdown (Ly30 = 0) had more thrombotic events than those with Ly30 > 0 (30% vs 0%, p = .03).ConclusionPatients with COVID-19 are often hypercoagulable based upon specific TEG parameters. While many TEG parameters are not associated with adverse outcomes, complete fibrinolysis shutdown is associated with an increased risk of thrombotic events. Further studies are warranted to assess the utility of TEG in this population.
Collapse
Affiliation(s)
- Alexander L Chen
- Department of General Surgery, Corewell Health William Beaumont University Hospital, Royal Oak, MI, USA
| | - Matthew Robbins
- Department of General Surgery, Corewell Health William Beaumont University Hospital, Royal Oak, MI, USA
| | - Sean Masters
- Department of General Surgery, Corewell Health William Beaumont University Hospital, Royal Oak, MI, USA
| | - Elizabeth Boudiab
- Department of General Surgery, Corewell Health William Beaumont University Hospital, Royal Oak, MI, USA
| | - Daniel Finn
- Department of General Surgery, Corewell Health William Beaumont University Hospital, Royal Oak, MI, USA
| | - Emanuela Peshel
- Department of General Surgery, Corewell Health William Beaumont University Hospital, Royal Oak, MI, USA
| | - Gregory Thomas
- Department of General Surgery, Corewell Health William Beaumont University Hospital, Royal Oak, MI, USA
| | - Diane Studzinski
- Department of General Surgery, Corewell Health William Beaumont University Hospital, Royal Oak, MI, USA
| | - Steven Truscott
- Special Chemistry and Toxicology Laboratories, Corewell Health William Beaumont University Hospital, Royal Oak, MI, USA
| | - Courtney Watterworth
- Beaumont Research Institute, Corewell Health William Beaumont University Hospital, Royal Oak, MI, USA
| | - Nathan Novotny
- Department of General Surgery, Corewell Health William Beaumont University Hospital, Royal Oak, MI, USA
| | - Felicia Ivascu
- Department of General Surgery, Corewell Health William Beaumont University Hospital, Royal Oak, MI, USA
| | - Anthony Iacco
- Department of General Surgery, Corewell Health William Beaumont University Hospital, Royal Oak, MI, USA
| |
Collapse
|
|
2
|
Mirus M, Schöchl H, Groene P, Bachler M, Koscielny J, Fries D, Heubner L. [Point of care coagulation diagnostics-Absolutely necessary or only a reasonable supplement?]. DIE ANAESTHESIOLOGIE 2025; 74:264-274. [PMID: 40172631 DOI: 10.1007/s00101-025-01524-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Accepted: 02/13/2025] [Indexed: 04/04/2025]
Abstract
Point of care (POC) coagulation diagnostics have become an integral part of clinical patient care. In particular, the strengths of POC viscoelastometry (VET) lie not only in the rapid availability of test results but also in the fact that VET provides insights into coagulation that cannot be detected by standard laboratory tests. The relevance of POC-VET in the optimal management of patients with acutely acquired bleeding disorders, such as trauma-induced coagulopathy, is now unquestioned and is also reflected in the corresponding guidelines; however, VET also provides important information about fibrinolysis and fibrinolytic activity and in combination with other laboratory values can possibly also be sensitive for prothrombotic coagulation disorders. Therefore, POC-VET is increasingly being used in intensive care medicine. The use of POC diagnostics is not subject to the same standards as central laboratory testing. In order to maintain high quality and avoid harming patients, the requirements for medical device manufacturers in particular have been increased as part of the in vitro diagnostic reagents (IVDR) regulations, which places high demands on quality management in particular. The variety of POC devices and the lack of comparability between them remains an unsolved problem. It should be critically discussed to what extent medical device manufacturers and pharmaceutical companies could be legally required to keep unique and urgently needed technologies on the market, especially if no comparable alternatives will be available in the foreseeable future. Overall, from today's perspective, the use of POC coagulation diagnostics is essential for optimal patient care.
Collapse
Affiliation(s)
- Martin Mirus
- Klinik und Poliklinik für Anästhesiologie und Intensivtherapie, Medizinische Fakultät und Universitätsklinikum Carl Gustav Carus, Technische Universität Dresden, Fetscherstraße 74, 01307, Dresden, Deutschland
| | - Herbert Schöchl
- Ludwig Boltzmann Institut Traumatologie Das Forschungszentrum in Kooperation mit der AUVA, Donaueschingenstr. 13, Wien, Österreich
| | - Philipp Groene
- Klinik für Anästhesiologie, Universitätsklinikum LMU München, München, Deutschland
| | - Mirjam Bachler
- Universitätsklinik für Anästhesiologie und Intensivmedizin, Medizinische Universität Innsbruck, Innsbruck, Österreich
| | - Jürgen Koscielny
- Gerinnungsambulanz mit Hämophiliezentrum, Charité, Universitätsmedizin Berlin, Berlin, Deutschland
| | - Dietmar Fries
- Universitätsklinik für Anästhesiologie und Intensivmedizin, Medizinische Universität Innsbruck, Innsbruck, Österreich
| | - Lars Heubner
- Klinik und Poliklinik für Anästhesiologie und Intensivtherapie, Medizinische Fakultät und Universitätsklinikum Carl Gustav Carus, Technische Universität Dresden, Fetscherstraße 74, 01307, Dresden, Deutschland.
| |
Collapse
|
|
3
|
Drotarova M, Asselta R, Caccia S, Skornova I, Zolkova J, Kolkova Z, Loderer D, Podusel V, Stasko J, Simurda T. A novel pathogenic variant in the fibrinogen gamma chain gene p.Glu275Lys causes congenital hypofibrinogenemia. Blood Coagul Fibrinolysis 2025:00001721-990000000-00200. [PMID: 40310436 DOI: 10.1097/mbc.0000000000001362] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2025] [Accepted: 03/27/2025] [Indexed: 05/02/2025]
Abstract
Congenital hypofibrinogenemia presents not only with bleeding, but also paradoxically with thrombosis. This heterogeneity of clinical phenotype complicates both diagnosis and management. The thrombotic phenotype is thought to arise from alterations in fibrin structure and stability, leading to abnormal clot formation and an increased risk of thrombosis. Coagulation assays, gene analysis, and protein modeling were utilized to elucidate the pathogenic variant. We highlight the pathophysiology of the novel missense variant in the FGG gene (c.823G/A, p.Glu275Lys), which causes mild hypofibrinogenemia and clinically manifests as an ischemic stroke. Protein modeling displays that the amino-acid substitution of glutamine with lysine at position 275 in mentioned missense variant causes local changes in the fibrinogen structure. The structural changes are mainly minor surface alterations and changes in physicochemical properties, which could potentially affect the recruitment of other proteins or lead to abnormal fibrin polymerization. This study provides novel insights into the pathophysiological mechanism, emphasizing the importance of molecular and structural analyses in understanding and managing atypical presentations of fibrinogen disorders.
Collapse
Affiliation(s)
- Miroslava Drotarova
- National Centre of Hemostasis and Thrombosis, Department of Hematology and Transfusiology, Comenius University in Bratislava, Jessenius Faculty of Medicine and University Hospital Martin, Slovakia
| | - Rosanna Asselta
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele
- IRCCS Humanitas Research Hospital, Rozzano
| | - Sonia Caccia
- Department of Biomedical and Clinical Sciences, University of Milan, Milan, Italy
| | - Ingrid Skornova
- National Centre of Hemostasis and Thrombosis, Department of Hematology and Transfusiology, Comenius University in Bratislava, Jessenius Faculty of Medicine and University Hospital Martin, Slovakia
| | - Jana Zolkova
- National Centre of Hemostasis and Thrombosis, Department of Hematology and Transfusiology, Comenius University in Bratislava, Jessenius Faculty of Medicine and University Hospital Martin, Slovakia
| | | | | | - Vladimir Podusel
- Department of Internal Medicine I., Comenius University in Bratislava, Jessenius Faculty of Medicine in Martin, Slovakia
| | - Jan Stasko
- National Centre of Hemostasis and Thrombosis, Department of Hematology and Transfusiology, Comenius University in Bratislava, Jessenius Faculty of Medicine and University Hospital Martin, Slovakia
| | - Tomas Simurda
- National Centre of Hemostasis and Thrombosis, Department of Hematology and Transfusiology, Comenius University in Bratislava, Jessenius Faculty of Medicine and University Hospital Martin, Slovakia
| |
Collapse
|
|
4
|
Zátroch I, Dinya E, Smudla A, Fazakas J. Fibrinolytic Dysregulation in Regional Hemostasis During Liver Transplantation: A Viscoelastometry-Based Pilot Study. J Clin Med 2025; 14:2925. [PMID: 40363956 PMCID: PMC12072297 DOI: 10.3390/jcm14092925] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2025] [Revised: 04/17/2025] [Accepted: 04/21/2025] [Indexed: 05/15/2025] Open
Abstract
Background/Objectives: In chronic liver disease, a rebalanced coagulation state often results in an increased risk of thrombosis, particularly in the splanchnic region. While systemic coagulation abnormalities are well documented, alterations in regional (portal) hemostasis remain underexplored. This study aimed to compare systemic and portal hemostasis during liver transplantation and to determine whether systemic parameters can accurately predict regional coagulation status. Methods: Thirty-five liver transplant recipients were included in this study. Systemic blood samples (S1-S5) were collected from the external jugular vein at five surgical time points, while portal blood samples (R3) were obtained immediately before reperfusion simultaneously with S3. All samples were analyzed using ClotPro® viscoelastic assays, conventional coagulation tests, and blood gas analysis. Results: The EX-test comparison between S3 and R3 samples revealed a discrepancy between systemic and regional hemostasis in 45.7% of patients. Among these, eight regional samples exhibited hypocoagulation characterized by coagulation factor consumption and hyperfibrinolysis. Another eight samples demonstrated hypercoagulation with fibrinolytic shutdown, which was confirmed by a fibrin-rich thrombus identified via scanning electron microscopy. Systemic samples failed to predict these regional variations. Conclusions: Regional (portal) hemostasis significantly differs from systemic coagulation and cannot be accurately predicted using systemic assays alone. These findings suggest that fibrinolytic shutdown in the portal vein may contribute to intraoperative and long-term graft damage, highlighting a potential need for regional coagulation assessment during liver transplantation.
Collapse
Affiliation(s)
- István Zátroch
- Doctoral College, Semmelweis University, 1085 Budapest, Hungary;
| | - Elek Dinya
- Institute of Digital Health Sciences, Semmelweis University, 1094 Budapest, Hungary;
| | - Anikó Smudla
- Department of Surgery, Transplantation and Interventional Gastroenterology, Semmelweis University, 1085 Budapest, Hungary;
- Department of Anesthesiology and Intensive Therapy, Semmelweis University, 1085 Budapest, Hungary
| | - János Fazakas
- Department of Surgery, Transplantation and Interventional Gastroenterology, Semmelweis University, 1085 Budapest, Hungary;
- Department of Anesthesiology and Intensive Therapy, Semmelweis University, 1085 Budapest, Hungary
| |
Collapse
|
|
5
|
Yang X, Cai Y, Ke L, Wei B. Hypercoagulable state and effect of low-molecular-weight heparin prophylaxis on coagulation after lung cancer resection: results from thrombo-elastography. Gen Thorac Cardiovasc Surg 2025; 73:180-189. [PMID: 39060847 PMCID: PMC11829937 DOI: 10.1007/s11748-024-02062-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2024] [Accepted: 07/08/2024] [Indexed: 07/28/2024]
Abstract
BACKGROUND Lung cancer patients undergoing surgery are at increased risk for Venous thromboembolism (VTE). We monitored changes in perioperative coagulation status through Thrombo-elastography (TEG), and monitored the anticoagulant effect of low molecular weight heparin through TEG for the first time. METHODS From July 2019 to January 2020, 207 patients receiving curative surgery were retrospectively screened. and 23 patients were excluded because they did not meet the inclusion criteria. Blood samples were required at three time points (prior to, the first and third day after surgery). Some patients were administrated nadroparin calcium daily from the first day after surgery. Repeated measures ANOVA and Chi-square test were used to analyze the coagulation states variation. To balance the confounders, propensity score matching (PSM) was used to determine the differences of coagulation states between patients with or without Low-molecular-weight heparin (LMWH) prophylaxis. RESULTS In 184 patients, TEG parameters displayed significant procoagulant changes after lung surgery but conventional coagulation tests exhibited paradoxical trends. There were 6.5% (12/184) of patients identified as hypercoagulability before surgery. According to TEG results, the proportion of patients with hypercoagulability rose from 21.7% to 25% postoperatively, but more were classified into platelet or mixed hypercoagulability at third day compared with that at first day (3.8% vs 14.1%, P < 0.001). By PSM analysis, there were no significant differences in the proportion of hypercoagulable patients postoperatively between chemoprophylactic and nonprophylactic group. CONCLUSIONS TEG was eligible to distinguish changing states of hypercoagulability postoperatively and indicate the role of platelet in blood hypercoagulability. Administration of postoperative LMWH prophylaxis showed little mitigation on hypercoagulable states.
Collapse
Affiliation(s)
- Xiaoxiao Yang
- Department of Thoracic Surgery, Beijing Tiantan Hospital Affiliated to Capital Medical University, Beijing, China
| | - Yongsheng Cai
- Department of Thoracic Surgery, Beijing Tiantan Hospital Affiliated to Capital Medical University, Beijing, China
| | - Lihui Ke
- Department of Thoracic Surgery, Beijing Tiantan Hospital Affiliated to Capital Medical University, Beijing, China
| | - Bo Wei
- Department of Thoracic Surgery, Beijing Tiantan Hospital Affiliated to Capital Medical University, Beijing, China.
| |
Collapse
|
|
6
|
Sieh L, Peasley E, Mao E, Mitchell A, Heinonen G, Ghoshal S, Agarwal S, Park S, Connolly ES, Claassen J, Moore EE, Hansen K, Hod EA, Francis RO, Roh DJ. Admission Viscoelastic Hemostatic Assay Parameters Predict Poor Long-Term Intracerebral Hemorrhage Outcomes. Neurocrit Care 2025; 42:100-107. [PMID: 38955933 DOI: 10.1007/s12028-024-02051-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2024] [Accepted: 06/13/2024] [Indexed: 07/04/2024]
Abstract
BACKGROUND Viscoelastic hemostatic assays (VHAs) provide more comprehensive assessments of coagulation compared with conventional coagulation assays. Although VHAs have enabled guided hemorrhage control therapies, improving clinical outcomes in life-threatening hemorrhage, the role of VHAs in intracerebral hemorrhage (ICH) is unclear. If VHAs can identify coagulation abnormalities relevant for ICH outcomes, this would support the need to investigate the role of VHAs in ICH treatment paradigms. Thus, we investigated whether VHA assessments of coagulation relate to long-term ICH outcomes. METHODS Patients with spontaneous ICH enrolled into a single-center cohort study receiving admission Rotational Thromboelastometry (ROTEM) VHA testing between 2013 and 2020 were assessed. Patients with previous anticoagulant use or coagulopathy on conventional coagulation assays were excluded. Primary ROTEM exposure variables were coagulation kinetics and clot strength assessments. Poor long-term outcome was defined as modified Rankin Scale ≥ 4 at 6 months. Logistic regression analyses assessed associations of ROTEM parameters with clinical outcomes after adjusting for ICH severity and hemoglobin concentration. RESULTS Of 44 patients analyzed, the mean age was 64 years, 57% were female, and the median ICH volume was 23 mL. Poor 6-month outcome was seen in 64% of patients. In our multivariable regression models, slower, prolonged coagulation kinetics (adjusted odds ratio for every second increase in clot formation time 1.04, 95% confidence interval 1.00-1.09, p = 0.04) and weaker clot strength (adjusted odds ratio for every millimeter increase of maximum clot firmness 0.84, 95% confidence interval 0.71-0.99, p = 0.03) were separately associated with poor long-term outcomes. CONCLUSIONS Slower, prolonged coagulation kinetics and weaker clot strength on admission VHA ROTEM testing, not attributable to anticoagulant use, were associated with poor long-term outcomes after ICH. Further work is needed to clarify the generalizability and the underlying mechanisms of these VHA findings to assess whether VHA-guided treatments should be incorporated into ICH care.
Collapse
Affiliation(s)
- Laura Sieh
- Department of Neurology, Vagelos College of Physicians and Surgeons, Columbia University, 177 Fort Washington Ave, New York, NY, 10032, USA
| | - Emma Peasley
- Department of Neurology, Vagelos College of Physicians and Surgeons, Columbia University, 177 Fort Washington Ave, New York, NY, 10032, USA
| | - Eric Mao
- Department of Neurology, Vagelos College of Physicians and Surgeons, Columbia University, 177 Fort Washington Ave, New York, NY, 10032, USA
| | - Amanda Mitchell
- Department of Neurology, Vagelos College of Physicians and Surgeons, Columbia University, 177 Fort Washington Ave, New York, NY, 10032, USA
| | - Gregory Heinonen
- Department of Neurology, Vagelos College of Physicians and Surgeons, Columbia University, 177 Fort Washington Ave, New York, NY, 10032, USA
| | - Shivani Ghoshal
- Department of Neurology, Vagelos College of Physicians and Surgeons, Columbia University, 177 Fort Washington Ave, New York, NY, 10032, USA
| | - Sachin Agarwal
- Department of Neurology, Vagelos College of Physicians and Surgeons, Columbia University, 177 Fort Washington Ave, New York, NY, 10032, USA
| | - Soojin Park
- Department of Neurology, Vagelos College of Physicians and Surgeons, Columbia University, 177 Fort Washington Ave, New York, NY, 10032, USA
| | - E Sander Connolly
- Department of Neurological Surgery, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY, USA
| | - Jan Claassen
- Department of Neurology, Vagelos College of Physicians and Surgeons, Columbia University, 177 Fort Washington Ave, New York, NY, 10032, USA
| | - Ernest E Moore
- Department of Surgery, Ernest E. Moore Shock Trauma Center at Denver Health, Denver, CO, USA
| | - Kirk Hansen
- Department of Biochemistry and Molecular Genetics, University of Colorado Denver, Aurora, CO, USA
| | - Eldad A Hod
- Department of Pathology and Cell Biology, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY, USA
| | - Richard O Francis
- Department of Pathology and Cell Biology, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY, USA
| | - David J Roh
- Department of Neurology, Vagelos College of Physicians and Surgeons, Columbia University, 177 Fort Washington Ave, New York, NY, 10032, USA.
| |
Collapse
|
|
7
|
Shaw JR, Nopp S, Stavik B, Youkhana K, Michels AL, Kennes S, Rak J, ten Cate H. Thrombosis, Translational Medicine, and Biomarker Research: Moving the Needle. J Am Heart Assoc 2025; 14:e038782. [PMID: 39719414 PMCID: PMC12054438 DOI: 10.1161/jaha.124.038782] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/26/2024]
Abstract
Arterial and venous thromboembolism are leading causes of morbidity and death worldwide. Despite significant advances in the diagnosis, prognostication, and treatment of thrombotic diseases over the past 3 decades, the adoption of findings stemming from translational biomarker research in clinical practice remains limited. Biomarkers provide an opportunity to enhance our understanding of pathophysiological processes and optimize treatment strategies. They hold the promise of revolutionizing patient care. Still, this potential remains untapped, and several factors impede their use for near-patient applications. We sought to provide an overview of biomarker research in arterial and venous thromboembolic disease. We then aimed to discuss key barriers to the broader clinical implementation of biomarker research and highlight promising strategies to overcome them. We emphasize the merits of translational and implementation science to bridge the gaps from bench to bedside. Innovative trial design, data sharing, and collaborative efforts between academia and industry will be essential. Purposeful regression methodology using rational conceptual framework design, causal mediation analysis, and artificial intelligence might better leverage the use of observational data. Dedicated translational science training programs geared toward educating physicians on the appropriate measurement, interpretation, and integration of biomarker data in clinical practice should foster endorsement by frontline physicians. Finally, we make the case in support of a paradigm shift in cardiovascular medicine. Improved recognition of biomarker research and a greater emphasis on mechanistic evidence can better equip clinicians to deal with the uncertainty that defines the practice of thrombosis medicine.
