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Fontaine MJ, Lasola JJM, Martinez-Hernandez A, Marshall JN, Bentzen S, Zhan M, Lokhandwala PM, Tanaka K, Villa CH, Jones A, Atreya CD, Henderson RA. A prospective non-inferiority trial of pathogen reduced platelets compared to non-pathogen reduced platelets for correction of viscoelastic platelet function testing in cardiac surgery. Transfusion 2025. [PMID: 40371875 DOI: 10.1111/trf.18281] [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: 09/04/2024] [Revised: 03/27/2025] [Accepted: 05/01/2025] [Indexed: 05/16/2025]
Abstract
BACKGROUND Cardiac surgery on cardiopulmonary bypass (CPB) may alter platelet (PLT) function causing bleeding. The goal of this study is to evaluate the hemostatic effect of PRT-PLTs compared to untreated PLTs stored in platelet additive solution (PAS) following transfusion in bleeding patients undergoing cardiac surgery on CPB. METHODS In this single-center, prospective single-blinded two-arm noninferiority trial, patients being weaned off CPB were allocated to either a PRT-PLT or a standard PAS-PLT. The primary outcome was the change in maximum amplitude (ΔMA) on thromboelastographic testing (TEG) from pre- to post-transfusion. The non-inferiority margin was chosen as 50% of the ΔMA observed with PAS-PLT using a 1-sided 95% confidence interval. The secondary outcomes included the volume of chest tube drainage (CTD) and the number of blood products transfused during the first 24 h post-surgery. RESULTS A modified intention-to-treat analysis included 90 patients (48 PRT-PLTs; 42 PAS-PLTs). The ΔMA for PRT-PLT was 2.93 mm (95% CI 1.52-4.34) and was lower than that achieved with PAS-PLT at 5.68 mm (95% CI 3.26-8.09) (2-tailed p = .052). The ratio of ΔMA for PRT-PLT relative to PAS-PLT was estimated at .52 with a 90% confidence interval (.29, .89) and did not meet the non-inferiority criterion (>.5). The CTD and the number of blood products transfused during the first 24 h post-surgery were similar in both arms. CONCLUSION PRT-PLT transfusion results in lower responses in viscoelastic testing compared to PAS-PLT, although clinical outcomes with respect to blood component utilization and chest tube drainage were similar.
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Affiliation(s)
- Magali J Fontaine
- Department of Pathology, University of Maryland School of Medicine, Baltimore, Maryland, USA
| | - Jackline J M Lasola
- Department of Pathology, University of Maryland School of Medicine, Baltimore, Maryland, USA
| | | | - Juliana N Marshall
- Department of Pathology, University of Maryland School of Medicine, Baltimore, Maryland, USA
| | - Soren Bentzen
- Department of Epidemiology and Public Health, University of Maryland School of Medicine, Baltimore, Maryland, USA
| | - Min Zhan
- Department of Epidemiology and Public Health, University of Maryland School of Medicine, Baltimore, Maryland, USA
| | - Parvez M Lokhandwala
- Department of Pathology, University of Maryland School of Medicine, Baltimore, Maryland, USA
| | - Kenichi Tanaka
- Department of Anesthesia, University of Oklahoma Health Sciences Center, Oklahoma, Oklahoma, USA
| | - Carlos H Villa
- Office of Blood Research and Review, Center for Biologics Evaluation and Research (CBER), US Food and Drug Administration, Silver Spring, Maryland, USA
| | - Alexis Jones
- Department of Anesthesia, University of Maryland School of Medicine, Baltimore, Maryland, USA
| | - Chintamani D Atreya
- Office of Blood Research and Review, Center for Biologics Evaluation and Research (CBER), US Food and Drug Administration, Silver Spring, Maryland, USA
| | - Reney A Henderson
- Department of Anesthesia, University of Maryland School of Medicine, Baltimore, Maryland, USA
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Starcevic Z, Zrno-Mihaljevic M, Gasparovic H, Pasalic M, Petricevic M, Goerlinger K, Petricevic M. Perioperative Changes in Hemostatic Properties as Assessed by Multiplate, Siemens PFA-200, and ROTEM-A Comparative Study. J Clin Med 2025; 14:1640. [PMID: 40095585 PMCID: PMC11900509 DOI: 10.3390/jcm14051640] [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: 12/23/2024] [Revised: 02/11/2025] [Accepted: 02/20/2025] [Indexed: 03/19/2025] Open
Abstract
Objectives: This study sought to determine the platelet function and viscoelastic blood properties in the pre- and postoperative period using three different point-of-care (POC) devices (Multiplate®, Siemens PFA-200® and ROTEM®). We aimed to investigate the association between preoperative POC test results and bleeding outcomes. Postoperative changes in blood hemostatic properties were also evaluated, as well as the agreement between two platelet function analyzers and rotational thromboelastometry parameters. Methods: The study was conducted in a prospective observational fashion. Patients undergoing elective coronary artery bypass graft surgery (CABG) were enrolled. Hemostatic blood properties were assessed using three different POC devices; two platelet function analyzers were used: (1) Impedance aggregometry (Multiplate®) with the arachidonic acid (ASPI) test and adenosine diphosphate (ADP) test. (2) The Siemens INNOVANCE® PFA-200 System with the following assays: the PFA Collagen/EPI test, PFA Collagen/ADP test, and the INNOVANCE® PFA P2Y test. Viscoelastic blood properties were assessed using ROTEM® delta (TEM Innovations GmbH, Munich, Germany). POC tests were performed simultaneously at two different time points: (1) before surgery and (2) on postoperative day 4, respectively. The primary outcome was defined as amounts of perioperative bleeding and transfusion requirements, classified according to the universal definition for perioperative bleeding (UDPB) score. Results: The study recruited a total number of 63 patients undergoing elective isolated coronary artery bypass graft surgery (CABG). Based on the packed red blood cell (PRBC) transfusion requirements, patients with excessive bleeding were not just only frequently transfused (87.5% vs. 48.9%, p = 0.007) but were also transfused with higher amounts of PRBCs (1338.75 mL ± SD 1416.49 vs. 289.36 mL ± 373.07, p < 0.001). The FIBTEM A30 results significantly correlated with excessive bleeding (Correlation Coefficient Rho = -0.280, p = 0.028). Regression analysis revealed FIBTEM A 30 as a strongest predictor of 24 h chest tube output (CTO) (R Square 0.108, p = 0.009). The receiver operating characteristics curve (ROC) analysis showed that a preoperative FIBTEM A30 < 10.86 mm predicted excessive bleeding with 94% sensitivity and 50% specificity (ROC AUC 68.4%). The multiplate ASPI test results were significantly higher (35.24 AUC ± SD 22.24 vs. 19.43 AUC ± SD 10.74) and the proportion of Aspirin responders was significantly lower (42.4% vs. 76.7%, p = 0.006) in patients considered to have insignificant bleeding. On postoperative day 4, we found platelet hyperreactivity in the ASPItest coupled with a ROTEM-documented shift towards hypercoagulability. Conclusions: Modern hemostatic management and perioperative antiplatelet therapy (APT) administration/discontinuation management should be guided by thromboelastometry and platelet function testing. Prospective interventional trials are necessary to validate such an approach in multicentric studies.
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Affiliation(s)
- Zrinka Starcevic
- Department of Cardiac Surgery, University Hospital Centre Zagreb, 10000 Zagreb, Croatia; (Z.S.); (M.Z.-M.); (H.G.)
| | - Martina Zrno-Mihaljevic
- Department of Cardiac Surgery, University Hospital Centre Zagreb, 10000 Zagreb, Croatia; (Z.S.); (M.Z.-M.); (H.G.)
| | - Hrvoje Gasparovic
- Department of Cardiac Surgery, University Hospital Centre Zagreb, 10000 Zagreb, Croatia; (Z.S.); (M.Z.-M.); (H.G.)
| | - Marijan Pasalic
- Department of Cardiovascular Diseases, University Hospital Centre Zagreb, 10000 Zagreb, Croatia;
| | - Mirna Petricevic
- Department of Health Studies, University of Split, 21000 Split, Croatia;
| | - Klaus Goerlinger
- Department of Anesthesiology and Intensive Care Medicine, University Hospital Essen, University Duisburg-Essen, 45127 Essen, Germany;
- Medical Department, Tem Innovations, 81829 Munich, Germany
| | - Mate Petricevic
- Department of Health Studies, University of Split, 21000 Split, Croatia;
- School of Medicine, University Hospital of Split, University of Split, 21000 Split, Croatia
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Noteboom SH, Kho E, Veelo DP, van der Ster BJP, van Haeren MMT, Viersen VA, Müller MCA, Hermanns H, Vlaar APJ, Schenk J. Interpretation of Viscoelastic Hemostatic Assays in Cardiac Surgery Patients: Importance of Clinical Context. Anesth Analg 2025:00000539-990000000-01113. [PMID: 39841608 DOI: 10.1213/ane.0000000000007400] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/24/2025]
Abstract
BACKGROUND Rotational thromboelastometry (ROTEM) is widely used for point-of-care coagulation testing to reduce blood transfusions. Accurate interpretation of ROTEM data is crucial and requires substantial training. This study investigates the inter- and intrarater reliability of ROTEM interpretation among experts and compares their interpretations with a ROTEM-guided algorithm. METHODS This study was conducted at Amsterdam University Medical Center and included 90 cardiac surgery patients. ROTEM data were collected at 4 surgical stages: before induction, after aortic declamping, postcoagulation correction, and within 2 hours of intensive care unit (ICU) admission. An international panel of 7 cardiovascular anesthesiologists and one intensivist interpreted the data. Interrater reliability was assessed using Fleiss' kappa for binary decisions and the simple matching coefficient (SMC) for multiple-choice questions. Intrarater reliability with the ROTEM-guided algorithm was also evaluated. RESULTS Three hundred forty-three ROTEM measurements were analyzed. The interrater reliability for binary decisions was substantial to almost perfect, except after declamping (Fleiss' kappa = 0.34). The SMC for determining type of abnormality and interventions ranged from good to excellent across all ROTEM measuring moments (SMC ≥0.75). Intrarater reliability was almost perfect for binary questions (intraclass correlation coefficient [ICC] ≥0.81) and showed excellent agreement for multiple-choice questions. Comparing expert recommendations with the algorithm resulted in an average SMC of 0.70 indicating differences in intervention recommendations, with experts frequently recommending fibrinogen and protamine over the algorithm's suggestions of plasma and PCC. CONCLUSIONS This study demonstrates high inter- and intrarater reliability in ROTEM interpretation among trained professionals in cardiac surgery, with almost perfect agreement on abnormalities and interventions. However, differences between expert evaluations and the ROTEM-guided algorithm underscore the need for advanced clinical decision-making tools. Future efforts should focus on developing personalized, data-driven algorithms without predefined cutoff values to improve accuracy and patient outcomes.
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Affiliation(s)
- Sijm H Noteboom
- From the Department of Anesthesiology, Amsterdam University Medical Center, University of Amsterdam, Amsterdam Cardiovascular Sciences, Amsterdam, the Netherlands
- Department of Intensive Care, Amsterdam University Medical Center, University of Amsterdam, Amsterdam Cardiovascular Sciences, Amsterdam, the Netherlands
| | - Eline Kho
- From the Department of Anesthesiology, Amsterdam University Medical Center, University of Amsterdam, Amsterdam Cardiovascular Sciences, Amsterdam, the Netherlands
- Department of Intensive Care, Amsterdam University Medical Center, University of Amsterdam, Amsterdam Cardiovascular Sciences, Amsterdam, the Netherlands
| | - Denise P Veelo
- From the Department of Anesthesiology, Amsterdam University Medical Center, University of Amsterdam, Amsterdam Cardiovascular Sciences, Amsterdam, the Netherlands
| | - Björn J P van der Ster
- From the Department of Anesthesiology, Amsterdam University Medical Center, University of Amsterdam, Amsterdam Cardiovascular Sciences, Amsterdam, the Netherlands
| | - Maite M T van Haeren
- Department of Intensive Care, Amsterdam University Medical Center, University of Amsterdam, Amsterdam Cardiovascular Sciences, Amsterdam, the Netherlands
| | - Victor A Viersen
- From the Department of Anesthesiology, Amsterdam University Medical Center, University of Amsterdam, Amsterdam Cardiovascular Sciences, Amsterdam, the Netherlands
| | - Marcella C A Müller
- Department of Intensive Care, Amsterdam University Medical Center, University of Amsterdam, Amsterdam Cardiovascular Sciences, Amsterdam, the Netherlands
| | - Henning Hermanns
- From the Department of Anesthesiology, Amsterdam University Medical Center, University of Amsterdam, Amsterdam Cardiovascular Sciences, Amsterdam, the Netherlands
| | - Alexander P J Vlaar
- Department of Intensive Care, Amsterdam University Medical Center, University of Amsterdam, Amsterdam Cardiovascular Sciences, Amsterdam, the Netherlands
- Laboratory of Experimental Intensive Care and Anesthesiology, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, the Netherlands
| | - Jimmy Schenk
- From the Department of Anesthesiology, Amsterdam University Medical Center, University of Amsterdam, Amsterdam Cardiovascular Sciences, Amsterdam, the Netherlands
- Department of Epidemiology and Data Science, Amsterdam University Medical Center, University of Amsterdam, Amsterdam Public Health, Amsterdam, the Netherlands
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Williams B, Henderson R, Mazzeffi M, Tanaka K. FEIBA: Too Potent a Potion or Just Right for Post-CPB Bleeding? J Cardiothorac Vasc Anesth 2024; 38:1882-1884. [PMID: 38972817 DOI: 10.1053/j.jvca.2024.06.018] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/07/2024] [Accepted: 06/13/2024] [Indexed: 07/09/2024]
Affiliation(s)
- Brittney Williams
- Department of Anesthesiology, University of Maryland School of Medicine, Baltimore, MD
| | - Reney Henderson
- Department of Anesthesiology, University of Maryland School of Medicine, Baltimore, MD
| | - Michael Mazzeffi
- Department of Anesthesiology, University of Virginia School of Medicine, Charlottesville, VA
| | - Kenichi Tanaka
- Department of Anesthesiology, University of Oklahoma Health Sciences Center, Oklahoma City, OK
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Yoon I, Han JH, Jeon HJ. Advances in Platelet-Dysfunction Diagnostic Technologies. Biomolecules 2024; 14:714. [PMID: 38927117 PMCID: PMC11201885 DOI: 10.3390/biom14060714] [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: 04/30/2024] [Revised: 06/07/2024] [Accepted: 06/11/2024] [Indexed: 06/28/2024] Open
Abstract
The crucial role of platelets in hemostasis and their broad implications under various physiological conditions underscore the importance of accurate platelet-function testing. Platelets are key to clotting blood and healing wounds. Therefore, accurate diagnosis and management of platelet disorders are vital for patient care. This review outlines the significant advancements in platelet-function testing technologies, focusing on their working principles and the shift from traditional diagnostic methods to more innovative approaches. These improvements have deepened our understanding of platelet-related disorders and ushered in personalized treatment options. Despite challenges such as interpretation of complex data and the costs of new technologies, the potential for artificial-intelligence integration and the creation of wearable monitoring devices offers exciting future possibilities. This review underscores how these technological advances have enhanced the landscape of precision medicine and provided better diagnostic and treatment options for platelet-function disorders.
