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Bolliger D, Frei I, Tanaka K. Transfusion, Bleeding, or Coagulopathy: What Matters Most in Patients After Cardiac Surgery? J Cardiothorac Vasc Anesth 2025; 39:1615-1618. [PMID: 40307133 DOI: 10.1053/j.jvca.2025.03.043] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/26/2025] [Accepted: 03/27/2025] [Indexed: 05/02/2025]
Affiliation(s)
- Daniel Bolliger
- Clinic for Anaesthesia, Intermediate Care, Prehospital Emergency Medicine and Pain Therapy, University Hospital Basel, University of Basel, Switzerland; University of Basel, Medical Faculty, Basel, Switzerland.
| | - Isabelle Frei
- Clinic for Anaesthesia, Intermediate Care, Prehospital Emergency Medicine and Pain Therapy, University Hospital Basel, University of Basel, Switzerland; University of Basel, Medical Faculty, Basel, Switzerland
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2
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Kataria S, Juneja D, Singh O. Redefining haemostasis: Role of rotational thromboelastometry in critical care settings. World J Crit Care Med 2025; 14:102521. [PMID: 40491886 PMCID: PMC11891846 DOI: 10.5492/wjccm.v14.i2.102521] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/21/2024] [Revised: 01/20/2025] [Accepted: 02/08/2025] [Indexed: 02/27/2025] Open
Abstract
Management of patients with acute hemorrhage requires addressing the source of bleeding, replenishing blood volume, and addressing any coagulopathy that may be present. Assessing coagulopathy and predicting blood requirements in real-time in patients experiencing ongoing bleeding can pose substantial challenges. In these patients, transfusion concepts based on ratios do not effectively address coagulopathy or reduce mortality. Moreover, ratio-based concepts do not stop bleeding; instead, they just give physicians more time to identify the bleeding source and plan management strategies. In clinical practice, standard laboratory coagulation tests (SLCT) are frequently used to assess various aspects of blood clotting. However, these tests may not always offer a comprehensive understanding of clinically significant coagulopathy and the severity of blood loss. Furthermore, the SLCT have a considerable turnaround time, which may not be ideal for making prompt clinical decisions. In recent years, there has been a growing interest in point-of-care viscoelastic assays like rotational thromboelastometry, which provide real-time, dynamic information about clot formation and dissolution.
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Affiliation(s)
- Sahil Kataria
- Department of Critical Care Medicine, Holy Family Hospital, New Delhi 110025, India
| | - Deven Juneja
- Institute of Critical Care Medicine, Max Super Speciality Hospital, New Delhi 110017, India
| | - Omender Singh
- Institute of Critical Care Medicine, Max Super Speciality Hospital, New Delhi 110017, India
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3
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Casselman FPA, Lance MD, Ahmed A, Ascari A, Blanco-Morillo J, Bolliger D, Eid M, Erdoes G, Haumann RG, Jeppsson A, van der Merwe HJ, Ortmann E, Petricevic M, Weltert LP, Milojevic M, EACTS/EACTAIC/EBCP Scientific Document Group
. 2024 EACTS/EACTAIC Guidelines on patient blood management in adult cardiac surgery in collaboration with EBCP. Eur J Cardiothorac Surg 2025; 67:ezae352. [PMID: 39385500 DOI: 10.1093/ejcts/ezae352] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Collaborators] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/25/2024] [Revised: 08/08/2024] [Accepted: 10/01/2024] [Indexed: 10/12/2024] Open
Affiliation(s)
- Filip P A Casselman
- Department of Cardiovascular Surgery, Heart Center OLV Clinic, Aalst, Belgium
| | - Marcus D Lance
- Aga Khan University Hospital Nairobi, Department of Anesthesiology, Nairobi, Kenya
| | - Aamer Ahmed
- Department of Anaesthesia and Critical Care, Glenfield Hospital, University Hospitals of Leicester NHS Trust, Leicester, United Kingdom
- Department of Cardiovascular Sciences, University of Leicester, Leicester, United Kingdom
| | - Alice Ascari
- Department of Cardiovascular Anesthesia and Intensive Care, IRCCS Policlinico San Donato, San Donato Milanese, Milan, Italy
| | - Juan Blanco-Morillo
- ECLS Care and Perfusion Unit, Cardiac Surgery Department, University Hospital Virgen de la Arrixaca, Murcia, Spain
| | - Daniel Bolliger
- Clinic for Anaesthesia, Intermediate Care, Prehospital Emergency Medicine and Pain Therapy, University Hospital Basel, Basel, Switzerland
| | - Maroua Eid
- University Hospital of Angers, Department of Cardiac Surgery, Angers, France
| | - Gabor Erdoes
- Department of Anesthesiology and Pain Medicine, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
| | - Renard Gerhardus Haumann
- Department of Cardio-thoracic surgery, Thoraxcentrum Twente, Medisch Spectrum Twente, Enschede, The Netherlands
- Department Of Biomechanical Engineering, TechMed Centre, University of Twente, Enschede, The Netherlands
| | - Anders Jeppsson
- Department of Cardiothoracic Surgery, Sahlgrenska University Hospital, Gothenburg, Sweden
- Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| | - Hendrik J van der Merwe
- Netcare Blaauwberg and Christiaan Barnard Memorial Hospital, The Keyhole Thorax Centre, Cape Town, South Africa
| | - Erik Ortmann
- Department of Anaesthesiology Schüchtermann-Klinik Heart Centre, Bad Rothenfelde, Germany
| | - Mate Petricevic
- Department of Cardiac Surgery, University Hospital Center Split, Split, Croatia
- University Department of Health Studies, University of Split, Split, Croatia
| | - Luca Paolo Weltert
- European Hospital, Cardiac Surgery Department, Rome, Italy
- Saint Camillus International University for Health Sciences, Heart Surgery Department, Rome, Italy
| | - Milan Milojevic
- Department of Cardiac Surgery and Cardiovascular Research, Dedinje Cardiovascular Institute, Belgrade, Serbia
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Collaborators
J Rafael Sadaba, Marco Ranucci, Seema Agrawal, Adrian Bauer, Denis Berdajs, Stuart A McCluskey, Daniel Engelman, Tomas Gudbjartsson, Emma Hansson, Andreas Koster, Filip De Somer, Eric De Waal, Alexander Wahba, Fernando Yévenes,
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Satpathy C, Mishra TK, Jha AK. Factor XI and XII inhibitors-Dawn of a new era. Indian Heart J 2025; 77:122-129. [PMID: 40015552 DOI: 10.1016/j.ihj.2025.02.007] [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: 08/19/2024] [Revised: 02/20/2025] [Accepted: 02/22/2025] [Indexed: 03/01/2025] Open
Abstract
The history of coagulation cascade dates back to 17th century. The extrinsic and intrinsic pathways were proposed in 1998. Extrinsic pathway includes the tissue factor and stable factor which activates factor X and with help of factor V, this converts prothrombin to thrombin which is stabilised by factor XIII. This helps to seal the bleeding vessel and is a physiological process as there is only "limited" production of thrombin which doe not expand beyond the damaged site due to absence of tissue factor. On the other hand intrinsic pathway is activated by polyanions, neutrophilic extracellular traps which are present during infection and inflammation. These activate factor XI which activates factor X with the help of factor IX and VIII and then the common pathway ensues. But newer discoveries have shown that this is a very simplified way of explaining the coagulation system. The researches propose that haemostasis is divided into initiation, amplification and propagation phase. Also, the factor VII-tissue factor complex formed activates factor IX and leads to sustained thrombin production as the amount of thrombin produced by extrinsic pathway alone is not sufficient to form a haemostatic plug. Thrombin also activates factor XI and lead to self perpetuation of intrinsic pathway. All the anticoagulants have an inherent property of bleeding. So the newer factor XI and XII inhibitors focus to inhibit the excessive thrombin production without hampering the physiological haemostasis process. This is supported by the fact that congenital factor XI and XII deficiency does not cause excessive bleeding but increased levels did make patients more vulnerable to thromboembolism. This review shall focus on the various factor XI and XII inhibitors which are in the pipeline.
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Affiliation(s)
- Chhabi Satpathy
- Department of Cardiology, MKCG Medical College and Hospital, Berhampur, Odisha, India
| | - Trinath Kumar Mishra
- Department of Cardiology, MKCG Medical College and Hospital, Berhampur, Odisha, India.
| | - Anshu Kumar Jha
- Department of Cardiology, MKCG Medical College and Hospital, Berhampur, Odisha, India
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5
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Sieh L, Peasley E, Mao E, Mitchell A, Heinonen G, Ghoshal S, Agarwal S, Park S, Connolly ES, Claassen J, Moore EE, Hansen K, Hod EA, Francis RO, Roh DJ. Admission Viscoelastic Hemostatic Assay Parameters Predict Poor Long-Term Intracerebral Hemorrhage Outcomes. Neurocrit Care 2025; 42:100-107. [PMID: 38955933 DOI: 10.1007/s12028-024-02051-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2024] [Accepted: 06/13/2024] [Indexed: 07/04/2024]
Abstract
BACKGROUND Viscoelastic hemostatic assays (VHAs) provide more comprehensive assessments of coagulation compared with conventional coagulation assays. Although VHAs have enabled guided hemorrhage control therapies, improving clinical outcomes in life-threatening hemorrhage, the role of VHAs in intracerebral hemorrhage (ICH) is unclear. If VHAs can identify coagulation abnormalities relevant for ICH outcomes, this would support the need to investigate the role of VHAs in ICH treatment paradigms. Thus, we investigated whether VHA assessments of coagulation relate to long-term ICH outcomes. METHODS Patients with spontaneous ICH enrolled into a single-center cohort study receiving admission Rotational Thromboelastometry (ROTEM) VHA testing between 2013 and 2020 were assessed. Patients with previous anticoagulant use or coagulopathy on conventional coagulation assays were excluded. Primary ROTEM exposure variables were coagulation kinetics and clot strength assessments. Poor long-term outcome was defined as modified Rankin Scale ≥ 4 at 6 months. Logistic regression analyses assessed associations of ROTEM parameters with clinical outcomes after adjusting for ICH severity and hemoglobin concentration. RESULTS Of 44 patients analyzed, the mean age was 64 years, 57% were female, and the median ICH volume was 23 mL. Poor 6-month outcome was seen in 64% of patients. In our multivariable regression models, slower, prolonged coagulation kinetics (adjusted odds ratio for every second increase in clot formation time 1.04, 95% confidence interval 1.00-1.09, p = 0.04) and weaker clot strength (adjusted odds ratio for every millimeter increase of maximum clot firmness 0.84, 95% confidence interval 0.71-0.99, p = 0.03) were separately associated with poor long-term outcomes. CONCLUSIONS Slower, prolonged coagulation kinetics and weaker clot strength on admission VHA ROTEM testing, not attributable to anticoagulant use, were associated with poor long-term outcomes after ICH. Further work is needed to clarify the generalizability and the underlying mechanisms of these VHA findings to assess whether VHA-guided treatments should be incorporated into ICH care.
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Affiliation(s)
- Laura Sieh
- Department of Neurology, Vagelos College of Physicians and Surgeons, Columbia University, 177 Fort Washington Ave, New York, NY, 10032, USA
| | - Emma Peasley
- Department of Neurology, Vagelos College of Physicians and Surgeons, Columbia University, 177 Fort Washington Ave, New York, NY, 10032, USA
| | - Eric Mao
- Department of Neurology, Vagelos College of Physicians and Surgeons, Columbia University, 177 Fort Washington Ave, New York, NY, 10032, USA
| | - Amanda Mitchell
- Department of Neurology, Vagelos College of Physicians and Surgeons, Columbia University, 177 Fort Washington Ave, New York, NY, 10032, USA
| | - Gregory Heinonen
- Department of Neurology, Vagelos College of Physicians and Surgeons, Columbia University, 177 Fort Washington Ave, New York, NY, 10032, USA
| | - Shivani Ghoshal
- Department of Neurology, Vagelos College of Physicians and Surgeons, Columbia University, 177 Fort Washington Ave, New York, NY, 10032, USA
| | - Sachin Agarwal
- Department of Neurology, Vagelos College of Physicians and Surgeons, Columbia University, 177 Fort Washington Ave, New York, NY, 10032, USA
| | - Soojin Park
- Department of Neurology, Vagelos College of Physicians and Surgeons, Columbia University, 177 Fort Washington Ave, New York, NY, 10032, USA
| | - E Sander Connolly
- Department of Neurological Surgery, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY, USA
| | - Jan Claassen
- Department of Neurology, Vagelos College of Physicians and Surgeons, Columbia University, 177 Fort Washington Ave, New York, NY, 10032, USA
| | - Ernest E Moore
- Department of Surgery, Ernest E. Moore Shock Trauma Center at Denver Health, Denver, CO, USA
| | - Kirk Hansen
- Department of Biochemistry and Molecular Genetics, University of Colorado Denver, Aurora, CO, USA
| | - Eldad A Hod
- Department of Pathology and Cell Biology, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY, USA
| | - Richard O Francis
- Department of Pathology and Cell Biology, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY, USA
| | - David J Roh
- Department of Neurology, Vagelos College of Physicians and Surgeons, Columbia University, 177 Fort Washington Ave, New York, NY, 10032, USA.
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Bezati S, Ventoulis I, Verras C, Boultadakis A, Bistola V, Sbyrakis N, Fraidakis O, Papadamou G, Fyntanidou B, Parissis J, Polyzogopoulou E. Major Bleeding in the Emergency Department: A Practical Guide for Optimal Management. J Clin Med 2025; 14:784. [PMID: 39941455 PMCID: PMC11818891 DOI: 10.3390/jcm14030784] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2024] [Revised: 01/15/2025] [Accepted: 01/22/2025] [Indexed: 02/16/2025] Open
Abstract
Major bleeding is a life-threatening condition with high morbidity and mortality. Trauma, gastrointestinal bleeding, haemoptysis, intracranial haemorrhage or other causes of bleeding represent major concerns in the Emergency Department (ED), especially when complicated by haemodynamic instability. Severity and source of bleeding, comorbidities, and prior use of anticoagulants are pivotal factors affecting both the clinical status and the patients' differential response to haemorrhage. Thus, risk stratification is fundamental in the initial assessment of patients with bleeding. Aggressive resuscitation is the principal step for achieving haemodynamic stabilization of the patient, which will further allow appropriate interventions to be made for the definite control of bleeding. Overall management of major bleeding in the ED should follow a holistic individualized approach which includes haemodynamic stabilization, repletion of volume and blood loss, and reversal of coagulopathy and identification of the source of bleeding. The aim of the present practical guide is to provide an update on recent epidemiological data about the most common etiologies of bleeding and summarize the latest evidence regarding the bundles of care for the management of patients with major bleeding of traumatic or non-traumatic etiology in the ED.
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Affiliation(s)
- Sofia Bezati
- Department of Emergency Medicine, Attikon University Hospital, National and Kapodistrian University of Athens, 12462 Athens, Greece; (C.V.); (A.B.); (J.P.); (E.P.)
| | - Ioannis Ventoulis
- Department of Occupational Therapy, University of Western Macedonia, 50200 Ptolemaida, Greece;
| | - Christos Verras
- Department of Emergency Medicine, Attikon University Hospital, National and Kapodistrian University of Athens, 12462 Athens, Greece; (C.V.); (A.B.); (J.P.); (E.P.)
| | - Antonios Boultadakis
- Department of Emergency Medicine, Attikon University Hospital, National and Kapodistrian University of Athens, 12462 Athens, Greece; (C.V.); (A.B.); (J.P.); (E.P.)
| | - Vasiliki Bistola
- Second Department of Cardiology, Attikon University Hospital, National and Kapodistrian University of Athens, 12462 Athens, Greece;
| | - Nikolaos Sbyrakis
- Department of Emergency Medicine, University Hospital of Heraklion, 71500 Crete, Greece;
| | - Othon Fraidakis
- Department of Emergency Medicine, Venizelion Hospital of Heraklion, 71409 Crete, Greece;
| | - Georgia Papadamou
- Department of Emergency Medicine, University Hospital of Larissa, 41334 Larissa, Greece;
| | - Barbara Fyntanidou
- Department of Emergency Medicine, AHEPA University Hospital, Aristotle University of Thessaloniki, 54636 Thessaloniki, Greece;
| | - John Parissis
- Department of Emergency Medicine, Attikon University Hospital, National and Kapodistrian University of Athens, 12462 Athens, Greece; (C.V.); (A.B.); (J.P.); (E.P.)
| | - Effie Polyzogopoulou
- Department of Emergency Medicine, Attikon University Hospital, National and Kapodistrian University of Athens, 12462 Athens, Greece; (C.V.); (A.B.); (J.P.); (E.P.)