Collapse
Affiliation(s)
- Joseph R. Shaw
- Department of MedicineUniversity of Ottawa, and The Ottawa Hospital Research InstituteOttawaCanada
| | - Stephan Nopp
- Clinical Division of Hematology and HemostaseologyMedical University of ViennaAustria
| | - Benedicte Stavik
- Department of Hematology and The Research Institute of Internal MedicineOslo University HospitalOsloNorway
| | | | - Alison L. Michels
- Department of Surgery, Division of Vascular SurgeryMcMaster UniversityHamiltonCanada
| | - Soetkin Kennes
- Department of HematologyGhent University HospitalGhentBelgium
| | - Janusz Rak
- Department of Pediatrics and the Division of Experimental MedicineMcGill UniversityMontrealCanada
| | - Hugo ten Cate
- Cardiovascular Research Institute Maastricht, Maastricht UniversityMaastrichtNetherlands
| |
Collapse
|
|
8
|
Kim RS, Yoon U. Unexpected normal ROTEM results in protein C deficiency with IVC thrombosis. BMJ Case Rep 2024; 17:e262718. [PMID: 39551573 DOI: 10.1136/bcr-2024-262718] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/19/2024] Open
Abstract
Protein C deficiency is a hereditary disorder that increases the risk of thrombotic events but has unclear effects on rotational thromboelastometry (ROTEM) analysis. A man in his 60s with a history of protein C deficiency and multiple thrombotic events underwent inferior vena cava (IVC) filter removal, iliocaval thrombectomy and infrarenal IVC placement for IVC-related complete iliocaval and common femoral vein thromboses. A ROTEM analysis showed normal coagulation in NATEM and EXTEM and only a slight shortening in A10 and A20 in INTEM, which was unexpected given his diagnosis of protein C deficiency. Normal results indicate that there is complexity and variability of coagulation to maintain a balanced state even in individuals with underlying coagulation disorders.
Collapse
Affiliation(s)
- Rachel Seunah Kim
- Anesthesiology, Thomas Jefferson University Hospitals, Philadelphia, Pennsylvania, USA
| | - Uzung Yoon
- Anesthesiology, Thomas Jefferson University Hospitals, Philadelphia, Pennsylvania, USA
| |
Collapse
|
|
9
|
Yassen KA, Shahwar DI, Alrasasi AQ, Aldandan F, Alali DS, Almuslem MY, Hassanein N, Khan I, Görlinger K. Viscoelastic Hemostatic Testing as a Diagnostic Tool for Hypercoagulability in Liver Transplantation: A Narrative Review. J Clin Med 2024; 13:6279. [PMID: 39458229 PMCID: PMC11508851 DOI: 10.3390/jcm13206279] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2024] [Revised: 10/08/2024] [Accepted: 10/16/2024] [Indexed: 10/28/2024] Open
Abstract
Liver transplantation is a complex surgical procedure in which various forms of coagulation dysfunction can occur, including perioperative hypercoagulability. The hemostasis balance in liver graft recipients with end-stage liver disease can shift to thrombosis or haemorrhage, depending on the associated risk factors and clinical conditions. Hypercoagulability can result in serious complications such as thromboembolism, which can affect the vessels of the newly transplanted liver graft. Standard coagulation tests (SCTs), such as prothrombin time and activated partial thromboplastin time (aPTT), have a poor ability to diagnose and monitor an early stage of hypercoagulability. Recent studies demonstrated that viscoelastic hemostatic elastic tests (VETs), such as rotational thromboelastometry (ROTEM) and thromboelastography (TEG), are promising alternative tools for diagnosing hypercoagulability disorders. VETs measure clotting and clot formation time, clot strength (maximum clot firmness), fibrin and platelet contribution to clot firmness, and fibrinolysis, which makes them more sensitive in identifying liver graft recipients at risk for thrombosis as compared with SCTs. However, developing evidence-based guidelines for the prophylaxis and treatment of hypercoagulability based on VET results is still needed.
Collapse
Affiliation(s)
- Khaled Ahmed Yassen
- Anaesthesia Unit, Surgery Department, College of Medicine, King Faisal University, P.O. Box 400, AlAhsa 31982, Saudi Arabia;
| | - Dur I Shahwar
- Anaesthesia Unit, Surgery Department, College of Medicine, King Faisal University, P.O. Box 400, AlAhsa 31982, Saudi Arabia;
| | - Aqeel Qasem Alrasasi
- Alumini, College of Medicine, King Faisal University, P.O. Box 400, AlAhsa 31982, Saudi Arabia; (A.Q.A.); (D.S.A.); (M.Y.A.)
| | - Feras Aldandan
- Alumini, College of Medicine, King Faisal University, P.O. Box 400, AlAhsa 31982, Saudi Arabia; (A.Q.A.); (D.S.A.); (M.Y.A.)
| | - Danah Sami Alali
- Alumini, College of Medicine, King Faisal University, P.O. Box 400, AlAhsa 31982, Saudi Arabia; (A.Q.A.); (D.S.A.); (M.Y.A.)
| | - Maryam Yousef Almuslem
- Alumini, College of Medicine, King Faisal University, P.O. Box 400, AlAhsa 31982, Saudi Arabia; (A.Q.A.); (D.S.A.); (M.Y.A.)
| | - Nouran Hassanein
- Alumini, College of Medicine, Alfaisal University, P.O. Box 50927, Riyadh 11533, Saudi Arabia;
| | - Imtiyaz Khan
- Surgery Department, College of Medicine, King Faisal University, P.O. Box 400, AlAhsa 31982, Saudi Arabia;
| | - Klaus Görlinger
- Medical Director, Tem Innovations GmbH, 81829 Munich, Germany;
| |
Collapse
|
|
10
|
Cilek N, Ugurel E, Eren OC, Yalcin O, Akay OM. A global assessment of hemostatic function of healthy allogeneic stem cell donors undergoing apheresis by rotational thromboelastometry. Ther Apher Dial 2024; 28:657-663. [PMID: 38462734 DOI: 10.1111/1744-9987.14120] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2024] [Revised: 02/13/2024] [Accepted: 02/26/2024] [Indexed: 03/12/2024]
Abstract
INTRODUCTION Peripheral blood stem cell (PBSC) collection via apheresis requires the administration of granulocyte colony-stimulating factor (filgrastim) to stem cell donors. Several reports have shown that filgrastim administration and apheresis procedure induce a hypercoagulable state across PBSC collection, which might predispose certain donors to thrombotic complications. METHODS We evaluated the hemostatic functions of healthy allogeneic stem cell donors by rotational thromboelastometry (ROTEM). Blood samples from healthy donors (n = 30) were collected at defined time points: before filgrastim (baseline), on the day of apheresis before and after the procedure, and 1 week after apheresis. RESULTS The results indicated that hemostatic changes are temporary since all parameters in both EXTEM and INTEM assays are restored to their initial values 1 week after the apheresis. CONCLUSION We concluded that stem cell apheresis does not induce a hypercoagulable state in healthy donors. This is the first study evaluating the hemostatic functions of stem cell donors by ROTEM.
Collapse
Affiliation(s)
- Neslihan Cilek
- Research Center for Translational Medicine (KUTTAM), Koc University, Istanbul, Turkey
- Graduate School of Health Sciences, Koc University, Istanbul, Turkey
| | - Elif Ugurel
- Research Center for Translational Medicine (KUTTAM), Koc University, Istanbul, Turkey
- Department of Physiology, School of Medicine, Koc University, Istanbul, Turkey
| | - Ozgur Can Eren
- Department of Pathology, Koc University Hospital, Istanbul, Turkey
| | - Ozlem Yalcin
- Research Center for Translational Medicine (KUTTAM), Koc University, Istanbul, Turkey
- Department of Physiology, School of Medicine, Koc University, Istanbul, Turkey
| | - Olga Meltem Akay
- Department of Haematology, Koc University Hospital, Istanbul, Turkey
| |
Collapse
|
|
11
|
Matsuoka T, Fujikawa T, Kawamura Y, Hasegawa S. Impact of Preoperative Continued Aspirin Therapy on Perioperative Bleeding Complications in Patients Undergoing Gastrectomy for Malignancy. Cureus 2024; 16:e65303. [PMID: 39184653 PMCID: PMC11343640 DOI: 10.7759/cureus.65303] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/24/2024] [Indexed: 08/27/2024] Open
Abstract
Background The question of whether antiplatelet therapy (APT) should be discontinued prior to gastrectomy is controversial. In this study, we investigated the impact of continuing aspirin preoperatively on perioperative bleeding and thromboembolic complications in patients receiving gastrectomy for malignancy. Methods The study cohort comprised 1001 patients with malignant gastric tumors who had undergone gastrectomy between 2005 and 2021. This study excludes emergency surgery. The patients were allocated to the following three groups: those who continued aspirin monotherapy prior to surgery (cAPT group), those who stopped receiving it seven days prior to surgery (dAPT group), and those who did not take APT at any stage (non-APT group). The differences between the groups in intraoperative and postoperative complications, such as bleeding and thromboembolism, were examined. Results The non-APT group comprised 682 patients, the dAPT group had 164, and the cAPT group had 155. There were 22 bleeding events (2.2%) in the whole cohort, 11 (1.1%) of which occurred in the non-APT group, six (3.7%) in the dAPT group, and five (3.2%) in the cAPT group. The differences between the three groups were not significant in terms of bleeding complications. There were 10 (1.0%) thromboembolic events in the whole cohort, five (0.7%) of which occurred in the non-APT group, four (2.4%) in the dAPT group, and one (0.6%) in the cAPT group. The differences between the three groups were not significant in terms of thromboembolic complications. In a multivariate analysis of the whole cohort, intraoperative blood loss (≥1000 mL) (p < 0.001, odds ratio (OR) = 11.8) and multidrug APT (p < 0.001, OR = 7.8) were both independent predictors of bleeding complications. However, continuing to take aspirin before surgery was not a risk factor for bleeding complications. Conclusions In patients with malignant gastric tumors, preoperative continuation of aspirin monotherapy has no impact on either intraoperative or postoperative bleeding. Gastrectomy can be performed safely, even in patients who continue aspirin treatment.
Collapse
Affiliation(s)
| | | | | | - Suguru Hasegawa
- Gastroenterological Surgery, Fukuoka University Hospital, Fukuoka, JPN
| |
Collapse
|
|
12
|
Pamulapati S, Conroy M, Madireddy S, Kamaraju S, Cortina C, Moore H, Hartmann J. Applications of Viscoelastic Testing in Breast Cancer Patients: A Systematic Review Focusing on Hypercoagulability and Free Flap Thrombosis. Semin Thromb Hemost 2024; 50:413-422. [PMID: 37327882 DOI: 10.1055/s-0043-1769937] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/18/2023]
Abstract
Viscoelastic testing is a clinically available method to assess hypercoagulability. This systematic review aims to provide a comprehensive overview of the existing literature and the potential use of such testing in patients with breast cancer. A systematic literature search for studies investigating the application of viscoelastic testing for patients with breast cancer was conducted. Studies were included as long as they were original, peer-reviewed, and in the English language. Studies were excluded if they were review articles, did not include breast cancer patients, or if the full text was unavailable. This review identified 10 articles that met the inclusion criteria. Two of the studies utilized rotational thromboelastometry, and an additional four studies used thromboelastography, to assess hypercoagulability in patients with breast cancer. Three of the identified articles discussed the use of thromboelastometry in free flap breast reconstruction for patients with breast cancer. One study was a retrospective chart review looking at thromboelastography and microsurgical breast reconstruction. Current literature regarding the application of viscoelastic testing in breast cancer and free flap breast reconstruction is limited, with no randomized trials thus far. However, some studies suggest that there may be potential utility in viscoelastic testing to assess risk for thromboembolism in breast cancer patients, and future research in this area is warranted.
Collapse
Affiliation(s)
| | | | | | - Sailaja Kamaraju
- Division of Hematology and Oncology, Medical College of Wisconsin, Milwaukee, Wisconsin
| | - Chandler Cortina
- Division of Surgical Oncology, Medical College of Wisconsin, Milwaukee, Wisconsin
| | - Hunter Moore
- Division of Surgery-Transplant, University of Colorado School of Medicine, Aurora, Colorado
| | | |
Collapse
|
|
13
|
Duque P, Perez-Peña JM, Alarcon-Perez L, Olmedilla L, Varela JA, Pascual C, Rodriguez-Huerta AM, Asencio JM, Lopez-Baena JÁ, Garutti I. The link between high factor VIII to protein C ratio values and poor liver function after major hepatectomy. Blood Coagul Fibrinolysis 2024; 35:82-93. [PMID: 38305104 DOI: 10.1097/mbc.0000000000001277] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/03/2024]
Abstract
Our goal was to assess the coagulation profile in the immediate postoperative time after major liver surgery and its association with the liver function. Our hypothesis is that a decreased synthesis of the coagulation factor levels reflects an impaired liver synthesis following hepatic resection and will be associated with poor outcomes. This is a prospective, observational study recruiting consecutive patients scheduled for major liver resection in a tertiary hospital. Coagulation profile was assessed by conventional assays, viscoelastic assays and coagulation factor levels preoperatively and, on postoperative days 1, 2 and 6. Factor VIII to protein C (FVIII/PC) ratio has been used as a surrogate marker of hemostatic imbalance. Liver function was measured with conventional and indocyanine green (ICG) clearance tests, which were obtained preoperatively and on postoperative days 1 and 2. Sixty patients were recruited and 51 were included in the study. There is a clear increase in FVIII/PC ratio after surgery, which was significantly associated with low liver function, being more pronounced beyond postoperative day 2 and in patients with poorer liver function ( P < 0.001). High FVIII/PC ratio values were significantly associated with higher postoperative morbidity, prolonged ICU and hospital stay and less survival ( P < 0.05). High FVIII/PC ratio on postoperative day 2 was found to be predictor of posthepatectomy liver failure (PHLF; area under the ROC curve = 0.8129). Early postoperative high FVIII/PC ratio values are associated with low liver function, PHLF and poorer outcomes in patients undergoing major hepatic resection.
Collapse
Affiliation(s)
- Patricia Duque
- Anesthesiology Department
- Gregorio Marañon Health Research Institute
| | | | | | - Luis Olmedilla
- Anesthesiology Department
- Gregorio Marañon Health Research Institute
| | | | | | | | - José Manuel Asencio
- General Surgery Department, Gregorio Marañon Hospital
- Gregorio Marañon Health Research Institute
- Medical Faculty, Complutense University, Madrid, Spain
| | - Jose Ángel Lopez-Baena
- General Surgery Department, Gregorio Marañon Hospital
- Gregorio Marañon Health Research Institute
| | - Ignacio Garutti
- Anesthesiology Department
- Gregorio Marañon Health Research Institute
- Medical Faculty, Complutense University, Madrid, Spain
| |
Collapse
|
|
14
|
Sieh L, Peasley E, Mao E, Mitchell A, Heinonen G, Ghoshal S, Agarwal S, Park S, Connolly ESS, Claassen J, Moore EE, Hansen K, Hod EA, Francis RO, Roh D. Admission viscoelastic hemostatic assay parameters predict poor long-term intracerebral hemorrhage outcomes. RESEARCH SQUARE 2024:rs.3.rs-4087284. [PMID: 38585893 PMCID: PMC10996822 DOI: 10.21203/rs.3.rs-4087284/v1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 04/09/2024]
Abstract
Background Viscoelastic hemostatic assays (VHA) provide more comprehensive assessments of coagulation compared to conventional coagulation assays. While VHAs have enabled guided hemorrhage control therapies, improving clinical outcomes in life-threatening hemorrhage, the role of VHAs in intracerebral hemorrhage (ICH) is unclear. If VHAs can identify coagulation abnormalities relevant for ICH outcomes, this would support the need to investigate the role of VHAs in ICH treatment paradigms. Thus, we investigated whether VHA assessments of coagulation relate to long-term ICH outcomes. Methods Spontaneous ICH patients enrolled into a single-center cohort study receiving admission Rotational Thromboelastometry (ROTEM) VHA testing between 2013 and 2020 were assessed. Patients with prior anticoagulant use or coagulopathy on conventional coagulation assays were excluded. Primary ROTEM exposure variables were coagulation kinetics and clot strength assessments. Poor long-term outcome was defined as modified Rankin Scale ≥ 4 at 6 months. Logistic regression analyses assessed associations of ROTEM parameters with clinical outcomes after adjusting for ICH severity and hemoglobin concentration. Results Of 44 patients analyzed, mean age was 64, 57% were female, and the median ICH volume was 23 mL. Poor 6-month outcome was seen in 64%. In our multivariable regression models, slower, prolonged coagulation kinetics (adjusted OR for every second increase in clot formation time: 1.04, 95% CI: 1.00-1.09, p = 0.04) and weaker clot strength (adjusted OR for every millimeter increase of maximum clot firmness: 0.84, 95% CI: 0.71-0.99, p = 0.03) were separately associated with poor long-term outcomes. Conclusions Slower, prolonged coagulation kinetics and weaker clot strength on admission VHA ROTEM testing, not attributable to anticoagulant use, were associated with poor long-term outcomes after ICH. Further work is needed to clarify the generalizability and the underlying mechanisms of these VHA findings to assess whether VHA guided treatments should be incorporated into ICH care.
Collapse
Affiliation(s)
- Laura Sieh
- Columbia University Vagelos College of Physicians and Surgeons
| | | | | | | | | | | | | | | | | | | | | | | | | | | | | |
Collapse
|
|
15
|
Simurda T, Marchi R, Casini A, Neerman-Arbez M, Drotarova M, Skornova I, Zolkova J, Kolkova Z, Loderer D, Brunclikova M, Belakova KM, Stasko J. Diagnostic value of clot formation parameters determined by rotational thromboelastometry in 63 patients with congenital dysfibrinogenemia. Blood Coagul Fibrinolysis 2024; 35:56-61. [PMID: 38251440 PMCID: PMC10927300 DOI: 10.1097/mbc.0000000000001274] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2023] [Revised: 01/02/2024] [Accepted: 01/08/2024] [Indexed: 01/23/2024]
Abstract
Rotational thromboelastometry (ROTEM) is a global hemostasis assay. The diagnosis added value of ROTEM in congenital dysfibrinogenemia remains to be established. The aim of this study was to analyze clot formation by ROTEM in a cohort of dysfibrinogenemic patients and to establish correlations with genotype, clinical features, and coagulation parameters. The study included genetically confirmed congenital dysfibrinogenemia cases (n = 63) and healthy controls ( n = 50). EXTEM, INTEM, FIBTEM tests were used to measure ROTEM parameters, that is, clotting time (CT), clot formation time (CFT), maximal clot firmness (MCF) and amplitude 10 min after CT (A10). The ISTH bleeding assessment tool was used to determine bleeding episodes. CT (INTEM) was statistically significantly shorter in congenital dysfibrinogenemia patients compared to controls while CFT (EXTEM) was prolonged. Patients's MCF in EXTEM, INTEM, and FIBTEM were similar to controls while A10 (FIBTEM) was statistically significantly lower. Fibrinogen activity was positively correlated with fibrinogen antigen, A10 and MCF in all three assays. Bleeding phenotypes were observed in 23 (36.5%) patients. Only CFT in EXTEM and CT in INTEM were statistically different in patients with bleeding phenotype versus controls. Carriers of the FGA mutation p.Arg35His had a CT (EXTEM) slightly prolonged and a reduced A10 (FIBTEM) compared to controls. Some ROTEM parameters were able to distinguish congenital dysfibrinogenemia patients from controls, and patients with a bleeding phenotype. Prolonged CFT in EXTEM were associated with congenital dysfibrinogenemia and bleeding phenotype. Bleeding episodes in most patients were generally mild and prevalence of thrombosis was very low.