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Affiliation(s)
- Inkwon Yoon
- Department of Smart Health Science and Technology, Kangwon National University, Chuncheon 24341, Republic of Korea
| | - Jong Hyeok Han
- Department of Smart Health Science and Technology, Kangwon National University, Chuncheon 24341, Republic of Korea
| | - Hee-Jae Jeon
- Department of Smart Health Science and Technology, Kangwon National University, Chuncheon 24341, Republic of Korea
- Department of Mechanical and Biomedical Engineering, Kangwon National University, Chuncheon 24341, Republic of Korea
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Ko SH, Nan Z, Soh S, Shim JK, Lee HW, Kwak YL, Song JW. Effect of Retrograde Autologous Priming on Coagulation Assessed by Rotation Thromboelastometry in Patients Undergoing Valvular Cardiac Surgery. J Cardiothorac Vasc Anesth 2024; 38:939-945. [PMID: 38262805 DOI: 10.1053/j.jvca.2023.12.038] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/03/2023] [Revised: 12/20/2023] [Accepted: 12/27/2023] [Indexed: 01/25/2024]
Abstract
OBJECTIVES To investigate the effect of retrograde autologous priming (RAP) on coagulation function using rotation thromboelastometry (ROTEM) in patients undergoing valvular cardiac surgery. DESIGN A prospective, randomized, patient- and outcome assessor-blinded study. SETTING At a single-center university hospital. PARTICIPANTS Patients aged 20 years or older undergoing valvular cardiac surgery. INTERVENTIONS A total of 104 patients were allocated to the RAP or control group (1:1 ratio). In the RAP group, the prime was displaced into the collection bag before bypass initiation. ROTEM was performed at the induction of anesthesia, at the beginning of rewarming, and after the reversal of heparinization. Allogeneic plasma products and platelet concentrates were transfused according to ROTEM-based algorithms. MEASUREMENTS AND MAIN RESULTS An average volume of 635 ± 114 mL was removed using RAP (from the 1,600 mL initial prime volume). The hematocrit 10 minutes after cardiopulmonary bypass (CPB) was 24.7 ± 3.5% in the control group, and 26.1 ± 4.1% in the RAP group (p = 0.330). ROTEM, including EXTEM, INTEM, and FIBTEM, showed prolonged clotting time and decreased maximal clot firmness after CPB in both groups without intergroup differences. The number of patients who received intraoperative erythrocytes (27% v 25%, control versus RAP, p = 0.823), fresh frozen plasma (14% v 8%, control versus RAP, p = 0.339), cryoprecipitate (21% v 12%, control versus RAP, p = 0.185), or platelet concentrate transfusion (19% v 12%, control versus RAP, p = 0.277) did not differ between the groups. CONCLUSIONS Cardiopulmonary bypass induced impaired coagulation function on ROTEM. However, RAP did not improve coagulation function when compared with conventional priming in patients undergoing valvular cardiac surgery.
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Affiliation(s)
- Seo Hee Ko
- Department of Anesthesiology and Pain Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea; Anesthesia and Pain Research Institute, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Zhengyu Nan
- Department of Anesthesiology and Pain Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea; Anesthesia and Pain Research Institute, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Sarah Soh
- Department of Anesthesiology and Pain Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea; Anesthesia and Pain Research Institute, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Jae-Kwang Shim
- Department of Anesthesiology and Pain Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea; Anesthesia and Pain Research Institute, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Hee Won Lee
- Department of Anesthesiology and Pain Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea; Anesthesia and Pain Research Institute, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Young Lan Kwak
- Department of Anesthesiology and Pain Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea; Anesthesia and Pain Research Institute, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Jong Wook Song
- Department of Anesthesiology and Pain Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea; Anesthesia and Pain Research Institute, Yonsei University College of Medicine, Seoul, Republic of Korea.
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Rapier JJ, Daley M, Smith SE, Goh SL, Margale S, Smith I, Thomson BM, Tesar PJ, Pearse BL. Implementation of Patient Blood Management in Orthotopic Heart Transplants: A Single Centre Retrospective Observational Review. Heart Lung Circ 2024; 33:518-523. [PMID: 38365499 DOI: 10.1016/j.hlc.2024.01.010] [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: 10/06/2023] [Revised: 12/20/2023] [Accepted: 01/01/2024] [Indexed: 02/18/2024]
Abstract
BACKGROUND Blood transfusion in the perioperative cardiothoracic setting has accepted risks including deep sternal wound infection, increased intensive care unit length of stay, lung injury, and cost. It has an immunomodulatory effect which may cause allo-immunisation. This may influence long-term survival through immune-mediated factors. Targeting coagulation defects to reduce unnecessary or inappropriate transfusions may reduce these complications. METHODS In 2012, an institution-wide patient blood management evidence-based algorithmic bleeding management protocol was implemented at The Prince Charles Hospital, Brisbane, Australia. The benefit of this has been previously reported in our lung transplant and cardiac surgery (excluding transplants) cohorts. This study aimed to investigate the effect of this on our orthotopic heart transplant recipients. RESULTS After the implementation of the protocol, despite no difference in preoperative haemoglobin levels and higher risk patients (EuroSCORE 20 vs 26; p=0.013), the use of packed red blood cells (13.0 U vs 4.4 U; p=0.046) was significantly lower postoperatively and fresh frozen plasma was significantly lower both intra- and postoperatively (7.4 U vs 0.6 U; p<0.001, and 3.3 U vs 0.6 U; p=0.011 respectively). Concurrently, the use of prothrombin complex concentrate (33% vs 78%; p<0.001) and desmopressin (5% vs 22%; p=0.0028) was significantly higher in the post-protocol group, while there was less use of recombinant factor VIIa (15% vs 4%; p=0.058). Intraoperative units of cryoprecipitate also rose from 0.9 to 2.0 (p=0.006). CONCLUSIONS We have demonstrated that a targeted patient blood management protocol with point-of-care testing for heart transplant recipients is correlated with fewer blood products used postoperatively, with some increase in haemostatic products and no evidence of increased adverse events.
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Affiliation(s)
- Jacob J Rapier
- Department of Cardiothoracic Surgery, The Prince Charles Hospital, Brisbane, Qld, Australia.
| | - Michael Daley
- Department of Cardiothoracic Surgery, The Prince Charles Hospital, Brisbane, Qld, Australia
| | - Susan E Smith
- Department of Cardiothoracic Surgery, The Prince Charles Hospital, Brisbane, Qld, Australia
| | - Sean L Goh
- Department of Cardiothoracic Surgery, The Prince Charles Hospital, Brisbane, Qld, Australia
| | - Swaroop Margale
- Department of Anaesthesia and Perfusion, The Prince Charles Hospital, Brisbane, Qld, Australia
| | - Ian Smith
- Department of Anaesthesia and Perfusion, The Prince Charles Hospital, Brisbane, Qld, Australia
| | - Bruce M Thomson
- Department of Cardiothoracic Surgery, The Prince Charles Hospital, Brisbane, Qld, Australia
| | - Peter J Tesar
- Department of Cardiothoracic Surgery, The Prince Charles Hospital, Brisbane, Qld, Australia
| | - Bronwyn L Pearse
- Department of Surgery and Critical Care, The Prince Charles Hospital, Brisbane, Qld, Australia
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Malik M, Al-Ghafry M, Haimed A, Su J, Lema M, Shore-Lessersson L, Acharya SS. Exploration of rotational thromboelastometry (ROTEM) to characterize the coagulation profiles of newly diagnosed pediatric leukemia patients. Thromb Res 2024; 233:109-118. [PMID: 38039723 DOI: 10.1016/j.thromres.2023.11.019] [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: 08/11/2023] [Revised: 10/18/2023] [Accepted: 11/15/2023] [Indexed: 12/03/2023]
Abstract
BACKGROUND Viscoelastic testing has been used in adult hematologic malignancies in conjunction with conventional coagulation tests (CCTs) to predict coagulopathies and tailor blood product replacement. However, there is a paucity of similar pediatric studies. OBJECTIVES Analyze and correlate leukemia-associated coagulopathy in newly diagnosed pediatric leukemia patients using CCT's and Rotational Thromboelastometry (ROTEM). METHODS Pediatric patients with newly diagnosed acute leukemia underwent testing with ROTEM and CCTs on days 0, 15 and 29 of induction chemotherapy. RESULTS Sixty-two patients were enrolled. At presentation, 54.8 % of patients had platelets <50 K/μL, 73 % had prolonged PT, 1.6 % had fibrinogen <150 mg/dL. Fifteen patients (24.2 %) had WHO grade 1 bleeding and two patients (3 %) had WHO grade 4 bleeding. EXTEM/INTEM values at presentation (day 0) reflected hypocoagulability, however FIBTEM revealed hypercoagulability. Patients showed a progressive hypocoagulability in all ROTEM assays by day 15 (day 0 vs day 15, p < 0.001), with improvement by day 29 (day 15 vs day 29, p < 0.001). Day 0 ROTEM parameters were comparable to day 29. Fibrinogen strongly correlated with ROTEM at all three time points (p < 0.0001), along with platelet count with moderate correlations (p < 0.001). CONCLUSION Fibrinogen and platelets appear to be the drivers of leukemia associated coagulopathy in the pediatric population, suggesting the utility of using CCTs and ROTEM in this population to better evaluate hemostatic function and guide blood product replacement.
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Affiliation(s)
- Marium Malik
- Division of Pediatric Hematology, Oncology and Stem Cell Transplant - Cohen Children's Medical Center, New Hyde Park, New York, United States of America; Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, New York, United States of America
| | - Maha Al-Ghafry
- Division of Pediatric Hematology, Oncology and Stem Cell Transplant - Cohen Children's Medical Center, New Hyde Park, New York, United States of America; Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, New York, United States of America
| | - Abraham Haimed
- Department of Pediatrics - Cohen Children's Medical Center, New Hyde Park, New York, United States of America; Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, New York, United States of America
| | - Julia Su
- Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, New York, United States of America
| | - Maribel Lema
- Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, New York, United States of America
| | - Linda Shore-Lessersson
- Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, New York, United States of America; Division of Anesthesiology, North Shore University Hospital, Manhasset, New York, United States of America
| | - Suchitra S Acharya
- Division of Pediatric Hematology, Oncology and Stem Cell Transplant - Cohen Children's Medical Center, New Hyde Park, New York, United States of America; Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, New York, United States of America.
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Wyssusek KH, Wagner MK, Lee J, Okano S, Wullschleger M, van Zundert AA. Blood management practices during rapid transfer of urgent trauma patients pre- and post-implementation of ROTEM ®-guided transfusion. TRAUMA-ENGLAND 2023. [DOI: 10.1177/14604086231159687] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/07/2023]
Abstract
Objective The ‘Red Blanket’ protocol fast tracks trauma patients with severe blood loss to the designated trauma operating theatre directly from the hospital helipad or Emergency Department. This study aimed to assess the impact of patient blood management (PBM) strategies on severely injured trauma patients treated under the ‘Red Blanket’ protocol at a quaternary referral hospital. Methods This retrospective review was conducted on all urgent trauma cases that were treated under the ‘Red Blanket’ protocol in a ten-year period between January 2007 and December 2017. The use of blood products and patient outcomes was compared between the 3.5-year periods pre- and post-ROTEM® implementation on 30th June 2014 (Jan 2011-June 2014 versus July 2014-Dec 2017). Results During the study period, 120 trauma patients were treated under the ‘Red Blanket’ protocol at our institution. Intention to treat analysis showed a reduction in fresh frozen plasma usage following the introduction of ROTEM®-guided transfusion. Furthermore, subgroup analysis suggested reduced blood product usage in patients who survived. Conclusions Patient blood management is a coordinated package of systems and tools, including education, patient logistics, anaemia management, intraoperative cell salvage, rotational thromboelastometry and massive transfusion protocols that together conserve blood products and improve outcomes. The implementation of ROTEM®-guided transfusion demonstrated a reduction in fresh frozen plasma usage.