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7
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Erdoes G, Goobie SM, Haas T, Koster A, Levy JH, Steiner ME. Perioperative considerations in the paediatric patient with congenital and acquired coagulopathy. BJA OPEN 2024; 12:100310. [PMID: 39376894 PMCID: PMC11456917 DOI: 10.1016/j.bjao.2024.100310] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 04/27/2024] [Accepted: 08/18/2024] [Indexed: 10/09/2024]
Abstract
Neonates, infants, and children undergoing major surgery or with trauma can develop severe coagulopathy perioperatively. Neonates and infants are at highest risk because their haemostatic system is not fully developed and underlying inherited bleeding disorders may not have been diagnosed before surgery. Historically, laboratory coagulation measurements have been used to diagnose and monitor coagulopathies. Contemporary dynamic monitoring strategies are evolving. Viscoelastic testing is increasingly being used to monitor coagulopathy, particularly in procedures with a high risk of bleeding. However, there is a lack of valid age-specific reference values for diagnosis and trigger or target values for appropriate therapeutic management. A promising screening tool of primary haemostasis that may be used to diagnose quantitative and qualitative platelet abnormalities is the in vitro closure time by platelet function analyser. Targeted individualised treatment strategies for haemostatic bleeding arising from inherited or acquired bleeding disorders may include measures such as tranexamic acid, administration of plasma, derived or recombinant factors such as fibrinogen concentrate, or allogeneic blood component transfusions (plasma, platelets, or cryoprecipitate). Herein we review current recommended perioperative guidelines, monitoring strategies, and treatment modalities for the paediatric patient with a coagulopathy. In the absence of data from adequately powered prospective studies, it is recommended that expert consensus be considered until additional research and validation of goal-directed perioperative bleeding management in paediatric patients is available.
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Affiliation(s)
- Gabor Erdoes
- Department of Anaesthesiology and Pain Medicine, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
| | - Susan M. Goobie
- Department of Anesthesiology, Critical Care & Pain Medicine, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA
| | - Thorsten Haas
- Department of Anesthesiology, College of Medicine, University of Florida, Gainesville, FL, USA
| | - Andreas Koster
- Institute of Anaesthesiology and Pain Therapy, Heart and Diabetes Centre NRW, Ruhr University Bochum, Bad Oeynhausen, Germany
| | - Jerrold H. Levy
- Departments of Anesthesiology, Critical Care, and Surgery, Duke University School of Medicine, Durham, NC, USA
| | - Marie E. Steiner
- Divisions of Critical Care and Hematology/Oncology, Department of Pediatrics, University of Minnesota, Minneapolis, MN, USA
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Petricevic M, Goerlinger K, Milojevic M, Petricevic M. Methodological Considerations for Studies Evaluating Bleeding Prediction Using Hemostatic Point-of-Care Tests in Cardiac Surgery. J Clin Med 2024; 13:6737. [PMID: 39597881 PMCID: PMC11595064 DOI: 10.3390/jcm13226737] [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: 07/28/2024] [Revised: 10/28/2024] [Accepted: 11/04/2024] [Indexed: 11/29/2024] Open
Abstract
A certain proportion of patients undergoing cardiac surgery may experience bleeding complications that worsen outcomes. Numerous studies have investigated bleeding in cardiac surgery and some evaluate the role of hemostatic point-of-care tests in cardiac surgery patients. The prevalence of excessive bleeding varies in the literature, and such variability stems from the lack of a standardized definition of excessive bleeding. Herein, we report numerous definitions of excessive bleeding and methodological considerations for studies evaluating bleeding using hemostatic point-of-care tests in cardiac surgery patients. We evaluated the role of hemostatic point-of-care devices in contemporary research on bleeding complications and hemostatic management in cardiac surgery. The type of studies (prospective vs. retrospective, interventional vs. observational), patient selection (less complex vs. complex cases), as well as data analysis with comprehensive statistical considerations have also been provided. This article provides a comprehensive insight into the research field of bleeding complications in cardiac surgery and may help readers to better understand methodological flaws and how they influence current evidence.
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Affiliation(s)
- Mirna Petricevic
- University 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, 80331 Munich, Germany
| | - Milan Milojevic
- Department of Cardiac Surgery and Cardiovascular Research, Dedinje Cardiovascular Institute, 101801 Belgrade, Serbia;
| | - Mate Petricevic
- University 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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Bruno J, Varayath M, Gahl B, Miazza J, Gebhard CE, Reuthebuch OT, Eckstein FS, Siegemund M, Hollinger A, Santer D. Conservative fluid resuscitation protocol does not reduce the incidence of reoperation for bleeding after emergency CABG. Sci Rep 2024; 14:21037. [PMID: 39251616 PMCID: PMC11383960 DOI: 10.1038/s41598-024-71028-8] [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: 11/16/2023] [Accepted: 08/23/2024] [Indexed: 09/11/2024] Open
Abstract
Reoperation for bleeding (ROB) after emergency coronary artery bypass grafting (eCABG) has been identified as an independent risk factor for mortality. Consecutively, the influence of fluid intake, fluid output, fluid balance, blood loss, and inotropic demand on ROB were analyzed. This retrospective single-center study included 265 patients undergoing eCABG between 2011 and 2020. From 2018, postoperative hemodynamic management was performed with lower volume administration and higher vasoactive support. The primary outcome measure was the incidence of ROB within 48 h according to altered fluid resuscitation strategy. Consecutively, the influence of fluid intake, fluid output, fluid balance, blood loss, and inotropic demand on ROB were analyzed. Incidence of ROB was independent from the volume resuscitation protocol (P = .3). The ROB group had a higher perioperative risk, which was observed in EuroSCORE II. Fluid intake (P = .021), fluid balance (P = .001), and norepinephrine administration (P = .004) were associated with ROB. Fluid output and blood loss were not associated with ROB (P = .22). Post-test probability was low among all variables. Although fluid management might have an impact on specific postoperative complications, different fluid resuscitation protocols did not alter the incidence of ROB after emergency CABG. TRIAL REGISTRATION www. CLINICALTRIALS gov registration number NCT04533698; date of registration: August 31, 2020 (retrospectively registered due to nature of the study); URL: https://classic. CLINICALTRIALS gov/ct2/show/NCT04533698.
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Affiliation(s)
- Jowita Bruno
- Intensive Care Unit, University Hospital Basel, Spitalstrasse 21, 4031, Basel, Switzerland
| | - Mascha Varayath
- Clinic for Anaesthesiology, University Hospital Basel, Basel, Switzerland
| | - Brigitta Gahl
- Department of Cardiac Surgery, University Hospital Basel, Basel, Switzerland
| | - Jules Miazza
- Department of Cardiac Surgery, University Hospital Basel, Basel, Switzerland
| | - Caroline E Gebhard
- Intensive Care Unit, University Hospital Basel, Spitalstrasse 21, 4031, Basel, Switzerland
- Medical Faculty of the University of Basel, Basel, Switzerland
| | - Oliver T Reuthebuch
- Department of Cardiac Surgery, University Hospital Basel, Basel, Switzerland
- Medical Faculty of the University of Basel, Basel, Switzerland
| | - Friedrich S Eckstein
- Department of Cardiac Surgery, University Hospital Basel, Basel, Switzerland
- Medical Faculty of the University of Basel, Basel, Switzerland
| | - Martin Siegemund
- Intensive Care Unit, University Hospital Basel, Spitalstrasse 21, 4031, Basel, Switzerland.
- Medical Faculty of the University of Basel, Basel, Switzerland.
| | - Alexa Hollinger
- Intensive Care Unit, University Hospital Basel, Spitalstrasse 21, 4031, Basel, Switzerland
- Medical Faculty of the University of Basel, Basel, Switzerland
| | - David Santer
- Department of Cardiac Surgery, University Hospital Basel, Basel, Switzerland
- Medical Faculty of the University of Basel, Basel, Switzerland
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10
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Bolliger D, Ranucci M. Improved outcome with individualised antifibrinolytic therapy: what is the evidence? Br J Anaesth 2024; 132:1187-1189. [PMID: 38729743 DOI: 10.1016/j.bja.2024.03.020] [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: 03/18/2024] [Accepted: 03/26/2024] [Indexed: 05/12/2024] Open
Abstract
Viscoelastic haemostatic testing (VHT) has been used to determine hyperfibrinolysis and hypofibrinolysis. When modified by addition of tissue plasminogen activator (tPA), VHT has been suggested to assess responses to antifibrinolytic therapy and to estimate the concentration of tranexamic acid in patients undergoing cardiac surgery. Despite some evidence that tPA-modified VHT might allow individualisation of antifibrinolytic therapy, further studies are warranted to prove its clinical benefit for postsurgical bleeding, transfusion of blood products, and thromboembolic events.
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Affiliation(s)
- Daniel Bolliger
- Clinic for Anaesthesia, Intermediate Care, Prehospital Emergency Medicine and Pain Therapy, University Hospital Basel, University of Basel, Basel, Switzerland.
| | - Marco Ranucci
- Department of Cardiovascular Anesthesia and Intensive Care, IRCCS Policlinico San Donato, San Donato Milanese, Milan, Italy
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11
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Yoshii R, Takahashi Y, Tanaka KA, Kawajiri H, Sawa T, Amaya F, Ogawa S. Point-of-care testing for tranexamic acid efficacy: a proof-of-concept study in cardiac surgical patients. Br J Anaesth 2024; 132:1211-1218. [PMID: 38677950 DOI: 10.1016/j.bja.2024.03.023] [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: 12/19/2023] [Revised: 03/03/2024] [Accepted: 03/08/2024] [Indexed: 04/29/2024] Open
Abstract
BACKGROUND Low-dose tranexamic acid (TXA) has been recently recommended for cardiopulmonary bypass (CPB) to reduce associated complications. Although point-of-care laboratory tests for TXA concentrations are unavailable, a novel TPA-test on the ClotPro® system can measure TXA-induced inhibition of fibrinolysis. We evaluated the performance of the TPA-test in vitro and in patients undergoing surgery requiring CPB. METHODS Blood samples were obtained from six volunteers for in vitro evaluation of tissue plasminogen activator (tPA)-triggered fibrinolysis and the effects of TXA. This was followed by an observational study in 20 cardiac surgery patients to assess clinical effects of TXA on the TPA-test. RESULTS Hyperfibrinolysis induced by tPA was inhibited by TXA ≥2 mg L-1 in a concentration-dependent manner, and was completely inhibited at TXA ≥10 mg L-1. In patients undergoing CPB, antifibrinolytic effect was detectable on TPA-test parameters after a 0.1 g bolus of TXA at the end of CPB, and complete inhibition of fibrinolysis was obtained with TXA ≥0.5 g. The antifibrinolytic effects of 1 g TXA on TPA-test parameters were gradually attenuated over 18 h after surgery. However, the fibrinolytic inhibition continued in four patients with estimated glomerular filtration rate (eGFR) ≤30 ml min-1 1.73 m-2. The eGFR had strong correlations with TPA-test parameters at 18 h after surgery (r=0.86-0.92; P<0.0001). CONCLUSIONS The TPA-test is sensitive to low concentrations of TXA and serves as a practical monitoring tool for postoperative fibrinolytic activity in cardiac surgery patients. This test might be particularly useful in patients with severe renal impairment.
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Affiliation(s)
- Ryogo Yoshii
- Department of Anesthesiology, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Yuya Takahashi
- Department of Anesthesiology, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Kenichi A Tanaka
- Department of Anesthesiology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA
| | - Hidetake Kawajiri
- Department of Cardiovascular Surgery, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Teiji Sawa
- Department of Anesthesiology, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Fumimasa Amaya
- Department of Pain Management and Palliative Care Medicine, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Satoru Ogawa
- Department of Anesthesiology, Kyoto Prefectural University of Medicine, Kyoto, Japan; Department of Pain Management and Palliative Care Medicine, Kyoto Prefectural University of Medicine, Kyoto, Japan.
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12
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Groenewoud R, Gunning D, Fava C, Sharpe R, Valchanov K, Shayan H. Successful thrombolysis of early bioprosthetic mitral valve thrombosis following extracorporeal membrane oxygenation: Case report. Perfusion 2024; 39:640-642. [PMID: 36796035 DOI: 10.1177/02676591231157200] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/18/2023]
Abstract
Introduction: Bioprosthetic mitral valve thrombosis (BPMVT) following post-operative extracorporeal membrane oxygenation (ECMO) is a rare complication with high mortality.Case Report: A 75-year-old man with a flail posterior mitral leaflet underwent a bioprosthetic mitral valve replacement and was subsequently placed on central veno-arterial high flow ECMO following intractable shock after protamine administration. He developed BPMVT over the following 48 hr, which did not resolve with 3 weeks of systemic heparin. He was then treated successfully with 3 days of continuous low dose (1 mg/hr) Tissue Plasminogen Activator (TPA). He suffered no bleeding consequences and had a complete cardiac and end-organ recovery.Discussion: Slow TPA infusion may be an acceptable treatment strategy for alleviating thrombotic burden from a bioprosthetic valve, even in the post-operative setting.
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Affiliation(s)
- Rosalind Groenewoud
- Undergraduate Medical Education, University of British Columbia, Vancouver, BC, Canada
| | - Derek Gunning
- Royal Columbian Hospital, New Westminster, BC, Canada
- Division of Cardiac Surgery, University of British Columbia, Vancouver, BC, Canada
- Division of Critical Care, University of British Columbia, Vancouver, BC, Canada
| | - Craig Fava
- Royal Columbian Hospital, New Westminster, BC, Canada
- Division of Critical Care, University of British Columbia, Vancouver, BC, Canada
| | - Rob Sharpe
- Royal Columbian Hospital, New Westminster, BC, Canada
- Division of Critical Care, University of British Columbia, Vancouver, BC, Canada
| | - Kamen Valchanov
- Royal Columbian Hospital, New Westminster, BC, Canada
- Department of Anesthesia, University of British Columbia, Vancouver, BC, Canada
- Department of Anaesthesia and Perioperative Medicine, Singapore General Hospital, Singapore
| | - Hossein Shayan
- Royal Columbian Hospital, New Westminster, BC, Canada
- Division of Cardiac Surgery, University of British Columbia, Vancouver, BC, Canada
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13
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Lee J, Lee DK, Kwon WK, Lee S, Oh CS, Görlinger K, Kim TY. Effect of ultrafiltration on whole blood coagulation profile during cardiopulmonary bypass in cardiac surgery: a retrospective analysis. Korean J Anesthesiol 2024; 77:236-245. [PMID: 38287212 PMCID: PMC10982537 DOI: 10.4097/kja.23698] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2023] [Revised: 01/02/2024] [Accepted: 01/07/2024] [Indexed: 01/31/2024] Open
Abstract
BACKGROUND Ultrafiltration (UF) would enhance coagulation profiles by concentrating coagulation elements during cardiopulmonary bypass (CPB) for cardiac surgery. METHODS We retrospectively reviewed electronic medical records of 75 patients who had undergone cardiac surgery with rotational thromboelastometry-based coagulation management in a university hospital and analyzed the UF-induced changes in the maximum clot firmness (MCF) of extrinsically activated test with tissue factor (EXTEM) during CPB in 30 patients. RESULTS The median volume of filtered-free water was 1,350 ml, and median hematocrit was significantly increased from 22.5% to 25.5%. As the primary measure, UF significantly increased the median MCF-EXTEM from 48.0 mm to 50.5 mm (P = 0.015, effect size r = 0.44). The area under the receiver operating characteristic curve pre-UF MCF-EXTEM for discrimination of any increase of MCF-EXTEM after applying UF was 0.89 (95% CI [0.77, 1.00], P < 0.001), and its cut-off value was 50.5 mm (specificity of 81.8% and sensitivity of 84.2% in Youden's J statistic). In the secondary analyses using the cut-off value, UF significantly increased the median MCF-EXTEM from 40.5 mm to 42.5 mm in 18 patients with pre-UF MCF-EXTEM ≤ 50.5 mm. However, it did not increase MCF-EXTEM in 12 patients with pre-UF MCF-EXTEM > 50.5 mm. There was a significant interaction between pre-UF MCF-EXTEM values and applying UF (P < 0.001 for the subgroup, P = 0.046 for UF, P = 0.003 for interaction). CONCLUSIONS Applying UF improved clot firmness, and the improvement was more pronounced when pre-UF MCF-EXTEM had been reduced during CPB.