Collapse
Affiliation(s)
- Tomas Simurda
- National Centre of Hemostasis and Thrombosis, Department of Hematology and Transfusiology, Comenius University in Bratislava, Jessenius Faculty of Medicine in Martin and University Hospital in Martin, Martin, Slovakia
| | - Rita Marchi
- Division of Angiology and Hemostasis, University Hospitals of Geneva and Faculty of Medicine
| | - Alessandro Casini
- Division of Angiology and Hemostasis, University Hospitals of Geneva and Faculty of Medicine
| | - Marguerite Neerman-Arbez
- Department of Genetic Medicine and Development, Faculty of Medicine, University of Geneva, Geneva, Switzerland
| | - Miroslava Drotarova
- National Centre of Hemostasis and Thrombosis, Department of Hematology and Transfusiology, Comenius University in Bratislava, Jessenius Faculty of Medicine in Martin and University Hospital in Martin, Martin, Slovakia
| | - Ingrid Skornova
- National Centre of Hemostasis and Thrombosis, Department of Hematology and Transfusiology, Comenius University in Bratislava, Jessenius Faculty of Medicine in Martin and University Hospital in Martin, Martin, Slovakia
| | - Jana Zolkova
- National Centre of Hemostasis and Thrombosis, Department of Hematology and Transfusiology, Comenius University in Bratislava, Jessenius Faculty of Medicine in Martin and University Hospital in Martin, Martin, Slovakia
| | - Zuzana Kolkova
- Biomedical Center Martin, Comenius University in Bratislava, Jessenius Faculty of Medicine in Martin, Martin, Slovakia
| | - Dusan Loderer
- Biomedical Center Martin, Comenius University in Bratislava, Jessenius Faculty of Medicine in Martin, Martin, Slovakia
| | - Monika Brunclikova
- National Centre of Hemostasis and Thrombosis, Department of Hematology and Transfusiology, Comenius University in Bratislava, Jessenius Faculty of Medicine in Martin and University Hospital in Martin, Martin, Slovakia
| | - Kristina Maria Belakova
- National Centre of Hemostasis and Thrombosis, Department of Hematology and Transfusiology, Comenius University in Bratislava, Jessenius Faculty of Medicine in Martin and University Hospital in Martin, Martin, Slovakia
| | - Jan Stasko
- National Centre of Hemostasis and Thrombosis, Department of Hematology and Transfusiology, Comenius University in Bratislava, Jessenius Faculty of Medicine in Martin and University Hospital in Martin, Martin, Slovakia
| |
Collapse
|
|
16
|
Beznoshchenco OS, Romanov AY, Dolgushina NV, Gorodnova EA, Ivanets TY, Yarotskaya EL, Pyregov AV, Grachev SV, Sukhikh GT. Procoagulant Status and Fibrinolytic Activity in COVID-19 Patients during Illness and Convalescence. Biomedicines 2023; 12:42. [PMID: 38255149 PMCID: PMC10813055 DOI: 10.3390/biomedicines12010042] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2023] [Revised: 12/11/2023] [Accepted: 12/15/2023] [Indexed: 01/24/2024] Open
Abstract
SARS-CoV-2 (Severe Acute Respiratory Syndrome-related CoronaVirus 2) activates the immune system, causing thrombin dysregulation and tissue damage and reduces endothelium anticoagulant function, leading to excessive thrombin formation. Hypercoagulability, which causes multiple organ failure in critically ill COVID-19 (COronaVIrus Disease 2019) patients, can be detected by viscoelastic tests like thromboelastography and rotational thromboelastometry (ROTEM). We aimed to assess the coagulation system status and fibrinolytic activity using ROTEM thromboelastometry in patients with COVID-19 and convalescents. The observational prospective study included 141 patients with COVID-19: Group 1-patients with mild (n = 39), Group 2-patients with moderate (n = 65), and Group 3-patients with severe (n = 37) COVID-19. The coagulation status was assessed twice-during the disease and in convalescence. The male gender, age > 56 years, overweight, and obesity were risk factors for developing severe COVID-19. During the disease in patients with moderate and severe COVID-19, the hemostatic system was characterized by a procoagulant status, which persists during the period of convalescence. Fibrinolysis shutdown was detected in both moderate and severe patients with COVID-19. The procoagulant status of the coagulation system and the shutdown of fibrinolysis are typical for patients with moderate to severe COVID-19. In convalescents, activation of coagulation remains, which indicates the need to monitor the hemostatic system after Illness.
Collapse
Affiliation(s)
- Olga S. Beznoshchenco
- National Medical Research Center for Obstetrics, Gynecology and Perinatology Named after Academician V.I. Kulakov of the Ministry of Health of the Russian Federation, 117997 Moscow, Russia; (O.S.B.); (N.V.D.); (E.A.G.); (T.Y.I.); (E.L.Y.); (A.V.P.); (G.T.S.)
| | - Andrey Yu. Romanov
- National Medical Research Center for Obstetrics, Gynecology and Perinatology Named after Academician V.I. Kulakov of the Ministry of Health of the Russian Federation, 117997 Moscow, Russia; (O.S.B.); (N.V.D.); (E.A.G.); (T.Y.I.); (E.L.Y.); (A.V.P.); (G.T.S.)
| | - Nataliya V. Dolgushina
- National Medical Research Center for Obstetrics, Gynecology and Perinatology Named after Academician V.I. Kulakov of the Ministry of Health of the Russian Federation, 117997 Moscow, Russia; (O.S.B.); (N.V.D.); (E.A.G.); (T.Y.I.); (E.L.Y.); (A.V.P.); (G.T.S.)
- Federal State Autonomous Educational Institution of Higher Education I.M. Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation (Sechenov University), Ministry of Health of the Russian Federation, 119048 Moscow, Russia;
| | - Elena A. Gorodnova
- National Medical Research Center for Obstetrics, Gynecology and Perinatology Named after Academician V.I. Kulakov of the Ministry of Health of the Russian Federation, 117997 Moscow, Russia; (O.S.B.); (N.V.D.); (E.A.G.); (T.Y.I.); (E.L.Y.); (A.V.P.); (G.T.S.)
| | - Tatiana Yu. Ivanets
- National Medical Research Center for Obstetrics, Gynecology and Perinatology Named after Academician V.I. Kulakov of the Ministry of Health of the Russian Federation, 117997 Moscow, Russia; (O.S.B.); (N.V.D.); (E.A.G.); (T.Y.I.); (E.L.Y.); (A.V.P.); (G.T.S.)
| | - Ekaterina L. Yarotskaya
- National Medical Research Center for Obstetrics, Gynecology and Perinatology Named after Academician V.I. Kulakov of the Ministry of Health of the Russian Federation, 117997 Moscow, Russia; (O.S.B.); (N.V.D.); (E.A.G.); (T.Y.I.); (E.L.Y.); (A.V.P.); (G.T.S.)
| | - Aleksey V. Pyregov
- National Medical Research Center for Obstetrics, Gynecology and Perinatology Named after Academician V.I. Kulakov of the Ministry of Health of the Russian Federation, 117997 Moscow, Russia; (O.S.B.); (N.V.D.); (E.A.G.); (T.Y.I.); (E.L.Y.); (A.V.P.); (G.T.S.)
| | - Sergej V. Grachev
- Federal State Autonomous Educational Institution of Higher Education I.M. Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation (Sechenov University), Ministry of Health of the Russian Federation, 119048 Moscow, Russia;
| | - Gennady T. Sukhikh
- National Medical Research Center for Obstetrics, Gynecology and Perinatology Named after Academician V.I. Kulakov of the Ministry of Health of the Russian Federation, 117997 Moscow, Russia; (O.S.B.); (N.V.D.); (E.A.G.); (T.Y.I.); (E.L.Y.); (A.V.P.); (G.T.S.)
- Federal State Autonomous Educational Institution of Higher Education I.M. Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation (Sechenov University), Ministry of Health of the Russian Federation, 119048 Moscow, Russia;
| |
Collapse
|
|
17
|
Abstract
Viscoelastic testing methods examine the real-time formation of a clot in a whole blood sample, and include thromboelastography (TEG), rotational thromboelastometry (ROTEM), and several other testing platforms. They allow for concurrent assessment of multiple aspects of clotting, including plasmatic coagulation factors, platelets, fibrinogen, and the fibrinolytic pathway. This testing is rapid and may be performed at the point-of-care, allowing for prompt identification of coagulopathies to guide focused and rational administration of blood products as well as the identification of anticoagulant effect. With recent industry progression towards user-friendly, cartridge-based, portable instruments, viscoelastic testing has emerged in the 21st century as a powerful tool to guide blood transfusions in the bleeding patient, and to identify and treat both bleeding and thrombotic conditions in many operative settings, including trauma surgery, liver transplant surgery, cardiac surgery, and obstetrics. In these settings, the use of transfusion algorithms guided by viscoelastic testing data has resulted in widespread improvements in patient blood management as well as modest improvements in select patient outcomes. To address the increasingly wide adoption of viscoelastic methods and the growing number of medical and laboratory personnel tasked with implementing, performing, and interpreting these methods, this chapter provides an overview of the history, physiology, and technology behind viscoelastic testing, as well as a practical review of its clinical utility and current evidence supporting its use. Also included is a review of testing limitations and the contextual role played by viscoelastic methods among all coagulation laboratory testing.
Collapse
Affiliation(s)
- Timothy Carll
- Department of Pathology, University of Chicago, Chicago, IL, United States.
| |
Collapse
|
|
18
|
Wool GD, Carll T. Viscoelastic testing: Critical appraisal of new methodologies and current literature. Int J Lab Hematol 2023; 45:643-658. [PMID: 37559473 DOI: 10.1111/ijlh.14144] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2023] [Accepted: 07/25/2023] [Indexed: 08/11/2023]
Abstract
United States Food and Drug Administration (FDA)-approved viscoelastic testing (VET) methodologies have significantly changed in the last 10 years, with the availability of cartridge-based VET. Some of these cartridge-based methodologies use harmonic resonance-based clot detection. While VET has always allowed for the evaluation of real-time clot formation, cartridge-based VET provides increased ease of use as well as greater portability and robustness of results in out-of-laboratory environments. Here we review the use of VET in a variety of clinical contexts, including cardiac surgery, trauma, liver transplant, obstetrics, and hypercoagulable states such as COVID-19. As of now, high quality randomized trial evidence for new generation VET (TEG 6s, HemoSonics Quantra, ROTEM sigma) is limited. Nevertheless, the use of VET-guided transfusion algorithms appears to result in reduced blood usage without worsening of patient outcomes. Future work comparing the new generation VET instruments and continuing to validate clinically important cut-offs will help move the field of point-of-care coagulation monitoring forward and increase the quality of transfusion management in bleeding patients.
Collapse
Affiliation(s)
- Geoffrey D Wool
- Department of Pathology, University of Chicago, Chicago, Illinois, USA
| | - Timothy Carll
- Department of Pathology, University of Chicago, Chicago, Illinois, USA
| |
Collapse
|
|
19
|
Wilson S, Joseph J, Danta M, Rabbolini DJ. Viscoelastometry to Manage Bleeding in Liver Disease. Cureus 2023; 15:e41401. [PMID: 37546051 PMCID: PMC10402654 DOI: 10.7759/cureus.41401] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/05/2023] [Indexed: 08/08/2023] Open
Abstract
A state of "re-balanced haemostasis" describes complex coagulation changes that arise in patients with liver disease. Changes include alterations in procoagulant and anticoagulant proteins, platelets and von Willebrand factor, as well as the fibrinolytic system. Various circumstances including infection, trauma, or surgery may disrupt this balance and predispose an individual to bleeding or thrombosis. The prothrombin time, international normalised ratio, and activated partial thromboplastin time are conventional coagulation screening tests that are routinely employed by clinicians to investigate unexplained bleeding, monitor anticoagulation, and inform preoperative assessments of bleeding risk. These standard coagulation tests assess quantitative defects in procoagulant clotting factors and are insensitive to levels of natural anticoagulants, which together with procoagulant factors, are often perturbed in liver disease. Therefore, the prolongation of clotting times measured by these tests often does not reflect the multifaceted alterations of haemostasis in these patients. Viscoelastic testing (VET) provides a more encompassing assessment of clotting function by recording real-time viscoelastic changes in whole blood and includes parameters that provide information on coagulation factor function, platelet contribution to clot formation, as well as fibrinolysis. To date, VET has been employed to predict and inform transfusion support in obstetric, trauma, and cardiac surgical fields, and its use in patients undergoing liver transplantation is well established. The ability of VET to accurately predict bleeding risk and precisely guide transfusion algorithms for patients with liver disease undergoing other invasive procedures or experiencing bleeding complications has been the topic of research over the last decade. This review is a critical summary of this data and provides a detailed snapshot of the position of VET as a clinical tool in patients with liver disease.
Collapse
Affiliation(s)
- Samantha Wilson
- Gastroenterology and Hepatology, School of Clinical Medicine, St. Vincent's Healthcare Campus, Faculty of Medicine, University of New South Wales, Sydney, AUS
| | - Joanne Joseph
- Hematology, School of Clinical Medicine, St. Vincent's Healthcare Campus, Faculty of Medicine, University of New South Wales, Sydney, AUS
- Hematology, St. Vincent's Centre for Applied Medical Research, St Vincent's Hospital, Sydney, AUS
| | - Mark Danta
- Gastroenterology and Hepatology, School of Clinical Medicine, St. Vincent's Healthcare Campus, Faculty of Medicine, University of New South Wales, Sydney, AUS
- Gastroenterology and Hepatology, St. Vincent's Hospital, Sydney, AUS
| | - David J Rabbolini
- Faculty of Medicine and Health, University of Sydney, Sydney, AUS
- Haematology, Oxford University Hospitals NHS Foundation Trust, Oxford, GBR
| |
Collapse
|
|
20
|
Pérez-Calatayud AA, Hofmann A, Pérez-Ferrer A, Escorza-Molina C, Torres-Pérez B, Zaccarias-Ezzat JR, Sanchez-Cedillo A, Manuel Paez-Zayas V, Carrillo-Esper R, Görlinger K. Patient Blood Management in Liver Transplant—A Concise Review. Biomedicines 2023; 11:biomedicines11041093. [PMID: 37189710 DOI: 10.3390/biomedicines11041093] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2023] [Revised: 03/09/2023] [Accepted: 03/13/2023] [Indexed: 04/07/2023] Open
Abstract
Transfusion of blood products in orthotopic liver transplantation (OLT) significantly increases post-transplant morbidity and mortality and is associated with reduced graft survival. Based on these results, an active effort to prevent and minimize blood transfusion is required. Patient blood management is a revolutionary approach defined as a patient-centered, systematic, evidence-based approach to improve patient outcomes by managing and preserving a patient’s own blood while promoting patient safety and empowerment. This approach is based on three pillars of treatment: (1) detecting and correcting anemia and thrombocytopenia, (2) minimizing iatrogenic blood loss, detecting, and correcting coagulopathy, and (3) harnessing and increasing anemia tolerance. This review emphasizes the importance of the three-pillar nine-field matrix of patient blood management to improve patient outcomes in liver transplant recipients.
Collapse
Affiliation(s)
| | - Axel Hofmann
- Faculty of Health and Medical Sciences, Discipline of Surgery, The University of Western Australia, Perth 6907, WA, Australia
- Institute of Anesthesiology, University of Zurich and University Hospital Zurich, 8057 Zurich, Switzerland
| | - Antonio Pérez-Ferrer
- Department of Anesthesiology, Infanta Sofia University Hospital, 28700 San Sebastián de los Reyes, Spain
- Department of Anesthesiology, European University of Madrid, 28702 Madrid, Spain
| | - Carla Escorza-Molina
- Departmen of Anesthesiology, Hospital General de México Dr. Eduardo Liceaga, Mexico City 06720, Mexico
| | - Bettina Torres-Pérez
- Department of Anesthesiology, Pediatric Transplant, Centro Medico de Occidente, Instituto Mexicano del Seguro Social, Guadalajara 44329, Mexico
| | | | - Aczel Sanchez-Cedillo
- Transplant Department Hospital General de México Dr. Eduardo Liceaga, Mexico City 06720, Mexico
| | - Victor Manuel Paez-Zayas
- Gastroenterology Department Hospital General de México Dr. Eduardo Liceaga, Mexico City 06720, Mexico
| | | | - Klaus Görlinger
- Department of Anesthesiology and Intensive Care Medicine, University Hospital Essen, University Duisburg-Essen, 45131 Essen, Germany
- TEM Innovations GmbH, 81829 Munich, Germany
| |
Collapse
|
|
21
|
Lim HY, Ho P. Thrombosis Risk Assessment in Myeloproliferative Neoplasm-Is There a Role for Viscoelastic Testing? Semin Thromb Hemost 2023; 49:173-181. [PMID: 36055269 DOI: 10.1055/s-0042-1753483] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Philadelphia chromosome-negative myeloproliferative neoplasms include polycythemia vera, essential thrombocythemia, and myelofibrosis. They are associated with increased thrombotic events, and the primary goal of therapy, in particular those with polycythemia vera and essential thrombocythemia, is the prevention of thrombotic complications typically with antiplatelet therapy and/or cytoreduction. While several patient-, disease-, and genomic-related factors have been identified to influence thrombotic risks, there are no routine laboratory investigations to date that are sufficiently accurate to assess the underlying procoagulant state and predict the thrombotic risks. Conventional coagulation testing only measures time to clot formation and cannot reliably predict bleeding and thrombotic risks. Global coagulation assays such as thromboelastography, thrombin, and fibrin generation may provide a more thorough assessment of hemostatic function. Thromboelastography and thromboelastometry are viscoelastic tests which measure the mechanical properties of the hemostatic process, including the global dynamics of clot formation, stabilization, and dissolution. While viscoelastic testing is gaining traction in the investigations of coagulopathies and goal-directed blood product replacement in trauma and massive transfusion settings, the role of these assays in thrombosis is less well defined. Here, we provide a review of the current evidence of the role of viscoelastic testing in myeloproliferative neoplasm, particularly in the thrombotic risk assessment.