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Affiliation(s)
- Kerstin H. Wyssusek
- Department of Anesthesia & Perioperative Medicine, Royal Brisbane & Women's Hospital, St Herston, QLD, Australia
- School of Clinical Medicine, The University of Queensland, Herston, QLD, Australia
| | - Matthew K. Wagner
- Department of Anesthesia & Perioperative Medicine, Royal Brisbane & Women's Hospital, St Herston, QLD, Australia
- School of Clinical Medicine, The University of Queensland, Herston, QLD, Australia
| | - Julie Lee
- Department of Anesthesia & Perioperative Medicine, Royal Brisbane & Women's Hospital, St Herston, QLD, Australia
- School of Clinical Medicine, The University of Queensland, Herston, QLD, Australia
| | - Satomi Okano
- Statistics Unit, QIMR Berghofer Medical Research Institute, Herston, QLD, Australia
| | - Martin Wullschleger
- School of Clinical Medicine, The University of Queensland, Herston, QLD, Australia
- Department of Trauma Service, Royal Brisbane and Women’s Hospital, Herston, QLD, Australia
| | - André A. van Zundert
- Department of Anesthesia & Perioperative Medicine, Royal Brisbane & Women's Hospital, St Herston, QLD, Australia
- School of Clinical Medicine, The University of Queensland, Herston, QLD, Australia
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10
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Larsson M, Zindovic I, Sjögren J, Svensson PJ, Strandberg K, Nozohoor S. A prospective, controlled study on the utility of rotational thromboelastometry in surgery for acute type A aortic dissection. Sci Rep 2022; 12:18950. [PMID: 36347972 PMCID: PMC9643344 DOI: 10.1038/s41598-022-23701-z] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2022] [Accepted: 11/03/2022] [Indexed: 11/11/2022] Open
Abstract
To evaluate the hemostatic system with ROTEM in patients undergoing surgery for acute type aortic dissection (ATAAD) using elective aortic procedures as controls. This was a prospective, controlled, observational study. The study was performed at a tertiary referral center and university hospital. Twenty-three patients with ATAAD were compared to 20 control patients undergoing elective surgery of the ascending aorta or the aortic root. ROTEM (INTEM, EXTEM, HEPTEM and FIBTEM) was tested at 6 points in time before, during and after surgery for ATAAD or elective aortic surgery. The ATAAD group had an activated coagulation coming into the surgical theatre. The two groups showed activation of both major coagulation pathways during surgery, but the ATAAD group consistently had larger deficiencies. Reversal of the coagulopathy was successful, although none of the groups reached elective baseline until postoperative day 1. ROTEM did not detect low levels of clotting factors at heparin reversal nor low levels of platelets. This study demonstrated that ATAAD is associated with a coagulopathic state. Surgery causes additional damage to the hemostatic system in ATAAD patients as well as in patients undergoing elective surgery of the ascending aorta or the aortic root. ROTEM does not adequately catch the full coagulopathy in ATAAD. A transfusion protocol in ATAAD should be specifically created to target this complex coagulopathic state and ROTEM does not negate the need for routine laboratory tests.
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Affiliation(s)
- Mårten Larsson
- grid.411843.b0000 0004 0623 9987Department of Clinical Sciences, Department of Cardiothoracic Surgery, Skåne University Hospital, Lund University, 221 85 Lund, Sweden
| | - Igor Zindovic
- grid.411843.b0000 0004 0623 9987Department of Clinical Sciences, Department of Cardiothoracic Surgery, Skåne University Hospital, Lund University, 221 85 Lund, Sweden
| | - Johan Sjögren
- grid.411843.b0000 0004 0623 9987Department of Clinical Sciences, Department of Cardiothoracic Surgery, Skåne University Hospital, Lund University, 221 85 Lund, Sweden
| | - Peter J. Svensson
- grid.411843.b0000 0004 0623 9987Department of Coagulation Disorders, Skåne University Hospital, Lund University, Malmö, Sweden
| | - Karin Strandberg
- University and Regional Laboratories, Region Skåne, Malmö, Sweden
| | - Shahab Nozohoor
- grid.411843.b0000 0004 0623 9987Department of Clinical Sciences, Department of Cardiothoracic Surgery, Skåne University Hospital, Lund University, 221 85 Lund, Sweden
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11
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Girish A, Jolly K, Alsaadi N, de la Fuente M, Recchione A, An R, Disharoon D, Secunda Z, Raghunathan S, Luc NF, Desai C, Knauss E, Han X, Hu K, Wang H, Sekhon UDS, Rohner N, Gurkan UA, Nieman M, Neal MD, Sen Gupta A. Platelet-Inspired Intravenous Nanomedicine for Injury-Targeted Direct Delivery of Thrombin to Augment Hemostasis in Coagulopathies. ACS NANO 2022; 16:16292-16313. [PMID: 35916497 PMCID: PMC10195184 DOI: 10.1021/acsnano.2c05306] [Citation(s) in RCA: 26] [Impact Index Per Article: 8.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/20/2023]
Abstract
Severe hemorrhage associated with trauma, surgery, and congenital or drug-induced coagulopathies can be life-threatening and requires rapid hemostatic management via topical, intracavitary, or intravenous routes. For injuries that are not easily accessible externally, intravenous hemostatic approaches are needed. The clinical gold standard for this is transfusion of blood products, but due to donor dependence, specialized storage requirements, high risk of contamination, and short shelf life, blood product use faces significant challenges. Consequently, recent research efforts are being focused on designing biosynthetic intravenous hemostats, using intravenous nanoparticles and polymer systems. Here we report on the design and evaluation of thrombin-loaded injury-site-targeted lipid nanoparticles (t-TLNPs) that can specifically localize at an injury site via platelet-mimetic anchorage to the von Willebrand factor (vWF) and collagen and directly release thrombin via diffusion and phospholipase-triggered particle destabilization, which can locally augment fibrin generation from fibrinogen for hemostatic action. We evaluated t-TLNPs in vitro in human blood and plasma, where hemostatic defects were created by platelet depletion and anticoagulation. Spectrophotometric studies of fibrin generation, rotational thromboelastometry (ROTEM)-based studies of clot viscoelasticity, and BioFlux-based real-time imaging of fibrin generation under simulated vascular flow conditions confirmed that t-TLNPs can restore fibrin in hemostatic dysfunction settings. Finally, the in vivo feasibility of t-TLNPs was tested by prophylactic administration in a tail-clip model and emergency administration in a liver-laceration model in mice with induced hemostatic defects. Treatment with t-TLNPs was able to significantly reduce bleeding in both models. Our studies demonstrate an intravenous nanomedicine approach for injury-site-targeted direct delivery of thrombin to augment hemostasis.
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Affiliation(s)
- Aditya Girish
- Department of Biomedical Engineering, Case Western Reserve University, Cleveland, Ohio 44106, United States
| | - Ketan Jolly
- Department of Biomedical Engineering, Case Western Reserve University, Cleveland, Ohio 44106, United States
| | - Nijmeh Alsaadi
- Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania 15123, United States
| | - Maria de la Fuente
- Department of Pharmacology, Case Western Reserve University, Cleveland, Ohio 44106, United States
| | - Arielle Recchione
- Department of Biomedical Engineering, Case Western Reserve University, Cleveland, Ohio 44106, United States
| | - Ran An
- Department of Mechanical and Aerospace Engineering, Case Western Reserve University, Cleveland, Ohio 44106, United States
| | - Dante Disharoon
- Department of Biomedical Engineering, Case Western Reserve University, Cleveland, Ohio 44106, United States
| | - Zachary Secunda
- Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania 15123, United States
| | - Shruti Raghunathan
- Department of Biomedical Engineering, Case Western Reserve University, Cleveland, Ohio 44106, United States
| | - Norman F Luc
- Department of Biomedical Engineering, Case Western Reserve University, Cleveland, Ohio 44106, United States
| | - Cian Desai
- Department of Biomedical Engineering, Case Western Reserve University, Cleveland, Ohio 44106, United States
| | - Elizabeth Knauss
- Department of Pharmacology, Case Western Reserve University, Cleveland, Ohio 44106, United States
| | - Xu Han
- Department of Pharmacology, Case Western Reserve University, Cleveland, Ohio 44106, United States
| | - Keren Hu
- Department of Biomedical Engineering, Case Western Reserve University, Cleveland, Ohio 44106, United States
| | - Hanyang Wang
- Department of Biomedical Engineering, Case Western Reserve University, Cleveland, Ohio 44106, United States
| | - Ujjal Didar Singh Sekhon
- Department of Biomedical Engineering, Case Western Reserve University, Cleveland, Ohio 44106, United States
| | - Nathan Rohner
- Department of Biomedical Engineering, Case Western Reserve University, Cleveland, Ohio 44106, United States
| | - Umut A Gurkan
- Department of Mechanical and Aerospace Engineering, Case Western Reserve University, Cleveland, Ohio 44106, United States
| | - Marvin Nieman
- Department of Pharmacology, Case Western Reserve University, Cleveland, Ohio 44106, United States
| | - Matthew D Neal
- Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania 15123, United States
| | - Anirban Sen Gupta
- Department of Biomedical Engineering, Case Western Reserve University, Cleveland, Ohio 44106, United States
- Department of Pharmacology, Case Western Reserve University, Cleveland, Ohio 44106, United States
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12
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Yoshii R, Sawa T, Kawajiri H, Amaya F, Tanaka KA, Ogawa S. A comparison of the ClotPro system with rotational thromboelastometry in cardiac surgery: a prospective observational study. Sci Rep 2022; 12:17269. [PMID: 36241854 PMCID: PMC9568545 DOI: 10.1038/s41598-022-22119-x] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/09/2022] [Accepted: 10/10/2022] [Indexed: 01/06/2023] Open
Abstract
Viscoelastic coagulation tests have been increasingly used for hemostasis management in cardiac surgery. The ClotPro system is a novel viscoelastic device based on principles of rotational thromboelastometry. We aimed to compare ClotPro with ROTEM and plasma coagulation assays in cardiopulmonary bypass (CPB) patients. Blood samples were collected from 25 CPB patients at (1) baseline, (2) start of CPB, (3) end of CPB, and (4) end of surgery. The EX-test, IN-test, HI-test, FIB-test parameters on ClotPro were compared with corresponding ROTEM assay (EXTEM, INTEM, HEPTEM, and FIBTEM). Standard plasma coagulation assays and endogenous thrombin generation (TG) were simultaneously evaluated. Pearson correlation analyses showed moderate correlations between clotting times (CTs) (r = 0.63-0.67; p < 0.001, respectively), and strong correlations with maximal clot firmness (MCF) (r = 0.93-0.98; p < 0.001, respectively) between ClotPro and ROTEM. EX-test and IN-test MCF parameters were interchangeable with acceptable percentage errors (EX-test MCF: 7.3%, IN-test MCF: 8.3%), but FIB-test MCF (27.0%) and CT results were not (EX-test CT: 44.7%, IN-test CT: 31.4%). The correlations of PT/INR or peak TG with EX-test CTs were higher than with EXTEM CTs (PT/INR: r = 0.80 and 0.41, peak TG: 0.43 and 0.18, respectively). FIB-test MCF has strong correlation with plasma fibrinogen and factor XIII level (r = 0.84 and 0.66, respectively). ROC analyses showed that ClotPro was capable of emulating well-established ROTEM thresholds (area under curves: 0.83-1.00). ClotPro demonstrated strong correlations in MCF parameters of ROTEM in CPB patients. It may be reasonable to modify ROTEM-based transfusion algorithm pertaining to MCF parameters to establish cut-off values for ClotPro device.
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Affiliation(s)
- Ryogo Yoshii
- grid.272458.e0000 0001 0667 4960Department of Anesthesiology, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Teiji Sawa
- grid.272458.e0000 0001 0667 4960Department of Anesthesiology, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Hidetake Kawajiri
- grid.272458.e0000 0001 0667 4960Department of Cardiovascular Surgery, Kyoto Prefectural University of Medicine, Kyoto, Kyoto, Japan
| | - Fumimasa Amaya
- grid.272458.e0000 0001 0667 4960Department of Pain Management and Palliative Care Medicine, Kyoto Prefectural University of Medicine, Kawaramachi Hirokoji, Kamigyo, Kyoto, 602-8566 Japan
| | - Kenichi A. Tanaka
- grid.266902.90000 0001 2179 3618Department of Anesthesiology, University of Oklahoma Health Sciences Center, Oklahoma, USA
| | - Satoru Ogawa
- grid.272458.e0000 0001 0667 4960Department of Anesthesiology, Kyoto Prefectural University of Medicine, Kyoto, Japan ,grid.272458.e0000 0001 0667 4960Department of Pain Management and Palliative Care Medicine, Kyoto Prefectural University of Medicine, Kawaramachi Hirokoji, Kamigyo, Kyoto, 602-8566 Japan
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13
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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.
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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
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14
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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.
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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
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15
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A Matzelle S, F Preuss J, M Weightman W, M Gibbs N. An audit of the diagnostic accuracy of the ROTEM®sigma for the identification of hypofibrinogenaemia in cardiac surgical patients. Anaesth Intensive Care 2022; 50:388-395. [PMID: 35722887 DOI: 10.1177/0310057x211067807] [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: 11/16/2022]
Abstract
The ROTEM®delta (TEM Innovations GmbH, Munich, Germany) has been used extensively worldwide for the assessment of coagulation in cardiac surgical patients. Recently, a new cartridge-based ROTEM device (ROTEM®sigma, TEM Innovations GmbH, Munich, Germany) has become available. In this paper we report an audit of the diagnostic accuracy of the ROTEM sigma for the identification of hypofibrinogenaemia in cardiac surgical patients. We hypothesised that the diagnostic accuracy of the ROTEMsigma for the identification of hypofibrinogenaemia would be in a similar range to that previously reported for the ROTEMdelta. Simultaneous blood samples for Clauss laboratory fibrinogen and ROTEMsigma FIBTEM measurements were obtained immediately after heparin reversal post-cardiopulmonary bypass in 200 adult cardiac surgical patients. The sensitivity, specificity, and positive and negative predictive values for FIBTEM A5 and A10 for the identification of hypofibrinogenaemia (Clauss fibrinogen <1.5 g/l) were calculated. The prevalence of hypofibrinogenaemia across the 200 patients was 8%. The mean sensitivity and specificity of FIBTEM A10 ≤8 mm for the identification of hypofibrinogenaemia were 0.75 and 0.90 respectively, which are in a similar range to that reported in several previous studies using the ROTEMdelta. For FIBTEM A5 ≤6 mm the values were 0.63 and 0.98 respectively. The predictive values were also in a similar range to those previously reported for the ROTEMdelta, with low false negative rates (2% for A10 ≤8 mm; 3% for A5 ≤6 mm). These findings support the use of the ROTEMsigma as an alternative to the ROTEMdelta for the identification of hypofibrinogenaemia post-cardiopulmonary bypass in cardiac surgical patients. However, further studies are required in other settings.