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Affiliation(s)
- Jaemoon Lee
- Department of Anesthesiology, Konkuk University Medical Center, Konkuk University School of Medicine, Seoul, Korea
| | - Dong-Kyu Lee
- Department of Anesthesiology and Pain Medicine, Dongguk University Ilsan Hospital, Goyang, Korea
| | - Won-Kyoung Kwon
- Department of Anesthesiology, Konkuk University Medical Center, Konkuk University School of Medicine, Seoul, Korea
| | - Sookyung Lee
- Department of Anesthesiology, Konkuk University Medical Center, Konkuk University School of Medicine, Seoul, Korea
| | - Chung-Sik Oh
- Department of Anesthesiology, Konkuk University Medical Center, Konkuk University School of Medicine, Seoul, Korea
| | - Klaus Görlinger
- Department of Anesthesiology and Intensive Care Medicine, University Hospital Essen, Essen, Germany
- Medical Department, TEM Innovations GmbH/Werfen PBM, Munich, Germany
| | - Tae-Yop Kim
- Department of Anesthesiology, Konkuk University Medical Center, Konkuk University School of Medicine, Seoul, Korea
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14
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Sieh L, Peasley E, Mao E, Mitchell A, Heinonen G, Ghoshal S, Agarwal S, Park S, Connolly ESS, Claassen J, Moore EE, Hansen K, Hod EA, Francis RO, Roh D. Admission viscoelastic hemostatic assay parameters predict poor long-term intracerebral hemorrhage outcomes. RESEARCH SQUARE 2024:rs.3.rs-4087284. [PMID: 38585893 PMCID: PMC10996822 DOI: 10.21203/rs.3.rs-4087284/v1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 04/09/2024]
Abstract
Background Viscoelastic hemostatic assays (VHA) provide more comprehensive assessments of coagulation compared to conventional coagulation assays. While VHAs have enabled guided hemorrhage control therapies, improving clinical outcomes in life-threatening hemorrhage, the role of VHAs in intracerebral hemorrhage (ICH) is unclear. If VHAs can identify coagulation abnormalities relevant for ICH outcomes, this would support the need to investigate the role of VHAs in ICH treatment paradigms. Thus, we investigated whether VHA assessments of coagulation relate to long-term ICH outcomes. Methods Spontaneous ICH patients enrolled into a single-center cohort study receiving admission Rotational Thromboelastometry (ROTEM) VHA testing between 2013 and 2020 were assessed. Patients with prior anticoagulant use or coagulopathy on conventional coagulation assays were excluded. Primary ROTEM exposure variables were coagulation kinetics and clot strength assessments. Poor long-term outcome was defined as modified Rankin Scale ≥ 4 at 6 months. Logistic regression analyses assessed associations of ROTEM parameters with clinical outcomes after adjusting for ICH severity and hemoglobin concentration. Results Of 44 patients analyzed, mean age was 64, 57% were female, and the median ICH volume was 23 mL. Poor 6-month outcome was seen in 64%. In our multivariable regression models, slower, prolonged coagulation kinetics (adjusted OR for every second increase in clot formation time: 1.04, 95% CI: 1.00-1.09, p = 0.04) and weaker clot strength (adjusted OR for every millimeter increase of maximum clot firmness: 0.84, 95% CI: 0.71-0.99, p = 0.03) were separately associated with poor long-term outcomes. Conclusions Slower, prolonged coagulation kinetics and weaker clot strength on admission VHA ROTEM testing, not attributable to anticoagulant use, were associated with poor long-term outcomes after ICH. Further work is needed to clarify the generalizability and the underlying mechanisms of these VHA findings to assess whether VHA guided treatments should be incorporated into ICH care.
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Affiliation(s)
- Laura Sieh
- Columbia University Vagelos College of Physicians and Surgeons
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15
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Crochemore T, Görlinger K, Lance MD. Early Goal-Directed Hemostatic Therapy for Severe Acute Bleeding Management in the Intensive Care Unit: A Narrative Review. Anesth Analg 2024; 138:499-513. [PMID: 37977195 PMCID: PMC10852045 DOI: 10.1213/ane.0000000000006756] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/16/2023] [Indexed: 11/19/2023]
Abstract
This is a narrative review of the published evidence for bleeding management in critically ill patients in different clinical settings in the intensive care unit (ICU). We aimed to describe "The Ten Steps" approach to early goal-directed hemostatic therapy (EGDHT) using point-of-care testing (POCT), coagulation factor concentrates, and hemostatic drugs, according to the individual needs of each patient. We searched National Library of Medicine, MEDLINE for publications relevant to management of critical ill bleeding patients in different settings in the ICU. Bibliographies of included articles were also searched to identify additional relevant studies. English-language systematic reviews, meta-analyses, randomized trials, observational studies, and case reports were reviewed. Data related to study methodology, patient population, bleeding management strategy, and clinical outcomes were qualitatively evaluated. According to systematic reviews and meta-analyses, EGDHT guided by viscoelastic testing (VET) has been associated with a reduction in transfusion utilization, improved morbidity and outcome in patients with active bleeding. Furthermore, literature data showed an increased risk of severe adverse events and poor clinical outcomes with inappropriate prophylactic uses of blood components to correct altered conventional coagulation tests (CCTs). Finally, prospective, randomized, controlled trials point to the role of goal-directed fibrinogen substitution to reduce bleeding and the amount of red blood cell (RBC) transfusion with the potential to decrease mortality. In conclusion, severe acute bleeding management in the ICU is still a major challenge for intensive care physicians. The organized and sequential approach to the bleeding patient, guided by POCT allows for rapid and effective bleeding control, through the rational use of blood components and hemostatic drugs, since VET can identify specific coagulation disorders in real time, guiding hemostatic therapy with coagulation factor concentrates and hemostatic drugs with individual goals.
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Affiliation(s)
- Tomaz Crochemore
- From the Department of Critical Care, Hospital Vila Nova Star, São Paulo, Brazil
- Department of Critical Care, Hospital Israelita Albert Einstein, São Paulo, Brazil
- Werfen LATAM, São Paulo, Brazil
| | - Klaus Görlinger
- Department of Anesthesiology and Intensive Care Medicine, University Hospital Essen, Essen, Germany
- TEM Innovations GmbH/Werfen PBM, Munich, Germany
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16
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James AH, James PD. What do we know about why women bleed and what do we not know? J Thromb Haemost 2024; 22:315-322. [PMID: 37709147 DOI: 10.1016/j.jtha.2023.08.034] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2023] [Revised: 08/07/2023] [Accepted: 08/31/2023] [Indexed: 09/16/2023]
Abstract
Women or people with a uterus are vulnerable to both normal and abnormal bleeding. During the reproductive years, the uterus is prepared physiologically to accept an embryo and support its growth and development during pregnancy, or in the absence of implantation of an embryo, recycle through the process of menstruation and accept an embryo a month or so later. If fertilization takes place and an embryo or embryos implant in the uterus, the fetal trophoblast, or outer cell layer of the embryo, invades and dilates the maternal spiral arteries and forms the placenta. No matter when in gestation a pregnancy ends, at the conclusion of pregnancy, the placenta should separate from the wall of the uterus and be expelled. Abnormal bleeding occurs during pregnancy or after delivery when the normal uteroplacental interface has not been established or is interrupted; during miscarriage; during ectopic pregnancy; during premature separation of the placenta; or during postpartum hemorrhage. Heavy menstrual bleeding, a subset of abnormal menstrual bleeding, can be quantitatively defined as >80 mL of blood loss per cycle. Unlike postpartum hemorrhage, heavy menstrual bleeding is significantly associated with an underlying bleeding disorder. While there is other reproductive tract bleeding in women, notably bleeding at the time of ovulation or with a life-threatening ruptured ectopic pregnancy, the unique bleeding that women experience is predominantly uterine in origin. Many of the unique aspects of uterine hemostasis, however, remain unknown.
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Affiliation(s)
- Andra H James
- Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Duke University Medical Center, Durham, Durham, USA; Division of Hematology, Department of Medicine, Duke University Medical Center, Durham, Durham, USA.
| | - Paula D James
- Departments of Medicine and Pathology & Molecular Medicine, Queen's University, Kingston, Ontario, Canada
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17
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Aiza-Haddad I, Cisneros-Garza LE, Morales-Gutiérrez O, Malé-Velázquez R, Rizo-Robles MT, Alvarado-Reyes R, Barrientos-Quintanilla LA, Betancourt-Sánchez F, Cerda-Reyes E, Contreras-Omaña R, Dehesa-Violante MB, Flores-García NC, Gómez-Almaguer D, Higuera-de la Tijera MF, Lira-Pedrin MA, Lira-Vera JE, Manzano-Cortés H, Meléndez-Mena DE, Muñoz-Ramírez MR, Pérez-Hernández JL, Ramos-Gómez MV, Sánchez-Ávila JF. Guidelines for the management of coagulation disorders in patients with cirrhosis. REVISTA DE GASTROENTEROLOGIA DE MEXICO (ENGLISH) 2024; 89:144-162. [PMID: 38600006 DOI: 10.1016/j.rgmxen.2023.08.008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/22/2023] [Accepted: 08/07/2023] [Indexed: 04/12/2024]
Abstract
Coagulation management in the patient with cirrhosis has undergone a significant transformation since the beginning of this century, with the concept of a rebalancing between procoagulant and anticoagulant factors. The paradigm that patients with cirrhosis have a greater bleeding tendency has changed, as a result of this rebalancing. In addition, it has brought to light the presence of complications related to thrombotic events in this group of patients. These guidelines detail aspects related to pathophysiologic mechanisms that intervene in the maintenance of hemostasis in the patient with cirrhosis, the relevance of portal hypertension, mechanical factors for the development of bleeding, modifications in the hepatic synthesis of coagulation factors, and the changes in the reticuloendothelial system in acute hepatic decompensation and acute-on-chronic liver failure. They address new aspects related to the hemorrhagic complications in patients with cirrhosis, considering the risk for bleeding during diagnostic or therapeutic procedures, as well as the usefulness of different tools for diagnosing coagulation and recommendations on the pharmacologic treatment and blood-product transfusion in the context of hemorrhage. These guidelines also update the knowledge regarding hypercoagulability in the patient with cirrhosis, as well as the efficacy and safety of treatment with the different anticoagulation regimens. Lastly, they provide recommendations on coagulation management in the context of acute-on-chronic liver failure, acute liver decompensation, and specific aspects related to the patient undergoing liver transplantation.
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Affiliation(s)
- I Aiza-Haddad
- Clínica de Enfermedades Hepáticas, Hospital Ángeles Lomas, Mexico City, Mexico.
| | - L E Cisneros-Garza
- Departamento de Gastroenterología y Hepatología, Hospital Christus Muguerza Alta Especialidad, Monterrey, Mexico
| | - O Morales-Gutiérrez
- Departamento de Gastroenterología y Hepatología, Hospital General de México «Dr. Eduardo Liceaga», Mexico City, Mexico
| | | | - M T Rizo-Robles
- Departamento de Gastroenterología y Hepatología, Instituto Mexicano del Seguro Social Centro Médico Nacional «La Raza», Mexico City, Mexico
| | - R Alvarado-Reyes
- Departamento de Hepatología, Hospital San José Tec Salud, Monterrey, Mexico
| | | | | | - E Cerda-Reyes
- Servicio de Gastroenterología, Hospital Central Militar, Mexico City, Mexico
| | - R Contreras-Omaña
- Centro de Investigación en Enfermedades Hepáticas y Gastroenterología (CIEHG) Pachuca, Hidalgo, México
| | | | - N C Flores-García
- Escuela de Medicina y Ciencias de la Salud. Tecnológico de Monterrey, Monterrey Nuevo Leon, México
| | | | - M F Higuera-de la Tijera
- Departamento de Gastroenterología y Hepatología, Hospital General de México «Dr. Eduardo Liceaga», Mexico City, Mexico
| | - M A Lira-Pedrin
- Departamento de Gastroenterología, Endoscopía Digestiva, Motilidad y Hepatología, Centro Médico Corporativo Galeana, Tijuana, México
| | - J E Lira-Vera
- Departamento de Gastroenterología y Hepatología, Hospital General de México «Dr. Eduardo Liceaga», Mexico City, Mexico
| | | | - D E Meléndez-Mena
- Hospital General de Especialidades «Maximino Ávila Camacho», IMSS, UMAE, Puebla, México
| | - M R Muñoz-Ramírez
- Departamento de Hepatología, Hospital San José Tec Salud, Monterrey, Mexico
| | - J L Pérez-Hernández
- Departamento de Gastroenterología y Hepatología, Hospital General de México «Dr. Eduardo Liceaga», Mexico City, Mexico
| | - M V Ramos-Gómez
- Departamento Hepatología, ISSSTE, Centro Médico Nacional «20 de noviembre», Ciudad de México, México
| | - J F Sánchez-Ávila
- Escuela de Medicina y Ciencias de la Salud. Tecnológico de Monterrey, Monterrey Nuevo Leon, México
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18
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Ichikawa J, Iba T, Okazaki R, Fukuda T, Kodaka M, Komori M, Levy JH. Hemostatic capability of ultrafiltrated fresh frozen plasma compared to cryoprecipitate. Sci Rep 2023; 13:21579. [PMID: 38062086 PMCID: PMC10703847 DOI: 10.1038/s41598-023-48759-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2023] [Accepted: 11/30/2023] [Indexed: 12/18/2023] Open
Abstract
This in vitro study evaluated the potential hemostatic effect of fresh frozen plasma (FFP) ultrafiltration on clotting factors, coagulation parameters, and plasma properties. ABO-specific units of FFP (n = 40) were prepared for the concentrated FFP and cryoprecipitate. Plasma water was removed from FFP by ultrafiltration using a dialyzer with a pump running at a 300 mL/min. The aliquot of each concentrated FFP after 50, 100, 200, and 250 mL of fluid removal were measured the standard coagulation assay, clotting activity, and plasma properties to compare those parameters of cryoprecipitate. Concentrated FFP contained 36.5% of fibrinogen in FFP with a mean concentration of 7.2 g/L, lower than the cryoprecipitate level. The levels of factor VIII (FVIII), von Willebrand factor (VWF):antigen (Ag), and VWF:ristocetin cofactor (RCo) were also lower in concentrated FFP, whereas the levels of factor V, factor IX, factor XIII, antithrombin and albumin was higher in concentrated FFP. Maximum clot firmness (MCF) in thromboelastometry was approximately one-half of that in cryoprecipitate. Although the levels of VWF:Ag, VWF:RCo, and FVIII differed depending on the ABO blood types, fibrinogen levels, and MCF were not significantly different among the ABO blood groups in FFP and concentrated FFP.