Collapse
Affiliation(s)
- Hui Yin Lim
- Department of Hematology, Northern Pathology Victoria, Northern Hospital, Epping VIC, Australia.,Australian Centre for Blood Diseases, Monash University, Melbourne VIC, Australia.,Department of Medicine, Northern Health, University of Melbourne, Heidelberg, VIC, Australia
| | - Prahlad Ho
- Department of Hematology, Northern Pathology Victoria, Northern Hospital, Epping VIC, Australia.,Australian Centre for Blood Diseases, Monash University, Melbourne VIC, Australia.,Department of Medicine, Northern Health, University of Melbourne, Heidelberg, VIC, Australia
| |
Collapse
|
|
22
|
Stewart E, Nydam TL, Hendrickse A, Pomposelli JJ, Pomfret EA, Moore HB. Viscoelastic Management of Coagulopathy during the Perioperative Period of Liver Transplantation. Semin Thromb Hemost 2023; 49:119-133. [PMID: 36318962 PMCID: PMC10366939 DOI: 10.1055/s-0042-1758058] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
Viscoelastic testing (VET) in liver transplantation (LT) has been used since its origin, in combination with standard laboratory testing (SLT). There are only a few, small, randomized controlled trials that demonstrated a reduction in transfusion rates using VET to guide coagulation management. Retrospective analyses contrasting VET to SLT have demonstrated mixed results, with a recent concern for overtreatment and the increase in postoperative thrombotic events. An oversight of many studies evaluating VET in LT is a single protocol that does not address the different phases of surgery, in addition to pre- and postoperative management. Furthermore, the coagulation spectrum of patients entering and exiting the operating room is diverse, as these patients can have varying anatomic and physiologic risk factors for thrombosis. A single transfusion strategy for all is short sighted. VET in combination with SLT creates the opportunity for personalized resuscitation in surgery which can address the many challenges in LT where patients are at a paradoxical risk for both life-threatening bleeding and clotting. With emerging data on the role of rebalanced coagulation in cirrhosis and hypercoagulability following LT, there are numerous potential roles in VET management of LT that have been unaddressed.
Collapse
Affiliation(s)
- Erin Stewart
- Department of Anesthesia, University of Colorado School of Medicine, Aurora, Colorado
| | - Trevor L. Nydam
- Division of Transplant Surgery, Department of Surgery, University of Colorado School of Medicine, Aurora, Colorado
| | - Adrian Hendrickse
- Department of Anesthesia, University of Colorado School of Medicine, Aurora, Colorado
| | - James J. Pomposelli
- Division of Transplant Surgery, Department of Surgery, University of Colorado School of Medicine, Aurora, Colorado
| | - Elizabeth A. Pomfret
- Division of Transplant Surgery, Department of Surgery, University of Colorado School of Medicine, Aurora, Colorado
| | - Hunter B. Moore
- Division of Transplant Surgery, Department of Surgery, University of Colorado School of Medicine, Aurora, Colorado
| |
Collapse
|
|
23
|
Yagi T, Fujita M, Harada K, Shin M, Esaki Y, Ayata R, Koga Y, Kaneda K, Tsuruta R. Time Course of Coagulopathy Evaluated with Rotational Thromboelastometry in Patients with Severe Coronavirus Disease 2019. Intern Med 2023; 62:717-722. [PMID: 36543214 PMCID: PMC10037019 DOI: 10.2169/internalmedicine.0993-22] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/12/2022] [Accepted: 11/13/2022] [Indexed: 12/24/2022] Open
Abstract
Objectives Coronavirus disease 2019 (COVID-19) reportedly causes thromboembolic complications due to coagulopathy with hypercoagulability and a hypofibrinolytic state. We evaluated the time-course of coagulopathy in patients with severe COVID-19 from admission to discharge from our intensive-care unit (ICU). Methods We conducted a retrospective study of adults with severe COVID-19 admitted to our ICU between January 20, 2021, and March 31, 2022. We obtained clinical information, laboratory data, and rotational thromboelastometry (ROTEM) parameters at admission and discharge. Results Fifteen patients were included. Fibrinogen and D-dimer values did not change significantly but were above the normal ranges at admission and discharge. Regarding ROTEM parameters, the maximum clot firmness in fibrinogen function (FIBTEM), a marker of hypercoagulability, did not change significantly but was above the normal range at admission and discharge [median (interquartile range), admission vs. discharge: 31 (25-34) mm vs. 31 (27-32) mm, p=0.589]. The maximum lysis at 60 minutes in the extrinsic coagulation pathway (EXTEM) and intrinsic coagulation pathway (INTEM), as markers of the fibrinolytic function, were both significantly lower at discharge than at admission [median (interquartile range), admission vs. discharge: EXTEM, 3 (2-4) vs. 1 (0-2), p=0.011; INTEM, 3 (1-6) vs. 1 (0-2), p=0.008]. Conclusion This study revealed a persistent hypercoagulable state at ICU discharge and a worse hypofibrinolytic state at discharge than at admission. These results may contribute to a better understanding of coagulopathies in the acute to subacute phases of severe COVID-19.
Collapse
Affiliation(s)
- Takeshi Yagi
- Advanced Medical Emergency and Critical Care Center, Yamaguchi University Hospital, Japan
| | - Motoki Fujita
- Advanced Medical Emergency and Critical Care Center, Yamaguchi University Hospital, Japan
| | - Kayoko Harada
- Advanced Medical Emergency and Critical Care Center, Yamaguchi University Hospital, Japan
| | - Masaru Shin
- Advanced Medical Emergency and Critical Care Center, Yamaguchi University Hospital, Japan
| | - Yusuke Esaki
- Advanced Medical Emergency and Critical Care Center, Yamaguchi University Hospital, Japan
| | - Ryo Ayata
- Advanced Medical Emergency and Critical Care Center, Yamaguchi University Hospital, Japan
| | - Yasutaka Koga
- Advanced Medical Emergency and Critical Care Center, Yamaguchi University Hospital, Japan
| | - Kotaro Kaneda
- Advanced Medical Emergency and Critical Care Center, Yamaguchi University Hospital, Japan
| | - Ryosuke Tsuruta
- Advanced Medical Emergency and Critical Care Center, Yamaguchi University Hospital, Japan
| |
Collapse
|
|
24
|
Tsantes AG, Loukopoulou I, Papadopoulos DV, Trikoupis IG, Sokou R, Tsante KA, Mantzios PG, Nikolopoulos GK, Koulouvaris P, Houhoula D, Piovani D, Papagelopoulos PJ, Bonovas S, Tsantes AE. Fibrinolysis shutdown and elevated D-dimer levels have high prognostic capacity for postoperative thromboembolic complications in patients with bone tumors. J Thromb Thrombolysis 2023; 55:536-544. [PMID: 36843157 DOI: 10.1007/s11239-023-02787-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 02/12/2023] [Indexed: 02/27/2023]
Abstract
Surgical resection of malignant bone tumors is associated with a high risk of venous thromboembolism (VTE). The purpose of this study was to evaluate the association between rotational thromboelastometry (ROTEM) parameters and VTE following oncologic resections, and to evaluate their prognostic capacity for this complication. A prospective observational study was conducted including 113 patients who underwent surgical resection of malignant bone tumors. ROTEM analysis and conventional coagulation studies were performed preoperatively and on the 2nd postoperative day, while patients were followed for the development of VTE. Logistic regression was used to assess the association between ROTEM parameters and occurrence of VTE. The area under the receiver operating characteristic curve (AUC), sensitivity and specificity were calculated as measures of discrimination and predictive accuracy. Fourteen patients (12.4%) developed symptomatic VTE. Development of VTE was associated with shortened INTEM CFT (Odds Ratio [OR] 0.90, 95% Confidence Interval [CI] 0.84 - 0.96, p = 0.004), higher INTEM A10 (OR 1.21, 95% CI 1.07 - 1.36, p = 0.002), higher INTEM MCF (OR 1.22, 95% CI 1.08 - 1.37, p = 0.001) and higher INTEM LI60 (OR 2.10, 95% CI 1.38 - 3.21, p = 0.001). An INTEM LI60 value indicative of fibrinolysis shutdown (≥ 98%) had the best predictive accuracy for VTE (AUC = 0.887, 95% CI 0.824 - 0.951, sensitivity = 100%, specificity = 67.0%), higher than that of D-dimer levels (p = 0.028). ROTEM parameters were promising predictors of symptomatic VTE. Fibrinolysis shutdown as reflected by ROTEM LI60 and high D-dimer levels can aid the identification of high-risk patients. Future studies should evaluate whether the addition of ROTEM findings to an expanded risk-assessing model can improve the predictive capacity and provide better guidance in thromboprophylaxis.
Collapse
Affiliation(s)
- Andreas G Tsantes
- Laboratory of Haematology and Blood Bank Unit, School of Medicine, "Attiko" Hospital, National and Kapodistrian University of Athens, Athens, Greece.
| | - Ilectra Loukopoulou
- Laboratory of Haematology and Blood Bank Unit, School of Medicine, "Attiko" Hospital, National and Kapodistrian University of Athens, Athens, Greece
| | - Dimitrios V Papadopoulos
- 2nd Academic Department of Orthopaedics, School of Medicine, Konstandopoulio General Hospital, National & Kapodistrian University of Athens, Athens, Greece
| | - Ioannis G Trikoupis
- First Department of Orthopaedics, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece
| | - Rozeta Sokou
- Laboratory of Haematology and Blood Bank Unit, School of Medicine, "Attiko" Hospital, National and Kapodistrian University of Athens, Athens, Greece
| | - Konstantina A Tsante
- Laboratory of Haematology and Blood Bank Unit, School of Medicine, "Attiko" Hospital, National and Kapodistrian University of Athens, Athens, Greece
| | - Petros G Mantzios
- Laboratory of Haematology and Blood Bank Unit, School of Medicine, "Attiko" Hospital, National and Kapodistrian University of Athens, Athens, Greece
| | - Georgios K Nikolopoulos
- Laboratory of Medical Statistics, Epidemiology and Public Health, Medical School, University of Cyprus, Nicosia, Cyprus
| | - Panagiotis Koulouvaris
- First Department of Orthopaedics, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece
| | - Dimitra Houhoula
- Laboratory of Haematology and Blood Bank Unit, School of Medicine, "Attiko" Hospital, National and Kapodistrian University of Athens, Athens, Greece
| | - Daniele Piovani
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy.,IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy
| | - Panayiotis J Papagelopoulos
- First Department of Orthopaedics, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece
| | - Stefanos Bonovas
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy.,IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy
| | - Argirios E Tsantes
- Laboratory of Haematology and Blood Bank Unit, School of Medicine, "Attiko" Hospital, National and Kapodistrian University of Athens, Athens, Greece
| |
Collapse
|
|
25
|
Roh DJ, Chang TR, Kumar A, Burke D, Torres G, Xu K, Yang W, Cottarelli A, Moore E, Sauaia A, Hansen K, Velazquez A, Boehme A, Vrosgou A, Ghoshal S, Park S, Agarwal S, Claassen J, Connolly ES, Wagener G, Francis RO, Hod E. Hemoglobin Concentration Impacts Viscoelastic Hemostatic Assays in ICU Admitted Patients. Crit Care Med 2023; 51:267-278. [PMID: 36661453 PMCID: PMC11149397 DOI: 10.1097/ccm.0000000000005700] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/21/2023]
Abstract
OBJECTIVES Low hemoglobin concentration impairs clinical hemostasis across several diseases. It is unclear whether hemoglobin impacts laboratory functional coagulation assessments. We evaluated the relationship of hemoglobin concentration on viscoelastic hemostatic assays in intracerebral hemorrhage (ICH) and perioperative patients admitted to an ICU. DESIGN Observational cohort study and separate in vitro laboratory study. SETTING Multicenter tertiary referral ICUs. PATIENTS Two acute ICH cohorts receiving distinct testing modalities: rotational thromboelastometry (ROTEM) and thromboelastography (TEG), and a third surgical ICU cohort receiving ROTEM were evaluated to assess the generalizability of findings across disease processes and testing platforms. A separate in vitro ROTEM laboratory study was performed utilizing ICH patient blood samples. INTERVENTIONS None. MEASUREMENTS AND MAIN RESULTS Relationships between baseline hemoglobin and ROTEM/TEG results were separately assessed across patient cohorts using Spearman correlations and linear regression models. A separate in vitro study assessed ROTEM tracing changes after serial hemoglobin modifications from ICH patient blood samples. In both our ROTEM (n = 34) and TEG (n = 239) ICH cohorts, hemoglobin concentrations directly correlated with coagulation kinetics (ROTEM r: 0.46; p = 0.01; TEG r: 0.49; p < 0.0001) and inversely correlated with clot strength (ROTEM r: -0.52, p = 0.002; TEG r: -0.40, p < 0.0001). Similar relationships were identified in perioperative ICU admitted patients (n = 121). We continued to identify these relationships in linear regression models. When manipulating ICH patient blood samples to achieve lower hemoglobin concentrations in vitro, we similarly identified that lower hemoglobin concentrations resulted in progressively faster coagulation kinetics and greater clot strength on ROTEM tracings. CONCLUSIONS Lower hemoglobin concentrations have a consistent, measurable impact on ROTEM/TEG testing in ICU admitted patients, which appear to be artifactual. It is possible that patients with low hemoglobin may appear to have normal viscoelastic parameters when, in fact, they have a mild hypocoagulable state. Further work is required to determine if these tests should be corrected for a patient's hemoglobin concentration.
Collapse
Affiliation(s)
- David J Roh
- Department of Neurology, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY
| | - Tiffany R Chang
- Department of Neurology and Neurosurgery, McGovern Medical School at UTHealth, Houston, TX
| | - Aditya Kumar
- Department of Neurology, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY
| | - Devin Burke
- Department of Neurology, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY
| | - Glenda Torres
- Department of Neurology and Neurosurgery, McGovern Medical School at UTHealth, Houston, TX
| | - Katherine Xu
- Department of Neurology, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY
| | - Winni Yang
- Department of Neurology, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY
| | - Azzurra Cottarelli
- Department of Pathology and Cell Biology, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY
| | - Ernest Moore
- Department of Surgery, University of Colorado Denver, Aurora, CO
| | - Angela Sauaia
- Department of Surgery, University of Colorado Denver, Aurora, CO
| | - Kirk Hansen
- Department of Biochemistry and Molecular Genetics, University of Colorado Denver, Aurora, CO
| | - Angela Velazquez
- Department of Neurology, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY
| | - Amelia Boehme
- Department of Neurology, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY
| | - Athina Vrosgou
- Department of Neurology, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY
| | - Shivani Ghoshal
- Department of Neurology, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY
| | - Soojin Park
- Department of Neurology, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY
| | - Sachin Agarwal
- Department of Neurology, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY
| | - Jan Claassen
- Department of Neurology, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY
| | - E Sander Connolly
- Department of Neurological Surgery, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY
| | - Gebhard Wagener
- Department of Anesthesiology, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY
| | - Richard O Francis
- Department of Pathology and Cell Biology, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY
| | - Eldad Hod
- Department of Pathology and Cell Biology, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY
| |
Collapse
|
|
26
|
Gurunathan U, Chiang L, Hines J, Pearse B, McKenzie S, Hay K, Mullany D, Nandurkar H, Eley V. Association Between Thromboelastometry Identified Hypercoagulability and Thromboembolic Complications After Arthroplasty: A Prospective Observational Study in Patients With Obesity. Clin Appl Thromb Hemost 2023; 29:10760296231199737. [PMID: 37814542 PMCID: PMC10566273 DOI: 10.1177/10760296231199737] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2023] [Revised: 08/09/2023] [Accepted: 08/22/2023] [Indexed: 10/11/2023] Open
Abstract
The prothrombotic state of obesity can increase the risk of thromboembolism. We aimed to investigate if there was an association between baseline hypercoagulable rotational thromboelastometry (ROTEM) profile and thromboembolic complications in arthroplasty patients with obesity. Patients with a body mass index ≥ 25 kg/m2 and/or waist circumference ≥94 cm (M) and 80 cm (F) undergoing hip and knee arthroplasty had pre- and postoperative ROTEM. ROTEM values were compared by outcome status using an independent sample equal-variance t-test. Of the 303 total participants, hypercoagulability defined as extrinsically activated thromboelastometry maximum clot firmness G score ≥ 11 K dyne/cm2, was observed in 90 (30%) of the 300 participants with preoperative ROTEM assays. Clinically significant thromboembolic complications occurred in 5 (1.7%) study participants before discharge and in 10 (3.3%) by 90 days. These included 6 with pulmonary emboli, 3 with deep venous thrombus, and 1 with myocardial infarction. We found no evidence for an association between baseline hypercoagulability and incident thromboembolic events, analysis limited by the number of events. Postoperative decrease in platelets and an increase in fibrinogen were observed. ROTEM parameter changes differed across obesity categories.
Collapse
Affiliation(s)
- Usha Gurunathan
- Department of Anaesthesia and Perfusion Services, The Prince Charles Hospital, Brisbane, QLD, Australia
- Faculty of Medicine, The University of Queensland, Brisbane, QLD, Australia
| | - Lily Chiang
- Department of Anaesthesia and Perfusion Services, The Prince Charles Hospital, Brisbane, QLD, Australia
- Faculty of Medicine, The University of Queensland, Brisbane, QLD, Australia
| | - Joel Hines
- Adult Intensive Care Unit, The Prince Charles Hospital, Brisbane, QLD, Australia
| | - Bronwyn Pearse
- Blood Management Unit, The Prince Charles Hospital, Brisbane, QLD, Australia
| | - Scott McKenzie
- Faculty of Medicine, The University of Queensland, Brisbane, QLD, Australia
- Department of Cardiology, The Prince Charles Hospital, Brisbane, QLD, Australia
| | - Karen Hay
- Faculty of Medicine, The University of Queensland, Brisbane, QLD, Australia
- QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia
| | - Daniel Mullany
- Department of Anaesthesia and Perfusion Services, The Prince Charles Hospital, Brisbane, QLD, Australia
- Faculty of Medicine, The University of Queensland, Brisbane, QLD, Australia
| | - Harshal Nandurkar
- Department of Haematology, Alfred Health, Melbourne, VIC, Australia
- Australian Centre for Blood Diseases, Monash University, Melbourne, VIC, Australia
| | - Victoria Eley
- Faculty of Medicine, The University of Queensland, Brisbane, QLD, Australia
- Department of Anaesthesia and Perioperative Medicine, The Royal Brisbane and Women's Hospital, Brisbane, QLD, Australia
| |
Collapse
|
|
27
|
Breel JS, Wensing AGCL, Eberl S, Preckel B, Schober P, Müller MCA, Klautz RJM, Hollmann MW, Hermanns H. Patients with infective endocarditis undergoing cardiac surgery have distinct ROTEM profiles and more bleeding complications compared to patients without infective endocarditis. PLoS One 2023; 18:e0284329. [PMID: 37053130 PMCID: PMC10101476 DOI: 10.1371/journal.pone.0284329] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2023] [Accepted: 03/28/2023] [Indexed: 04/14/2023] Open
Abstract
BACKGROUND The coagulation system is crucial in the pathogenesis of infective endocarditis and undergoes significant changes during course of the disease. However, little is known about the implications of those changes in the perioperative period. Aim of the present study was to delineate the specific coagulation patterns and their clinical consequence in patients undergoing cardiac surgery due to infective endocarditis. METHODS In this single-centre, exploratory, prospective observational study, we investigated the incidence and degree of coagulopathy in patients with (n = 31) and without infective endocarditis (n = 39) undergoing cardiac valve surgery. The primary outcome was the differences between these two groups in rotational thromboelastometry (ROTEM) results before, during and after surgery. The secondary outcomes were the differences between the groups in heparin sensitivity, bleeding complications, and transfusion requirements. RESULTS Most ROTEM parameters in EXTEM, INTEM and FIBTEM assays were significantly altered in patients with infective endocarditis. Clotting time in the EXTEM assay was significantly prolonged in the endocarditis group at all time-points, while all clot firmness parameters (A5, A10 and MCF) were significantly increased. The heparin sensitivity index was significantly lower in the endocarditis group (median index 0.99 vs 1.17s. IU-1.kg-1, p = .008), indicating increased heparin resistance. Patients with infective endocarditis had more bleeding complications as assessed by the universal definition of perioperative bleeding score (OR 3.0, p = .018), and more patients with endocarditis underwent early re-exploration (p = .018). CONCLUSIONS The findings of this exploratory investigation show significantly altered coagulation profiles in patients with infective endocarditis, with concomitant hyper- and hypocoagulability. Furthermore, the incidence of bleeding complications and transfusion requirements were increased in patients with endocarditis. These results show the potential of ROTEM to detect coagulation abnormalities in patients with infective endocarditis. Existing point-of-care coagulation testing guided algorithms for optimizing perioperative coagulation management possibly need to be adjusted for these high-risk patients undergoing cardiac surgery.