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Affiliation(s)
- Shannon A Matzelle
- Department of Anaesthesia, Sir Charles Gairdner Hospital, Australia.,Department of Anaesthesia, St John of God Hospital, Australia
| | - James F Preuss
- Department of Anaesthesia, Sir Charles Gairdner Hospital, Australia.,Department of Anaesthesia, St John of God Hospital, Australia
| | - William M Weightman
- Department of Anaesthesia, Sir Charles Gairdner Hospital, Australia.,Department of Anaesthesia, St John of God Hospital, Australia
| | - Neville M Gibbs
- Department of Anaesthesia, Sir Charles Gairdner Hospital, Australia.,Department of Anaesthesia, St John of God Hospital, Australia
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16
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Richards JE, Fedeles BT. Coagulation Management in Trauma: Do We Need a Viscoelastic Hemostatic Assay? CURRENT ANESTHESIOLOGY REPORTS 2022. [DOI: 10.1007/s40140-022-00532-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/18/2022]
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17
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Leyra F, Jofre C, Peña N, Olmos E, Del Campo JM, Aranzubia M, Moreno I. Prediction of platelet counts with ROTEM-sigma in cardiac surgery. Minerva Anestesiol 2022; 88:573-579. [PMID: 35381835 DOI: 10.23736/s0375-9393.22.15912-2] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Abstract
BACKGROUND Excessive bleeding is common after cardiac surgery. According to transfusion algorithms based on ROTEM results, platelet transfusion is recommended when FIBTEM amplitude is normal and EXTEM amplitude is reduced. The aim of this study is to evaluate whether ROTEM parameters may predict accurately platelet counts in cardiac surgery patients and to determine which of these parameters is the most useful for predicting platelet counts. METHODS In this retrospective single center study data from 83 patients who underwent cardiac surgery were reviewed. We analysed the results of patients for whom ROTEM and conventional laboratory tests were performed simultaneously. The derived ROTEM parameter PLTEM was used to estimate platelet count, PLTEM is calculated by subtracting FIBTEM from EXTEM. Correlation between ROTEM variables and platelet counts were determined. Logistic regression analyses were performed to predict platelet counts. RESULTS ROTEM A5 values show a high linear correlation with MCF values. PLTEM has a strong linear correlation with platelet counts. According to our results for PLTEM A5 < 32 mm the probability of platelet count < 150 x 109/L is 100%, for PLTEM A5 < 27 mm the probability of platelet count < 100 x 109/L is nearly 80%, and for PLTEM A5 < 22 the probability of platelet count < 75 x 109/L is 70%. CONCLUSIONS This study demonstrates the reliability of considering early ROTEM results and the feasibility of using PLTEM A5 to predict platelet counts and so improve our ability to decide the need of platelet transfusion in cardiac surgery patients.
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Affiliation(s)
- Fernando Leyra
- Anesthesiology Department, Hospital Universitario La Paz, Madrid, Spain -
| | - Cristina Jofre
- Anesthesiology Department, Hospital Universitario La Paz, Madrid, Spain
| | - Natalia Peña
- Anesthesiology Department, Hospital Universitario La Paz, Madrid, Spain
| | - Eva Olmos
- Anesthesiology Department, Hospital Universitario La Paz, Madrid, Spain
| | - José M Del Campo
- Anesthesiology Department, Hospital Universitario La Paz, Madrid, Spain
| | - Montserrat Aranzubia
- Anesthesiology Department, Hospital Universitario Fundación Jimenez Diaz, Madrid, Spain
| | - Isidro Moreno
- Anesthesiology Department, Hospital Universitario La Paz, Madrid, Spain
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18
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Abstract
Massive diffuse bleeding is still a problem in cardiovascular surgery. The first line treatment is platelet concentrate transfusion, although there is still insufficient information regarding efficacy, quantity, and timing. The objective of this prospective cohort study was to find out whether the amount of 4 apheresis platelet concentrates could reduce intraoperative bleeding and improve viscoelasticity and aggregometry.10 patients were enrolled intraoperatively because of life-threatening diffuse bleeding after cardiopulmonary bypass and received 4 apheresis platelet concentrates back-to-back. The units were given every 5 minutes. After every unit, thromboelastometry, performed by ROTEM®, and aggregometry, performed by Multiplate®, were done together with Hematocrit, Hemoglobin, and Platelet Count.Hematocrit and Hemoglobin showed a statistically significant decrease of 14%, whereas Platelet Count showed a statistically significant increase of 205%. MCE-EXTEM increased statistically significant: 46%. There was no statistically significant increase in both ADP and COL results.Even a series of 4 platelet concentrates did not comprehensively improve both essential components of an adequate hemostasis: viscoelasticity and aggregation. Just the transfusion of platelet concentrates alone did not build a sufficient strategy improving hemostasis and reducing bleeding. A positive effect of surgical packing on stopping the bleeding could be seen.
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Affiliation(s)
- Lisa Blath
- Department for Anesthesiology and Intensive Care Medicine, Franziskus Hospital Bielefeld, Bielefeld, Germany
| | - Jörg Martens
- Institute for Transfusion Medicine and Transplant Engineering, Hannover Medical School, Hannover, Germany
| | - Niels Rahe-Meyer
- Department for Anesthesiology and Intensive Care Medicine, Franziskus Hospital Bielefeld, Bielefeld, Germany.,Department for Anesthesiology and Intensive Care Medicine, Hannover Medical School, Hannover, Germany
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19
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Kell DB, Laubscher GJ, Pretorius E. A central role for amyloid fibrin microclots in long COVID/PASC: origins and therapeutic implications. Biochem J 2022; 479:537-559. [PMID: 35195253 PMCID: PMC8883497 DOI: 10.1042/bcj20220016] [Citation(s) in RCA: 138] [Impact Index Per Article: 46.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2022] [Revised: 02/08/2022] [Accepted: 02/09/2022] [Indexed: 12/15/2022]
Abstract
Post-acute sequelae of COVID (PASC), usually referred to as 'Long COVID' (a phenotype of COVID-19), is a relatively frequent consequence of SARS-CoV-2 infection, in which symptoms such as breathlessness, fatigue, 'brain fog', tissue damage, inflammation, and coagulopathies (dysfunctions of the blood coagulation system) persist long after the initial infection. It bears similarities to other post-viral syndromes, and to myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Many regulatory health bodies still do not recognize this syndrome as a separate disease entity, and refer to it under the broad terminology of 'COVID', although its demographics are quite different from those of acute COVID-19. A few years ago, we discovered that fibrinogen in blood can clot into an anomalous 'amyloid' form of fibrin that (like other β-rich amyloids and prions) is relatively resistant to proteolysis (fibrinolysis). The result, as is strongly manifested in platelet-poor plasma (PPP) of individuals with Long COVID, is extensive fibrin amyloid microclots that can persist, can entrap other proteins, and that may lead to the production of various autoantibodies. These microclots are more-or-less easily measured in PPP with the stain thioflavin T and a simple fluorescence microscope. Although the symptoms of Long COVID are multifarious, we here argue that the ability of these fibrin amyloid microclots (fibrinaloids) to block up capillaries, and thus to limit the passage of red blood cells and hence O2 exchange, can actually underpin the majority of these symptoms. Consistent with this, in a preliminary report, it has been shown that suitable and closely monitored 'triple' anticoagulant therapy that leads to the removal of the microclots also removes the other symptoms. Fibrin amyloid microclots represent a novel and potentially important target for both the understanding and treatment of Long COVID and related disorders.
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Affiliation(s)
- Douglas B. Kell
- Department of Biochemistry and Systems Biology, Institute of Systems, Molecular and Integrative Biology, Faculty of Health and Life Sciences, University of Liverpool, Liverpool L69 7ZB, U.K
- The Novo Nordisk Foundation Centre for Biosustainability, Technical University of Denmark, Kemitorvet 200, 2800 Kgs Lyngby, Denmark
- Department of Physiological Sciences, Faculty of Science, Stellenbosch University, Stellenbosch Private Bag X1 Matieland, 7602, South Africa
| | | | - Etheresia Pretorius
- Department of Physiological Sciences, Faculty of Science, Stellenbosch University, Stellenbosch Private Bag X1 Matieland, 7602, South Africa
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20
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Ho VK, Wong J, Martinez A, Winearls J. Trauma-induced coagulopathy: Mechanisms and clinical management. ANNALS OF THE ACADEMY OF MEDICINE, SINGAPORE 2022; 51:40-48. [PMID: 35091729 DOI: 10.47102/annals-acadmedsg.2020381] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/14/2023]
Abstract
INTRODUCTION Trauma-induced coagulopathy (TIC) is a form of coagulopathy unique to trauma patients and is associated with increased mortality. The complexity and incomplete understanding of TIC have resulted in controversies regarding optimum management. This review aims to summarise the pathophysiology of TIC and appraise established and emerging advances in the management of TIC. METHODS This narrative review is based on a literature search (MEDLINE database) completed in October 2020. Search terms used were "trauma induced coagulopathy", "coagulopathy of trauma", "trauma induced coagulopathy pathophysiology", "massive transfusion trauma induced coagulopathy", "viscoelastic assay trauma induced coagulopathy", "goal directed trauma induced coagulopathy and "fibrinogen trauma induced coagulopathy'. RESULTS TIC is not a uniform phenotype but a spectrum ranging from thrombotic to bleeding phenotypes. Evidence for the management of TIC with tranexamic acid, massive transfusion protocols, viscoelastic haemostatic assays (VHAs), and coagulation factor and fibrinogen concentrates were evaluated. Although most trauma centres utilise fixed-ratio massive transfusion protocols, the "ideal" transfusion ratio of blood to blood products is still debated. While more centres are using VHAs to guide blood product replacement, there is no agreed VHA-based transfusion strategy. The use of VHA to quantify the functional contributions of individual components of coagulation may permit targeted treatment of TIC but remains controversial. CONCLUSION A greater understanding of TIC, advances in point-of-care coagulation testing, and availability of coagulation factors and fibrinogen concentrates allows clinicians to employ a more goal-directed approach. Still, hospitals need to tailor their approaches according to available resources, provide training and establish local guidelines.
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Affiliation(s)
- Vui Kian Ho
- Surgical Intensive Care, Division of Anaesthesiology, Singapore General Hospital, Singapore
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21
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Sabljic N, Pantic N, Virijevic M, Bukumiric Z, Novakovic T, Pravdic Z, Rajic J, Vidovic A, Suvajdzic N, Jaradeh M, Fareed J, Antic D, Mitrovic M. Application of Rotational Thromboelastometry in Patients with Acute Promyelocytic Leukemia. Clin Appl Thromb Hemost 2022; 28:10760296221119809. [PMID: 35942712 PMCID: PMC9373117 DOI: 10.1177/10760296221119809] [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] [Indexed: 11/17/2022] Open
Abstract
Introduction Hemorrhagic early death (HED) remains a major cause of treatment failure
among patients with acute promyelocytic leukemia (APL). We aimed to
investigate the prognostic potential of rotational thromboelastometry
(ROTEM) for bleeding in patients with APL. Materials and Methods 31 newly-diagnosed APL patients (median age of 40 years; 14 female/17 male)
that underwent treatment at the Clinic of Hematology UCCS from 2016-2020
with all-trans retinoic acid and anthracyclines were recruited. CBCs
(complete blood count), conventional coagulation tests (CCTs), and ROTEM
parameters obtained before treatment initiation were evaluated. Results All patients demonstrated at least one ROTEM parameter out of the reference
range. ROTEM parameters associated with significant hemorrhage were EXTEM
clotting time (CT) (P = 0.041) and INTEM amplitude 10 (A10) (P = 0.039),
however, only EXTEM CT (P = 0.036) was associated with HED. Among CBCs and
CCTs, only platelets were associated with significant bleeding (P = 0.015),
while D-dimer was associated with both bleeding and HED (P = 0.001 and
P = 0.002, respectively). Conclusion Our results indicate that ROTEM parameters may reveal hypocoagulability in
APL patients and have the potential to improve current hemorrhage prognostic
methods. Additionally, these results suggest the combination of ROTEM and
CCTs might be useful in identifying patients at risk for HED.
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Affiliation(s)
- Nikica Sabljic
- Clinic of Hematology, 63740University Clinical Center of Serbia, Belgrade, Serbia
| | - Nikola Pantic
- Clinic of Hematology, 63740University Clinical Center of Serbia, Belgrade, Serbia
| | - Marijana Virijevic
- Clinic of Hematology, 63740University Clinical Center of Serbia, Belgrade, Serbia.,Faculty of Medicine, 54801University of Belgrade, Belgrade, Serbia
| | - Zoran Bukumiric
- Faculty of Medicine, 54801University of Belgrade, Belgrade, Serbia.,Faculty of Medicine, Institute for medical statistics and informatics, 54801University of Belgrade, Beograd, Serbia
| | - Tina Novakovic
- Clinic of Vascular Surgery, 63740University Clinical Center of Serbia, Belgrade, Serbia
| | - Zlatko Pravdic
- Clinic of Hematology, 63740University Clinical Center of Serbia, Belgrade, Serbia
| | - Jovan Rajic
- Clinic of Hematology, 63740University Clinical Center of Serbia, Belgrade, Serbia
| | - Ana Vidovic
- Clinic of Hematology, 63740University Clinical Center of Serbia, Belgrade, Serbia.,Faculty of Medicine, 54801University of Belgrade, Belgrade, Serbia
| | - Nada Suvajdzic
- Clinic of Hematology, 63740University Clinical Center of Serbia, Belgrade, Serbia.,Faculty of Medicine, 54801University of Belgrade, Belgrade, Serbia
| | - Mark Jaradeh
- Department of Molecular Pharmacology & Neuroscience, 25815Loyola University Medical Center, Maywood, USA
| | - Jawed Fareed
- Department of Molecular Pharmacology & Neuroscience, 25815Loyola University Medical Center, Maywood, USA
| | - Darko Antic
- Clinic of Hematology, 63740University Clinical Center of Serbia, Belgrade, Serbia.,Faculty of Medicine, 54801University of Belgrade, Belgrade, Serbia
| | - Mirjana Mitrovic
- Clinic of Hematology, 63740University Clinical Center of Serbia, Belgrade, Serbia.,Faculty of Medicine, 54801University of Belgrade, Belgrade, Serbia
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22
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Yamamoto Y, Sato Y, Takahashi M, Yamamoto H, Echizen M, Uchida T. TEG6s Platelet Mapping assay for the estimation of plasma fibrinogen concentration during cardiovascular surgery: a single-center prospective observational study. J Anesth 2021; 36:79-88. [PMID: 34643817 PMCID: PMC8807459 DOI: 10.1007/s00540-021-03009-4] [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: 05/04/2021] [Accepted: 09/30/2021] [Indexed: 11/24/2022]
Abstract
PURPOSE The Activator F (ActF) test on the TEG6s Platelet Mapping assay system is a means of quantifying blood viscoelasticity caused by fibrin network formation, triggered by reptilase and factor XIII, while platelets are inhibited. This unique methodology enables the measurement of blood viscoelasticity, even in highly heparinized blood. Here, we investigated whether fibrinogen concentration could be estimated using the ActF test in blood samples obtained during cardiopulmonary bypass (CPB) and after CPB in patients undergoing cardiovascular surgery. METHODS We performed a single-center prospective observational study at a university hospital. Forty patients aged ≥ 18 years who underwent elective cardiovascular surgery with CPB were enrolled. Blood samples were drawn after the induction of anesthesia, after declamping of the aorta during CPB, and after the reversal of heparinization using protamine (after CPB). Coagulation profiles were evaluated using the Platelet Mapping assay and standard laboratory tests. RESULTS There were strong correlations between the maximal amplitude of clot strength (MA) in the ActF test and fibrinogen concentration in samples drawn during CPB (R = 0.84, 95% confidence interval [CI] 0.72-0.91; P < 0.001) and after CPB (R = 0.83, 95% CI 0.70-0.91; P < 0.001). The areas under the receiver-operating characteristic curve for the ActF MA for fibrinogen concentrations < 150 mg/dL were 0.86 (95% CI 0.73-1.0) during CPB and 0.98 (95% CI 0.94-1.0) after CPB. CONCLUSION TEG6s Platelet Mapping ActF MA values strongly correlated with plasma fibrinogen concentration in highly heparinized blood during CPB and yielded highly accurate measurements of low fibrinogen concentrations.