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Affiliation(s)
- Junko Ichikawa
- Department of Anesthesiology, Tokyo Women's Medical University, Adachi Medical Center, 4-33-1 Kouhoku, Adachi-ku, Tokyo, 123-8858, Japan.
| | - Toshiaki Iba
- Department of Emergency and Disaster Medicine, Juntendo University Graduate School of Medicine, Tokyo, Japan
| | - Ryouta Okazaki
- Department of Anesthesiology, Tokyo Women's Medical University, Adachi Medical Center, 4-33-1 Kouhoku, Adachi-ku, Tokyo, 123-8858, Japan
| | - Tomoki Fukuda
- Department of Anesthesiology, Tokyo Women's Medical University, Adachi Medical Center, 4-33-1 Kouhoku, Adachi-ku, Tokyo, 123-8858, Japan
| | - Mitsuharu Kodaka
- Department of Anesthesiology, Tokyo Women's Medical University, Adachi Medical Center, 4-33-1 Kouhoku, Adachi-ku, Tokyo, 123-8858, Japan
| | - Makiko Komori
- Department of Anesthesiology, Tokyo Women's Medical University, Adachi Medical Center, 4-33-1 Kouhoku, Adachi-ku, Tokyo, 123-8858, Japan
| | - Jerrold H Levy
- Department of Anesthesiology, Critical Care, and Surgery, Duke University School of Medicine, Durham, NC, USA
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19
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Bekheit M, Grundy L, Salih AK, Bucur P, Vibert E, Ghazanfar M. Post-hepatectomy liver failure: A timeline centered review. Hepatobiliary Pancreat Dis Int 2023; 22:554-569. [PMID: 36973111 DOI: 10.1016/j.hbpd.2023.03.001] [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: 04/11/2022] [Accepted: 03/10/2023] [Indexed: 03/29/2023]
Abstract
BACKGROUND Post-hepatectomy liver failure (PHLF) is a leading cause of postoperative mortality after liver surgery. Due to its significant impact, it is imperative to understand the risk stratification and preventative strategies for PHLF. The main objective of this review is to highlight the role of these strategies in a timeline centered way around curative resection. DATA SOURCES This review includes studies on both humans and animals, where they addressed PHLF. A literature search was conducted across the Cochrane Library, Embase, MEDLINE/PubMed, and Web of Knowledge electronic databases for English language studies published between July 1997 and June 2020. Studies presented in other languages were equally considered. The quality of included publications was assessed using Downs and Black's checklist. The results were presented in qualitative summaries owing to the lack of studies qualifying for quantitative analysis. RESULTS This systematic review with 245 studies, provides insight into the current prediction, prevention, diagnosis, and management options for PHLF. This review highlighted that liver volume manipulation is the most frequently studied preventive measure against PHLF in clinical practice, with modest improvement in the treatment strategies over the past decade. CONCLUSIONS Remnant liver volume manipulation is the most consistent preventive measure against PHLF.
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Affiliation(s)
- Mohamed Bekheit
- Department of Surgery, NHS Grampian, Foresterhill Health Campus, Ashgrove Road, AB252ZN Aberdeen, UK; Institute of Medical Sciences, Medical School, Foresterhill Health Campus, Ashgrove Road, AB252ZN Aberdeen, UK; Hépatica, Integrated Center of HPB Care, Elite Hospital, Agriculture Road, Alexandria, Egypt.
| | - Lisa Grundy
- Department of Surgery, NHS Grampian, Foresterhill Health Campus, Ashgrove Road, AB252ZN Aberdeen, UK
| | - Ahmed Ka Salih
- Department of Surgery, NHS Grampian, Foresterhill Health Campus, Ashgrove Road, AB252ZN Aberdeen, UK; Institute of Medical Sciences, Medical School, Foresterhill Health Campus, Ashgrove Road, AB252ZN Aberdeen, UK
| | - Petru Bucur
- Department of Surgery, University Hospital Tours, Val de la Loire 37000, France
| | - Eric Vibert
- Centre Hépatobiliaire, Paul Brousse Hospital, 12 Paul Valliant Couturier, 94804 Villejuif, France
| | - Mudassar Ghazanfar
- Department of Surgery, NHS Grampian, Foresterhill Health Campus, Ashgrove Road, AB252ZN Aberdeen, UK
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20
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Erdoes G, Ahmed A, Kurz SD, Gerber D, Bolliger D. Perioperative hemostatic management of patients with type A aortic dissection. Front Cardiovasc Med 2023; 10:1294505. [PMID: 38054097 PMCID: PMC10694357 DOI: 10.3389/fcvm.2023.1294505] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2023] [Accepted: 11/06/2023] [Indexed: 12/07/2023] Open
Abstract
Coagulopathy is common in patients undergoing thoracic aortic repair for Stanford type A aortic dissection. Non-critical administration of blood products may adversely affect the outcome. It is therefore important to be familiar with the pathologic conditions that lead to coagulopathy in complex cardiac surgery. Adequate care of these patients includes the collection of the medical history regarding the use of antithrombotic and anticoagulant drugs, and a sophisticated diagnosis of the coagulopathy with viscoelastic testing and subsequently adapted coagulation therapy with labile and stable blood products. In addition to the above-mentioned measures, intraoperative blood conservation measures as well as good interdisciplinary coordination and communication contribute to a successful hemostatic management strategy.
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Affiliation(s)
- Gabor Erdoes
- Department of Anesthesiology and Pain Medicine, Inselspital, University Hospital Bern, University of Bern, Bern, Switzerland
| | - Aamer Ahmed
- Consultant Cardiothoracic Anaesthesiologist, Department of Anaesthesia and Critical Care, Glenfield Hospital, University Hospitals of Leicester NHS Trust, Leicester, United Kingdom
| | - Stephan D. Kurz
- Department of Cardiothoracic and Vascular Surgery, Deutsches Herzzentrum der Charité (DHZC), Berlin, Germany
| | - Daniel Gerber
- Department of Anesthesiology and Pain Medicine, Inselspital, University Hospital Bern, University of Bern, Bern, Switzerland
| | - Daniel Bolliger
- Clinic for Anaesthesia, Intermediate Care, Prehospital Emergency Medicine and Pain Therapy, University Hospital Basel, University of Basel, Basel, Switzerland
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21
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Hong C, He Y, Bowen PA, Belcher AM, Olsen BD, Hammond PT. Engineering a Two-Component Hemostat for the Treatment of Internal Bleeding through Wound-Targeted Crosslinking. Adv Healthc Mater 2023; 12:e2202756. [PMID: 37017403 PMCID: PMC10964210 DOI: 10.1002/adhm.202202756] [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: 10/25/2022] [Revised: 03/01/2023] [Indexed: 04/06/2023]
Abstract
Primary hemostasis (platelet plug formation) and secondary hemostasis (fibrin clot formation) are intertwined processes that occur upon vascular injury. Researchers have sought to target wounds by leveraging cues specific to these processes, such as using peptides that bind activated platelets or fibrin. While these materials have shown success in various injury models, they are commonly designed for the purpose of treating solely primary or secondary hemostasis. In this work, a two-component system consisting of a targeting component (azide/GRGDS PEG-PLGA nanoparticles) and a crosslinking component (multifunctional DBCO) is developed to treat internal bleeding. The system leverages increased injury accumulation to achieve crosslinking above a critical concentration, addressing both primary and secondary hemostasis by amplifying platelet recruitment and mitigating plasminolysis for greater clot stability. Nanoparticle aggregation is measured to validate concentration-dependent crosslinking, while a 1:3 azide/GRGDS ratio is found to increase platelet recruitment, decrease clot degradation in hemodiluted environments, and decrease complement activation. Finally, this approach significantly increases survival relative to the particle-only control in a liver resection model. In light of prior successes with the particle-only system, these results emphasize the potential of this technology in aiding hemostasis and the importance of a holistic approach in engineering new treatments for hemorrhage.
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Affiliation(s)
- Celestine Hong
- Department of Chemical EngineeringMassachusetts Institute of TechnologyCambridgeMA02139USA
- Institute for Soldier NanotechnologiesMassachusetts Institute of TechnologyCambridgeMA02139USA
| | - Yanpu He
- Department of Biological EngineeringMassachusetts Institute of TechnologyCambridgeMA02139USA
| | - Porter A. Bowen
- Department of Chemical EngineeringMassachusetts Institute of TechnologyCambridgeMA02139USA
| | - Angela M. Belcher
- Department of Biological EngineeringMassachusetts Institute of TechnologyCambridgeMA02139USA
| | - Bradley D. Olsen
- Department of Chemical EngineeringMassachusetts Institute of TechnologyCambridgeMA02139USA
- Institute for Soldier NanotechnologiesMassachusetts Institute of TechnologyCambridgeMA02139USA
| | - Paula T. Hammond
- Department of Chemical EngineeringMassachusetts Institute of TechnologyCambridgeMA02139USA
- Institute for Soldier NanotechnologiesMassachusetts Institute of TechnologyCambridgeMA02139USA
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22
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Ali-Mohamad N, Cau MF, Zenova V, Baylis JR, Beckett A, McFadden A, Donnellan F, Kastrup CJ. Self-propelling thrombin powder enables hemostasis with no observable recurrent bleeding or thrombosis over 3 days in a porcine model of upper GI bleeding. Gastrointest Endosc 2023; 98:245-248. [PMID: 37061138 DOI: 10.1016/j.gie.2023.04.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/23/2023] [Revised: 03/18/2023] [Accepted: 04/07/2023] [Indexed: 04/17/2023]
Abstract
BACKGROUND AND AIMS Hemostatic powders used to manage upper GI bleeding continue to exhibit high recurrent bleeding rates. Previously, self-propelling thrombin powder (SPTP) sprayed endoscopically managed severe Forrest class 1A bleeding. Here, we evaluate SPTP in a 3-day recovery model of diffuse ulcerated bleeding. METHODS Five anesthetized pigs underwent an endoscopic mucosal snare resection to trigger diffuse ulcer bleeding and were treated with SPTP. The time to hemostasis and the amount of powder delivered were measured. Pigs were recovered and monitored. RESULTS Five pigs achieved hemostasis in 4.5 ± 1.2 minutes At 3 days after the procedure, the pigs were rescoped and showed no recurrent bleeding. Measured blood parameters were not significantly different from baseline. There were no signs of foreign bodies or thromboembolism during gross necropsy and histopathology of key organs. CONCLUSIONS SPTP is a promising novel material that stopped diffuse ulcer bleeding in 5 pigs without recurrent bleeding or adverse local or systemic events.
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Affiliation(s)
| | - Massimo F Cau
- Michael Smith Laboratories; School of Biomedical Engineering
| | | | - James R Baylis
- CoMotion Drug Delivery Systems Inc, Vancouver, British Columbia, Canada
| | - Andrew Beckett
- Royal Canadian Medical Service, Ottawa, Ontario, Canada; Department of Surgery, St Michael's Hospital, University of Toronto, Toronto, Ontario, Canada
| | | | | | - Christian J Kastrup
- Michael Smith Laboratories; Department of Biochemistry and Molecular Biology, University of British Columbia, Vancouver, British Columbia, Canada; Versiti Blood Research Institute, Milwaukee, Wisconsin, USA; Departments of Surgery, Biochemistry, Biomedical Engineering, and Pharmacology and Toxicology, Medical College of Wisconsin, Milwaukee, Wisconsin, USA
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23
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de Lloyd L, Jenkins PV, Bell SF, Mutch NJ, Martins Pereira JF, Badenes PM, James D, Ridgeway A, Cohen L, Roberts T, Field V, Collis RE, Collins PW. Acute obstetric coagulopathy during postpartum hemorrhage is caused by hyperfibrinolysis and dysfibrinogenemia: an observational cohort study. J Thromb Haemost 2023; 21:862-879. [PMID: 36696216 DOI: 10.1016/j.jtha.2022.11.036] [Citation(s) in RCA: 19] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2022] [Revised: 10/21/2022] [Accepted: 11/13/2022] [Indexed: 01/26/2023]
Abstract
BACKGROUND Postpartum hemorrhage (PPH) may be exacerbated by hemostatic impairment. Information about PPH-associated coagulopathy is limited, often resulting in treatment strategies based on data derived from trauma studies. OBJECTIVES To investigate hemostatic changes associated with PPH. PATIENTS/METHODS From a population of 11 279 maternities, 518 (4.6%) women were recruited with PPH ≥ 1000 mL or placental abruption, amniotic fluid embolism, or concealed bleeding. Routine coagulation and viscoelastometric results were collated. Stored plasma samples were used to investigate women with bleeds > 2000 mL or those at increased risk of coagulopathy defined as placenta abruption, amniotic fluid embolism, or need for blood components. Procoagulant factors were assayed and global hemostasis was assessed using thrombin generation. Fibrinolysis was investigated with D-dimer and plasmin/antiplasmin complexes. Dysfibrinogenemia was assessed using the Clauss/antigen ratio. RESULTS At 1000 mL blood loss, Clauss fibrinogen was ≤2 g/L in 2.4% of women and 6/27 (22.2%) cases of abruption. Women with very large bleeds (>3000 mL) had evidence of a dilutional coagulopathy, although hemostatic impairment was uncommon. A subgroup of 12 women (1.06/1000 maternities) had a distinct coagulopathy characterized by massive fibrinolysis (plasmin/antiplasmin > 40 000 ng/mL), increased D-dimer, hypofibrinogenemia, dysfibrinogenemia, reduced factor V and factor VIII, and increased activated protein C, termed acute obstetric coagulopathy. It was associated with fetal or neonatal death in 50% of cases and increased maternal morbidity. CONCLUSIONS Clinically significant hemostatic impairment is uncommon during PPH, but a subgroup of women have a distinct and severe coagulopathy characterized by hyperfibrinolysis, low fibrinogen, and dysfibrinogenemia associated with poor fetal outcomes.
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Affiliation(s)
- Lucy de Lloyd
- Department of Anaesthetics and Pain Control, Cardiff and Vale University Health Board, Heath Park, Cardiff, UK
| | - Peter V Jenkins
- Department of Haematology, Cardiff and Vale University Health Board, Heath Park, Cardiff, UK; Institute of Infection and Immunity, School of Medicine, Cardiff University, UK
| | - Sarah F Bell
- Department of Anaesthetics and Pain Control, Cardiff and Vale University Health Board, Heath Park, Cardiff, UK
| | - Nicola J Mutch
- Aberdeen Cardiovascular and Diabetes Centre, School of Medicine, Medical Sciences and Nutrition, University of Aberdeen, UK
| | | | | | - Donna James
- Department of Obstetrics and Gynaecology, Cardiff and Vale University Health Board, Heath Park, Cardiff, UK
| | - Anouk Ridgeway
- Department of Obstetrics and Gynaecology, Cardiff and Vale University Health Board, Heath Park, Cardiff, UK
| | - Leon Cohen
- Department of Anaesthetics and Pain Control, Cardiff and Vale University Health Board, Heath Park, Cardiff, UK
| | - Thomas Roberts
- Department of Anaesthetics and Pain Control, Cardiff and Vale University Health Board, Heath Park, Cardiff, UK
| | - Victoria Field
- Department of Anaesthetics and Pain Control, Cardiff and Vale University Health Board, Heath Park, Cardiff, UK
| | - Rachel E Collis
- Department of Anaesthetics and Pain Control, Cardiff and Vale University Health Board, Heath Park, Cardiff, UK
| | - Peter W Collins
- Department of Haematology, Cardiff and Vale University Health Board, Heath Park, Cardiff, UK; Institute of Infection and Immunity, School of Medicine, Cardiff University, UK.