Collapse
Affiliation(s)
- Jennifer S Breel
- Department of Anaesthesiology, Amsterdam University Medical Centres, Amsterdam, the Netherlands
| | - Agnes G C L Wensing
- Department of Anaesthesiology, Amsterdam University Medical Centres, Amsterdam, the Netherlands
| | - Susanne Eberl
- Department of Anaesthesiology, Amsterdam University Medical Centres, Amsterdam, the Netherlands
| | - Benedikt Preckel
- Department of Anaesthesiology, Amsterdam University Medical Centres, Amsterdam, the Netherlands
| | - Patrick Schober
- Department of Anaesthesiology, Amsterdam University Medical Centres, Amsterdam, the Netherlands
| | - Marcella C A Müller
- Department of Intensive Care, Amsterdam University Medical Centres, Amsterdam, the Netherlands
| | - Robert J M Klautz
- Department of Cardiac Surgery, Amsterdam University Medical Centres, Amsterdam, the Netherlands
| | - Markus W Hollmann
- Department of Anaesthesiology, Amsterdam University Medical Centres, Amsterdam, the Netherlands
| | - Henning Hermanns
- Department of Anaesthesiology, Amsterdam University Medical Centres, Amsterdam, the Netherlands
| |
Collapse
|
|
28
|
Hypercoagulability in critically ill patients with COVID 19, an observational prospective study. PLoS One 2022; 17:e0277544. [PMID: 36417476 PMCID: PMC9683576 DOI: 10.1371/journal.pone.0277544] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2022] [Accepted: 10/30/2022] [Indexed: 11/25/2022] Open
Abstract
OBJECTIVE COVID 19 is often associated with hypercoagulability and thromboembolic (TE) events. The aim of this study was to assess the characteristics of hypercoagulability and its relationship with new-onset TE events and the composite outcome of need for intubation and/or death in intensive care unit (ICU) patients admitted for COVID. DESIGN Prospective observational study. SETTING Monocentric, intensive care, University Hospital of Clermont Ferrand, France. PATIENTS Patients admitted to intensive care from January 2020 to May 2021 for COVID-19 pneumonia. INTERVENTIONS Standard hemostatic tests and rotational thromboelastometry (ROTEM) were performed on admission and on day 4. Hypercoagulability was defined by at least one of the following criteria: D-dimers > 3000 μg/dL, fibrinogen > 8 g/L, EXTEM CFT below the normal range, EXTEM A5, MCF, Li 60 above the normal range, and EXTEM G-score ((5000 x MCF) / (100-MCF)) ≥ 11 dyne/cm2. MEASUREMENTS AND MAIN RESULTS Of the 133 patients included, 17 (12.7%) developed new-onset TE events, and 59 (44.3%) required intubation and/or died in the ICU. ROTEM was performed in 133 patients on day 1 and in 67 on day 4. Hypercoagulability was present on day 1 in 115 (86.4%) patients. None of the hypercoagulability indices were associated with subsequent new-onset TE events on days 1 and 4 nor with the need for intubation and/or ICU death. Hyperfibrinogenemia > 8g/dL, higher D-dimers and higher EXTEM Li 60 on day 4 were predictive of need for intubation and/or of ICU death. CONCLUSIONS Our study confirmed that most COVID-19 ICU patients have hypercoagulability on admission and almost all on day 4. Hyperfibrinogenemia or fibrinolysis shutdown on day 4 were associated with unfavorable outcome.
Collapse
|
|
29
|
Seifert SM, Lumbreras-Marquez MI, Goobie SM, Carusi DA, Fields KG, Bateman BT, Farber MK. Tranexamic acid administered during cesarean delivery in high-risk patients: maternal pharmacokinetics, pharmacodynamics, and coagulation status. Am J Obstet Gynecol 2022; 227:763.e1-763.e10. [PMID: 35679896 DOI: 10.1016/j.ajog.2022.06.001] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2022] [Revised: 06/01/2022] [Accepted: 06/02/2022] [Indexed: 11/01/2022]
Abstract
BACKGROUND Tranexamic acid is frequently administered for postpartum hemorrhage. The World Health Organization recommends 1 g intravenous dosing, repeated once after 30 minutes for ongoing bleeding. Understanding the pharmacokinetics and pharmacodynamics of tranexamic acid in patients at high risk of postpartum hemorrhage may enable dosage tailoring for optimal antifibrinolysis with minimal adverse events, such as thrombosis or renal cortical necrosis. OBJECTIVE This study aimed to report tranexamic acid pharmacokinetics and pharmacodynamics after 1 g intravenous dosing during cesarean delivery in patients at risk of hemorrhage. The primary endpoint was tranexamic acid plasma concentration of >10 μg/mL, known to inhibit 80% of fibrinolysis. In addition, the correlation between patient demographics and rotational thromboelastometry coagulation changes were analyzed. STUDY DESIGN In this prospective study, 20 women aged 18 to 50 years, ≥23 weeks of gestation undergoing cesarean delivery with at least 1 major (placenta previa, suspected placenta accreta spectrum, or active bleeding) or 2 minor (≥2 previous cesarean deliveries, previous postpartum hemorrhage, chorioamnionitis, polyhydramnios, macrosomia, obesity, or suspected placental abruption) risk factors for postpartum hemorrhage were recruited. The exclusion criteria were allergy to tranexamic acid, inherited thrombophilia, previous or current thrombosis, seizure history, renal or liver dysfunction, anticoagulation, or category III fetal heart tracing. Tranexamic acid 1 g was administered after umbilical cord clamping. Blood samples were drawn at 3, 7, 15, and 30 minutes and then at 30-minute intervals up to 5 hours. Plasma concentrations were evaluated as mean (standard error). Serial rotational thromboelastometry was performed and correlated with tranexamic acid plasma concentrations. RESULTS The median age of participants was 37.5 years (interquartile range, 35.0-39.5), and the median body mass index was 28.6 kg/m2 (interquartile range, 24.9-35.0). The median blood loss (estimated or quantitative) was 1500 mL (interquartile range, 898.5-2076.0). Of note, 9 of 20 (45%) received a transfusion of packed red blood cells. The mean peak tranexamic acid plasma concentration at 3 minutes was 59.8±4.7 μg/mL. All patients had a plasma concentration >10 μg/mL for 1 hour after infusion. Plasma concentration was >10 μg/mL in more than half of the patients at 3 hours and fell <10 μg/mL in all patients at 5 hours. There was a moderate negative correlation between body mass index and the plasma concentration area under the curve (r=-0.49; 95% confidence interval, -0.77 to -0.07; P=.026). Rotational thromboelastometry EXTEM maximum clot firmness had a weak positive correlation with longitudinal plasma concentration (r=0.32; 95% confidence interval, 0.21-0.46; P<.001). EXTEM maximum clot lysis was 0% after infusion in 18 patients (90%), and no patient in the study demonstrated a maximum lysis of >15% at any interval from 3 minutes to 5 hours. There was no significant correlation between EXTEM clot lysis at 30 minutes and longitudinal tranexamic acid plasma concentrations (r=0.10; 95% confidence interval, -0.20 to 0.19; P=.252). CONCLUSION After standard 1 g intravenous dosing of tranexamic acid during cesarean delivery in patients at high risk of hemorrhage, a plasma concentration of ≥10 μg/mL was sustained for at least 60 minutes. Plasma tranexamic acid levels correlated inversely with body mass index. The concurrent use of rotational thromboelastometry may demonstrate tranexamic acid's impact on clot firmness but not a hyperfibrinolysis-derived trigger for therapy.
Collapse
Affiliation(s)
- Sebastian M Seifert
- Department of Anesthesiology, Perioperative and Pain Medicine, Brigham & Women's Hospital, Harvard Medical School, Boston, MA.
| | - Mario I Lumbreras-Marquez
- Department of Anesthesiology, Perioperative and Pain Medicine, Brigham & Women's Hospital, Harvard Medical School, Boston, MA
| | - Susan M Goobie
- Department of Anesthesiology, Critical Care & Pain Medicine, Boston Children's Hospital, Boston, MA
| | - Daniela A Carusi
- Department of Obstetrics and Gynecology, Brigham & Women's Hospital, Harvard Medical School, Boston, MA
| | - Kara G Fields
- Department of Anesthesiology, Perioperative and Pain Medicine, Brigham & Women's Hospital, Harvard Medical School, Boston, MA
| | - Brian T Bateman
- Department of Anesthesiology, Perioperative and Pain Medicine, Brigham & Women's Hospital, Harvard Medical School, Boston, MA; Department of Anesthesiology, Perioperative and Pain Medicine, Stanford Hospital, Stanford University School of Medicine, Stanford, CA
| | - Michaela K Farber
- Department of Anesthesiology, Perioperative and Pain Medicine, Brigham & Women's Hospital, Harvard Medical School, Boston, MA
| |
Collapse
|
|
30
|
Matkovic E, Lindholm PF. Role of Viscoelastic and Conventional Coagulation Tests for Management of Blood Product Replacement in the Bleeding Patient. Semin Thromb Hemost 2022; 48:785-795. [PMID: 36174609 DOI: 10.1055/s-0042-1756192] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/14/2022]
Abstract
An important aim of viscoelastic testing (VET) is to implement transfusion algorithms based on coagulation test results to help reduce transfusion rates and improve patient outcomes. Establishing a rapid diagnosis and providing timely treatment of coagulopathy is the cornerstone of management of severely bleeding patients in trauma, postpartum hemorrhage, and major surgery. As the nature of acute bleeding and trauma leads to an unstable and tenuous physiologic state, conventional coagulation tests (CCTs) are too slow to diagnose, manage, and also course correct any hemostatic abnormalities that accompany an acute critical illness. Viscoelastic point-of-care tests strongly correlate with results from standard laboratory tests but are designed to enable clinicians to make timely, informed bleeding management decisions when time to intervene is critical. These assays provide an individualized and goal-oriented approach to patient blood management and are increasingly becoming involved in transfusion algorithms. The scope of this review aims to evaluate the current literature on VETs and their impact on actionable outputs in clinical decision making and their relationship to CCT.
Collapse
Affiliation(s)
- Eduard Matkovic
- Department of Pathology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois
| | - Paul F Lindholm
- Department of Pathology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois
| |
Collapse
|
|
31
|
Bunch CM, Berquist M, Ansari A, McCoy ML, Langford JH, Brenner TJ, Aboukhaled M, Thomas SJ, Peck E, Patel S, Cancel E, Al-Fadhl MD, Zackariya N, Thomas AV, Aversa JG, Greene RB, Seder CW, Speybroeck J, Miller JB, Kwaan HC, Walsh MM. The Choice between Plasma-Based Common Coagulation Tests and Cell-Based Viscoelastic Tests in Monitoring Hemostatic Competence: Not an either-or Proposition. Semin Thromb Hemost 2022; 48:769-784. [PMID: 36174601 DOI: 10.1055/s-0042-1756302] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/14/2022]
Abstract
There has been a significant interest in the last decade in the use of viscoelastic tests (VETs) to determine the hemostatic competence of bleeding patients. Previously, common coagulation tests (CCTs) such as the prothrombin time (PT) and partial thromboplastin time (PTT) were used to assist in the guidance of blood component and hemostatic adjunctive therapy for these patients. However, the experience of decades of VET use in liver failure with transplantation, cardiac surgery, and trauma has now spread to obstetrical hemorrhage and congenital and acquired coagulopathies. Since CCTs measure only 5 to 10% of the lifespan of a clot, these assays have been found to be of limited use for acute surgical and medical conditions, whereby rapid results are required. However, there are medical indications for the PT/PTT that cannot be supplanted by VETs. Therefore, the choice of whether to use a CCT or a VET to guide blood component therapy or hemostatic adjunctive therapy may often require consideration of both methodologies. In this review, we provide examples of the relative indications for CCTs and VETs in monitoring hemostatic competence of bleeding patients.
Collapse
Affiliation(s)
- Connor M Bunch
- Department of Emergency Medicine, Henry Ford Hospital, Detroit, Michigan
| | - Margaret Berquist
- Department of Emergency Medicine, Saint Joseph Regional Medical Center, Mishawaka, Indiana
| | - Aida Ansari
- Department of Emergency Medicine, Saint Joseph Regional Medical Center, Mishawaka, Indiana
| | - Max L McCoy
- Department of Emergency Medicine, Saint Joseph Regional Medical Center, Mishawaka, Indiana
| | - Jack H Langford
- Department of Emergency Medicine, Saint Joseph Regional Medical Center, Mishawaka, Indiana
| | - Toby J Brenner
- Department of Emergency Medicine, Saint Joseph Regional Medical Center, Mishawaka, Indiana
| | - Michael Aboukhaled
- Department of Emergency Medicine, Saint Joseph Regional Medical Center, Mishawaka, Indiana
| | - Samuel J Thomas
- Department of Emergency Medicine, Saint Joseph Regional Medical Center, Mishawaka, Indiana
| | - Ethan Peck
- Department of Emergency Medicine, Saint Joseph Regional Medical Center, Mishawaka, Indiana
| | - Shivani Patel
- Department of Emergency Medicine, Saint Joseph Regional Medical Center, Mishawaka, Indiana
| | - Emily Cancel
- Department of Emergency Medicine, Saint Joseph Regional Medical Center, Mishawaka, Indiana
| | - Mahmoud D Al-Fadhl
- Indiana University School of Medicine, Notre Dame Campus, South Bend, Indiana
| | - Nuha Zackariya
- Indiana University School of Medicine, Notre Dame Campus, South Bend, Indiana
| | - Anthony V Thomas
- Indiana University School of Medicine, Notre Dame Campus, South Bend, Indiana
| | - John G Aversa
- Department of Surgery, Indiana University School of Medicine, Indianapolis, Indiana
| | - Ryan B Greene
- Department of Interventional Radiology, St. Joseph Regional Medical Center, Mishawaka, Indiana
| | - Christopher W Seder
- Department of Cardiovascular and Thoracic Surgery, Rush University Medical Center, Chicago, Illinois
| | - Jacob Speybroeck
- Department of Orthopedic Surgery, Case Western Medical Center, Cleveland, Ohio
| | - Joseph B Miller
- Department of Emergency Medicine, Henry Ford Hospital, Detroit, Michigan
| | - Hau C Kwaan
- Division of Hematology and Oncology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois
| | - Mark M Walsh
- Department of Emergency Medicine, Saint Joseph Regional Medical Center, Mishawaka, Indiana.,Indiana University School of Medicine, Notre Dame Campus, South Bend, Indiana
| |
Collapse
|
|
32
|
O’Keefe D, Lim HY, Hui L, Ho P. Risk stratification for pregnancy-associated venous thromboembolism: Potential role for global coagulation assays. Obstet Med 2022; 15:168-175. [PMID: 36262814 PMCID: PMC9574445 DOI: 10.1177/1753495x211025397] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2020] [Revised: 05/27/2021] [Accepted: 05/27/2021] [Indexed: 09/03/2023] Open
Abstract
Risk assessment for venous thromboembolism in pregnancy and the puerperium is currently limited to stratifying clinical surrogate risk factors without high-quality evidence. While the absolute risk of pregnancy-associated venous thromboembolism is low for the vast majority of women, associated morbidity and mortality remains significant. As guidelines for thromboprophylaxis vary widely, some women may be under- or over-anticoagulated, contributing to poor outcomes. New global coagulation assays provide a holistic view of coagulation and may have the potential to detect hypercoagulability in pregnancy, unlike clinically available coagulation assays. However, there are major technical challenges to overcome before global coagulation assays can be realistically proposed as an adjunct to risk assessment for pregnancy-associated venous thromboembolism. This review summarises the literature and controversies in the prediction and prevention of pregnancy-associated venous thromboembolism and outlines the new tools in haematology that may assist in our future understanding of hypercoagulability in pregnancy.
Collapse
Affiliation(s)
- David O’Keefe
- Department of Obstetrics & Gynaecology, The University of
Melbourne, The University of Melbourne, Parkville, Australia
- Department of Obstetrics & Gynaecology, Northern Health,
Epping, Australia
| | - Hui Yin Lim
- Department of Haematology, Northern Pathology Victoria, Epping,
Australia
- Department of Haematology, Northern Health, Epping,
Australia
| | - Lisa Hui
- Department of Obstetrics & Gynaecology, The University of
Melbourne, The University of Melbourne, Parkville, Australia
- Department of Obstetrics & Gynaecology, Northern Health,
Epping, Australia
| | - Prahlad Ho
- Department of Haematology, Northern Pathology Victoria, Epping,
Australia
- Department of Haematology, Northern Health, Epping,
Australia
- Australian Centre for Blood Diseases, Monash University,
Melbourne, Australia
| |
Collapse
|
|
33
|
Tsantes AG, Loukopoulou I, Papadopoulos DV, Trikoupis IG, Roustemis AG, Goumenos S, Sokou R, Tsante KA, Kriebardis AG, Koulouvaris P, Houhoula D, Piovani D, Papagelopoulos PJ, Bonovas S, Tsantes AE. The Hypercoagulable Profile of Patients with Bone Tumors: A Pilot Observational Study Using Rotational Thromboelastometry. Cancers (Basel) 2022; 14:3930. [PMID: 36010924 PMCID: PMC9406421 DOI: 10.3390/cancers14163930] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2022] [Revised: 08/12/2022] [Accepted: 08/12/2022] [Indexed: 11/16/2022] Open
Abstract
Introduction: A detailed evaluation of the malignancy-associated coagulopathy (MAC) in surgical patients with bone tumors may allow for more effective thromboprophylactic measures. The purpose of this study was to assess the perioperative hemostatic changes in patients with bone tumors, using rotational thromboelastometry (ROTEM). Methods: An observational study was performed, including 50 patients with bone tumors who underwent oncologic resection and 30 healthy controls, matched for age and gender. The preoperative and postoperative laboratory evaluation of coagulation in both groups included conventional coagulation tests and a ROTEM analysis. The results of the conventional coagulation tests and the ROTEM analysis were compared between the two groups. Results: The results of the conventional coagulation tests were comparable between the tumor patients and the healthy controls. However, compared to the healthy adults, the tumor patients had lower CT (p < 0.001) and CFT (p < 0.001) values suggesting a rapid induction of the coagulation cascade, elevated A10 (p < 0.001) and MCF (p < 0.001) values indicating a higher clot strength and platelet activation, and elevated LI60 (p < 0.001) values indicating hypofibrinolysis in patients with bone tumors. The multiple linear regression analysis (controlling for potential confounding factors) confirmed the independent association of bone tumors with these hemostatic changes. Conclusions: Our results support the advantageous use of a ROTEM in patients with bone tumors over conventional coagulation tests because the qualitative changes in the hemostatic profile of these patients that can be detected by a ROTEM analysis cannot be identified by conventional tests. The ROTEM results indicate that the hypercoagulable state in patients with bone tumors is caused by the malignancy-associated activation of the coagulation cascade, platelet activation, and hypofibrinolysis.