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Affiliation(s)
- Yudai Yamamoto
- Department of Anesthesiology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8510, Japan.
| | - Yunosuke Sato
- Department of Anesthesiology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8510, Japan
| | - Miri Takahashi
- Department of Anesthesiology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8510, Japan
| | - Hiroto Yamamoto
- Department of Anesthesiology, Medical Hospital, Tokyo Medical and Dental University, Tokyo, Japan
| | - Mayumi Echizen
- Department of Anesthesiology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8510, Japan
| | - Tokujiro Uchida
- Department of Anesthesiology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8510, Japan
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Schroeder JA, Kuether EA, Fang J, Jing W, Weiler H, Wilcox DA, Montgomery RR, Shi Q. Thromboelastometry assessment of hemostatic properties in various murine models with coagulopathy and the effect of factor VIII therapeutics. J Thromb Haemost 2021; 19:2417-2427. [PMID: 34245090 PMCID: PMC8865566 DOI: 10.1111/jth.15456] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2021] [Accepted: 07/07/2021] [Indexed: 12/31/2022]
Abstract
BACKGROUND Rotational thromboelastometry (ROTEM) has been commonly used to assess the viscoelastic properties of the blood clotting process in the clinic for patients with a hemostatic or prothrombotic disorder. OBJECTIVE To evaluate the capability of ROTEM in assessing hemostatic properties in whole blood from various mouse models with genetic bleeding or clotting disease and the effect of factor VIII (FVIII) therapeutics in FVIIInull mice. METHODS Mice with a genetic deficiency in either a coagulation factor or a platelet glycoprotein were used in this study. The properties of platelet- or plasma-FVIII were also assessed. Citrated blood from mice was recalcified and used for ROTEM analysis. RESULTS We found that blood collected from the vena cava could generate reliable results from ROTEM analysis, but not blood collected from the tail vein, retro-orbital plexus, or submandibular vein. Age and sex did not significantly affect the hemostatic properties determined by ROTEM analysis. Clotting time (CT) and clot formation time (CFT) were significantly prolonged in FVIIInull (5- and 9-fold, respectively) and FIXnull (4- and 5.7-fold, respectively) mice compared to wild-type (WT)-C57BL/6J mice. Platelet glycoprotein (GP)IIIanull mice had significantly prolonged CFT (8.4-fold) compared to WT-C57BL/6J mice. CT and CFT in factor V (FV) Leiden mice were significantly shortened with an increased α-angle compared to WT-C57BL/6J mice. Using ROTEM analysis, we showed that FVIII expressed in platelets or infused into whole blood restored hemostasis of FVIIInull mice in a dose-dependent manner. CONCLUSION ROTEM is a reliable and sensitive assay for assessing therapeutics on hemostatic properties in mouse models with a bleeding or clotting disorder.
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Affiliation(s)
- Jocelyn A. Schroeder
- Blood Research Institute, Versiti Wisconsin, Milwaukee, Wisconsin, USA
- Department of Pediatrics, Medical College of Wisconsin, Milwaukee, Wisconsin, USA
- Children’s Research Institute, Children’s Wisconsin, Milwaukee, Wisconsin, USA
- MACC Fund Research Center, Milwaukee, Wisconsin, USA
| | - Erin A. Kuether
- Blood Research Institute, Versiti Wisconsin, Milwaukee, Wisconsin, USA
- Department of Pediatrics, Medical College of Wisconsin, Milwaukee, Wisconsin, USA
- Children’s Research Institute, Children’s Wisconsin, Milwaukee, Wisconsin, USA
- MACC Fund Research Center, Milwaukee, Wisconsin, USA
| | - Juan Fang
- Department of Pediatrics, Medical College of Wisconsin, Milwaukee, Wisconsin, USA
- MACC Fund Research Center, Milwaukee, Wisconsin, USA
| | - Weiqing Jing
- Blood Research Institute, Versiti Wisconsin, Milwaukee, Wisconsin, USA
| | - Hartmut Weiler
- Blood Research Institute, Versiti Wisconsin, Milwaukee, Wisconsin, USA
| | - David A. Wilcox
- Department of Pediatrics, Medical College of Wisconsin, Milwaukee, Wisconsin, USA
- Children’s Research Institute, Children’s Wisconsin, Milwaukee, Wisconsin, USA
- MACC Fund Research Center, Milwaukee, Wisconsin, USA
| | - Robert R. Montgomery
- Blood Research Institute, Versiti Wisconsin, Milwaukee, Wisconsin, USA
- Department of Pediatrics, Medical College of Wisconsin, Milwaukee, Wisconsin, USA
- Children’s Research Institute, Children’s Wisconsin, Milwaukee, Wisconsin, USA
- MACC Fund Research Center, Milwaukee, Wisconsin, USA
| | - Qizhen Shi
- Blood Research Institute, Versiti Wisconsin, Milwaukee, Wisconsin, USA
- Department of Pediatrics, Medical College of Wisconsin, Milwaukee, Wisconsin, USA
- Children’s Research Institute, Children’s Wisconsin, Milwaukee, Wisconsin, USA
- MACC Fund Research Center, Milwaukee, Wisconsin, USA
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24
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Sayce AC, Neal MD, Leeper CM. Viscoelastic monitoring in trauma resuscitation. Transfusion 2021; 60 Suppl 6:S33-S51. [PMID: 33089933 DOI: 10.1111/trf.16074] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2020] [Revised: 06/13/2020] [Accepted: 06/14/2020] [Indexed: 12/21/2022]
Abstract
BACKGROUND Traumatic injury results in both physical and physiologic insult. Successful care of the trauma patient depends upon timely correction of both physical and biochemical injury. Trauma-induced coagulopathy is a derangement of hemostasis and thrombosis that develops rapidly and can be fatal if not corrected. Viscoelastic monitoring (VEM) assays have been developed to provide rapid, accurate, and relatively comprehensive depictions of an individual's coagulation profile. VEM are increasingly being integrated into trauma resuscitation guidelines to provide dynamic and individualized guidance to correct coagulopathy. STUDY DESIGN AND METHODS We performed a narrative review of the search terms viscoelastic, thromboelastography, thromboelastometry, TEG, ROTEM, trauma, injury, resuscitation, and coagulopathy using PubMed. Particular focus was directed to articles describing algorithms for management of traumatic coagulopathy based on VEM assay parameters. RESULTS Our search identified 16 papers with VEM-guided resuscitation strategies in adult patients based on TEG, 12 such protocols in adults based on ROTEM, 1 protocol for children based on TEG, and 2 protocols for children based on ROTEM. CONCLUSIONS This review presents evidence to support VEM use to detect traumatic coagulopathy, discusses the role of VEM in trauma resuscitation, provides a summary of proposed treatment algorithms, and discusses pending questions in the field.
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Affiliation(s)
- Andrew C Sayce
- Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
| | - Matthew D Neal
- Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
| | - Christine M Leeper
- Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
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25
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Effects of dexmedetomidine on blood coagulation: an in vitro study using rotational thromboelastometry. J Anesth 2021; 35:633-637. [PMID: 34268623 DOI: 10.1007/s00540-021-02969-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2021] [Accepted: 07/01/2021] [Indexed: 10/20/2022]
Abstract
PURPOSE To assess the effects of various concentrations of dexmedetomidine on the human blood coagulation profile using rotational thromboelastometry (ROTEM). METHODS Venous blood samples were collected from 11 healthy volunteers and divided into four specimen bottles; dexmedetomidine was added to attain final sample concentrations of 0, 0.5, 1.0, and 1.5 ng/mL. ROTEM was performed on each study sample. RESULTS The concentration of dexmedetomidine increased, and the ROTEM values showed a hypercoagulable state. The change in clotting time (CT) for INTEM was larger in samples with a dexmedetomidine concentration of 1.5 ng/mL (- 34%) than in the 0.5 ng/mL samples (- 16%) (P = 0.010). The change in clot formation time (CFT) for INTEM was greater in 1.5 ng/mL samples (- 16%) than in 0.5 ng/mL samples (- 4%) (P = 0.004). A greater decrease in CT for EXTEM was identified in the 1.0 ng/mL and 1.5 ng/mL samples (- 36% and - 37%, respectively) than in the 0.5 ng/mL samples (- 12%) (P = 0.003 for both categories). The change in CFT for EXTEM was greater in the 1.0 ng/mL and 1.5 ng/mL samples (- 11% and - 13%, respectively) than in the 0.5 ng/mL samples (- 4%) (P = 0.006 and P = 0.001, respectively). A bigger change in maximum clot firmness (MCF) for EXTEM was observed in the 1.5 ng/mL samples (4%) than in the 0.5 ng/mL samples (0%) (P = 0.002). The change in MCF for FIBTEM was greater in the 1.5 ng/mL samples (19%) than in the 0.5 ng/mL samples (5%) (P = 0.001). CONCLUSIONS All coagulation pathways showed a hypercoagulable state as the concentration of dexmedetomidine increased. Nevertheless, most of the values of ROTEM were maintained within the reference ranges. Clinical Trial NCT04269278.
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26
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Comparison between intraoperative bleeding score and ROTEM® measurements to assess coagulopathy during major pediatric surgery. Transfus Apher Sci 2021; 60:103191. [PMID: 34215519 DOI: 10.1016/j.transci.2021.103191] [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: 02/16/2021] [Revised: 06/01/2021] [Accepted: 06/11/2021] [Indexed: 11/23/2022]
Abstract
PURPOSE Intraoperative bleeding should be regularly assessed visually to guide coagulation management. Whereas viscoelastic testing with ROTEM® measurement has been proven to be useful in detecting coagulopathies, the visual assessment is not standardized. This study therefore aims to compare a standardized visual assessment with ROTEM® results. METHODS A 5-point bleeding score was created and applied in a recently published randomized controlled trial in major pediatric non-cardiac surgery. This score assesses overall bleeding tendency and the occurrence of diffuse bleeding, aqueous bleeding, bleeding outside the operative field, and the ability to control bleeding. Validity of this score was tested by post hoc comparison to the results of simultaneously performed ROTEM® measurements. RESULTS Signs of coagulopathic bleeding were assessed at 183 time points. Mild to moderate bleeding intensity was judged at 103 time points, in 42 % abnormal ROTEM® traces were obtained simultaneously. When severe bleeding was scored, abnormal ROTEM values occurred in 58 %, and FIBTEM-values were significantly lower than in the "no bleeding group". Altogether, the correlation between bleeding score and ROTEM® measurements was not significant. CONCLUSIONS The standardized visual assessment did not correlate well with ROTEM® measurements, suggesting that it is not useful to detect coagulopathy. Trial registry number: ClinicalTrials.gov identifier No. NCT01487837.
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27
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Stanciakova L, Dobrotova M, Holly P, Zolkova J, Vadelova L, Skornova I, Ivankova J, Bolek T, Samos M, Grendar M, Danko J, Kubisz P, Stasko J. How Can Rotational Thromboelastometry as a Point-of-Care Method Be Useful for the Management of Secondary Thromboprophylaxis in High-Risk Pregnant Patients? Diagnostics (Basel) 2021; 11:diagnostics11050828. [PMID: 34063712 PMCID: PMC8147835 DOI: 10.3390/diagnostics11050828] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2021] [Revised: 04/22/2021] [Accepted: 04/28/2021] [Indexed: 11/16/2022] Open
Abstract
Thromboprophylaxis with low-molecular-weight heparin (LMWH) for patients with a history of venous thromboembolism (VTE) is suggested. Rotational thromboelastometry (ROTEM®) represents an innovative point-of-care method enabling the complex and quick evaluation of hemostasis. However, there are only episodic cases of its use for hemostasis assessment and guidance of LMWH in pregnancy. Therefore, we provide the results of unique prospective and longitudinal monitoring of hemostasis in high-risk pregnant women, which we used for the individualized optimalization of secondary thromboprophylaxis. According to the shortening of clot formation time (CFT) in EXTEM (p = 0.0007 from the 26th gestational week vs. controls) and INTEM (p = 0.002 from the 35th gestational week), increase in alpha angle (AA) in EXTEM, INTEM, and HEPTEM, and the persistence of increase in maximum clot firmness (MCF) in EXTEM, INTEM, and HEPTEM (p < 0.001 from the 26th and 35th gestational week vs. controls for EXTEM and INTEM, p = 0.0012 from the 26th gestational week in HEPTEM), LMWH dose was modified. Even after the postpartum period, AA in EXTEM was steeper than in controls (p = 0.0007), indicating that hemostasis is not fully normalized after 6–8 weeks following delivery. Therefore, ROTEM may be a useful tool for the individual evaluation of the termination of anticoagulant thromboprophylaxis.
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Affiliation(s)
- Lucia Stanciakova
- National Center of Hemostasis and Thrombosis, Department of Hematology and Transfusion Medicine, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, Martin University Hospital, 03659 Martin, Slovakia; (M.D.); (P.H.); (J.Z.); (L.V.); (I.S.); (J.I.); (P.K.); (J.S.)