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24
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Effect of fibrinogen replacement therapy on bleeding outcomes and 1-year mortality in patients undergoing thoracic aortic surgery: a retrospective cohort study. J Anesth 2023; 37:119-129. [PMID: 36436075 DOI: 10.1007/s00540-022-03140-w] [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: 07/16/2022] [Accepted: 11/14/2022] [Indexed: 11/28/2022]
Abstract
PURPOSE This study aimed to examine the effect of fibrinogen replacement therapy with cryoprecipitate or fibrinogen concentrate on bleeding outcomes and 1-year mortality in patients undergoing thoracic aortic surgery. METHODS We retrospectively studied 439 consecutive patients who underwent thoracic aortic surgery with cardiopulmonary bypass between January 1st, 2010 and December 31st, 2019 and identified patients who received cryoprecipitate or fibrinogen concentrate (the fibrinogen replacement group) and those who did not (the control group). Multivariate analyses were performed to examine the associations of fibrinogen replacement therapy with perioperative major bleeding (i.e., excessive hemorrhage or blood transfusion), re-exploration for bleeding, and 1-year mortality. RESULTS There were 285 patients in the fibrinogen replacement group who received 2.2 ± 1.0 g of concentrated fibrinogen amount and 154 patients in the control group. The incidence of major bleeding in the fibrinogen replacement group was less than that in the control group in patients with fibrinogen level < 150 mg/dL during cardiopulmonary bypass (49.7% versus 74.6%, p = 0.0007, multivariate odds ratio; 0.33, 95% confidence intervals; 0.12-0.91, p = 0.03), but not in patients with fibrinogen level ≥ 150 mg/dL (25.0% versus 29.6%, p = 0.51). No significant difference was found in re-exploration for bleeding (1.0% versus 1.3%, p = 1.00) or 1-year mortality (10.4% versus 5.3%, multivariate Cox proportional-hazard ratio; 1.03, 95% confidence intervals; 0.82-1.31, p = 0.74) between the fibrinogen replacement group and the control group. CONCLUSIONS The results of this study indicate that 2-3 g of fibrinogen replacement reduces the incidence of major bleeding in patients with hypofibrinogenemia during cardiopulmonary bypass in thoracic aortic surgery.
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25
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Devaney GL, Tarrant SM, Weaver N, King KL, Balogh ZJ. Major Pelvic Ring Injuries: Fewer Transfusions Without Deaths from Bleeding During the Last Decade. World J Surg 2023; 47:1136-1143. [PMID: 36648519 PMCID: PMC10070203 DOI: 10.1007/s00268-023-06897-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/14/2022] [Indexed: 01/18/2023]
Abstract
BACKGROUND Pelvic fracture-associated bleeding can be difficult to control with historically high mortality rates. The impact of resuscitation advancements for trauma patients with unstable pelvic ring injuries is unknown. We hypothesized that the time elapsed since introduction of our protocol would be associated with decreased blood transfusion requirements. METHODS A level 1 trauma center's prospective pelvic fracture database was reviewed from 01/01/2009-31/12/2018. All patients with unstable pelvic ring injuries initially presenting to our institution were included. Adjusted regression analysis was performed on the overall cohort and separately for patients in traumatic shock (TS). The primary outcome was 24 h packed red blood cell (PRBC) requirements. Secondary outcomes were 24 h plasma, cryoprecipitate, platelet and intravenous fluid (IVF) requirements, length of stay and mortality. RESULTS Patients with mechanically unstable pelvic ring injuries (n = 144, median [Q1-Q3] age 44 [28-55] years, 74% male) received a median (Q1-Q3) of 0 (0-4) units PRBC within 24 h, with TS patients (n = 47, 42 [28-60] years, 74% male) receiving 6 (4-9) units PRBC. There was no decrease in 24 h PRBC requirements for the overall cohort (years; IRR = 0.91, 95% CI 0.83-1.01; p = 0.07). TS patients had decreases in 24 h PRBC (years; IRR = 0.90, 95%CI 0.84-0.96; p = 0.002), plasma (IRR = 0.92, 95%CI 0.85-0.99; p = 0.019), cryoprecipitate (IRR = 0.88, 95%CI 0.81-0.95; p = 0.001) and IVF (IRR = 0.94, 95%CI 0.90-0.98; p = 0.004). There were 5 deaths (5/144, 3.5%) with no deaths due to acute hemorrhage. CONCLUSIONS Over this 10-year period, there was no hemorrhage-related mortality among patients presenting with pelvic fractures. Crystalloid and transfusion requirements decreased for patients presenting with traumatic shock.
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Affiliation(s)
- Giles L Devaney
- Department of Traumatology, John Hunter Hospital, Lookout Rd, Newcastle, NSW, 2305, Australia
| | - Seth M Tarrant
- Department of Traumatology, John Hunter Hospital, Lookout Rd, Newcastle, NSW, 2305, Australia.,School of Medicine and Public Health, University of Newcastle, Callaghan, NSW, 2308, Australia
| | - Natasha Weaver
- School of Medicine and Public Health, University of Newcastle, Callaghan, NSW, 2308, Australia
| | - Kate L King
- Department of Traumatology, John Hunter Hospital, Lookout Rd, Newcastle, NSW, 2305, Australia.,School of Medicine and Public Health, University of Newcastle, Callaghan, NSW, 2308, Australia
| | - Zsolt J Balogh
- Department of Traumatology, John Hunter Hospital, Lookout Rd, Newcastle, NSW, 2305, Australia. .,School of Medicine and Public Health, University of Newcastle, Callaghan, NSW, 2308, Australia.
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26
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Roman G, Stavik B, Lauritzen KH, Sandset PM, Harrison SP, Sullivan GJ, Chollet ME. "iPSC-derived liver organoids and inherited bleeding disorders: Potential and future perspectives". Front Physiol 2023; 14:1094249. [PMID: 36711019 PMCID: PMC9880334 DOI: 10.3389/fphys.2023.1094249] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2022] [Accepted: 01/02/2023] [Indexed: 01/15/2023] Open
Abstract
The bleeding phenotype of hereditary coagulation disorders is caused by the low or undetectable activity of the proteins involved in hemostasis, due to a broad spectrum of genetic alterations. Most of the affected coagulation factors are produced in the liver. Therefore, two-dimensional (2D) cultures of primary human hepatocytes and recombinant overexpression of the factors in non-human cell lines have been primarily used to mimic disease pathogenesis and as a model for innovative therapeutic strategies. However, neither human nor animal cells fully represent the hepatocellular biology and do not harbor the exact genetic background of the patient. As a result, the inability of the current in vitro models in recapitulating the in vivo situation has limited the studies of these inherited coagulation disorders. Induced Pluripotent Stem Cell (iPSC) technology offers a possible solution to overcome these limitations by reprogramming patient somatic cells into an embryonic-like pluripotent state, thus giving the possibility of generating an unlimited number of liver cells needed for modeling or therapeutic purposes. By combining this potential and the recent advances in the Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/Cas9 technology, it allows for the generation of autologous and gene corrected liver cells in the form of three-dimensional (3D) liver organoids. The organoids recapitulate cellular composition and organization of the liver, providing a more physiological model to study the biology of coagulation proteins and modeling hereditary coagulation disorders. This advanced methodology can pave the way for the development of cell-based therapeutic approaches to treat inherited coagulation disorders. In this review we will explore the use of liver organoids as a state-of-the-art methodology for modeling coagulation factors disorders and the possibilities of using organoid technology to treat the disease.
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Affiliation(s)
- Giacomo Roman
- Department of Hematology, Oslo University Hospital, Oslo, Norway
- Research Institute of Internal Medicine, Oslo University Hospital, Oslo, Norway
- Institute of Clinical Medicine, University of Oslo, Oslo, Norway
| | - Benedicte Stavik
- Department of Hematology, Oslo University Hospital, Oslo, Norway
- Research Institute of Internal Medicine, Oslo University Hospital, Oslo, Norway
| | - Knut H. Lauritzen
- Department of Hematology, Oslo University Hospital, Oslo, Norway
- Research Institute of Internal Medicine, Oslo University Hospital, Oslo, Norway
- Institute of Clinical Medicine, University of Oslo, Oslo, Norway
| | - Per Morten Sandset
- Department of Hematology, Oslo University Hospital, Oslo, Norway
- Research Institute of Internal Medicine, Oslo University Hospital, Oslo, Norway
- Institute of Clinical Medicine, University of Oslo, Oslo, Norway
| | - Sean P. Harrison
- Department of Pediatric Research, Oslo University Hospital, Oslo, Norway
| | - Gareth J. Sullivan
- Department of Pediatric Research, Oslo University Hospital, Oslo, Norway
- Department of Immunology, Institute of Clinical Medicine, University of Oslo, Oslo, Norway
| | - Maria Eugenia Chollet
- Department of Hematology, Oslo University Hospital, Oslo, Norway
- Research Institute of Internal Medicine, Oslo University Hospital, Oslo, Norway
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27
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Caballero M, Sabate A, Gutierrez R, Beltran J, Pérez L, Pujol R, Viguera L, Costa M, Reyes R, Martinez A, Ojinaga G, Leon A, Navarro A, Barquero M, Alonso G, Puig G, Blasi A. Blood component requirements in liver transplantation: effect of 2 thromboelastometry-guided strategies for bolus fibrinogen infusion-the TROMBOFIB randomized trial. JOURNAL OF THROMBOSIS AND HAEMOSTASIS : JTH 2023; 21:37-46. [PMID: 36695394 DOI: 10.1016/j.jtha.2022.10.025] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/12/2022] [Revised: 09/28/2022] [Accepted: 10/18/2022] [Indexed: 01/11/2023]
Abstract
BACKGROUND A low plasma fibrinogen level influences blood component transfusion. Thromboelastometry provides clinical guidance for fibrinogen replacement in liver transplantation (LT). OBJECTIVES We hypothesized that infusions of fibrinogen concentrate to reach an A10FibTem value of 11 mm during LT could reduce red blood cell (RBC) and other component and fluid requirements in comparison to standard care. METHODS This randomized, blinded, multicenter trial in 3 hospitals enrolled 189 LT-scheduled patients allocated to an intervention target (A10FibTem, 11 mm) or a standard target (A10FibTem, 8 mm); 176 patients underwent LT with fibrinogen replacement. Data were analyzed by intention-to-treat (intervention group, 91; control group, 85). Blood was extracted, and fibrinogen kits were prepared to bring each patient's fibrinogen level to the assigned target at the start of LT, after portal vein clamping, and after graft reperfusion. The main outcome was the proportion of patients requiring RBC transfusion during LT or within 24 hours. RESULTS The proportion of patients requiring RBCs did not differ between the groups: intervention, 74.7% (95% CI, 65.5%-83.3%); control, 72.9% (95% CI, 62.2%-82.0%); absolute difference, 1.8% (95% CI, -11.1% to 14.78%) (P = .922). Thrombotic events occurred in 4% of the patients in both groups; reoperation and retransplantation rates and mortality did not differ. Nearly 70% of the patients in both groups required fibrinogen concentrate to reach the target. Using an 11-mm A10FibTem target increased the maximum clot firmness without affecting safety. However, this change provided no clinical benefits. CONCLUSION The similar low plasma fibrinogen concentrations could explain the lack of significant between-group outcomes.
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Affiliation(s)
- Marta Caballero
- Department of Anesthesiology, University Hospital of Bellvitge. University of Barcelona Health Campus, IDIBELL, Barcelona, Spain
| | - Antoni Sabate
- Department of Anesthesiology, University Hospital of Bellvitge. University of Barcelona Health Campus, IDIBELL, Barcelona, Spain.
| | - Rosa Gutierrez
- Department of Anesthesiology, University Hospital of Cruces, Bilbao, Spain
| | - Joan Beltran
- Department of Anesthesiology, Clinic Hospital. University of Barcelona Health Campus, IDIBAPS, Barcelona, Spain
| | - Lourdes Pérez
- Department of Anesthesiology, University Hospital of Bellvitge. University of Barcelona Health Campus, IDIBELL, Barcelona, Spain
| | - Roger Pujol
- Department of Anesthesiology, Clinic Hospital. University of Barcelona Health Campus, IDIBAPS, Barcelona, Spain
| | - Laura Viguera
- Department of Anesthesiology, University Hospital of Bellvitge. University of Barcelona Health Campus, IDIBELL, Barcelona, Spain
| | - Marta Costa
- Department of Anesthesiology, University Hospital of Bellvitge. University of Barcelona Health Campus, IDIBELL, Barcelona, Spain
| | - Raquel Reyes
- Department of Anesthesiology, University Hospital of Bellvitge. University of Barcelona Health Campus, IDIBELL, Barcelona, Spain
| | - Alberto Martinez
- Department of Anesthesiology, University Hospital of Cruces, Bilbao, Spain
| | - Gorka Ojinaga
- Department of Anesthesiology, University Hospital of Cruces, Bilbao, Spain
| | - Ariadna Leon
- Department of Anesthesiology, University Hospital of Bellvitge. University of Barcelona Health Campus, IDIBELL, Barcelona, Spain
| | - Antonio Navarro
- Department of Anesthesiology, University Hospital of Bellvitge. University of Barcelona Health Campus, IDIBELL, Barcelona, Spain
| | - Marta Barquero
- Department of Anesthesiology, University Hospital of Bellvitge. University of Barcelona Health Campus, IDIBELL, Barcelona, Spain
| | - Guillermo Alonso
- Department of Anesthesiology, University Hospital of Bellvitge. University of Barcelona Health Campus, IDIBELL, Barcelona, Spain
| | - Guillermo Puig
- Department of Anesthesiology, University Hospital of Bellvitge. University of Barcelona Health Campus, IDIBELL, Barcelona, Spain
| | - Annabel Blasi
- Department of Anesthesiology, Clinic Hospital. University of Barcelona Health Campus, IDIBAPS, Barcelona, Spain
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28
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Gupta A, Bhandari S, Anand A, Sharma SK, Gautam A, Priyanka KC, Acharya N, Singh S. Management of snake bite during third trimester of pregnancy with coagulopathy and delivery of a live baby in resource-limited setting in Nepal: a case report. Oxf Med Case Reports 2022; 2022:omac105. [PMID: 36299668 PMCID: PMC9589466 DOI: 10.1093/omcr/omac105] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2022] [Revised: 08/20/2022] [Accepted: 08/30/2022] [Indexed: 11/05/2022] Open
Abstract
We reported a case of snakebite in an 18-year-old woman, Gravida 2 Para 1+0 in the third trimester of pregnancy who presented with pain and swelling over the left hand and forearm and vaginal spotting. The laboratory investigations revealed coagulopathy attributed to green pit viper envenomation. On the fourth day of admission, the patient developed sudden abdominal pain and massive per vaginal bleeding with haemorrhagic shock, most likely abruptio placentae. In Nepal, no anti-snake venom has been developed for green pit-viper. So, she was managed conservatively, including blood transfusion, and delivered a single live female baby without any foetal complications. The patient was discharged along with the baby after 8 days of hospitalization. This case demonstrated that vigilant observation and appropriate resuscitation with fluids and blood products could save mother and baby in pit viper envenomation cases in settings where specific anti-snake venom is unavailable.