Collapse
Affiliation(s)
- Andreas G. Tsantes
- Laboratory of Haematology and Blood Bank Unit, “Attiko” Hospital, School of Medicine, National and Kapodistrian University of Athens, 15772 Athens, Greece
| | - Ilectra Loukopoulou
- Laboratory of Haematology and Blood Bank Unit, “Attiko” Hospital, School of Medicine, National and Kapodistrian University of Athens, 15772 Athens, Greece
| | | | - Ioannis G. Trikoupis
- First Department of Orthopaedics, School of Medicine, National and Kapodistrian University of Athens, 15772 Athens, Greece
| | - Anastasios G. Roustemis
- First Department of Orthopaedics, School of Medicine, National and Kapodistrian University of Athens, 15772 Athens, Greece
| | - Stavros Goumenos
- First Department of Orthopaedics, School of Medicine, National and Kapodistrian University of Athens, 15772 Athens, Greece
| | - Rozeta Sokou
- Laboratory of Haematology and Blood Bank Unit, “Attiko” Hospital, School of Medicine, National and Kapodistrian University of Athens, 15772 Athens, Greece
| | - Konstantina A. Tsante
- Laboratory of Haematology and Blood Bank Unit, “Attiko” Hospital, School of Medicine, National and Kapodistrian University of Athens, 15772 Athens, Greece
| | - Anastasios G. Kriebardis
- Laboratory of Reliability and Quality Control in Laboratory Hematology, Department of Biomedical Science, School of Health and Caring Science, University of West Attica, 12243 Athens, Greece
| | - Panagiotis Koulouvaris
- First Department of Orthopaedics, School of Medicine, National and Kapodistrian University of Athens, 15772 Athens, Greece
| | - Dimitra Houhoula
- Laboratory of Haematology and Blood Bank Unit, “Attiko” Hospital, School of Medicine, National and Kapodistrian University of Athens, 15772 Athens, Greece
| | - Daniele Piovani
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, 20072 Milan, Italy
- IRCCS Humanitas Research Hospital, Rozzano, 20089 Milan, Italy
| | - Panayiotis J. Papagelopoulos
- First Department of Orthopaedics, School of Medicine, National and Kapodistrian University of Athens, 15772 Athens, Greece
| | - Stefanos Bonovas
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, 20072 Milan, Italy
- IRCCS Humanitas Research Hospital, Rozzano, 20089 Milan, Italy
| | - Argirios E. Tsantes
- Laboratory of Haematology and Blood Bank Unit, “Attiko” Hospital, School of Medicine, National and Kapodistrian University of Athens, 15772 Athens, Greece
| |
Collapse
|
|
34
|
Choi JK, Prabhakaran K, Latifi R, Smiley A, Klein J, Lombardo G, Rhee P. Serial rotational thromboelastography (ROTEM) in mechanically ventilated patients with COVID-19 demonstrates hypercoagulopathy despite therapeutic heparinization. Trauma Surg Acute Care Open 2022; 7:e000603. [PMID: 35291340 PMCID: PMC8914399 DOI: 10.1136/tsaco-2020-000603] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2020] [Accepted: 05/10/2021] [Indexed: 12/18/2022] Open
Abstract
Background Clinical hypercoagulopathy in patients with COVID-19 has been anecdotally described, but there is lack of evidence due to the novelty of this disease. Our study reports the results of rotational thromboelastography (ROTEM) in relation to traditional laboratory coagulation tests and acute phase markers among a cohort of severely ill, mechanically ventilated patients with COVID-19. Methods Patients with COVID-19 (N=21) with respiratory failure requiring mechanical ventilation were included in this prospective case series. ROTEM was serially obtained for all patients on three different days during their intensive care unit (ICU) stay and analyzed using repeated measures analysis. Demographic variables, symptoms at the time of presentation, ROTEM values, laboratory values for traditionally measured coagulation profiles, and acute phase reactants were analyzed, in addition to the use of anticoagulation and clinical hypercoagulopathic complications. Results The average age of our cohort was 57.9 years old (SD=14.4) and 76.2% were male. The mortality rate was 14.3% (3 of 21). Two patients (12.5%) were identified to have new-onset deep vein thrombosis, two patients (12.5%) were found to have ≥3 episodes of central venous catheter thrombosis, and three patients (18.7%) had confirmed stroke. ROTEM demonstrated elevated EXTEM and INTEM clotting times, including elevated FIBTEM maximum clot firmness (MCFFIB). All patients treated with therapeutic anticoagulation still demonstrated hypercoagulopathy within the MCFFIB tests. Discussion Repeated measure ROTEMs were able to detect hypercoagulopathy in ICU patients with COVID-19 despite therapeutic anticoagulation with heparin. Level of evidence III.
Collapse
Affiliation(s)
- James K Choi
- Department of Surgery, Westchester Medical Center, Valhalla, New York, USA
| | - Kartik Prabhakaran
- Department of Surgery, Westchester Medical Center, Valhalla, New York, USA
| | - Rifat Latifi
- Department of Surgery, Westchester Medical Center, Valhalla, New York, USA
| | - Abbas Smiley
- Department of Surgery, Westchester Medical Center, Valhalla, New York, USA
| | - Joshua Klein
- Department of Surgery, Westchester Medical Center, Valhalla, New York, USA
| | - Gary Lombardo
- Department of Surgery, Westchester Medical Center, Valhalla, New York, USA
| | - Peter Rhee
- Department of Surgery, Westchester Medical Center, Valhalla, New York, USA
| |
Collapse
|
|
35
|
The Composition and Physical Properties of Clots in COVID-19 Pathology. Diagnostics (Basel) 2022; 12:diagnostics12030580. [PMID: 35328132 PMCID: PMC8947364 DOI: 10.3390/diagnostics12030580] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2022] [Revised: 02/18/2022] [Accepted: 02/21/2022] [Indexed: 01/01/2023] Open
Abstract
Hemostasis is a finely tuned process of which dysregulation can lead either to bleeding or thrombotic complications. The latter is often caused by the hypercoagulable state as it is also seen in patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, i.e., in COVID-19 patients. COVID-19 patients requiring hospitalization often suffer from thrombotic events that could not be predicted using routine coagulation assays. Recently, several studies have reported ROtational ThromboElastoMetry (ROTEM) as a promising tool to predict outcomes in COVID-19 patients. In this review we give an overview of ROTEM with a particular focus on the interpretation of the symmetrical clot formation curve in relation to coagulopathy in COVID-19 patients. Furthermore, we have introduced new parameters that might help to better distinguish between COVID-19 patients and outcomes.
Collapse
|
|
36
|
Abstract
The management of infective endocarditis is complex and inherently requires multidisciplinary cooperation. About half of all patients diagnosed with infective endocarditis will meet the criteria to undergo cardiac surgery, which regularly takes place in urgent or emergency settings. The pathophysiology and clinical presentation of infective endocarditis make it a unique disorder within cardiac surgery that warrants a thorough understanding of specific characteristics in the perioperative period. This includes, among others, echocardiography, coagulation, bleeding management, or treatment of organ dysfunction. In this narrative review article, the authors summarize the current knowledge on infective endocarditis relevant for the clinical anesthesiologist in perioperative management of respective patients. Furthermore, the authors advocate for the anesthesiologist to become a structural member of the endocarditis team.
Collapse
|
|
37
|
Pavoni V, Gianesello L, Pazzi M, Dattolo P, Prisco D. Questions about COVID-19 associated coagulopathy: possible answers from the viscoelastic tests. J Clin Monit Comput 2022; 36:55-69. [PMID: 34264472 PMCID: PMC8280589 DOI: 10.1007/s10877-021-00744-7] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2021] [Accepted: 07/09/2021] [Indexed: 12/30/2022]
Abstract
Abnormal coagulation parameters are often observed in patients with coronavirus disease 2019 (COVID-19) and the severity of derangement has been associated with a poor prognosis. The COVID-19 associated coagulopathy (CAC) displays unique features that include a high risk of developing thromboembolic complications. Viscoelastic tests (VETs), such as thromboelastometry (ROTEM), thromboelastography (TEG) and Quantra Hemostasis Analyzer (Quantra), provide "dynamic" data on clot formation and dissolution; they are used in different critical care settings, both in hemorrhagic and in thrombotic conditions. In patients with severe COVID-19 infection VETs can supply to clinicians more information about the CAC, identifying the presence of hypercoagulable and hypofibrinolysis states. In the last year, many studies have proposed to explain the underlying characteristics of CAC; however, there remain many unanswered questions. We tried to address some of the important queries about CAC through VETs analysis.
Collapse
Affiliation(s)
- Vittorio Pavoni
- Emergency Department and Critical Care Area, Anesthesia and Intensive Care Unit, Santa Maria Annunziata Hospital, Bagno a Ripoli, Florence, Italy
| | - Lara Gianesello
- Department of Anesthesia and Intensive Care, Orthopedic Anesthesia, University-Hospital Careggi, Largo Palagi, 1, 50139, Florence, Italy.
| | - Maddalena Pazzi
- Emergency Department and Critical Care Area, Anesthesia and Intensive Care Unit, Santa Maria Annunziata Hospital, Bagno a Ripoli, Florence, Italy
| | - Pietro Dattolo
- Nephrology Unit Florence 1, Santa Maria Annunziata Hospital, Bagno a Ripoli, Florence, Italy
| | - Domenico Prisco
- Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy
| |
Collapse
|
|
38
|
Aires RB, Soares AADSM, Gomides APM, Nicola AM, Teixeira-Carvalho A, da Silva DLM, de Gois ET, Xavier FD, Martins FP, Santos GPJ, Schulte HL, Luz IS, Espindola LS, do Amaral LR, Felicori LF, Naves LA, de Carvalho MRM, Gomes MDS, Nóbrega OT, Albuquerque P, Fontes W, Gomes CM, Kurizky PS, Albuquerque CP, Martins-Filho OA, da Mota LMH. Thromboelastometry demonstrates endogenous coagulation activation in nonsevere and severe COVID-19 patients and has applicability as a decision algorithm for intervention. PLoS One 2022; 17:e0262600. [PMID: 35030224 PMCID: PMC8759688 DOI: 10.1371/journal.pone.0262600] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2021] [Accepted: 12/28/2021] [Indexed: 12/17/2022] Open
Abstract
In patients with severe forms of COVID-19, thromboelastometry has been reported to display a hypercoagulant pattern. However, an algorithm to differentiate severe COVID-19 patients from nonsevere patients and healthy controls based on thromboelastometry parameters has not been developed. Forty-one patients over 18 years of age with positive qRT-PCR for SARS-CoV-2 were classified according to the severity of the disease: nonsevere (NS, n = 20) or severe (S, n = 21). A healthy control (HC, n = 9) group was also examined. Blood samples from all participants were tested by extrinsic (EXTEM), intrinsic (INTEM), non-activated (NATEM) and functional assessment of fibrinogen (FIBTEM) assays of thromboelastometry. The thrombodynamic potential index (TPI) was also calculated. Severe COVID-19 patients exhibited a thromboelastometry profile with clear hypercoagulability, which was significantly different from the NS and HC groups. Nonsevere COVID-19 cases showed a trend to thrombotic pole. The NATEM test suggested that nonsevere and severe COVID-19 patients presented endogenous coagulation activation (reduced clotting time and clot formation time). TPI data were significantly different between the NS and S groups. The maximum clot firmness profile obtained by FIBTEM showed moderate/elevated accuracy to differentiate severe patients from NS and HC. A decision tree algorithm based on the FIBTEM-MCF profile was proposed to differentiate S from HC and NS. Thromboelastometric parameters are a useful tool to differentiate the coagulation profile of nonsevere and severe COVID-19 patients for therapeutic intervention purposes.
Collapse
Affiliation(s)
- Rodrigo B. Aires
- Programa de Pós-graduação em Ciências Médicas da Faculdade de Medicina da Universidade de Brasília (UnB), Brasília, Distrito Federal, Brazil
- Serviço de Anestesiologia, Hospital Santa Lúcia Sul, Brasília, Distrito Federal, Brazil
- * E-mail: (RBA); (PSK)
| | - Alexandre A. de S. M. Soares
- Programa de Pós-graduação em Ciências Médicas da Faculdade de Medicina da Universidade de Brasília (UnB), Brasília, Distrito Federal, Brazil
| | - Ana Paula M. Gomides
- Faculdade de Ciências da Saúde, Centro Universitário de Brasília, Brasília, Distrito Federal, Brazil
| | - André M. Nicola
- Programa de Pós-graduação em Ciências Médicas da Faculdade de Medicina da Universidade de Brasília (UnB), Brasília, Distrito Federal, Brazil
| | - Andréa Teixeira-Carvalho
- Grupo Integrado de Pesquisa em Biomarcadores, Fundação Oswaldo Cruz (FIOCRUZ), Belo Horizonte, Minas Gerais, Brazil
| | - Dayde Lane M. da Silva
- Departamento de Farmácia, Universidade de Brasília (UnB), Brasília, Distrito Federal, Brazil
| | - Eliana T. de Gois
- Programa de Pós-graduação em Ciências Médicas da Faculdade de Medicina da Universidade de Brasília (UnB), Brasília, Distrito Federal, Brazil
- Unidade de Clínica Médica, Hospital Regional do Gama (HRG), Brasília, Distrito Federal, Brazil
| | - Flávia D. Xavier
- Programa de Pós-graduação em Ciências Médicas da Faculdade de Medicina da Universidade de Brasília (UnB), Brasília, Distrito Federal, Brazil
| | - Francielle P. Martins
- Programa de Pós-graduação em Ciências Médicas da Faculdade de Medicina da Universidade de Brasília (UnB), Brasília, Distrito Federal, Brazil
- Núcleo de Gestão Interna de Leitos, Hospital Regional da Asa Norte (HRAN), Brasília, Distrito Federal, Brazil
| | - Gabriela P. J. Santos
- Programa de Pós-graduação em Ciências Médicas da Faculdade de Medicina da Universidade de Brasília (UnB), Brasília, Distrito Federal, Brazil
- Unidade de Medicina Interna, Hospital Regional de Taguatinga, Brasília, Distrito Federal, Brazil
| | - Heidi Luise Schulte
- Programa de Pós-graduação em Ciências Médicas da Faculdade de Medicina da Universidade de Brasília (UnB), Brasília, Distrito Federal, Brazil
| | - Isabelle S. Luz
- Laboratório de Bioquímica e Química de Proteínas, Departamento de Biologia Celular, Instituto de Ciências Biológicas, Universidade de Brasília (UnB), Brasília, Distrito Federal, Brazil
| | - Laila S. Espindola
- Programa de Pós-graduação em Ciências Médicas da Faculdade de Medicina da Universidade de Brasília (UnB), Brasília, Distrito Federal, Brazil
- Laboratório de Farmacognosia, Faculdade de Ciências da Saúde, Universidade de Brasília (UnB), Brasília, Distrito Federal, Brazil
| | - Laurence R. do Amaral
- Laboratório de Bioinformática e Análises Moleculares, Rede Multidisciplinar de Pesquisa, Ciência e Tecnologia (RMPCT), Universidade Federal de Uberlândia, Patos de Minas, Minas Gerais, Brazil
| | - Liza F. Felicori
- Laboratório de Biologia Sintética e Biomiméticos, Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, Minas Gerais, Brazil
| | - Luciana A. Naves
- Programa de Pós-graduação em Ciências Médicas da Faculdade de Medicina da Universidade de Brasília (UnB), Brasília, Distrito Federal, Brazil
- Serviço de Endocrinologia, Hospital Universitário de Brasília, Universidade de Brasília (UnB), Brasília, Distrito Federal, Brazil
| | - Maíra R. M. de Carvalho
- Programa de Pós-graduação em Ciências Médicas da Faculdade de Medicina da Universidade de Brasília (UnB), Brasília, Distrito Federal, Brazil
- Unidade de Medicina Interna, Hospital Regional da Asa Norte (HRAN), Brasília, Distrito Federal, Brazil
| | - Matheus de S. Gomes
- Laboratório de Bioinformática e Análises Moleculares, Rede Multidisciplinar de Pesquisa, Ciência e Tecnologia (RMPCT), Universidade Federal de Uberlândia, Patos de Minas, Minas Gerais, Brazil
| | - Otávio T. Nóbrega
- Programa de Pós-graduação em Ciências Médicas da Faculdade de Medicina da Universidade de Brasília (UnB), Brasília, Distrito Federal, Brazil
| | - Patrícia Albuquerque
- Faculdade UnB Ceilândia, Universidade de Brasília (UnB), Brasília, Distrito Federal, Brazil
| | - Wagner Fontes
- Laboratório de Bioquímica e Química de Proteínas, Departamento de Biologia Celular, Instituto de Ciências Biológicas, Universidade de Brasília (UnB), Brasília, Distrito Federal, Brazil
| | - Ciro M. Gomes
- Programa de Pós-graduação em Ciências Médicas da Faculdade de Medicina da Universidade de Brasília (UnB), Brasília, Distrito Federal, Brazil
- Serviço de Dermatologia, Hospital Universitário de Brasília, Universidade de Brasília (UnB), Brasília, Distrito Federal, Brazil
| | - Patricia S. Kurizky
- Programa de Pós-graduação em Ciências Médicas da Faculdade de Medicina da Universidade de Brasília (UnB), Brasília, Distrito Federal, Brazil
- Serviço de Dermatologia, Hospital Universitário de Brasília, Universidade de Brasília (UnB), Brasília, Distrito Federal, Brazil
- * E-mail: (RBA); (PSK)
| | - Cleandro P. Albuquerque
- Programa de Pós-graduação em Ciências Médicas da Faculdade de Medicina da Universidade de Brasília (UnB), Brasília, Distrito Federal, Brazil
- Serviço de Reumatologia, Hospital Universitário de Brasília, Universidade de Brasília (UnB), Brasília, Distrito Federal, Brazil
| | - Olindo A. Martins-Filho
- Grupo Integrado de Pesquisa em Biomarcadores, Fundação Oswaldo Cruz (FIOCRUZ), Belo Horizonte, Minas Gerais, Brazil
| | - Licia Maria H. da Mota
- Programa de Pós-graduação em Ciências Médicas da Faculdade de Medicina da Universidade de Brasília (UnB), Brasília, Distrito Federal, Brazil
- Serviço de Reumatologia, Hospital Universitário de Brasília, Universidade de Brasília (UnB), Brasília, Distrito Federal, Brazil
| |
Collapse
|
|
39
|
Miltiades A, Houck PJ, Monteleone M, Harrison NL, Cabrera-Garcia D, Roh D, Wagener G. Insights into Fibrinogen-Mediated COVID-19 Hypercoagubility in Critically Ill Patients. J Neurosurg Anesthesiol 2022; 34:136-140. [PMID: 34870637 DOI: 10.1097/ana.0000000000000812] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/04/2021] [Accepted: 09/08/2021] [Indexed: 12/29/2022]
Abstract
Coronavirus disease-2019 (COVID-19) is associated with hypercoagulability that may cause thromobembolic complications. We describe our recent studies investigating the mechanisms of hypercoagulability in patients with severe COVID-19 requiring mechanical ventilation during the COVID-19 crisis in New York City in spring 2020. Using rotational thombelastometry we found that almost all patients with severe COVID-19 had signs of hypercoagulability compared with non-COVID-19 controls. Specifically, the maximal clot firmness in the fibrin-based extrinsically activated test was almost twice the upper limit of normal in COVID patients, indicating a fibrin-mediated cause for hypercoagulability. To better understand the mechanism of this hypercoagulability we measured the components of the fibrinolytic pathways. Fibrinogen, tissue plasminogen activator and plasminogen activator inhibitor-1, but not plasminogen levels were elevated in patients with severe COVID-19. Our studies indicate that hypercoagulability in COVID-19 may be because of decreased fibrinolysis resulting from inhibition of plasmin through high levels of plasminogen activator inhibitor-1. Clinicians creating treatment protocols for anticoagulation in critically ill COVID-19 patients should consider these potential mechanisms of hypercoaguability.