- Correspondence: ; Tel.: +42-143-420-3696
| | - Miroslava Dobrotova
- National Center of Hemostasis and Thrombosis, Department of Hematology and Transfusion Medicine, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, Martin University Hospital, 03659 Martin, Slovakia; (M.D.); (P.H.); (J.Z.); (L.V.); (I.S.); (J.I.); (P.K.); (J.S.)
| | - Pavol Holly
- National Center of Hemostasis and Thrombosis, Department of Hematology and Transfusion Medicine, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, Martin University Hospital, 03659 Martin, Slovakia; (M.D.); (P.H.); (J.Z.); (L.V.); (I.S.); (J.I.); (P.K.); (J.S.)
| | - Jana Zolkova
- National Center of Hemostasis and Thrombosis, Department of Hematology and Transfusion Medicine, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, Martin University Hospital, 03659 Martin, Slovakia; (M.D.); (P.H.); (J.Z.); (L.V.); (I.S.); (J.I.); (P.K.); (J.S.)
| | - Lubica Vadelova
- National Center of Hemostasis and Thrombosis, Department of Hematology and Transfusion Medicine, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, Martin University Hospital, 03659 Martin, Slovakia; (M.D.); (P.H.); (J.Z.); (L.V.); (I.S.); (J.I.); (P.K.); (J.S.)
- Center of Immunology in Martin, 03601 Martin, Slovakia
| | - Ingrid Skornova
- National Center of Hemostasis and Thrombosis, Department of Hematology and Transfusion Medicine, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, Martin University Hospital, 03659 Martin, Slovakia; (M.D.); (P.H.); (J.Z.); (L.V.); (I.S.); (J.I.); (P.K.); (J.S.)
| | - Jela Ivankova
- National Center of Hemostasis and Thrombosis, Department of Hematology and Transfusion Medicine, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, Martin University Hospital, 03659 Martin, Slovakia; (M.D.); (P.H.); (J.Z.); (L.V.); (I.S.); (J.I.); (P.K.); (J.S.)
| | - Tomas Bolek
- Department of Internal Medicine I., Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, Martin University Hospital, 03659 Martin, Slovakia; (T.B.); (M.S.)
| | - Matej Samos
- Department of Internal Medicine I., Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, Martin University Hospital, 03659 Martin, Slovakia; (T.B.); (M.S.)
| | - Marian Grendar
- Biomedical center Martin, Laboratory of Bioinformatics and Biostatistics, Comenius University in Bratislava, Jessenius Faculty of Medicine in Martin, 03601 Martin, Slovakia;
- Laboratory of Theoretical Methods, Institute of Measurement Science, Slovak Academy of Sciences, 84104 Karlova Ves, Slovakia
| | - Jan Danko
- Department of Gynecology and Obstetrics, Jessenius Faculty of Medicine in Martin and University Hospital in Martin, Comenius University in Bratislava, 03659 Martin, Slovakia;
| | - Peter Kubisz
- National Center of Hemostasis and Thrombosis, Department of Hematology and Transfusion Medicine, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, Martin University Hospital, 03659 Martin, Slovakia; (M.D.); (P.H.); (J.Z.); (L.V.); (I.S.); (J.I.); (P.K.); (J.S.)
| | - Jan Stasko
- National Center of Hemostasis and Thrombosis, Department of Hematology and Transfusion Medicine, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, Martin University Hospital, 03659 Martin, Slovakia; (M.D.); (P.H.); (J.Z.); (L.V.); (I.S.); (J.I.); (P.K.); (J.S.)
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Kahan J, Gibson CJ, Strauss SB, Bronstein M, Winchell RJ, Barie PS, Segal AZ. Cervical spinal cord infarction associated with coronavirus infectious disease (COVID)-19. J Clin Neurosci 2021; 87:89-91. [PMID: 33863542 PMCID: PMC7938747 DOI: 10.1016/j.jocn.2021.02.027] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2020] [Revised: 02/07/2021] [Accepted: 02/25/2021] [Indexed: 02/07/2023]
Abstract
Coronavirus disease (COVID-19) has a number of emerging neurological manifestations in addition to pneumonia and respiratory distress. In what follows, we describe a case of a previously healthy young man with severe COVID-19 who subsequently developed an acute flaccid paralysis. Work up revealed a lesion in his cervical spinal cord concerning for spinal infarction or transverse myelitis. He received empiric pulsed steroids without improvement. Taken together, we felt his presentation was most consistent with spinal cord infarction in the setting of critical illness with COVID-19. We believe this is a rare case of spinal cord stroke associated with COVID-19.
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Affiliation(s)
- Joshua Kahan
- Department of Neurology, Weill Cornell Medicine, New York, NY, USA
| | - Cameron J Gibson
- Department of Surgery, Weill Cornell Medicine, New York, NY, USA
| | - Sara B Strauss
- Department of Radiology, Weill Cornell Medicine, New York, NY, USA
| | | | | | - Philip S Barie
- Department of Surgery, Weill Cornell Medicine, New York, NY, USA; Department of Medicine, Weill Cornell Medicine, New York, NY, USA
| | - Alan Z Segal
- Department of Neurology, Weill Cornell Medicine, New York, NY, USA.
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29
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Bolliger D, Kamber F, Mauermann E. Same Same but Different: Viscoelastic Hemostatic Assays in Cardiac Surgery. J Cardiothorac Vasc Anesth 2021; 35:1037-1039. [PMID: 33483267 DOI: 10.1053/j.jvca.2021.01.001] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/30/2020] [Accepted: 01/01/2021] [Indexed: 11/11/2022]
Affiliation(s)
- Daniel Bolliger
- Department for Anesthesia, Prehospital Emergency Medicine and Pain Therapy, University Hospital Basel, University of Basel, Basel, Switzerland
| | - Firmin Kamber
- Department for Anesthesia, Prehospital Emergency Medicine and Pain Therapy, University Hospital Basel, University of Basel, Basel, Switzerland
| | - Eckhard Mauermann
- Department for Anesthesia, Prehospital Emergency Medicine and Pain Therapy, University Hospital Basel, University of Basel, Basel, Switzerland
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30
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Alvitigala BY, Gooneratne LV, Constantine GR, Wijesinghe RANK, Arawwawala LDAM. Pharmacokinetic, pharmacodynamic, and pharmacogenetic assays to monitor clopidogrel therapy. Pharmacol Res Perspect 2020; 8:e00686. [PMID: 33200888 PMCID: PMC7670852 DOI: 10.1002/prp2.686] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2020] [Revised: 10/20/2020] [Accepted: 10/21/2020] [Indexed: 12/11/2022] Open
Abstract
Clopidogrel is the most common and widely used antiplatelet agent for patients with coronary artery disease following confirmation by electrocardiographic studies. The nonresponsiveness of patients to clopidogrel and the possibility of testing for clopidogrel resistance by platelet function assays (PFA) are contentious issues. Light transmission aggregometry (LTA) is considered as the gold standard test among all PFA. In this review, the most commonly used PFA used for monitoring the effect of clopidogrel, LTA, vasodilator-stimulated phosphoprotein assay phosphorylation, rotational thromboelastometry (ROTEM) delta and ROTEM platelet, thromboelastography, PFA-100, VerifyNow P2Y12 assay, Multiplate analyzer, Plateletworks assay and pharmacogenetic studies, are comparatively discussed including their principles of action, advantages, and disadvantages. VerifyNow P2Y12 assay can be accepted as the ideal point of care test out of the discussed assays. However, modified assays are required which could overcome the limitations associated with currently available assays.
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Affiliation(s)
- Bhawani Yasassri Alvitigala
- Department of Medical Laboratory ScienceFaculty of Health SciencesThe Open University of Sri LankaNugegodaSri Lanka
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Grazioli A, Athale J, Tanaka K, Madathil R, Rabin J, Kaczorowski D, Mazzeffi M. Perioperative Applications of Therapeutic Plasma Exchange in Cardiac Surgery: A Narrative Review. J Cardiothorac Vasc Anesth 2020; 34:3429-3443. [DOI: 10.1053/j.jvca.2020.01.054] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/15/2019] [Revised: 01/26/2020] [Accepted: 01/31/2020] [Indexed: 12/17/2022]
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Atari B, Ito T, Nagasato T, Ohnishi T, Hosokawa K, Yasuda T, Maruyama I, Kakihana Y. A modified microchip-based flow chamber system for evaluating thrombogenicity in patients with thrombocytopenia. Thromb J 2020; 18:31. [PMID: 33292286 PMCID: PMC7602342 DOI: 10.1186/s12959-020-00244-9] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2020] [Accepted: 10/22/2020] [Indexed: 02/02/2023] Open
Abstract
BACKGROUND In the intensive care unit (ICU), patients with thrombocytopenia are at high risk for bleeding and should be assessed for their thrombogenic potential. However, the analytical conditions of conventional hemostatic tests are unsuitable for the evaluation of low-platelet samples. Here we aimed to establish suitable analytical conditions with the Total Thrombus-formation Analysis System (T-TAS) for quantitative assessment of thrombogenic potential in patients with thrombocytopenia and to investigate how T-TAS values relate to bleeding symptoms and the effects of platelet transfusion. METHODS Modified chips with a different chamber depth were developed for the analysis of low-platelet samples in the T-TAS. We included 10 adult patients admitted to the ICU of Kagoshima University Hospital who required platelet transfusion. Patients were divided into major and minor bleeding groups according to their bleeding scale before platelet transfusion. The thrombogenic potential of these patients before and after platelet transfusion was assessed with hemostatic function tests, including rotational thromboelastometry, multiplate aggregometry, and the T-TAS. RESULTS Analysis of low-platelet samples revealed that, compared with the conventional chip (80-μm-deep chamber), the modified chip (50-μm-deep chamber) achieved higher sensitivity in detecting elevation of flow pressure caused by growth of an occlusive thrombus in the T-TAS analytical chamber. All patients in the minor bleeding group retained thrombogenic potential that occluded the modified chip (occlusion time 16.3 ± 3.3 min), whereas most patients in the major bleeding group were unable to occlude the modified chip during the 30-min measurement (P < 0.01). The recovery of thrombogenic potential after platelet transfusion was confirmed with the T-TAS and correlated with the function, rather than the count, of transfused platelets. Among all evaluated parameters in hemostatic function tests, only the T-TAS showed significant differences in occlusion time and area under the curve both between the minor and major bleeding groups and between pre- and post-platelet transfusion. CONCLUSIONS We developed a modified microchip-based flow chamber system that reflects the hemostatic function of patients with thrombocytopenia.
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Affiliation(s)
- Bengo Atari
- Department of Emergency and Intensive Care Medicine, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan
| | - Takashi Ito
- Department of Systems Biology in Thromboregulation, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima, 890-8544, Japan.
| | - Tomoka Nagasato
- Research Institute, Fujimori Kogyo Co., Ltd., Yokohama, Japan
| | - Tomoko Ohnishi
- Research Institute, Fujimori Kogyo Co., Ltd., Yokohama, Japan
| | - Kazuya Hosokawa
- Research Institute, Fujimori Kogyo Co., Ltd., Yokohama, Japan
| | - Tomotsugu Yasuda
- Department of Emergency and Intensive Care Medicine, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan
| | - Ikuro Maruyama
- Department of Systems Biology in Thromboregulation, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima, 890-8544, Japan
| | - Yasuyuki Kakihana
- Department of Emergency and Intensive Care Medicine, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan
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Gibbs NM, Weightman WM. Diagnostic accuracy of viscoelastic point-of-care identification of hypofibrinogenaemia in cardiac surgical patients: A systematic review. Anaesth Intensive Care 2020; 48:339-353. [DOI: 10.1177/0310057x20948868] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
Hypofibrinogenaemia during cardiac surgery may increase blood loss and bleeding complications. Viscoelastic point-of-care tests provide more rapid diagnosis than laboratory measurement, allowing earlier treatment. However, their diagnostic test accuracy for hypofibrinogenaemia has never been reviewed systematically. We aimed to systematically review their diagnostic test accuracy for the identification of hypofibrinogenaemia during cardiac surgery. Two reviewers assessed relevant articles from seven electronic databases, extracted data from eligible articles and assessed quality. The primary outcomes were sensitivity, specificity and positive and negative predictive values. A total of 576 articles were screened and 81 full texts were assessed, most of which were clinical agreement or outcome studies. Only 10 diagnostic test accuracy studies were identified and only nine were eligible (ROTEM delta 7; TEG5000 1; TEG6S 1, n = 1820 patients) (ROTEM, TEM International GmbH, Munich, Germany; TEG, Haemonetics, Braintree, MA, USA). None had a low risk of bias. Four ROTEM studies with a fibrinogen threshold less than 1.5–1.6 g/l and FIBTEM threshold A10 less than 7.5–8 mm had point estimates for sensitivity of 0.61–0.88; specificity 0.54–0.94; positive predictive value 0.42–0.70; and negative predictive value 0.74–0.98 (i.e. false positive rate 30%–58%; false negative rate 2%–26%). Two ROTEM studies with higher thresholds for both fibrinogen (<2 g/l) and FIBTEM A10 (<9.5 mm) had similar false positive rates (25%–46%), as did the two TEG studies (15%–48%). This review demonstrates that there have been few diagnostic test accuracy studies of viscoelastic point-of-care identification of hypofibrinogenaemia in cardiac surgical patients. The studies performed so far report false positive rates of up to 58%, but low false negative rates. Further diagnostic test accuracy studies of viscoelastic point-of-care identification of hypofibrinogenaemia are required to guide their better use during cardiac surgery.