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Affiliation(s)
| | - Sudeep Bhandari
- Department of Internal Medicine, B. P. Koirala Institute of Health Sciences, Dharan, Nepal
| | - Ayush Anand
- B. P. Koirala Institute of Health Sciences, Dharan, Nepal
| | - Sanjib Kumar Sharma
- Department of Internal Medicine, B. P. Koirala Institute of Health Sciences, Dharan, Nepal
| | - Arun Gautam
- Department of Internal Medicine, B. P. Koirala Institute of Health Sciences, Dharan, Nepal
| | - K C Priyanka
- Department of Internal Medicine, B. P. Koirala Institute of Health Sciences, Dharan, Nepal
| | - Neeraj Acharya
- Department of Internal Medicine, B. P. Koirala Institute of Health Sciences, Dharan, Nepal
| | - Sweta Singh
- B. P. Koirala Institute of Health Sciences, Dharan, Nepal
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29
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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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30
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Zhang T, Feng H, Xiao W, Li J, Liu Q, Feng X, Qi D, Fan X, Shan Y, Yu T, Zhao G, Wang T. Prophylactic administration of tranexamic acid combined with thromboelastography-guided hemostatic algorithm reduces allogeneic transfusion requirements during pediatric resective epilepsy surgery: A randomized controlled trial. Front Pharmacol 2022; 13:916017. [PMID: 36059956 PMCID: PMC9428586 DOI: 10.3389/fphar.2022.916017] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2022] [Accepted: 07/27/2022] [Indexed: 11/25/2022] Open
Abstract
Background: Intraoperative bleeding and allogeneic transfusion remain common problems in pediatric resective epilepsy surgery. Tranexamic acid (TXA) is a widely recommended antifibrinolytic drug that reduces blood loss and transfusion requirements for bleeding patients. Thromboelastography (TEG)-guided hemostatic algorithm is commonly used in bleeding management. This trial was designed to validate the efficacy of a multimodal coagulation therapy involving continuous TXA infusion with TEG-guided hemostatic algorithm in reducing allogeneic exposure risk in pediatric resective epilepsy surgery. Methods: Eighty-three children undergoing resective epilepsy surgery were randomized into a treatment group (Group T; n = 42) and a control group (Group C; n = 41). Group T received prophylactic TXA (10 mg/kg followed by 5 mg/kg/h) with TEG-guided hemostatic algorithm, whereas Group C received conventional coagulation management. The primary outcome was allogeneic transfusion rate during surgery, and the secondary outcomes were intraoperative blood loss, incidence of postoperative seizures, and thromboembolic events during hospitalization. Results: The incidence of intraoperative allogeneic transfusion reduced by 34.7% with the use of a multimodal coagulation therapy (19.0% in Group T vs. 53.7% in Group C; RR 0.355, 95% CI 0.179–0.704; p = 0.001). This was mainly triggered by a significant reduction (44.1%) in intraoperative plasma transfusion (7.1% in Group T vs. 51.2% in Group C; RR 0.139, 95% CI 0.045–0.432; p = 0.000). The risk of intraoperative RBC transfusion was lower in Group T than in Group C, but the difference was not statistically significant (14.3% in Group T vs. 29.3% in Group C; RR 0.488, 95% CI 0.202–1.177; p = 0.098). No platelets were transfused in both groups. Further, 19 (45.2%) patients in Group T received fibrinogen concentrates guided by TEG data, whereas 1 (2.4%) patient in Group C received fibrinogen concentrates empirically. There were no significant differences in estimated blood loss and postoperative seizures between the two groups, and no thromboembolic events were observed after surgery. Conclusion: Prophylactic administration of TXA combined with TEG-guided hemostatic algorithm can be an effective multimodal coagulation strategy for reducing allogeneic transfusion requirements during pediatric resective epilepsy surgery. Clinical Trial Registration:www.chictr.org.cn/index.aspx, identifier ChiCTR1800016188.
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Affiliation(s)
- Ting Zhang
- Department of Anesthesiology, Xuanwu Hospital, Capital Medical University, Beijing, China
| | - Hua Feng
- Department of Anesthesiology, Xuanwu Hospital, Capital Medical University, Beijing, China
| | - Wei Xiao
- Department of Anesthesiology, Xuanwu Hospital, Capital Medical University, Beijing, China
| | - Jingsheng Li
- Department of Anesthesiology, Xuanwu Hospital, Capital Medical University, Beijing, China
| | - Qinghai Liu
- Department of Anesthesiology, Xuanwu Hospital, Capital Medical University, Beijing, China
| | - Xuexin Feng
- Department of Anesthesiology, Xuanwu Hospital, Capital Medical University, Beijing, China
| | - Dezhou Qi
- Department of Anesthesiology, Xuanwu Hospital, Capital Medical University, Beijing, China
| | - Xiaotong Fan
- Department of Neurosurgery, Xuanwu Hospital, Capital Medical University, Beijing, China
| | - Yongzhi Shan
- Department of Neurosurgery, Xuanwu Hospital, Capital Medical University, Beijing, China
| | - Tao Yu
- Department of Functional Neurosurgery, Xuanwu Hospital, Capital Medical University, Beijing, China
| | - Guoguang Zhao
- Department of Neurosurgery, Xuanwu Hospital, Capital Medical University, Beijing, China
| | - Tianlong Wang
- Department of Anesthesiology, Xuanwu Hospital, Capital Medical University, Beijing, China
- *Correspondence: Tianlong Wang,
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31
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Zhao HQ, Serrano K, Culibrk B, Chen Z, Devine DV. Cold-stored platelets are effective in an in vitro model of massive transfusion protocol assessed by rotational thromboelastometry. Transfusion 2022; 62 Suppl 1:S53-S62. [PMID: 35748809 DOI: 10.1111/trf.16974] [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: 11/09/2021] [Revised: 02/09/2022] [Accepted: 02/09/2022] [Indexed: 11/27/2022]
Abstract
BACKGROUND Platelets are a key component of massive transfusion in treating actively bleeding patients. While optimized for prophylactic transfusions, the effectiveness of the current standard room temperature stored platelets (RPs) in treating actively bleeding patients is not clear. Cold-stored platelets (CPs) have been shown to have superior hemostatic functions and the potential to extend shelf life. In this study, we explored the effect of using CPs versus RPs in an in vitro transfusion model based on the massive transfusion protocol. STUDY DESIGN AND METHODS RPs or CPs were combined with RBCs and plasma in a 1:1:1 volume ratio to make transfusion packages. Whole blood was collected and then either diluted to 20% hematocrit or mixed with tPA (8.8 μg/ml). By volume, 70% of transfusion package was mixed with 30% whole blood to simulate massive transfusions and analyzed by rotational thromboelastometry. Transfusion package supernatant was analyzed for PAI-1 activity as well. RESULTS Both transfusion packages restored the clot characteristics of hemodiluted or hyperfibrinolytic whole blood. Specifically, only transfusion packages made with CPs significantly reduced the maximum clot lysis of hyperfibrinolytic whole blood. PAI-1 activity in CPs transfusion packages were also significantly higher. DISCUSSION Transfusion packages containing cold-stored platelets may be able to restore the blood hemostatic profile of bleeding patients. In addition, transfusion packages made from CPs may provide additional benefit of resisting hyperfibrinolysis in bleeding patients. In trauma where post-transfusion platelet recovery is less of a concern, CPs are a viable option to restore hemostasis.
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Affiliation(s)
- Han Qi Zhao
- Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada.,Centre for Blood Research, University of British Columbia, Vancouver, British Columbia, Canada.,Centre for Innovation, Canadian Blood Services, Vancouver, British Columbia, Canada
| | - Katherine Serrano
- Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada.,Centre for Blood Research, University of British Columbia, Vancouver, British Columbia, Canada.,Centre for Innovation, Canadian Blood Services, Vancouver, British Columbia, Canada
| | - Brankica Culibrk
- Centre for Innovation, Canadian Blood Services, Vancouver, British Columbia, Canada
| | - Zhongming Chen
- Centre for Innovation, Canadian Blood Services, Vancouver, British Columbia, Canada
| | - Dana V Devine
- Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada.,Centre for Blood Research, University of British Columbia, Vancouver, British Columbia, Canada.,Centre for Innovation, Canadian Blood Services, Vancouver, British Columbia, Canada
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32
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Soule EE, Yu H, Olson L, Naqvi I, Kumar S, Krishnaswamy S, Sullenger BA. Generation of an anticoagulant aptamer that targets factor V/Va and disrupts the FVa-membrane interaction in normal and COVID-19 patient samples. Cell Chem Biol 2022; 29:215-225.e5. [PMID: 35114109 PMCID: PMC8808741 DOI: 10.1016/j.chembiol.2022.01.009] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2021] [Revised: 11/11/2021] [Accepted: 01/11/2022] [Indexed: 11/29/2022]
Abstract
Coagulation cofactors profoundly regulate hemostasis and are appealing targets for anticoagulants. However, targeting such proteins has been challenging because they lack an active site. To address this, we isolate an RNA aptamer termed T18.3 that binds to both factor V (FV) and FVa with nanomolar affinity and demonstrates clinically relevant anticoagulant activity in both plasma and whole blood. The aptamer also shows synergy with low molecular weight heparin and delivers potent anticoagulation in plasma collected from patients with coronavirus disease 2019 (COVID-19). Moreover, the aptamer's anticoagulant activity can be rapidly and efficiently reversed using protamine sulfate, which potentially allows fine-tuning of aptamer's activity post-administration. We further show that the aptamer achieves its anticoagulant activity by abrogating FV/FVa interactions with phospholipid membranes. Our success in generating an anticoagulant aptamer targeting FV/Va demonstrates the feasibility of using cofactor-binding aptamers as therapeutic protein inhibitors and reveals an unconventional working mechanism of an aptamer by interrupting protein-membrane interactions.
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Affiliation(s)
- Erin E. Soule
- Department of Pharmacology & Cancer Biology, Duke University, Durham, NC 27710, USA,Department of Surgery, Duke University Medical Center, Durham, NC 27710, USA
| | - Haixiang Yu
- Department of Surgery, Duke University Medical Center, Durham, NC 27710, USA
| | - Lyra Olson
- Department of Pharmacology & Cancer Biology, Duke University, Durham, NC 27710, USA,Department of Surgery, Duke University Medical Center, Durham, NC 27710, USA
| | - Ibtehaj Naqvi
- Department of Surgery, Duke University Medical Center, Durham, NC 27710, USA
| | - Shekhar Kumar
- The Children’s Hospital of Philadelphia, Division of Hematology, Department of Pediatrics, The University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA 19104, USA
| | - Sriram Krishnaswamy
- The Children’s Hospital of Philadelphia, Division of Hematology, Department of Pediatrics, The University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA 19104, USA
| | - Bruce A. Sullenger
- Department of Pharmacology & Cancer Biology, Duke University, Durham, NC 27710, USA,Department of Surgery, Duke University Medical Center, Durham, NC 27710, USA,Corresponding author
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33
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James AH, Federspiel JJ, Ahmadzia HK. Disparities in obstetric hemorrhage outcomes. Res Pract Thromb Haemost 2022; 6:e12656. [PMID: 35146237 PMCID: PMC8818495 DOI: 10.1002/rth2.12656] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2021] [Revised: 11/02/2021] [Accepted: 11/07/2021] [Indexed: 11/07/2022] Open
Abstract
Both the maternal and fetal outcomes of pregnancy vary greatly according to a pregnant woman’s community and her condition. The most devastating outcome is the death of a mother. In 2017, there were ≈295,000 maternal deaths globally with dramatic differences in maternal mortality based on geographic region, country, and women’s underlying conditions. Worldwide, the leading cause of maternal death is hemorrhage, comprising 94% of maternal deaths, with most cases occurring in low‐ or middle‐income countries. Whether a hemorrhage originates from inside the uterus (80%‐90%), from lacerations or incisions (10%‐20%), or from an underlying coagulopathy (<1%), an acute acquired coagulopathy will evolve unless the hemorrhage is controlled. In low‐ or middle‐income countries, the full range of resources to control hemorrhage is not available, but besides the usual obstetric measures, blood availability, hemostatic medication, and hematologic expertise are necessary to save mothers’ lives. Hemostasis and thrombosis experts can address the disparities in obstetric hemorrhage outcomes not only as providers but as consultants, researchers, and advocates.
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Affiliation(s)
- Andra H. James
- Department of Obstetrics and Gynecology Division of Maternal‐Fetal Medicine Duke University Durham North Carolina USA
| | - Jerome J. Federspiel
- Department of Obstetrics and Gynecology Division of Maternal‐Fetal Medicine Duke University Durham North Carolina USA
| | - Homa K. Ahmadzia
- Department of Obstetrics and Gynecology Division of Maternal‐Fetal Medicine The George Washington University Washington District of Columbia USA
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34
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Hayes SB, Munlemvo DM, Gillis HC, Tobias JD. Craniotomy Complicated by Severe Metabolic Acidosis Requiring Massive Transfusion in an Infant on Ketogenic Diet Therapy for Intractable Epilepsy. Int Med Case Rep J 2022; 15:47-54. [PMID: 35210870 PMCID: PMC8857972 DOI: 10.2147/imcrj.s349974] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2021] [Accepted: 01/25/2022] [Indexed: 11/23/2022] Open
Abstract
The induction of a ketotic state through dietary manipulation, known as the ketogenic diet (KD), is an alternative or supplementary treatment to drug-resistant epilepsy. By sustaining a ketogenic state, the KD results in various biological adaptations which contribute to its success as an anti-seizure therapy. While the induction and maintenance of ketosis generally results in only a low-grade metabolic acidosis, various exogenous stresses such as surgery and anesthetic care may disrupt homeostasis resulting in exaggerated ketosis and severe metabolic acidosis. Metabolic acidosis may have significant effects on various physiologic functions including cardiovascular performance, coagulation function, and electrolyte balance. We present a 7-month-old patient receiving a KD who presented for craniotomy and resection of an epileptogenic focus. During intraoperative care, progressive acidosis and hyperchloremia were noted with ongoing tissue fragility and hyperemia, parenchymal friability, and coagulopathy. Though the acidosis was temporarily blunted by administration of sodium bicarbonate and a change to sodium acetate containing fluids, ultimately poor hemostasis resulted requiring significant blood product transfusion. The metabolic effects of the KD are reviewed with emphasis on acid-base disturbances and impact on coagulation function.
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Affiliation(s)
- Seth B Hayes
- Department of Anesthesiology & Pain Medicine, Nationwide Children’s Hospital, Columbus, OH, USA
- Department of Anesthesiology & Pain Medicine, The Ohio State University College of Medicine, Columbus, OH, USA
- Correspondence: Seth B Hayes, Department of Anesthesiology & Pain Medicine, Nationwide Children’s Hospital, 700 Children’s Drive, Columbus, OH, 43205, USA, Tel +1 614 722-4200, Fax +1 614 722-4203, Email
| | - Dolly M Munlemvo
- Department of Anesthesiology & Pain Medicine, Nationwide Children’s Hospital, Columbus, OH, USA
| | - Holly C Gillis
- Department of Anesthesiology & Pain Medicine, Nationwide Children’s Hospital, Columbus, OH, USA
- Department of Anesthesiology & Pain Medicine, The Ohio State University College of Medicine, Columbus, OH, USA
| | - Joseph D Tobias
- Department of Anesthesiology & Pain Medicine, Nationwide Children’s Hospital, Columbus, OH, USA
- Department of Anesthesiology & Pain Medicine, The Ohio State University College of Medicine, Columbus, OH, USA
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35
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Tucker C, Winner A, Reeves R, Cooper ES, Hall K, Schildt J, Brown D, Guillaumin J. Resuscitation Patterns and Massive Transfusion for the Critical Bleeding Dog-A Multicentric Retrospective Study of 69 Cases (2007-2013). Front Vet Sci 2022; 8:788226. [PMID: 35071385 PMCID: PMC8766795 DOI: 10.3389/fvets.2021.788226] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2021] [Accepted: 11/17/2021] [Indexed: 11/13/2022] Open
Abstract
Objective: To describe resuscitation patterns of critically bleeding dogs, including those receiving massive transfusion (MT). Design: Retrospective study from three universities (2007-2013). Animals: Critically bleeding dogs, defined as dogs who received ≥ 25 ml/kg of blood products for treatment of hemorrhagic shock caused by blood loss. Measurements and Main Results: Sixty-nine dogs were included. Sources of critical bleeding were trauma (26.1%), intra/perioperative surgical period (26.1%), miscellaneous (24.6%), and spontaneous hemoabdomen (23.1%). Median (range) age was 7 years (0.5-18). Median body weight was 20 kg (2.6-57). Median pre-transfusion hematocrit, total protein, systolic blood pressure, and lactate were 25% (10-63), 4.1 g/dl (2-7.1), 80 mm Hg (20-181), and 6.4 mmol/L (1.1-18.2), respectively. Median blood product volume administered was 44 ml/kg (25-137.4). Median plasma to red blood cell ratio was 0.8 (0-4), and median non-blood product resuscitation fluid to blood product ratio was 0.5 (0-3.6). MT was given to 47.8% of dogs. Survival rate was 40.6%. The estimated odds of survival were higher by a factor of 1.8 (95% CI: 1.174, 3.094) for a dog with 1 g/dl higher total protein above reference interval and were lower by a factor of 0.6 (95% CI: 0.340, 0.915) per 100% prolongation of partial thromboplastin time above the reference interval. No predictors of MT were identified. Conclusions: Critical bleeding in dogs was associated with a wide range of resuscitation patterns and carries a guarded to poor prognosis.