Collapse
Affiliation(s)
| | | | - Matthew Monteleone
- Department of Anesthesiology, Cincinnati Children's Hospital, Cincinnati, OH
| | | | | | - David Roh
- Neurology, Columbia University Irving Medical Center, New York, NY
| | | |
Collapse
|
|
40
|
Tsantes AG, Papadopoulos DV, Trikoupis IG, Tsante KA, Mavrogenis AF, Koulouvaris P, Piovani D, Kriebardis AG, Gialeraki A, Nikolopoulos GK, Bonovas S, Papagelopoulos PJ, Tsantes AE. Rotational Thromboelastometry Findings Are Associated with Symptomatic Venous Thromboembolic Complications after Hip Fracture Surgery. Clin Orthop Relat Res 2021; 479:2457-2467. [PMID: 34076610 PMCID: PMC8509944 DOI: 10.1097/corr.0000000000001832] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/10/2020] [Accepted: 04/28/2021] [Indexed: 01/31/2023]
Abstract
BACKGROUND Venous thromboembolism is a common complication after hip fractures. However, there are no reliable laboratory assays to identify patients at risk for venous thromboembolic (VTE) events after major orthopaedic surgery. QUESTION/PURPOSES (1) Are rotational thromboelastometry (ROTEM) findings associated with the presence or development of symptomatic VTE after hip fracture surgery? (2) Were any other patient factors associated with the presence or development of symptomatic VTE after hip fracture surgery? (3) Which ROTEM parameters were the most accurate in terms of detecting the association of hypercoagulability with symptomatic VTE? METHODS This retrospective study was conducted over a 13-month period. In all, 354 patients with femoral neck and peritrochanteric fractures who underwent hip hemiarthoplasty or cephallomedullary nailing were assessed for eligibility. Of those, 99% (349 of 354) were considered eligible for the study, 1% (3 of 354) of patients were excluded due to coagulation disorders, and another 1% (2 of 354) were excluded because they died before the postoperative ROTEM analysis. An additional 4% (13 of 354) of patients were lost before the minimum study follow-up of 3 months, leaving 95% (336 of 354) for analysis. A ROTEM analysis was performed in all patients at the time of their hospital admission, within hours of the injury, and on the second postoperative day. The patients were monitored for the development of symptoms indicative of VTE, and the gold standard tests for diagnosing VTE, such as CT pulmonary angiography or vascular ultrasound, were selectively performed only in symptomatic patients and not routinely in all patients. Therefore, this study evaluates the association of ROTEM with only clinically evident VTE events and not with all VTE events. ROTEM results did not affect the clinical surveillance of the study group and the decision for further work up. To determine whether ROTEM findings were associated with the presence or development of symptomatic VTE, ROTEM parameters were compared between patients with and without symptomatic VTE. To establish whether any other patient factors were associated with the presence or development of symptomatic VTE after hip fracture surgery, clinical parameters and conventional laboratory values were also compared between patients with and without symptomatic VTE. Finally, to determine which ROTEM parameters were the most accurate in terms of detecting the association of hypercoagulability with symptomatic VTE, the area under the curve (AUC) for certain cut off values of ROTEM parameters was calculated. RESULTS We found several abnormal ROTEM values to be associated with the presence or development of symptomatic VTE. The preoperative maximum clot firmness was higher in patients with clinically evident VTE than in patients without these complications (median [interquartile range] 70 mm [68 to 71] versus 65 mm [61 to 68]; p < 0.001). The preoperative clot formation time was lower in patients with clinically evident VTE than those without clinically evident VTE (median 61 seconds [58 to 65] versus 70 seconds [67 to 74]; p < 0.001), and also the postoperative clot formation time was lower in patients with clinically evident VTE than those without these complications (median 52 seconds [49 to 59] versus 62 seconds [57 to 68]; p < 0.001). Increased BMI was also associated with clinically evident VTE (odds ratio 1.26 [95% confidence interval 1.07 to 1.53]; p < 0.001). We found no differences between patients with and without clinically evident VTE in terms of age, sex, smoking status, comorbidities, and preoperative use of anticoagulants. Lastly, preoperative clot formation time demonstrated the best performance for detecting the association of hypercoagulability with symptomatic VTE (AUC 0.89 [95% CI 0.81 to 0.97]), with 81% (95% CI 48% to 97%) sensitivity and 86% (95% CI 81% to 89%) specificity for clot formation time ≤ 65 seconds. CONCLUSION ROTEM's performance in this preliminary study was promising in terms of its association with symptomatic VTE. This study extended our earlier work by demonstrating that ROTEM has a high accuracy in detecting the level of hypercoagulability that is associated with symptomatic VTE. However, until its performance is validated in a study that applies a diagnostic gold standard (such as venography, duplex/Doppler, or chest CT) in all patients having ROTEM to confirm its performance, ROTEM should not be used as a regular part of clinical practice. LEVEL OF EVIDENCE Level IV, diagnostic study.
Collapse
Affiliation(s)
- Andreas G. Tsantes
- Laboratory of Haematology and Blood Bank Unit, Attiko Hospital, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece
| | - Dimitrios V. Papadopoulos
- Department of Orthopaedic Surgery, University of Pittsburgh Orthopedic Specialists, Pittsburgh, PA, USA
| | - Ioannis G. Trikoupis
- First Department of Orthopaedics, National and Kapodistrian University of Athens, School of Medicine, Athens, Greece
| | - Konstantina A. Tsante
- Laboratory of Reliability and Quality Control in Laboratory Hematology, Department of Biomedical Sciences, School of Health & Caring Sciences, University of West Attica, Egaleo, Greece
| | - Andreas F. Mavrogenis
- First Department of Orthopaedics, National and Kapodistrian University of Athens, School of Medicine, Athens, Greece
| | - Panagiotis Koulouvaris
- First Department of Orthopaedics, National and Kapodistrian University of Athens, School of Medicine, Athens, Greece
| | - Daniele Piovani
- Department of Biomedical Sciences, Humanitas University, Milan, Italy
- IRCCS Humanitas Research Hospital, Milan, Italy
| | - Anastasios G. Kriebardis
- Laboratory of Haematology and Blood Bank Unit, Attiko Hospital, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece
- Laboratory of Reliability and Quality Control in Laboratory Hematology, Department of Biomedical Sciences, School of Health & Caring Sciences, University of West Attica, Egaleo, Greece
| | - Argyri Gialeraki
- Laboratory of Haematology and Blood Bank Unit, Attiko Hospital, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece
| | | | - Stefanos Bonovas
- Department of Biomedical Sciences, Humanitas University, Milan, Italy
- IRCCS Humanitas Research Hospital, Milan, Italy
| | - Panayiotis J. Papagelopoulos
- Department of Orthopaedic Surgery, University of Pittsburgh Orthopedic Specialists, Pittsburgh, PA, USA
- First Department of Orthopaedics, National and Kapodistrian University of Athens, School of Medicine, Athens, Greece
| | - Argirios E. Tsantes
- Laboratory of Haematology and Blood Bank Unit, Attiko Hospital, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece
| |
Collapse
|
|
41
|
Özdemir ZC, Çolak E, Kar YD, Özen H, Bör Ö. Relationship between oxidant-antioxidant status and hypercoagulobility indices in children with iron deficiency anaemia. Blood Coagul Fibrinolysis 2021; 32:451-457. [PMID: 34148983 DOI: 10.1097/mbc.0000000000001060] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
Oxidative stress is a potential mechanism involved in the pathogenesis of iron deficiency anaemia (IDA). Although a tendency for hypercoagulability has been reported in IDA, its underlying mechanism is yet to be elucidated. This study investigated the probable relationship between oxidative stress and hypercoagulability in children with IDA. This study included 57 children diagnosed with IDA (IDA group) between October 2016 and October 2017 in addition to 48 healthy children (control group). The maximum clot firmness (MCF) index, and clot formation time (CFT) index, which are indicators of hypercoagulability in rotational thromboelastometry assays [intrinsic TEM (INTEM) and extrinsic TEM (EXTEM)] derived from our previous study, were recorded. Total oxidant status (TOS), total antioxidant capacity (TAC) and oxidative stress index (OSI) were analysed from serum samples of the individuals. In IDA group, OSI and TOS levels were higher and TAC level was lower compared to the control group (P < 0.001, for all). The EXTEM and INTEM MCF in the IDA group was higher than in the control group, while the INTEM CFT was lower than in the control group (P < 0.001, P < 0.001, P < 0.05, published data).TOS and OSI had a negative correlation with INTEM CFT (r:-0.361, P < 0.001 and r:-0.333, P = 0.001) and a positive correlation with INTEM MCF (r:+0.420, P < 0.001 and r:+0.367, P < 0.001) and EXTEM MCF (r:+0.476, P < 0.001 and r:+0.403, P < 0.001). However, TAC demonstrated no correlation with CFT and MCF index. The oxidant-antioxidant balance is disrupted in favour of oxidative stress in children with IDA. In addition, TOS and OSI, which are parameters of oxidative stress, are correlated with CFT and MCF indices. Oxidative stress appears to be an important factor for the development of tendency to hypercoagulability in IDA.
Collapse
Affiliation(s)
| | | | | | - Hülya Özen
- Department of Biostatistics, Eskişehir Osmangazi University Faculty of Medicine, Eskişehir, Turkey
| | - Özcan Bör
- Division of Pediatric Hematology/Oncology, Department of Pediatrics
| |
Collapse
|
|
42
|
Vasovic LV, Littlejohn J, Alqunaibit D, Dillard A, Qiu Y, Rand S, Bronstein M, Gibson CJ, Kelly AG, Lee C, Minneman JA, Narayan M, Shou J, Smith KE, Villegas CV, Winchell RJ, Cushing MM, Barie PS. Rotational thromboelastometry in patients with acute respiratory distress syndrome owing to coronavirus disease 2019: Is there a viscoelastic fingerprint and a role for predicting thrombosis? Surgery 2021; 171:1092-1099. [PMID: 35090739 PMCID: PMC8426191 DOI: 10.1016/j.surg.2021.08.051] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2021] [Revised: 08/09/2021] [Accepted: 08/27/2021] [Indexed: 12/29/2022]
Abstract
Objectives We evaluated rotational thromboelastometry tracings in 44 critically ill coronavirus disease 2019 patients, to determine whether there is a viscoelastic fingerprint and to test the hypothesis that the diagnosis and prediction of venous thromboembolism would be enhanced by the addition of rotational thromboelastometry testing. Results Rotational thromboelastometry values reflected an increase in clot strength for the EXTEM, INTEM, and FIBTEM assays beyond the reference range. No hyperfibrinolysis was noted. Fibrinolysis shutdown was present but did not correlate with thrombosis; 32% (14/44) of patients experienced a thrombotic episode. For every 1 mm increase of FIBTEM maximum clot formation, the odds of developing thrombosis increased 20% (95% confidence interval, 0–40%, P = .043), whereas for every 1,000 ng/mL increase in D-dimer, the odds of thrombosis increased by 70% (95% confidence interval, 20%–150%, P = .004), after adjustment for age and sex (AUC 0.96, 95% confidence interval, 0.90–1.00). There was a slight but significant improvement in model performance after adding FIBTEM maximum clot formation and EXTEM clot formation time to D-dimer in a multivariable model (P = .04). Conclusions D-dimer concentrations were more predictive of thrombosis in our patient population than any other parameter. Rotational thromboelastometry confirmed the hypercoagulable state of coronavirus disease 2019 intensive care unit patients. FIBTEM maximum clot formation and EXTEM clot formation time increased the predictability for thrombosis compared with only using D-dimer. Rotational thromboelastometry analysis is most useful in augmenting the information provided by the D-dimer concentration for venous thromboembolism risk assessment when the D-dimer concentration is between 1,625 and 6,900 ng/dL, but the enhancement is modest. Fibrinolysis shutdown did not correlate with thrombosis.
Collapse
Affiliation(s)
- Ljiljana V Vasovic
- Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY
| | - James Littlejohn
- Department of Anesthesiology, Weill Cornell Medicine, New York, NY.
| | | | - Alicia Dillard
- Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY
| | - Yuqing Qiu
- Department of Population Health Sciences, Weill Cornell Medicine, New York, NY
| | - Sophie Rand
- Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY
| | | | | | - Anton G Kelly
- Department of Surgery, Weill Cornell Medicine New York, NY
| | - Christina Lee
- Department of Surgery, Weill Cornell Medicine New York, NY
| | | | - Mayur Narayan
- Department of Surgery, Weill Cornell Medicine New York, NY
| | - Jian Shou
- Department of Surgery, Weill Cornell Medicine New York, NY
| | - Kira E Smith
- Department of Surgery, Weill Cornell Medicine New York, NY
| | | | | | - Melissa M Cushing
- Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY
| | - Philip S Barie
- Department of Surgery, Weill Cornell Medicine New York, NY; Department of Medicine, Weill Cornell Medicine, New York, NY
| |
Collapse
|
|
43
|
Spielbauer KK, Sunde J, Buchakjian M, Casper KA, Malloy KM, Stucken CL, Prince ME, Rosko AJ, Schechtman S, Chinn SB, Kumar SS, Spector ME. Use of rotational thromboelastometry (ROTEM®) to predict thrombotic complications of microvascular head and neck reconstruction. Oral Oncol 2021; 124:105515. [PMID: 34481704 DOI: 10.1016/j.oraloncology.2021.105515] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/27/2021] [Accepted: 08/28/2021] [Indexed: 10/20/2022]
Affiliation(s)
- Katie K Spielbauer
- Michigan Medicine, 1500 E Medical Center Dr, Ann Arbor, MI 48105, United States.
| | - Jumin Sunde
- University of Arkansas for Medical Sciences, 4301 W. Markham St, Little Rock, AR 72205, United States
| | - Marisa Buchakjian
- University of Iowa Health Care, 200 Hawkins Dr, Iowa City, IA 52242, United States
| | - Keith A Casper
- Michigan Medicine, 1500 E Medical Center Dr, Ann Arbor, MI 48105, United States
| | - Kelly M Malloy
- Michigan Medicine, 1500 E Medical Center Dr, Ann Arbor, MI 48105, United States
| | - Chaz L Stucken
- Michigan Medicine, 1500 E Medical Center Dr, Ann Arbor, MI 48105, United States
| | - Mark E Prince
- Michigan Medicine, 1500 E Medical Center Dr, Ann Arbor, MI 48105, United States
| | - Andrew J Rosko
- Michigan Medicine, 1500 E Medical Center Dr, Ann Arbor, MI 48105, United States
| | - Samuel Schechtman
- Michigan Medicine, 1500 E Medical Center Dr, Ann Arbor, MI 48105, United States
| | - Steven B Chinn
- Michigan Medicine, 1500 E Medical Center Dr, Ann Arbor, MI 48105, United States
| | - Sathish S Kumar
- Michigan Medicine, 1500 E Medical Center Dr, Ann Arbor, MI 48105, United States
| | - Matthew E Spector
- Michigan Medicine, 1500 E Medical Center Dr, Ann Arbor, MI 48105, United States
| |
Collapse
|
|
44
|
Perioperative Viscoelastic Assay Use for Monitoring Coagulation Among US Liver Transplantation Centers. Transplant Proc 2021; 53:2312-2317. [PMID: 34454730 DOI: 10.1016/j.transproceed.2021.07.018] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2021] [Accepted: 07/12/2021] [Indexed: 11/21/2022]
Abstract
BACKGROUND Viscoelastic assay has been used in liver transplantation since 1985 and shown to be beneficial in detecting coagulopathy and to guide transfusion. The objective of this study was to review and evaluate the current uses of viscoelastic assay among US liver transplantation programs. METHODS Anesthesia program directors at all 137 liver transplantation centers in the United States were contacted via email and asked to complete a 21-item survey. The primary outcome measure was the percentage of viscoelastic assay used in the perioperative management of liver transplantation. Secondary outcome measures were institutional demographics, physician training level, and device demographics. RESULTS Sixty-one of 137 (46%) centers responded. Liver transplantations were performed in the university setting at 48 of the 61 centers (77%), with a modal value of 11 to 50 liver transplantations a year and 74% in adult patients only. Most of the institutions (n = 57, 92%) had access to either rotational thromboelastometry or thrombelastography during liver transplantation. Most centers (n = 54; 87%) also used viscoelastic monitoring routinely (>60% of the time), including 42 (67.7%) that always used viscoelastic assay intraoperatively during liver transplantation. Thirty-five centers (59%) used it preoperatively, and 51 (84%) used it postoperatively. Most viscoelastic assay users (68%) learned how to use it through self-education and 10.5% learned during their fellowship or from a superuser or colleagues. CONCLUSION Currently, viscoelastic monitoring is widely available and routinely used in most US liver transplantation centers regardless of university or private practice setting, but training in it is limited. Only 21.1% of respondents reported that they received any type of official training in viscoelastic assay interpretation.
Collapse
|
|
45
|
Peng HT, Nascimento B, Rhind SG, da Luz L, Beckett A. Evaluation of trauma-induced coagulopathy in the fibrinogen in the initial resuscitation of severe trauma trial. Transfusion 2021; 61 Suppl 1:S49-S57. [PMID: 34269460 DOI: 10.1111/trf.16488] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2020] [Revised: 03/31/2021] [Accepted: 04/01/2021] [Indexed: 12/13/2022]
Abstract
BACKGROUND Coagulopathic bleeding is frequently present after major trauma. However, trauma-induced coagulopathy (TIC) remains incompletely understood. This laboratory analysis of blood samples derived from our completed trial on fibrinogen in the initial resuscitation of severe trauma (FiiRST) was conducted to evaluate TIC and associated responses to fibrinogen replacement. STUDY DESIGN AND METHODS We conducted a retrospective evaluation of TIC in 45 FiiRST trial patients based on rotational thromboelastometry (ROTEM), international normalized ratio (INR), and biomarkers for hemostasis and endotheliopathy. Whole blood was analyzed by ROTEM. Plasma was analyzed for INR and biomarkers. RESULTS Overall, 19.0% and 30.0% of the FiiRST trial patients were coagulopathic on admission defined by EXTEM maximum clot firmness out of the range of 40-71 mm and INR >1.2, respectively. The FiiRST patients showed lower fibrinogen, factor II and V levels, protein C and antiplasmin activities, higher activated protein C, tissue plasminogen activator, d-dimer, and thrombomodulin concentrations at admission than healthy controls. Most of the biomarkers changed their activities during 48-h hospitalization, but were at abnormal levels even 48-h after admission. The fibrinogen treatment reduced hypofibrinogenemia and increased factor XIII level, but had no significant effects on other biomarkers levels. Limited development of endotheliopathy was indicated by syndean-1, thrombomodulin, and sE-selectin. CONCLUSIONS About 19%-30% of the trauma patients in the FiiRST trial were coagulopathic on hospital admission depending on the definition of TIC. Analyses of the TIC biomarkers demonstrated that hemostasis would not return to normal after 48-h hospitalization, and fibrinogen replacement improved hypofibrinogenemia.