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Affiliation(s)
- Neville M Gibbs
- Department of Anaesthesia, Sir Charles Gairdner Hospital, Nedlands, Australia
- The University of Western Australia, Nedlands, Australia
| | - William M Weightman
- Department of Anaesthesia, Sir Charles Gairdner Hospital, Nedlands, Australia
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Agarwal S, Abdelmotieleb M. Viscoelastic testing in cardiac surgery. Transfusion 2020; 60 Suppl 6:S52-S60. [PMID: 32955756 DOI: 10.1111/trf.16075] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2020] [Revised: 06/30/2020] [Accepted: 06/30/2020] [Indexed: 11/30/2022]
Abstract
Bleeding complications are common in cardiac surgery and lead to an increase in morbidity and mortality. This is multifactorial in aetiology including the effects of cardiopulmonary bypass, the drugs given to manipulate the coagulation system and the vascular nature of the surgery itself. Viscoelastic tests provide a point of care, rapid assessment of coagulation which offer the advantage of faster turnaround times and a nuanced view of the elements of the coagulation system allowing targeted therapy to be delivered quickly. Both thomboelastography (TEG)and thromboelastometry (ROTEM) have been recommended for use in cardiac surgery, both have shown a reduction in transfusion and bleeding when used as part of a testing algorithm. They are particularly useful in assessing residual heparinisation and fibrinogen levels. Additionally, TEG allows the evaluation of the effects of anti-platelet agents on platelet function. This review discusses the mechanisms by which bleeding occurs in cardiac surgery and explores three uses of viscoelastic testing in cardiac surgery: to predict bleeding, to assess platelet function and peri-operative testing to reduce transfusion.
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Affiliation(s)
- Seema Agarwal
- Department of Cardiothoracic Anaesthesia and ICM, Manchester University Foundation Trust, Manchester, UK
| | - Mohamed Abdelmotieleb
- Department of Cardiothoracic Anaesthesia and ICM, Manchester University Foundation Trust, Manchester, UK
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Judd M, Strauss ER, Hasan S, Abuelkasem E, Li J, Deshpande S, Mazzeffi MA, Ogawa S, Tanaka KA. Clotting Time Results Are Not Interchangeable Between EXTEM and FIBTEM on Rotational Thromboelastometry. J Cardiothorac Vasc Anesth 2020; 34:1467-1473. [DOI: 10.1053/j.jvca.2019.12.030] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/11/2019] [Revised: 12/14/2019] [Accepted: 12/16/2019] [Indexed: 01/31/2023]
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Nguyen TH, Tran TT, Hoang THT, Nguyen TTT. Rotational thromboelastometry parameters as predicting factors for bleeding in immune thrombocytopenic purpura. Hematol Oncol Stem Cell Ther 2020; 14:27-32. [PMID: 32446931 DOI: 10.1016/j.hemonc.2020.05.003] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2019] [Accepted: 05/04/2020] [Indexed: 10/24/2022] Open
Abstract
OBJECTIVE/BACKGROUND Patients with immune thrombocytopenic purpura (ITP) often present with a severe reduction in platelet counts and suffer from an increased risk of bleeding. However, platelet counts do not accurately predict bleeding risk in these patients. METHODS We thereby conducted a case series prospective study to compare the ability to predict hemorrhage in ITP patients between platelet counts and various rotational thromboelastometry (ROTEM) parameters. RESULTS The inclusion criteria for patients diagnosed with acute, persistent, and chronic ITP were platelet counts of <30 × 109/L and no clinically significant bleeding (grade ≥ 2 according to the WHO Bleeding Scale) at the beginning of the study. After 24 hours of follow-up, of the 45 enrolled patients, 14 (31.1%) experienced clinically significant bleeding. The mean platelet counts of patients with and without clinically significant bleeding were not statistically different (p = .09). However, the mean EXTEM maximum clot firmness (MCF), EXTEM A10, EXTEM area under the curve (AUC), and platelet maximum clot elasticity (MCE) values of the two groups were statistically different (p < .05). There was also a significant difference in IPF values between these two groups (p < .05.) CONCLUSION: Results obtained from this preliminary study demonstrate that ROTEM parameters might be useful in predicting factors for hemorrhage in ITP patients. Future studies with a larger sample size is warranted to confirm our findings, which will allow prompt and effective bleeding management in ITP patients.
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Affiliation(s)
- Tuan H Nguyen
- Department of Hematology, Cho Ray Hospital, Ho Chi Minh City, Viet Nam.
| | - Tung T Tran
- Department of Hematology, Cho Ray Hospital, Ho Chi Minh City, Viet Nam
| | - Thuy-Ha T Hoang
- Department of Hematology, Cho Ray Hospital, Ho Chi Minh City, Viet Nam
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Bolliger D, Lancé MD. Factor Concentrate-Based Approaches to Blood Conservation in Cardiac Surgery: European Perspectives in 2020. CURRENT ANESTHESIOLOGY REPORTS 2020. [DOI: 10.1007/s40140-020-00382-w] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
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Rössler J, Meybohm P, Spahn DR, Zacharowski K, Braun J, Nöthiger CB, Tscholl DW. Improving decision making through presentation of viscoelastic tests as a 3D animated blood clot: the Visual Clot. Anaesthesia 2020; 75:1059-1069. [DOI: 10.1111/anae.14985] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/15/2019] [Indexed: 12/28/2022]
Affiliation(s)
- J. Rössler
- Institute of Anesthesiology University of Zurich and University Hospital Zurich Zurich Switzerland
| | - P. Meybohm
- Department of Anaesthesiology Intensive Care Medicine and Pain Therapy University Hospital Frankfurt Frankfurt/Main Germany
| | - D. R. Spahn
- Institute of Anesthesiology University of Zurich and University Hospital Zurich Zurich Switzerland
| | - K. Zacharowski
- Department of Anaesthesiology Intensive Care Medicine and Pain Therapy University Hospital Frankfurt Frankfurt/Main Germany
| | - J. Braun
- Departments of Epidemiology and Biostatistics, Epidemiology, Biostatistics and Prevention Institute University of Zurich Switzerland
| | - C. B. Nöthiger
- Institute of Anesthesiology University of Zurich and University Hospital Zurich Zurich Switzerland
| | - D. W. Tscholl
- Institute of Anesthesiology University of Zurich and University Hospital Zurich Zurich Switzerland
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Myers SP, Dyer MR, Hassoune A, Brown JB, Sperry JL, Meyer MP, Rosengart MR, Neal MD. Correlation of Thromboelastography with Apparent Rivaroxaban Concentration: Has Point-of-Care Testing Improved? Anesthesiology 2020; 132:280-290. [PMID: 31939843 DOI: 10.1097/aln.0000000000003061] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
BACKGROUND Concern remains over reliable point-of-care testing to guide reversal of rivaroxaban, a commonly used factor Xa inhibitor, in high-acuity settings. Thromboelastography (TEG), a point-of-care viscoelastic assay, may have the ability to detect the anticoagulant effect of rivaroxaban. The authors ascertained the association of apparent rivaroxaban concentration with thromboelastography reaction time, i.e., time elapsed from blood sample placement in analyzer until beginning of clot formation, as measured using TEG and TEG6S instruments (Haemonetics Corporation, USA), hypothesizing that reaction time would correlate to degree of functional factor Xa impairment. METHODS The authors prospectively performed a diagnostic accuracy study comparing coagulation assays to apparent (i.e., indirectly assessed) rivaroxaban concentration in trauma patients with and without preinjury rivaroxaban presenting to a single center between April 2016 and July 2018. Blood samples at admission and after reversal or 24 h postadmission underwent TEG, TEG6S, thrombin generation assay, anti-factor Xa chromogenic assay, prothrombin time (PT), and ecarin chromogenic assay testing. The authors determined correlation of kaolin TEG, TEG6S, and prothrombin time to apparent rivaroxaban concentration. Receiver operating characteristic curve compared capacity to distinguish therapeutic rivaroxaban concentration (i.e., greater than or equal to 50 ng/ml) from nontherapeutic concentrations. RESULTS Eighty rivaroxaban patients were compared to 20 controls. Significant strong correlations existed between rivaroxaban concentration and TEG reaction time (ρ = 0.67; P < 0.001), TEG6S reaction time (ρ = 0.68; P < 0.001), and prothrombin time (ρ = 0.73; P < 0.001), however reaction time remained within the defined normal range for the assay. Rivaroxaban concentration demonstrated strong but not significant association with coagulation assays postreversal (n = 9; TEG reaction time ρ = 0.62; P = 0.101; TEG6S reaction time ρ = 0.57; P = 0.112) and small nonsignificant association for controls (TEG reaction time: ρ = -0.04; P = 0.845; TEG6S reaction time: ρ = -0.09; P = 0.667; PT-neoplastine: ρ = 0.19; P = 0.301). Rivaroxaban concentration (area under the curve, 0.91) and TEG6S reaction time (area under the curve, 0.84) best predicted therapeutic rivaroxaban concentration and exhibited similar receiver operating characteristic curves (P = 0.180). CONCLUSIONS Although TEG6S demonstrates significant strong correlation with rivaroxaban concentration, values within normal range limit clinical utility rendering rivaroxaban concentration the gold standard in measuring anticoagulant effect.
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Affiliation(s)
- Sara P Myers
- From the Department of General Surgery, The University of Pittsburgh Medical Center (S.P.M., M.R.D., A.H., J.B.B., J.L.S., M.R.R., M.D.N.) the Institute for Transfusion Medicine (M.P.M.) the Pittsburgh Surgical Outcomes Research Center, University of Pittsburgh (M.R.R.), Pittsburgh, Pennsylvania
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Sabljić N, Mitrović M. Clinical utility of rotational thromboelastometry in detecting hemostatic disorders. MEDICINSKI PODMLADAK 2020. [DOI: 10.5937/mp71-27853] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/02/2022] Open
Abstract
Hemostasis represents an equilibrium between procoagulant and anticoagulant processes, but once this balance is shifted to one side, it leads to coagulopathy presented by pathological bleeding or thrombosis. Many conditions could cause coagulopathy. The most common are sepsis, severe traumas and malignancies. Widely used conventional coagulation tests (CCTs), focused only on clot initiation, are primary used to detect hypocoagulability. Viscoelastographic tests (VET), like rotational thromboelastometry (ROTEM), can detect problems in different stages of coagulation, from initiation thought clot elongation and propagation, to the clot lysis and might reveal both, hypercoagulability and hypocoagulability. Rotational thromboelastometry have gained popularity in the care of patients with TIC, as a tool to guide transfusion support. Nowadays it is widely used in other medical specialties, as well. Several studies in septic patients pointed out hypocoagulable ROTEM pattern as a predictor of poor prognosis. Additionally, there is great interest of ROTEM usage in malignancies, although limited research is currently available. It suggests ROTEM have the ability to identify a patient in high risk of thrombosis. Further investigation trough randomized studies is needed to confirm ROTEM utility and to help in making a consensus about its use in different medical occasions.
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Iwata S, Hirasaki Y, Nomura M, Ozaki M. Thromboelastometric evaluation of coagulation profiles of cold-stored autologous whole blood: A prospective observational study. Medicine (Baltimore) 2019; 98:e17357. [PMID: 31574880 PMCID: PMC6775353 DOI: 10.1097/md.0000000000017357] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/26/2022] Open
Abstract
Preoperative autologous blood donation is a well-established procedure to reduce the need for allogeneic blood transfusion. We hypothesized that coagulation activity is maintained in cold-stored whole blood, because the fundamental polymerization properties of fibrin are preserved.Fifty adult patients who underwent elective cardiothoracic surgery were enrolled.Autologous whole blood collected 2 to 4 times at almost 1-week intervals before surgery was stored at approximately 4°C until reinfusion at the time of surgery. Blood samples were drawn just before reinfusion, and rotational thromboelastometry variables and fibrinogen levels were measured.A total of 158 samples were analyzed. The mean duration of cold storage was 16.7 ± 7.4 days (range: 6-33 days). Platelet counts were very low due to collection through a leukoreduction filter. The mean fibrinogen level was 2.3 ± 0.6 g/L. Amplitude at 10 minutes after CT (A10), amplitude at 20 minutes after CT (A20), and maximum clot firmness (MCF) values as determined by FIBTEM analysis were 10.8 ± 3.8, 12.2 ± 4.2, and 13.1 ± 4.7 mm, respectively. Fibrinogen levels were strongly correlated with A10, A20, and FIBTEM-MCF values (ρ = 0.83, P < .0001, ρ = 0.84, P < .0001, ρ = 0.85, P < .0001, respectively). Fibrinogen levels were not correlated with the duration of cold storage (ρ = 0.06, P = .43).The results of the present study demonstrate that fibrin polymerization occurs in cold-stored autologous whole blood, and that such activity is strongly correlated with fibrinogen levels. Furthermore, our data suggest that cold-stored leukoreduced autologous whole blood retains fibrin polymerization properties throughout 33 days.
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Affiliation(s)
- Shihoko Iwata
- Department of Anesthesiology, Tokyo Women's Medical University Hospital
| | - Yuji Hirasaki
- Department of Anesthesia, IMS Tokyo-Katsushika General Hospital, Tokyo, Japan
| | - Minoru Nomura
- Department of Anesthesiology, Tokyo Women's Medical University Hospital
| | - Makoto Ozaki
- Department of Anesthesiology, Tokyo Women's Medical University Hospital
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Li T, Connor D, Parsi K. Circulating blood cells influence the fibrinolytic capacity of clots generated in the presence of detergent sclerosants. Phlebology 2019; 35:273-280. [PMID: 31324121 DOI: 10.1177/0268355519860724] [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: 11/17/2022]
Abstract
Objectives To investigate the effects of sodium tetradecyl sulphate and polidocanol on fibrinolytic potential of sclerosant-incubated clots. Methods Serial dilutions of sodium tetradecyl sulphate and polidocanol were incubated with platelet poor plasma and whole blood samples. Rotational thromboelastometry was used to determine the lysis of sclerosant-incubated clots in whole blood. Fibrin generation and fibrinolysis were quantified using an overall haemostatic potential assay on platelet poor plasma. Results Rotational thromboelastometry analysis of whole blood revealed increased maximum lysis in the presence of sodium tetradecyl sulphate but decreased maximum lysis at low concentrations of polidocanol. Clots generated using platelet poor plasma in the overall haemostatic potential assay demonstrated no significant change in fibrinolysis for both sclerosants at all concentrations measured. Discussion Sodium tetradecyl sulphate and polidocanol produce differing effects on the fibrinolytic potential depending on sample type and concentration. In whole blood, sodium tetradecyl sulphate produces clots more sensitive to lysis while polidocanol produced fibrinolytic-resistant clots.