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Affiliation(s)
- Claire Tucker
- Department of Clinical Sciences, Colorado State University, Fort Collins, CO, United States.,TetraMed, Fort Collins, CO, United States
| | - Anna Winner
- Department of Clinical Sciences, Colorado State University, Fort Collins, CO, United States
| | - Ryan Reeves
- Department of Clinical Sciences, Colorado State University, Fort Collins, CO, United States
| | - Edward S Cooper
- Department of Clinical Sciences, The Ohio State University, Columbus, OH, United States
| | - Kelly Hall
- Department of Clinical Sciences, Colorado State University, Fort Collins, CO, United States.,TetraMed, Fort Collins, CO, United States
| | - Julie Schildt
- Department of Clinical Sciences, The University of Tennessee, Knoxville, Knoxville, TN, United States
| | - David Brown
- Department of Statistics, Colorado State University, Fort Collins, CO, United States
| | - Julien Guillaumin
- Department of Clinical Sciences, Colorado State University, Fort Collins, CO, United States.,TetraMed, Fort Collins, CO, United States
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36
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Hemostatic Analysis of Simulated Gloydius ussuriensis Envenomation Using Canine Blood: A Comparison of Thromboelastography and Classical Coagulation Tests. Animals (Basel) 2022; 12:ani12030226. [PMID: 35158550 PMCID: PMC8833665 DOI: 10.3390/ani12030226] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2021] [Revised: 01/10/2022] [Accepted: 01/17/2022] [Indexed: 12/28/2022] Open
Abstract
Snake envenomation may lead to venom-induced consumptive coagulopathy (VICC), usually diagnosed by classical coagulation tests (CCTs), such as prothrombin time (PT) and activated partial thromboplastin time (aPTT). However, the results of CCTs are frequently normal in the initial stages, which may delay anti-venom treatments. Thromboelastography (TEG) is a point-of-care and real-time diagnostic tool that enables a comprehensive assessment of the coagulation process. This in vitro study aimed to determine concentration-dependent changes in canine blood caused by Gloydius ussuriensis (G. ussuriensis) envenomation using TEG and CCTs. Lyophilized G. ussuriensis venom was reconstructed using mouse intravenous lethal dose 50 (LD50iv) and serially diluted to 25% LD50iv, 50% LD50iv, and 75% LD50iv to reproduce VICC at different concentrations. Normal saline was used for the control. We compared TEG values of the reaction time (R), kinetic time (K), rate of clot formation (α-angle), maximum amplitude (MA), fibrinolysis at 30 min (LY30), and global strength of the clot (G) with those of PT, aPTT, fibrinogen, and platelet counts (PLTs). Most TEG parameters, except R and LY30, demonstrated statistically significant changes compared with the control at all concentrations. CCTs, except PLTs, revealed significant changes at ≥50% LD50iv. Thus, TEG could be a useful diagnostic strategy for early VICC and preventing treatment delay.
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37
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David JS, Lambert A, Taverna XJ, Incagnoli P, Geay-Baillat MO, Vassal O, Friggeri A, Inaba K. Which injured patients with moderate fibrinogen deficit need fibrinogen supplementation? Scand J Trauma Resusc Emerg Med 2021; 29:174. [PMID: 34952618 PMCID: PMC8709958 DOI: 10.1186/s13049-021-00988-x] [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: 09/03/2021] [Accepted: 12/13/2021] [Indexed: 11/10/2022] Open
Abstract
Background In severely injured patients, fibrinogen supplementation is recommended when fibrinogenemia is < 1.5 g L−1, but some teams have suggested to use higher thresholds (fibrinogenemia < 2.0 g L−1 or FIBTEM clot amplitude at 5 min (A5) values < 11 mm). The goal of this study was to specify in patients with a moderate fibrinogen deficit (MFD) whether some admission characteristics would be associated with fibrinogen administration at 24 h. Methods Prospective analysis of retrospectively collected data from a trauma registry (01/2011–12/2019). MFD-C was defined by a fibrinogenemia 1.51–1.99 g L−1 or the corresponding FIBTEM-A5 values (MFD-A5) that were determined from linear regression and ROC curve analysis. Administration of fibrinogen were described according to the following admission parameters: shock index (SI) > 1, hemoglobin level < 110 g L−1 (HemoCue®), and base deficit > 5 mEq L−1. Data are expressed as count (%), median [IQR]. Results 1076 patients were included in the study and 266 (27%) had MFD-C, among them, 122/266 (46%) received fibrinogen. Patients with MFD-C who received fibrinogen were more severely injured (ISS: 27 [19–36] vs. 24 [17–29]) and had more impaired vital signs (base deficit: 5.4 [3.6–7.8] vs. 3.8 [2.0–6.0]). Linear regression analysis found a positive correlation between fibrinogen level and FIBTEM-A5 (r: 0.805). For a fibrinogen level < 1.5 g L−1 and < 2.0 g L−1, FIBTEM-A5 thresholds were 6 mm (sensitivity 85%, specificity 83%, AUC: 0.934) and 9 mm (sensitivity 84%, specificity 69%, AUC: 0.874), respectively. MFD-A5 values (185 (27%) patients) were defined as a FIBTEM-A5 between 7 and 9 mm. More than 50% of MFD-C patients presenting a SI > 1, a hemoglobin level < 110 g L−1, or a base deficit > 5.0 mEq L−1 received fibrinogen. The relative risk [95% CI] for fibrinogen administration (SI > 1) were 1.39 [1.06–1.82] for MFD-C, and 2.17 [1.48–3.19] for MFD-A5. Results were not modified after adjustment on the ISS. Conclusions We have shown in this study an association between shock parameters and fibrinogen administration. Further studies are needed to determine how these parameters may be used to guide fibrinogen administration in trauma patients with MFD.
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Affiliation(s)
- Jean-Stephane David
- Service d'anesthésie-réanimation, Centre Hospitalier Lyon Sud, Hospices Civils de Lyon, 69495, Pierre Benite, France. .,Faculté de Médecine Lyon Est, Université Claude Bernard Lyon 1, Lyon, France. .,Research on Healthcare Performance (RESHAPE), INSERM U1290, Université Claude Bernard Lyon 1, Lyon, France. .,Service d'Anesthésie Réanimation, Centre Hospitalier Lyon Sud, 69495, Pierre Bénite cedex, France.
| | - Aline Lambert
- Service d'anesthésie-réanimation, Centre Hospitalier Lyon Sud, Hospices Civils de Lyon, 69495, Pierre Benite, France.,Faculté de Médecine Lyon Est, Université Claude Bernard Lyon 1, Lyon, France
| | - Xavier-Jean Taverna
- Service d'anesthésie-réanimation, Hôpital Edouard Herriot, Hospices Civils de Lyon, 69008, Lyon, France
| | - Pascal Incagnoli
- Service des Urgences - SAMU, Hôpital Universitaire de Dijon, Dijon, France
| | - Marie-Odile Geay-Baillat
- Laboratoire d'Hémostase, Hôpital Lyon Sud, Hospices Civils de Lyon, 69495, Pierre Benite, France
| | - Olivia Vassal
- Service d'anesthésie-réanimation, Centre Hospitalier Lyon Sud, Hospices Civils de Lyon, 69495, Pierre Benite, France.,Faculté de Médecine Lyon Est, Université Claude Bernard Lyon 1, Lyon, France
| | - Arnaud Friggeri
- Service d'anesthésie-réanimation, Centre Hospitalier Lyon Sud, Hospices Civils de Lyon, 69495, Pierre Benite, France.,Faculté de Médecine Lyon Est, Université Claude Bernard Lyon 1, Lyon, France
| | - Kenji Inaba
- Division of Trauma and Critical Care, Department of Surgery, LAC + USC Medical Center, University of Southern California, Los Angeles, CA, USA
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38
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Hofer S, Schlimp CJ, Casu S, Grouzi E. Management of Coagulopathy in Bleeding Patients. J Clin Med 2021; 11:jcm11010001. [PMID: 35011742 PMCID: PMC8745606 DOI: 10.3390/jcm11010001] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2021] [Revised: 12/10/2021] [Accepted: 12/14/2021] [Indexed: 02/06/2023] Open
Abstract
Early recognition of coagulopathy is necessary for its prompt correction and successful management. Novel approaches, such as point-of-care testing (POC) and administration of coagulation factor concentrates (CFCs), aim to tailor the haemostatic therapy to each patient and thus reduce the risks of over- or under-transfusion. CFCs are an effective alternative to ratio-based transfusion therapies for the correction of different types of coagulopathies. In case of major bleeding or urgent surgery in patients treated with vitamin K antagonist anticoagulants, prothrombin complex concentrate (PCC) can effectively reverse the effects of the anticoagulant drug. Evidence for PCC effectiveness in the treatment of direct oral anticoagulants-associated bleeding is also increasing and PCC is recommended in guidelines as an alternative to specific reversal agents. In trauma-induced coagulopathy, fibrinogen concentrate is the preferred first-line treatment for hypofibrinogenaemia. Goal-directed coagulation management algorithms based on POC results provide guidance on how to adjust the treatment to the needs of the patient. When POC is not available, concentrate-based management can be guided by other parameters, such as blood gas analysis, thus providing an important alternative. Overall, tailored haemostatic therapies offer a more targeted approach to increase the concentration of coagulation factors in bleeding patients than traditional transfusion protocols.
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Affiliation(s)
- Stefan Hofer
- Department of Anaesthesiology, Westpfalz-Klinikum Kaiserslautern, 67655 Kaiserlautern, Germany
- Correspondence: ; Tel.: +49-631-203-1030
| | - Christoph J. Schlimp
- Department of Anaesthesiology and Intensive Care, AUVA Trauma Hospital Linz, 4010 Linz, Austria;
- Ludwig Boltzmann Institute for Experimental and Clinical Traumatology, AUVA Research Center, 1200 Vienna, Austria
| | - Sebastian Casu
- Emergency Department, Asklepios Hospital Wandsbek, 22043 Hamburg, Germany;
| | - Elisavet Grouzi
- Transfusion Service and Clinical Hemostasis, Saint Savvas Oncology Hospital, 115 22 Athens, Greece;
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39
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Abstract
Fibrinogen plays a fundamental role in coagulation through its support for platelet aggregation and its conversion to fibrin. Fibrin stabilizes clots and serves as a scaffold and immune effector before being broken down by the fibrinolytic system. Given its importance, abnormalities in fibrin(ogen) and fibrinolysis result in a variety of disorders with hemorrhagic and thrombotic manifestations. This review summarizes (i) the basic elements of fibrin(ogen) and its role in coagulation and the fibrinolytic system; (ii) the laboratory evaluation for fibrin(ogen) disorders, including the use of global fibrinolysis assays; and (iii) the management of congenital and acquired disorders of fibrinogen and fibrinolysis.
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Affiliation(s)
- Jori E May
- Division of Hematology/Oncology, University of Alabama at Birmingham, 1720 2nd Avenue South, NP 2503, Birmingham, AL 35294, USA
| | - Alisa S Wolberg
- UNC Department of Pathology and Laboratory Medicine, UNC Blood Research Center, 8018A Mary Ellen Jones Building, CB7035, Chapel Hill, NC 27599-7035, USA
| | - Ming Yeong Lim
- Department of Internal Medicine, Division of Hematology and Hematologic Malignancies, University of Utah, 2000 Circle Hope Drive, Room 4126, Salt Lake City, UT 84112, USA.
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40
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Abstract
Abstract
Purpose of Review
This narrative review focuses on aging-related modifications in coagulation resulting in increased thromboembolic and hemorrhagic risk of the elderly. We further discuss the current evidence and emerging data relating the perioperative treatment of elderly patients with antithrombotic therapy.
Recent Findings
Relevant changes in all elements of the Virchow’s triad can be found with aging. Increased blood stasis due to immobility, progressive endothelial dysfunction with altered microcirculation, elevated concentrations of several coagulation factors, and increased platelet reactivity all lead to a procoagulant state. Elderly people are, therefore, commonly treated with oral anticoagulation and antiplatelet drugs. This antithrombotic therapy might be essentially causative for their increased bleeding risk.
Summary
Elderly patients are at increased risk for thromboembolism due to changes in the hemostatic system in combination with frailty and multimorbidity. Both the thromboembolic due to aging and bleeding risk due to antithrombotic therapy need special attention in the elderly surgical patients.
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41
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Tanaka KA, Shettar S, Vandyck K, Shea SM, Abuelkasem E. Roles of Four-Factor Prothrombin Complex Concentrate in the Management of Critical Bleeding. Transfus Med Rev 2021; 35:96-103. [PMID: 34551881 DOI: 10.1016/j.tmrv.2021.06.007] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2021] [Accepted: 06/27/2021] [Indexed: 12/19/2022]
Abstract
Four-factor prothrombin complex concentrate (4F-PCC) is the term used to describe a pathogen-reduced, lyophilized concentrate that contains therapeutic amounts of at least 4 coagulation factors: Factor II (FII), Factor VII (FVII), Factor IX (FIX), and Factor X (FX). 4F-PCC has proven to be an effective hemostatic agent compared to plasma transfusion in several prospective randomized trials in acute warfarin reversal. In recent years, 4F-PCC has been used in various acquired coagulopathies including post-cardiopulmonary bypass bleeding, trauma-induced coagulopathy, coagulopathy in liver failure, and major bleeding due to anti-FXa (anti-Xa) inhibitors (eg, rivaroxaban and apixaban). As transfusion of frozen plasma (FP) has not been found efficacious in the above critical bleeding scenarios, there is increasing interest in expanding the use of 4F-PCC. However, efficacy, safety, and clinical implications of expanded use of 4F-PCC have not been fully elucidated. Prothrombin time and international normalized ratio are commonly used to assess dose effects of 4F-PCC. Prothrombin time/international normalized ratio are standardly use for warfarin titration, but they are not suited for real-time monitoring of complex coagulopathies. Optimal dosing of 4F-PCC outside of the current approved use for vitamin K antagonist reversal is yet to be determined. In this review, we will discuss the use of 4F-PCC in four critical bleeding settings: cardiac surgery, major trauma, end-stage liver disease, and oral anti-Xa reversal. We will discuss recent studies in each area to explore the dosing, efficacy, and safety of 4F-PCC.
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Affiliation(s)
- Kenichi A Tanaka
- Department of Anesthesiology, University of Oklahoma College of Medicine, Oklahoma City, OK, USA.
| | - Shashank Shettar
- Department of Anesthesiology, University of Oklahoma College of Medicine, Oklahoma City, OK, USA
| | - Kofi Vandyck
- Department of Anesthesiology, University of Oklahoma College of Medicine, Oklahoma City, OK, USA
| | - Susan M Shea
- Department of Surgery, University of Pittsburgh, Pittsburgh, PA, USA
| | - Ezeldeen Abuelkasem
- Department of Anesthesiology and Perioperative Medicine, University of Pittsburgh, Pittsburgh, PA, USA
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Effect of Intra- and Post-Operative Fluid and Blood Volume on Postoperative Pulmonary Edema in Patients with Intraoperative Massive Bleeding. J Clin Med 2021; 10:jcm10184224. [PMID: 34575335 PMCID: PMC8467689 DOI: 10.3390/jcm10184224] [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: 08/06/2021] [Revised: 09/03/2021] [Accepted: 09/15/2021] [Indexed: 11/30/2022] Open
Abstract
In patients with intraoperative massive bleeding, the effects of fluid and blood volume on postoperative pulmonary edema are uncertain. Patients with intraoperative massive bleeding who had undergone a non-cardiac surgery in five hospitals were enrolled in this study. We evaluated the association of postoperative pulmonary edema risk and intra- and post-operatively administered fluid and blood volumes in patients with intraoperative massive bleeding. In total, 2090 patients were included in the postoperative pulmonary edema analysis, and 300 patients developed pulmonary edema within 72 h of the surgery. The postoperative pulmonary edema with hypoxemia analysis included 1660 patients, and the condition occurred in 161 patients. An increase in the amount of red blood cells transfused per hour after surgery increased the risk of pulmonary edema (hazard ratio: 1.03; 95% confidence interval: 1.01–1.05; p = 0.013) and the risk of pulmonary edema with hypoxemia (hazard ratio: 1.04; 95% confidence interval: 1.01–1.07; p = 0.024). An increase in the red blood cells transfused per hour after surgery increased the risk of developing pulmonary edema. This increase can be considered as a risk factor for pulmonary edema.