Collapse
Affiliation(s)
- Henry T Peng
- Defence Research and Development Canada, Toronto Research Centre, Toronto, Ontario, Canada
| | | | - Shawn G Rhind
- Defence Research and Development Canada, Toronto Research Centre, Toronto, Ontario, Canada
| | - Luis da Luz
- Department of Surgery, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada
| | - Andrew Beckett
- Department of Surgery, St. Michael's Hospital, Toronto, Ontario, Canada.,Royal Canadian Medical Services, Ottawa, Ontario, Canada
| |
Collapse
|
|
46
|
Walsh M, Kwaan H, McCauley R, Marsee M, Speybroeck J, Thomas S, Hatch J, Vande Lune S, Grisoli A, Wadsworth S, Shariff F, Aversa JG, Shariff F, Zackariya N, Khan R, Agostini V, Campello E, Simioni P, Scărlătescu E, Hartmann J. Viscoelastic testing in oncology patients (including for the diagnosis of fibrinolysis): Review of existing evidence, technology comparison, and clinical utility. Transfusion 2021; 60 Suppl 6:S86-S100. [PMID: 33089937 DOI: 10.1111/trf.16102] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2020] [Revised: 09/09/2020] [Accepted: 09/09/2020] [Indexed: 12/23/2022]
Abstract
The quantification of the coagulopathic state associated with oncologic and hematologic diseases is imperfectly assessed by common coagulation tests such as prothrombin time, activated partial thromboplastin time, fibrinogen levels, and platelet count. These tests provide a static representation of a component of hemostatic integrity, presenting an incomplete picture of coagulation in these patients. Viscoelastic tests (VETs), such as rotational thromboelastometry (ROTEM) and thromboelastography (TEG), as whole blood analyses, provide data related to the cumulative effects of blood components and all stages of the coagulation and fibrinolytic processes. The utility of VETs has been demonstrated since the late 1960s in guiding blood component therapy for patients undergoing liver transplantation. Since then, the scope of viscoelastic testing has expanded to become routinely used for cardiac surgery, obstetrics, and trauma. In the past decade, VETs' expanded usage has been most significant in trauma resuscitation. However, use of VETs for patients with malignancy-associated coagulopathy (MAC) and hematologic malignancies is increasing. For the purposes of this narrative review, we discuss the similarities between trauma-induced coagulopathy (TIC) and MAC. These similarities center on the thrombomodulin-thrombin complex as it switches between the thrombin-activatable fibrinolysis inhibitor coagulation pathway and activating the protein C anticoagulation pathway. This produces a spectrum of coagulopathy and fibrinolytic alterations ranging from shutdown to hyperfibrinolysis that are common to TIC, MAC, and hematologic malignancies. There is expanding literature regarding the utility of TEG and ROTEM to describe the hemostatic integrity of patients with oncologic and hematologic conditions, which we review here.
Collapse
Affiliation(s)
- Mark Walsh
- Departments of Emergency and Internal Medicine, Saint Joseph Regional Medical Center, Mishawaka, Indiana, USA.,Beacon Medical Group Trauma & Surgical Research Services, South Bend, Indiana, USA.,Indiana University School of Medicine, South Bend, Indiana, USA
| | - Hau Kwaan
- Department of Hematology Oncology, Northwestern University School of Medicine, Chicago, Illinois, USA
| | - Ross McCauley
- Indiana University School of Medicine, South Bend, Indiana, USA
| | - Mathew Marsee
- Indiana University School of Medicine, South Bend, Indiana, USA
| | | | - Scott Thomas
- Beacon Medical Group Trauma & Surgical Research Services, South Bend, Indiana, USA
| | - Jordan Hatch
- Indiana University School of Medicine, South Bend, Indiana, USA
| | | | - Anne Grisoli
- Indiana University School of Medicine, South Bend, Indiana, USA
| | - Sarah Wadsworth
- Beacon Medical Group Trauma & Surgical Research Services, South Bend, Indiana, USA
| | - Faisal Shariff
- Indiana University School of Medicine, South Bend, Indiana, USA
| | - John G Aversa
- Department of General Surgery, Indiana University School of Medicine, Indianapolis, Indiana, USA
| | - Faadil Shariff
- Departments of Emergency and Internal Medicine, Saint Joseph Regional Medical Center, Mishawaka, Indiana, USA
| | - Nuha Zackariya
- Departments of Emergency and Internal Medicine, Saint Joseph Regional Medical Center, Mishawaka, Indiana, USA
| | - Rashid Khan
- Michiana Hematology Oncology, Mishawaka, Indiana, USA
| | - Vanessa Agostini
- Department of Transfusion Medicine, IRCC Polyclinic Hospital San Marino, Genoa, Italy
| | - Elena Campello
- Thrombotic and Hemorrhagic Diseases Unit, Department of Medicine, Padua University Hospital, Padua, Italy
| | - Paolo Simioni
- Thrombotic and Hemorrhagic Diseases Unit, Department of Medicine, Padua University Hospital, Padua, Italy
| | - Escaterina Scărlătescu
- Department of Anaesthesia and Intensive Care, Fundeni Clinical Institute, Bucharest, Romania
| | - Jan Hartmann
- Department of Medical Affairs, Haemonetics Corporation, Boston, Massachusetts, USA
| |
Collapse
|
|
47
|
Speybroeck J, Marsee M, Shariff F, Zackariya N, Grisoli A, Lune SV, Larson EE, Hatch J, McCauley R, Shariff F, Aversa JG, Son M, Agostini V, Campello E, Simioni P, Scărlătescu E, Kwaan H, Hartmann J, Fries D, Walsh M. Viscoelastic testing in benign hematologic disorders: Clinical perspectives and future implications of point-of-care testing to assess hemostatic competence. Transfusion 2021; 60 Suppl 6:S101-S121. [PMID: 33089936 DOI: 10.1111/trf.16088] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/01/2020] [Revised: 09/04/2020] [Accepted: 09/05/2020] [Indexed: 01/04/2023]
Abstract
Viscoelastic tests (VETs) have been used routinely for liver transplantation, cardiac surgery, and trauma, but only recently have found clinical utility in benign hematologic disorders. Therefore, guidelines for diagnosis and treatment of these disorders based on viscoelastic variables have been adapted from the existing transplant, cardiothoracic surgery, and trauma resuscitation literature. As a result, diagnostic and therapeutic strategies for benign hematologic disorders utilizing VETs are not uniform. Accordingly, even though there has been a recent increase in the utilization of VET for the diagnosis and treatment of such disorders, the literature is still in its early stages. Analysis of point-of-care viscoelastic tracings from benign hematologic disorders has the potential to allow prompt recognition of disease and to guide patient-specific intervention. Here we present a review describing the application of VETs to benign hematologic disorders.
Collapse
Affiliation(s)
- Jacob Speybroeck
- Indiana University School of Medicine, Notre Dame Campus, South Bend, Indiana
| | - Mathew Marsee
- Indiana University School of Medicine, Notre Dame Campus, South Bend, Indiana
| | - Faadil Shariff
- Saint Joseph Regional Medical Center, Mishawaka, Indiana
| | - Nuha Zackariya
- Saint Joseph Regional Medical Center, Mishawaka, Indiana
| | - Anne Grisoli
- Indiana University School of Medicine, Notre Dame Campus, South Bend, Indiana
| | - Stefani Vande Lune
- Indiana University School of Medicine, Notre Dame Campus, South Bend, Indiana
| | - Emilee E Larson
- Indiana University School of Medicine, Notre Dame Campus, South Bend, Indiana
| | - Jordan Hatch
- Indiana University School of Medicine, Notre Dame Campus, South Bend, Indiana
| | - Ross McCauley
- Indiana University School of Medicine, Notre Dame Campus, South Bend, Indiana
| | - Faisal Shariff
- Indiana University School of Medicine, Notre Dame Campus, South Bend, Indiana
| | - John G Aversa
- Department of General Surgery, Indiana University School of Medicine, Indianapolis, Indiana
| | - Michael Son
- Saint Joseph Regional Medical Center, Mishawaka, Indiana
| | - Vanessa Agostini
- Department of Transfusion Medicine, IRCC Polyclinic Hospital San Marino, Genoa, Italy
| | - Elena Campello
- Thrombotic and Hemorrhagic Diseases Unit, Department of Medicine, Padua University Hospital, Padua, Italy
| | - Paolo Simioni
- Thrombotic and Hemorrhagic Diseases Unit, Department of Medicine, Padua University Hospital, Padua, Italy
| | - Escaterina Scărlătescu
- Department of Anaesthesia and Intensive Care, Fundeni Clinical Institute, Bucharest, Romania
| | - Hau Kwaan
- Department of Hematology Oncology, Northwestern University School of Medicine, Chicago, Illinois
| | - Jan Hartmann
- Department of Medical Affairs, Haemonetics Corporation, Boston, Massachusetts
| | - Dietmar Fries
- Department of General and Surgical Critical Care Medicine, Medical University of Innsbruck, Innsbruck, Austria
| | - Mark Walsh
- Indiana University School of Medicine, Notre Dame Campus, South Bend, Indiana.,Saint Joseph Regional Medical Center, Mishawaka, Indiana
| |
Collapse
|
|
48
|
Carll T, Wool GD. Basic principles of viscoelastic testing. Transfusion 2021; 60 Suppl 6:S1-S9. [PMID: 33089939 DOI: 10.1111/trf.16071] [Citation(s) in RCA: 24] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/01/2020] [Revised: 06/02/2020] [Accepted: 06/03/2020] [Indexed: 12/15/2022]
Abstract
BACKGROUND Viscoelastic testing is a method of hemostatic analysis that provides a real-time, holistic view of ex vivo clotting. It allows for examination of both cellular and plasma protein contributions to clotting including platelet number and function, fibrin(ogen) function, and coagulation factor function. The method assesses physical clot properties during the transition of blood from a liquid to a gel state, either by measurement of clot shear modulus using physical force transduction or by measurement of clot resonance frequency using sonometric interrogation. Results are reported in a live trace, with different trace parameters reflecting different contributors to hemostasis. These reported parameters vary between testing platforms. RESULTS In the United States, there are several commonly used Food and Drug Administration (FDA)-approved viscoelastic instruments available on the market. Those instruments that use sonometric clot assessment are more recently available and allow for improved portability for use near the patient's bedside. These instruments generally feature different reagent kits that allow more specific interrogation of different hemostatic pathways. Viscoelastic testing can predict the results of traditional plasma-based coagulation assays and has the added benefit of detecting hypercoagulability and severe hyperfibrinolysis. Implementation of viscoelastic testing in many clinical settings is becoming widespread and has proven to be efficacious in reducing blood transfusion rates in many settings. An impact on overall mortality and morbidity has not yet been demonstrated. CONCLUSION This article provides a narrative review of the basic principles of viscoelastic testing, including the science and technology behind the method, as well as currently available testing platforms and reagents.
Collapse
Affiliation(s)
- Timothy Carll
- Department of Pathology, University of Chicago, Chicago, Illinois, USA
| | - Geoffrey D Wool
- Department of Pathology, University of Chicago, Chicago, Illinois, USA
| |
Collapse
|
|
49
|
Tsantes AG, Papadopoulos DV, Trikoupis IG, Goumenos S, Piovani D, Tsante KA, Mavrogenis AF, Vaiopoulos AG, Koulouvaris P, Nikolopoulos GK, Papagelopoulos PJ, Bonovas S, Tsantes AE. The Procoagulant Effect of COVID-19 on the Thrombotic Risk of Patients with Hip Fractures Due to Enhanced Clot Strength and Fibrinolysis Shutdown. J Clin Med 2021; 10:jcm10153397. [PMID: 34362178 PMCID: PMC8347467 DOI: 10.3390/jcm10153397] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2021] [Revised: 07/24/2021] [Accepted: 07/29/2021] [Indexed: 12/11/2022] Open
Abstract
Introduction: Coronavirus disease 2019 (COVID-19) in patients with hip fractures is associated with increased incidence of venous thromboembolism (VTE). The purpose of this study was to evaluate the hemostatic alterations of COVID-19 that are associated with a higher thrombotic risk using rotational thromboelastometry (ROTEM). Methods: A retrospective observational study was performed including 20 COVID-19 patients with hip fractures. To compare the coagulopathy of patients with mild COVID-19 and hip fractures with the coagulopathy associated with each of these two conditions separately, we used two previously recruited groups of patients; 198 hip fracture patients without COVID-19 and 21 COVID-19 patients without hip fractures. The demographics, clinical parameters, conventional coagulation parameters and ROTEM findings of the three groups were analyzed and compared. Results: COVID-19 hip fracture patients had higher amplitude of clot firmness at 10 min (p < 0.001), higher alpha angle (p < 0.001), higher lysis index at 60 min (p < 0.001), and shorter clot formation time (p < 0.001) than non-COVID-19 hip fracture patients, indicating increased clot strength and impaired fibrinolysis due to COVID-19. The value of lysis index at 60 min (99%) in COVID-19 patients with hip fractures was consistent with fibrinolysis shut down. Multivariable linear regression analysis further confirmed that COVID-19 resulted in increased amplitude of clot firmness at 10 min (p < 0.001), increased maximum clot firmness (p < 0.001), increased lysis index at 60 min (p < 0.001) and increased alpha angle (p < 0.001), but significantly shortened clot formation time (p < 0.001). Discussion: The higher thrombotic risk in COVID-19 patients with hip fractures is characterized by increased clot strength and fibrinolysis shutdown, as shown by ROTEM findings. Further prospective studies are warranted to evaluate the need for modification of thromboprophylaxis to balance the hemostatic derangements of COVID-19 patients with hip fractures.
Collapse
Affiliation(s)
- Andreas G. Tsantes
- Laboratory of Haematology and Blood Bank Unit, “Attiko” Hospital, School of Medicine, National and Kapodistrian University of Athens, 12462 Athens, Greece; (K.A.T.); (A.G.V.); (A.E.T.)
- Correspondence: (A.G.T.); (S.B.); Tel.: +30-6984533617 (A.G.T.)
| | | | - Ioannis G. Trikoupis
- First Department of Orthopaedics, National and Kapodistrian, School of Medicine, University of Athens, 12462 Athens, Greece; (I.G.T.); (S.G.); (A.F.M.); (P.K.); (P.J.P.)
| | - Stavros Goumenos
- First Department of Orthopaedics, National and Kapodistrian, School of Medicine, University of Athens, 12462 Athens, Greece; (I.G.T.); (S.G.); (A.F.M.); (P.K.); (P.J.P.)
| | - Daniele Piovani
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, 20090 Milan, Italy;
- IRCCS Humanitas Research Hospital, Rozzano, 20089 Milan, Italy
| | - Konstantina A. Tsante
- Laboratory of Haematology and Blood Bank Unit, “Attiko” Hospital, School of Medicine, National and Kapodistrian University of Athens, 12462 Athens, Greece; (K.A.T.); (A.G.V.); (A.E.T.)
| | - Andreas F. Mavrogenis
- First Department of Orthopaedics, National and Kapodistrian, School of Medicine, University of Athens, 12462 Athens, Greece; (I.G.T.); (S.G.); (A.F.M.); (P.K.); (P.J.P.)
| | - Aristeidis G. Vaiopoulos
- Laboratory of Haematology and Blood Bank Unit, “Attiko” Hospital, School of Medicine, National and Kapodistrian University of Athens, 12462 Athens, Greece; (K.A.T.); (A.G.V.); (A.E.T.)
| | - Panagiotis Koulouvaris
- First Department of Orthopaedics, National and Kapodistrian, School of Medicine, University of Athens, 12462 Athens, Greece; (I.G.T.); (S.G.); (A.F.M.); (P.K.); (P.J.P.)
| | - Georgios K. Nikolopoulos
- Department of Epidemiology and Public Health, Medical School, University of Cyprus, Nicosia 1678, Cyprus;
| | - Panayiotis J. Papagelopoulos
- First Department of Orthopaedics, National and Kapodistrian, School of Medicine, University of Athens, 12462 Athens, Greece; (I.G.T.); (S.G.); (A.F.M.); (P.K.); (P.J.P.)
| | - Stefanos Bonovas
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, 20090 Milan, Italy;
- IRCCS Humanitas Research Hospital, Rozzano, 20089 Milan, Italy
- Correspondence: (A.G.T.); (S.B.); Tel.: +30-6984533617 (A.G.T.)
| | - Argirios E. Tsantes
- Laboratory of Haematology and Blood Bank Unit, “Attiko” Hospital, School of Medicine, National and Kapodistrian University of Athens, 12462 Athens, Greece; (K.A.T.); (A.G.V.); (A.E.T.)
| |
Collapse
|
|
50
|
Lee CF, Hung HC, Lee WC. Using Rotational Thromboelastometry to Identify Early Allograft Dysfunction after Living Donor Liver Transplantation. J Clin Med 2021; 10:jcm10153401. [PMID: 34362183 PMCID: PMC8347977 DOI: 10.3390/jcm10153401] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2021] [Revised: 07/27/2021] [Accepted: 07/29/2021] [Indexed: 12/23/2022] Open
Abstract
Background: Diagnostic tests for early allograft dysfunction (EAD) after living donor liver transplantation (LDLT) vary widely. We aimed to evaluate the predictive value of rotational thromboelastometry (ROTEM)-derived parameters in EAD. Materials and Methods: A total of 121 patients were reviewed. The definition of EAD proposed by Olthoff et al. included the presence of any of the following at postoperative day 7: bilirubin level ≥ 10 mg/dL, INR ≥ 1.6, or serum AST or ALT levels > 2000 IU/L. All patients underwent ROTEM assay, which consisted of an extrinsically activated thromboelastometric test (EXTEM) before and 24 h after LDLT. Results: The 1-year/2-year OS were 68.%8/64.5% and 94.4%/90.8% for the EAD and non-EAD groups, respectively (p = 0.001). Two independent risks were identified for EAD, the postoperative clotting time (CT, p = 0.026) and time to maximum clot firmness (maximum clot firmness (MCF)-t, p = 0.009) on the EXTEM. CT yielded a specificity of 82.0% and negative predictive value of 83.0%, and MCF-t displayed a specificity of 76.4% and negative predictive value of 81.9% in diagnosing EAD. The use of the 24 h post-LDLT ROTEM increased the effectiveness of predicting overall survival (OS) compared to using the Olthoff’s EAD criteria alone (p < 0.001). Conclusion: We conclude that CT and MCF on EXTEM were independent predictors of EAD. The 24 h post-LDLT ROTEM can be used with conventional laboratory tests to diagnose EAD. It increases the effectiveness of predicting OS.
Collapse
Affiliation(s)
- Chen-Fang Lee
- Department of Liver and Transplantation Surgery, Chang-Gung Memorial Hospital at Linkou, Taoyuan City 333, Taiwan; (C.-F.L.); (W.-C.L.)
- College of Medicine, Chang-Gung University, Taoyuan City 333, Taiwan
| | - Hao-Chien Hung
- Department of Liver and Transplantation Surgery, Chang-Gung Memorial Hospital at Linkou, Taoyuan City 333, Taiwan; (C.-F.L.); (W.-C.L.)
- Correspondence: ; Tel.: +886-3-3281200 (ext. 3366); Fax: +886-3-3285818
| | - Wei-Chen Lee
- Department of Liver and Transplantation Surgery, Chang-Gung Memorial Hospital at Linkou, Taoyuan City 333, Taiwan; (C.-F.L.); (W.-C.L.)
- College of Medicine, Chang-Gung University, Taoyuan City 333, Taiwan
| |
Collapse
|