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Affiliation(s)
- Tom Li
- Dermatology, Phlebology and Fluid Mechanics Research Laboratory, St Vincent's Centre for Applied Medical Research, Darlinghurst, NSW, Australia.,Faculty of Medicine, University of New South Wales, Sydney, NSW, Australia
| | - David Connor
- Dermatology, Phlebology and Fluid Mechanics Research Laboratory, St Vincent's Centre for Applied Medical Research, Darlinghurst, NSW, Australia.,Faculty of Medicine, University of New South Wales, Sydney, NSW, Australia
| | - Kurosh Parsi
- Dermatology, Phlebology and Fluid Mechanics Research Laboratory, St Vincent's Centre for Applied Medical Research, Darlinghurst, NSW, Australia.,Faculty of Medicine, University of New South Wales, Sydney, NSW, Australia
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Letson HL, Morris J, Biros E, Dobson GP. Conventional and Specific-Pathogen Free Rats Respond Differently to Anesthesia and Surgical Trauma. Sci Rep 2019; 9:9399. [PMID: 31253875 PMCID: PMC6599031 DOI: 10.1038/s41598-019-45871-z] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2019] [Accepted: 06/12/2019] [Indexed: 02/08/2023] Open
Abstract
Specific-pathogen free (SPF) animals were introduced in the 1960s to minimize disease and infection as variables in biomedical research. Our aim was to examine differences in physiological response in rat colonies bred and housed in a conventional versus SPF facility, and implications for research. Sprague-Dawley rats were anesthetized and catheterized for blood and pressure monitoring, and electrocardiogram (ECG) leads implanted. Hematology was assessed, and coagulation profile using rotational thromboelastometry. Health screening was outsourced to Cerberus Sciences. SPF rats had significantly lower pulse pressure (38% decrease), arrhythmias and prolonged QTc (27% increase) compared to conventional rats. No arrhythmias were found in conventional rats. SPF rats had significantly higher white cell, monocyte, neutrophil and lymphocyte counts, and were hyperfibrinolytic, indicated by EXTEM maximum lysis >15%. Independent assessment revealed similar pathogen exclusion between colonies, with the exception of Proteus in SPF animals. Returning to a conventional facility restored normal host physiology. We conclude that SPF animals displayed an abnormal hemodynamic, hematological and hemostatic phenotype in response to anesthesia and surgery, and provide a number of recommendations to help standardize research outcomes and translation.
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Affiliation(s)
- Hayley L Letson
- Heart, Trauma and Sepsis Research Laboratory, College of Medicine and Dentistry, James Cook University, Queensland, 4811, Australia
| | - Jodie Morris
- Heart, Trauma and Sepsis Research Laboratory, College of Medicine and Dentistry, James Cook University, Queensland, 4811, Australia
| | - Erik Biros
- Heart, Trauma and Sepsis Research Laboratory, College of Medicine and Dentistry, James Cook University, Queensland, 4811, Australia
| | - Geoffrey P Dobson
- Heart, Trauma and Sepsis Research Laboratory, College of Medicine and Dentistry, James Cook University, Queensland, 4811, Australia.
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Bolliger D, Tanaka KA. Platelet Count and Function—Can We Kill Two Birds With an Ultrasound Wave? J Cardiothorac Vasc Anesth 2019; 33:1599-1600. [DOI: 10.1053/j.jvca.2019.02.038] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/19/2019] [Accepted: 02/19/2019] [Indexed: 11/11/2022]
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Rotational thormboelastolmetry guided transfusion practice in living donor liver transplantation, A retrospective comparative study. EGYPTIAN JOURNAL OF ANAESTHESIA 2019. [DOI: 10.1016/j.egja.2018.03.004] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022] Open
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Stettler GR, Moore EE, Moore HB, Nunns GR, Silliman CC, Banerjee A, Sauaia A. Redefining postinjury fibrinolysis phenotypes using two viscoelastic assays. J Trauma Acute Care Surg 2019; 86:679-685. [PMID: 30562328 PMCID: PMC6870942 DOI: 10.1097/ta.0000000000002165] [Citation(s) in RCA: 52] [Impact Index Per Article: 8.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/15/2023]
Abstract
INTRODUCTION Fibrinolysis was initially defined using rapid thrombelastography (rTEG). The cutoffs for the pathologic extremes of the fibrinolytic system, hyperfibrinolysis and shutdown, were both defined based on association with mortality. We propose to redefine these phenotypes for both TEG and for rotational thrombelastometry, the other commonly used viscoelastic assay. METHODS Rotational thrombelastometry, rTEG, and clinical data were prospectively collected on trauma patients admitted to an urban Level I trauma center from 2010 to 2016. Hyperfibrinolysis was defined as the Youden index from EXTEM-clot lysis index 60 minutes after clotting time (CLI60) and rTEG-fibrinolysis 30 minutes after achieving MA (LY30) for predicting massive transfusion (>10 red blood cell units, or death per 6 hours after injury) as a surrogate for severe bleeding. Patients identified as having hyperfibrinolysis were then removed from the data set, and the cutoff for fibrinolysis shutdown was derived as the optimal cutoff for predicting mortality in the remaining patients. RESULTS Overall, 216 patients (median age, 36 years (interquartile range, 27-49 years), 82% men, 58% blunt injury) were included. Of these, 16% required massive transfusion, and 12.5% died. Rapid thrombelastography phenotypes were redefined as hyperfibrinolysis: rTEG-LY30 greater than7.7%, physiologic rTEG-LY30 0.6% to7.6%, and shutdown rTEG-LY30 less than 0.6%. EXTEM-CLI60 fibrinolysis phenotypes were hyperfibrinolysis CLI60 less than 82%, physiologic (CLI60, 82-97.9%), and shutdown (CLI60 > 98%). Weighted kappa statistics revealed moderate agreement between rotational thrombelastometry- and rTEG-defined fibrinolysis (k = 0.51; 95% confidence interval, 0.39-0.63), with disagreement mostly in the shutdown and physiologic categories. CONCLUSION We confirmed the U-shaped distribution of death related to fibrinolysis system abnormalities. Both rTEG LY30 and EXTEM CLI60 can identify the spectrum of fibrinolytic phenotypes, have moderate agreement, and can be used to guide hemostatic resuscitation. LEVEL OF EVIDENCE Diagnostic study, level III.
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Affiliation(s)
- Gregory R Stettler
- From the Department of Surgery (G.R.S., E.E.M., H.B.M., G.R.N., C.C.S., A.B., A.S.), University of Colorado School of Medicine, Aurora, Colorado; Denver Health Medical Center (E.E.M.), Denver, Colorado; Department of Pediatrics (C.C.S.), University of Colorado School of Medicine; Bonfils Blood Center (C.C.S.), Denver, Colorado; and University of Colorado School of Public Health (A.S.), Aurora, Colorado
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Cushing MM, Asmis LM, Harris RM, DeSimone RA, Hill S, Ivascu N, Haas T. Efficacy of a new pathogen-reduced cryoprecipitate stored 5 days after thawing to correct dilutional coagulopathy in vitro. Transfusion 2019; 59:1818-1826. [PMID: 30719724 DOI: 10.1111/trf.15157] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2018] [Revised: 12/27/2018] [Accepted: 12/29/2018] [Indexed: 12/29/2022]
Abstract
BACKGROUND Fibrinogen supplementation during bleeding restores clot strength and hemostasis. Cryoprecipitate, a concentrated source of fibrinogen, has prolonged preparation time for thawing, a short shelf life resulting in frequent wastage, and infectious disease risk. This in vitro study investigated the efficacy of a new pathogen-reduced cryoprecipitate thawed and stored at room temperature for 5 days (PR Cryo) to treat dilutional hypofibrinogenemia, compared to immediately thawed standard cryoprecipitate (Cryo) or fibrinogen concentrate (FC). STUDY DESIGN AND METHODS Ten phlebotomy specimens from healthy volunteers were diluted 1:1 with crystalloid and supplemented with PR Cryo and Cryo (at a dose replicating transfusion of two pooled doses [10 units]) and FC at a dose replicating 50 mg/kg. Changes in clot firmness (thromboelastometry) and in coagulation factor activity were assessed at baseline, after dilution, and after supplementation. RESULTS Clinical dosing was used, as described above, and consequently the FC dose contained 24% and 36% more fibrinogen versus PR Cryo and Cryo, respectively. At baseline, subjects had a median FIBTEM maximum clot firmness of 13.5 mm, versus 6.5 mm after 50% dilution (p = 0.005). After supplementation with PR Cryo, a median FIBTEM maximum clot firmness of 13 mm was observed versus 9.0 mm for Cryo (p = 0.005) or 16.5 mm for FC (p = 0.005). Median factor XIII was higher after PR Cryo (64.8%) versus Cryo (48.3%) (p = 0.005). Fibrinogen activity was higher after FC (269.0 mg/dL) versus PR Cryo (187.0 mg/dL; p = 0.005) or Cryo (193.5 mg/dL; p = 0.005); the difference between PR Cryo and Cryo supplementation (p = 0.445) was not significant. CONCLUSION PR Cryo used 5 days after thawing effectively restores clot strength after in vitro dilution.
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Affiliation(s)
- Melissa M Cushing
- Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, New York.,Department of Anesthesiology, Weill Cornell Medicine, New York, New York
| | - Lars M Asmis
- Centre for Perioperative Thrombosis and Haemostasis, Zurich, Switzerland
| | - Rebecca M Harris
- Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, New York
| | - Robert A DeSimone
- Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, New York
| | - Shanna Hill
- Department of Anesthesiology, Weill Cornell Medicine, New York, New York
| | - Natalia Ivascu
- Department of Anesthesiology, Weill Cornell Medicine, New York, New York
| | - Thorsten Haas
- Department of Anaesthesia, Zurich University Children's Hospital, Zurich, Switzerland
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Bolliger D, Tanaka KA. Transfusion Makeovers by Thromboelastometry—Does It Work for Everyone? J Cardiothorac Vasc Anesth 2019; 33:318-320. [DOI: 10.1053/j.jvca.2018.09.040] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/23/2018] [Indexed: 01/31/2023]
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Fukuhara K, Kondo T, Miyoshi H, Hamada H, Kawamoto M. Rotational thromboelastometry-guided perioperative management of coagulation in a patient with Heyde's syndrome undergoing transcatheter aortic valve implantation. JA Clin Rep 2019; 5:3. [PMID: 32026002 PMCID: PMC6966723 DOI: 10.1186/s40981-019-0224-3] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2018] [Accepted: 01/03/2019] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Changes in coagulability during the hyperacute phase within 24 h after transcatheter aortic valve implantation (TAVI) for Heyde's syndrome, or aortic stenosis complicated by gastrointestinal angiodysplasia and acquired coagulation dysfunction, have not been clarified. We evaluated perioperative changes in coagulability using rotational thromboelastometry (ROTEM). CASE PRESENTATION A female patient with Heyde's syndrome in her 80s underwent TAVI. ROTEM showed coagulation dysfunction before and at 6 h after surgery. Improvements in coagulation function started at 12 h after surgery. Based on ROTEM findings, oral administration of antiplatelet agents was started on the day after surgery. No hemorrhagic complications were observed in the postoperative phase. CONCLUSIONS Evaluation of coagulation function using ROTEM was useful for monitoring perioperative hemostasis and coagulation in this patient.
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Affiliation(s)
- Kumi Fukuhara
- Department of Anesthesiology and Critical Care, Hiroshima University Hospital, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan.
| | - Takashi Kondo
- Department of Anesthesiology and Critical Care, Hiroshima University Hospital, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan
| | - Hirotsugu Miyoshi
- Department of Anesthesiology and Critical Care, Hiroshima University Hospital, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan
| | - Hiroshi Hamada
- Department of Anesthesiology and Critical Care, Hiroshima University Hospital, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan
| | - Masashi Kawamoto
- Department of Anesthesiology and Critical Care, Hiroshima University Hospital, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan
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Matzelle SA, Weightman WM, Gibbs NM. An Audit of the Diagnostic Accuracy of Rotational Thromboelastometry for the Identification of Hypofibrinogenaemia and Thrombocytopenia during Cardiopulmonary Bypass. Anaesth Intensive Care 2018; 46:620-626. [DOI: 10.1177/0310057x1804600614] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
We audited the diagnostic accuracy of ROTEM® (TEM Innovations, GmbH, Munich, Germany) measurements of hypofibrinogenaemia (fibrinogen <1.5 g/l) and thrombocytopenia (platelet count <100 × 109/l) in 200 adult non-transplant patients during cardiopulmonary bypass (CPB). Blood samples were obtained for FIBTEM (assay for the fibrin part of the clot), PLTEM (calculated platelet-specific component), and laboratory measurements simultaneously. Our thresholds for FIBTEM and PLTEM were A10 (clot firmness 10 minutes after clotting time) ≤8 mm, and <35 mm respectively. We also calculated the accuracy of smaller thresholds and earlier indices. We found that FIBTEM A10 ≤8 mm had low sensitivity (0.62) for hypofibrinogenaemia. With the 13% hypofibrinogenaemia prevalence in our sample, the positive predictive value (PPV) was 0.47. In contrast, FIBTEM A10 ≤8 mm had higher specificity (0.90) (negative predictive value [NPV] 0.94). Of the other FIBTEM values analysed, only A5 ≤6 mm had similar or superior accuracy. The PLTEM results were less encouraging (sensitivity 0.81, specificity 0.62). With our prevalence of thrombocytopenia (also 13%), the PPV was only 0.24. However, the NPV was high (0.96). Of the other PLTEM values analysed, only A5 <25 mm had similar or superior accuracy. These findings indicate that during CPB FIBTEM A10 ≤8 mm and PLTEM A10 <35 mm have greater accuracy in identifying the absence of hypofibrinogenaemia and thrombocytopenia respectively than their presence. On the basis of these results we would be reassured by FIBTEM A10 values >8 mm and PLTEM A10 values ≥35 mm, but would continue to use laboratory measurements for confirmation. We would not use FIBTEM A10 ≤8 mm or PLTEM A10 <35 mm values alone to guide replacement therapy unless clinical conditions warranted an immediate decision before laboratory measurements were available.
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Affiliation(s)
- S. A. Matzelle
- Department of Anaesthesia, Sir Charles Gairdner Hospital, Perth, Western Australia
| | - W. M. Weightman
- Department of Anaesthesia, Sir Charles Gairdner Hospital, Perth, Western Australia
| | - N. M. Gibbs
- Department of Anaesthesia, Sir Charles Gairdner Hospital, Perth, Western Australia
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