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Goals for Collaborative Management of Obstetric Hemorrhage. Obstet Gynecol Clin North Am 2021; 48:151-171. [PMID: 33573784 DOI: 10.1016/j.ogc.2020.11.001] [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: 11/21/2022]
Abstract
Hemorrhage remains a leading cause of preventable maternal morbidity and mortality worldwide and in the United States. Postpartum hemorrhage is the number one cause of severe morbidity during hospitalization for birth, despite hospital, state, and national initiatives. In addition, studies show that more than 90% of maternal deaths related to obstetric hemorrhage are preventable. This article reviews relevant physiologic changes of pregnancy that may have an impact on hemorrhage management and describes collaborative approaches for management of hemorrhage in this unique population.
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Yoh N, Sisti J, Connolly ES, Chang TR, Roh D. Can We Utilize Whole Blood Viscoelastic Coagulation Assays to Better Identify and Treat Coagulopathy in Patients With Intracerebral Hemorrhage? World Neurosurg 2021; 147:217-219. [PMID: 33685002 DOI: 10.1016/j.wneu.2021.01.107] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/19/2022]
Affiliation(s)
- Nina Yoh
- Department of Neurological Surgery, Columbia University, New York, New York, USA
| | - Jonathan Sisti
- Department of Neurological Surgery, Columbia University, New York, New York, USA
| | - E Sander Connolly
- Department of Neurological Surgery, Columbia University, New York, New York, USA
| | - Tiffany R Chang
- Department of Neurosurgery, McGovern Medical School at UTHealth, Houston, Texas, USA
| | - David Roh
- Department of Neurology, Columbia University, New York, New York, USA.
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Gilbert BW, Ott MJ, Philip GJ. Thromboelastography utilization for dabigatran reversal in a patient with acute kidney injury. Am J Health Syst Pharm 2021; 78:1382-1384. [PMID: 33895798 DOI: 10.1093/ajhp/zxab182] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/14/2022] Open
Abstract
PURPOSE This case report describes utilization of thromboelastography (TEG) in the setting of an acute major bleed in a patient on dabigatran who had concomitant acute kidney injury. SUMMARY An 80-year-old female presented to the emergency department after a fall with complaints of pain in her knee, shoulder, and hip. Her medical history was significant for coronary artery disease, for which she took clopidogrel 75 mg daily, and atrial fibrillation, for which she took dabigatran 150 mg twice daily. The physical exam was remarkable for pain within the shoulder, hip, and knee, which had swelling and ecchymosis that extended into the right thigh. Given the possibility of compartment syndrome with multiple possible etiologies of coagulopathy, TEG and computed tomography angiography (CTa) of the right lower extremity were performed. The initial TEG showed prolonged R time and activated clotting time, indicating clotting factor dysfunction with no additional coagulopathy noted, including antiplatelet effects. On the basis of the TEG and CTa findings, it was decided to reverse dabigatran with 5 grams of idarucizumab. Approximately 1 hour after administration of idarucizumab, the patient was taken to interventional radiology where a limited angiogram of the right lower extremity showed no active extravasation. Because of the patient's renal dysfunction and the possibility of rebound hypercoaguability, repeat TEG tests were ordered at 4 and 8 hours after the initial reversal to ensure clearance of idarucizumab-dabigatran complexes. The repeat TEG values showed complete reversal of the initial coagulopathy noted. During the admission, the patient required no blood transfusions or surgical interventions and all her initial laboratory results improved. CONCLUSION Serial TEG testing was successful at managing multiple coagulopathies in a patient at risk for trauma-induced compartment syndrome.
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Affiliation(s)
- Brian W Gilbert
- Department of Pharmacy, Wesley Medical Center, Wichita, KS, USA
| | - M Jacob Ott
- Department of Emergency Medicine, Wesley Medical Center, Wichita, KS, USA
| | - George J Philip
- Acute Care Trauma & Surgery, Wesley Medical Center, Wichita, KS, USA
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Colomina MJ, Méndez E, Sabate A. Altered Fibrinolysis during and after Surgery. Semin Thromb Hemost 2021; 47:512-519. [PMID: 33878781 DOI: 10.1055/s-0041-1722971] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
Abstract
Major surgery induces hemostatic changes related to surgical stress, tissue destruction, and inflammatory reactions. These changes involve a shift of volume from extravascular space to intravascular and interstitial spaces, a "physiologic" hemodilution of coagulation proteins, and an increase of plasmatic fibrinogen concentration and platelets. Increases in fibrinogen and platelets together with a simultaneous dilution of pro- and anticoagulant factors and development of a hypofibrinolytic status result in a postoperative hypercoagulable state. This profile is accentuated in more extensive surgery, but the balance can shift toward hemorrhagic tendency in specific types of surgeries, for example, in prolonged cardiopulmonary bypass or in patients with comorbidities, especially liver diseases, sepsis, and hematological disorders. Also, acquired coagulopathy can develop in patients with trauma, during obstetric complications, and during major surgery as a result of excessive blood loss and subsequent consumption of coagulation factors as well as hemodilution. In addition, an increasing number of patients receive anticoagulants and antiplatelet drugs preoperatively that might influence the response to surgical hemostasis. This review focuses on those situations that may change normal hemostasis and coagulation during surgery, producing both hyperfibrinolysis and hypofibrinolysis, such as overcorrection with coagulation factors, bleeding and hyperfibrinolysis that may occur with extracorporeal circulation and high aortic-portal-vena cava clamps, and hyperfibrinolysis related to severe maintained hemodynamic disturbances. We also evaluate the role of tranexamic acid for prophylaxis and treatment in different surgical settings, and finally the value of point-of-care testing in the operating room is commented with regard to investigation of fibrinolysis.
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Affiliation(s)
- Maria J Colomina
- Department of Anaesthesia and Critical Care, Bellvitge University Hospital, L'Hospitalet de LLobregat, Barcelona, Spain.,Universidad de Barcelona, Barcelona, Spain
| | - Esther Méndez
- Department of Anaesthesia and Critical Care, Bellvitge University Hospital, L'Hospitalet de LLobregat, Barcelona, Spain
| | - Antoni Sabate
- Department of Anaesthesia and Critical Care, Bellvitge University Hospital, L'Hospitalet de LLobregat, Barcelona, Spain.,Universidad de Barcelona, Barcelona, Spain
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Monaco F, Barucco G, Licheri M, Mattioli C, Ortalda A, Lombardi G, Pallanch O, De Luca M, Chiesa R, Melissano G, Zangrillo A. Trigger and Target for Fibrinogen Supplementation Using Thromboelastometry (ROTEM) in Patients Undergoing Open Thoraco-Abdominal Aortic Aneurysm Repair. Eur J Vasc Endovasc Surg 2021; 61:799-808. [PMID: 33773905 DOI: 10.1016/j.ejvs.2021.02.046] [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: 05/21/2020] [Revised: 02/02/2021] [Accepted: 02/23/2021] [Indexed: 10/21/2022]
Abstract
OBJECTIVE To determine the relationship between the value of fibrinogen assessed by the FIBTEM clot amplitude at 10 minutes (A10 FIBTEM) measured on admission to the intensive care unit (ICU) and the amount of drainage output at 24 hours, to investigate whether the A10 FIBTEM predicts severe bleeding (SB), and to define A10 FIBTEM thresholds to prevent (trigger) and treat (target) severe bleeding by fibrinogen supplementation. METHODS In a single centre, retrospective observational study, 166 patients underwent elective open thoraco-abdominal aortic aneurysm (TAAA) repair between March 2016 and January 2019. Exclusion criteria were emergency, congenital, or acquired coagulopathy, or administration of P2Y12 inhibitor antiplatelet agents in the five days before surgery. All patients were managed intra-operatively and post-operatively according to a rotational thromboelastometry driven transfusion protocol. The principal endpoint was a composite outcome, which included bleeding, large volume transfusion, and re-operation. RESULTS FIBTEM clot amplitude after 10 minutes measured on ICU admission and post-operative bleeding at 24 hours showed an inverse linear relationship (R2 = .03; p = .026). Performance of A10 FIBTEM in predicting SB evaluated by Receiving Operating Curve analysis showed an area under the curve of 0.63 (95% CI 0.56 - 0.70; p = .026) with a best cutoff of 9 mm. An A10 FIBTEM of 3 mm was the cutoff associated with a positive predictive value of 50%, while an A10 FIBTEM of 9 mm showed a negative predictive value of 92%. On multivariable analysis, an A10 FIBTEM ≤ 3 mm remained independently associated with SB. CONCLUSION The present investigation shows for the first time in a population undergoing open TAAA repair that an A10 FIBTEM ≤ 3mm on ICU admission is associated with post-operative severe bleeding. Trigger and target values for fibrinogen supplementation, based on A10 FIBTEM, have been provided. The transferability and reliability of these cutoff values require further study.
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Affiliation(s)
- Fabrizio Monaco
- Department of Anaesthesia and Intensive Care, IRCCS San Raffaele Scientific Institute, Milan, Italy.
| | - Gaia Barucco
- Department of Anaesthesia and Intensive Care, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Margherita Licheri
- Department of Anaesthesia and Intensive Care, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Cristina Mattioli
- Department of Anaesthesia and Intensive Care, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Alessandro Ortalda
- Department of Anaesthesia and Intensive Care, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Gaetano Lombardi
- Department of Anaesthesia and Intensive Care, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Ottavia Pallanch
- Department of Anaesthesia and Intensive Care, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Monica De Luca
- Department of Anaesthesia and Intensive Care, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Roberto Chiesa
- Department of Vascular Surgery, IRCCS San Raffaele Scientific Institute, Milan, Italy; University Vita-Salute San Raffaele, Milan, Italy
| | - Germano Melissano
- Department of Vascular Surgery, IRCCS San Raffaele Scientific Institute, Milan, Italy; University Vita-Salute San Raffaele, Milan, Italy
| | - Alberto Zangrillo
- Department of Anaesthesia and Intensive Care, IRCCS San Raffaele Scientific Institute, Milan, Italy; University Vita-Salute San Raffaele, Milan, Italy
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Ito T, Kakuuchi M, Maruyama I. Endotheliopathy in septic conditions: mechanistic insight into intravascular coagulation. Crit Care 2021; 25:95. [PMID: 33685461 PMCID: PMC7938685 DOI: 10.1186/s13054-021-03524-6] [Citation(s) in RCA: 37] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2020] [Accepted: 03/01/2021] [Indexed: 01/13/2023] Open
Abstract
Endothelial cells play a key role in maintaining intravascular patency through their anticoagulant properties. They provide a favorable environment for plasma anticoagulant proteins, including antithrombin, tissue factor pathway inhibitor, and protein C. Under septic conditions, however, the anticoagulant properties of endothelial cells are compromised. Rather, activated/injured endothelial cells can provide a scaffold for intravascular coagulation. For example, the expression of tissue factor, an important initiator of the coagulation pathway, is induced on the surface of activated endothelial cells. Phosphatidylserine, a high-affinity scaffold for gamma-carboxyglutamate domain containing coagulation factors, including FII, FVII, FIX, and FX, is externalized to the outer leaflet of the plasma membrane of injured endothelial cells. Hemodilution decreases not only coagulation factors but also plasma anticoagulant proteins, resulting in unleashed activation of coagulation on the surface of activated/injured endothelial cells. The aberrant activation of coagulation can be suppressed in part by the supplementation of recombinant antithrombin and recombinant thrombomodulin. This review aims to overview the physiological and pathological functions of endothelial cells along with proof-of-concept in vitro studies. The pathophysiology of COVID-19-associated thrombosis is also discussed.
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Affiliation(s)
- 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.
| | - Midori Kakuuchi
- Department of Systems Biology in Thromboregulation, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima, 890-8544, 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
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Zur M, Gorenbein P, Nachshon A, Radomislensky I, Tsur AM, Benov A, Wagnert-Avraham L, Glassberg E. Post-expiry stability of freeze-dried plasma under field conditions - Can shelf life be extended? Transfusion 2021; 61:1570-1577. [PMID: 33594694 DOI: 10.1111/trf.16319] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2020] [Revised: 11/15/2020] [Accepted: 01/11/2021] [Indexed: 12/18/2022]
Abstract
BACKGROUND This prospective study evaluated the effect of routine, uncontrolled, Israeli field storage conditions on the safety and efficacy of Lyo-Plas N Freeze-Dried Plasma (FDP) at the end of the manufacturer's shelf life, and up to 24 months post expiry. Clotting factors V, VIII and XI, proteins S, C, fibrinogen, PTT, ATIII, VWF, and INR as well as TEG, DDM, residual moisture, pH, and sterility of FDP returned from field units after uncontrolled storage were evaluated. STUDY DESIGN AND METHODS Parameters measured at the end of manufacturer shelf life, as well as 6, 12, 18, and 24 months after expiry, were compared to those of freshly supplied FDP doses. RESULTS Changes were found when comparing freshly supplied FDP to all field-stored groups in INR, PT, PTT, pH, fibrinogen, and factor VIII. A significant change was also seen in Factor XI in the 12, 18, and 24 months post-expiry samples, Factor V and R in the 24 months post-expiry samples, MA in the 12, 24 months post-expiry group, and Protein C in the 18 months post-expiry group. An increase in the residual moisture from 0.90% in freshly supplied FDP to 1.35% in 24 months post-expiry FDP.; all p < .05. No growth was found in sterility analysis. CONCLUSION Despite uncontrolled field storage conditions, the findings demonstrate that the safety and efficacy of FDP units, stored in uncontrolled conditions are only slightly affected, even beyond their expiration date. This information allows consideration of possibly extending the shelf life.
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Affiliation(s)
- Meital Zur
- Israel Defense Forces (IDF) Medical Corps, Tel Aviv, Israel
| | | | | | - Irina Radomislensky
- Israel Defense Forces (IDF) Medical Corps, Tel Aviv, Israel.,Israel National Center for Trauma and Emergency Medicine Research, Sheba Medical Center, Gertner Institute for Epidemiology and Public Health Policy Research, Ramat Gan, Israel
| | - Avishai M Tsur
- Israel Defense Forces (IDF) Medical Corps, Tel Aviv, Israel
| | - Avi Benov
- Israel Defense Forces (IDF) Medical Corps, Tel Aviv, Israel
| | - Linn Wagnert-Avraham
- Institute for Research in Military Medicine, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel
| | - Elon Glassberg
- Israel Defense Forces (IDF) Medical Corps, Tel Aviv, Israel.,Institute for Research in Military Medicine, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel.,Faculty of Medicine, Bar Ilan University, Safed, Israel.,Uniformed Services University of the Health Sciences, Bethesda, Maryland, USA
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50
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Meier N. Anesthetic Considerations for Pediatric Craniofacial Surgery. Anesthesiol Clin 2021; 39:53-70. [PMID: 33563386 DOI: 10.1016/j.anclin.2020.10.002] [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: 10/22/2022]
Abstract
Anesthetic management of craniosynostosis remains a challenging experience. It requires input and collaboration from multiple specialties to improve patient outcomes. Understanding the surgical corrective techniques and the underlying risks of each is essential to providing the best care to this patient population. The propensity for significant blood loss necessitates fundamental knowledge of pediatric resuscitation and the development of perioperative transfusion protocols that have been shown to reduce transfusion requirements in the peri-operative period.
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Affiliation(s)
- Nicholas Meier
- Department of Anesthesiology, Medical College of Wisconsin, Children's Hospital of Wisconsin, 9200 West Wisconsin Avenue, Milwaukee, WI 53226, USA.
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