Clinical Utility of Viscoelastic Tests of Coagulation (TEG/ROTEM) in Patients with Liver Disease and during Liver Transplantation

Abstract

The concept that patients with stable liver disease are at an increased risk of bleeding, based solely on abnormalities of conventional coagulation tests such as prothrombin time (PT) and international normalized ratio (INR), is now recognized to be an overly simplistic interpretation of an extremely complex situation. These tests are in fact very poor predictors of bleeding in patients with liver disease who undergo invasive or surgical procedures. Commercially available whole blood viscoelastic tests (thromboelastography [TEG] and thromboelastometry [ROTEM]) evaluate the kinetics of coagulation from initial clot formation to final clot strength. These dynamic tests provide a composite picture reflecting the interaction of plasma, blood cells, and platelets, and more closely reflect the situation in vivo than do PT/INR, which are performed on plasma samples and measure isolated end points. Despite prolonged PT/INR and low platelet counts, viscoelastic tests are within normal range in many patients with both acute and chronic liver disease, commensurate with the concept of rebalanced hemostasis, and in keeping with the fact that an increasing number of these patients undergo liver transplantation without the need for blood or blood products. In addition, these tests reveal important additional information, such as the presence of hypercoagulability and a prothrombotic state, and also information about the presence of endogenous heparinoids associated with vascular endothelial damage, due to sepsis or acute inflammation. This review provides an overview of the current literature on the potential clinical utility of viscoelastic tests of coagulation in patients with liver disease.

Keywords

coagulation - liver disease - viscoelastic tests

• References

• 1 Mannucci PM. Abnormal hemostasis tests and bleeding in chronic liver disease: are they related? No. J Thromb Haemost 2006; 4 (4) 721-723
• 2 Tripodi A, Mannucci PM. Abnormalities of hemostasis in chronic liver disease: reappraisal of their clinical significance and need for clinical and laboratory research. J Hepatol 2007; 46 (4) 727-733
• 3 Caldwell SH, Hoffman M, Lisman T , et al; Coagulation in Liver Disease Group. Coagulation disorders and hemostasis in liver disease: pathophysiology and critical assessment of current management. Hepatology 2006; 44 (4) 1039-1046
• 4 Lisman T, Porte RJ. Rebalanced hemostasis in patients with liver disease: evidence and clinical consequences. Blood 2010; 116 (6) 878-885
• 5 Tripodi A, Salerno F, Chantarangkul V , et al. Evidence of normal thrombin generation in cirrhosis despite abnormal conventional coagulation tests. Hepatology 2005; 41 (3) 553-558
• 6 Søgaard KK, Horváth-Puhó E, Grønbaek H, Jepsen P, Vilstrup H, Sørensen HT. Risk of venous thromboembolism in patients with liver disease: a nationwide population-based case-control study. Am J Gastroenterol 2009; 104 (1) 96-101
• 7 Massicotte L, Beaulieu D, Thibeault L , et al. Coagulation defects do not predict blood product requirements during liver transplantation. Transplantation 2008; 85 (7) 956-962
• 8 Ben-Ari Z, Panagou M, Patch D , et al. Hypercoagulability in patients with primary biliary cirrhosis and primary sclerosing cholangitis evaluated by thrombelastography. J Hepatol 1997; 26 (3) 554-559
• 9 Kargili A, Cipil H, Karakurt F , et al. Hemostatic alterations in fatty liver disease. Blood Coagul Fibrinolysis 2010; 21 (4) 325-327
• 10 Shore-Lesserson L, Manspeizer HE, DePerio M, Francis S, Vela-Cantos F, Ergin MA. Thromboelastography-guided transfusion algorithm reduces transfusions in complex cardiac surgery. Anesth Analg 1999; 88 (2) 312-319
• 11 Schöchl H, Frietsch T, Pavelka M, Jámbor C. Hyperfibrinolysis after major trauma: differential diagnosis of lysis patterns and prognostic value of thrombelastometry. J Trauma 2009; 67 (1) 125-131
• 12 Kashuk JL, Moore EE, Sabel A , et al. Rapid thrombelastography (r-TEG) identifies hypercoagulability and predicts thromboembolic events in surgical patients. Surgery 2009; 146 (4) 764-772 , discussion 772–774
• 13 Kang YG, Martin DJ, Marquez J , et al. Intraoperative changes in blood coagulation and thrombelastographic monitoring in liver transplantation. Anesth Analg 1985; 64 (9) 888-896
• 14 Tripodi A, Primignani M, Chantarangkul V , et al. The coagulopathy of cirrhosis assessed by thromboelastometry and its correlation with conventional coagulation parameters. Thromb Res 2009; 124 (1) 132-136
• 15 Stravitz RT. Potential applications of thromboelastography in patients with acute and chronic liver disease. Gastroenterol Hepatol (N Y) 2012; 8 (8) 513-520
• 16 Tripodi A, Chantarangkul V, Mannucci PM. Acquired coagulation disorders: revisited using global coagulation/anticoagulation testing. Br J Haematol 2009; 147 (1) 77-82
• 17 Mann KG, Butenas S, Brummel K. The dynamics of thrombin formation. Arterioscler Thromb Vasc Biol 2003; 23 (1) 17-25
• 18 Kamal AH, Tefferi A, Pruthi RK. How to interpret and pursue an abnormal prothrombin time, activated partial thromboplastin time, and bleeding time in adults. Mayo Clin Proc 2007; 82 (7) 864-873
• 19 Roberts HR, Monroe DM, Escobar MA. Current concepts of hemostasis: implications for therapy. Anesthesiology 2004; 100 (3) 722-730
• 20 Hoffman M, Monroe III DM. A cell-based model of hemostasis. Thromb Haemost 2001; 85 (6) 958-965
• 21 Wolberg AS. Thrombin generation and fibrin clot structure. Blood Rev 2007; 21 (3) 131-142
• 22 Hartert H. [Not Available]. Klin Wochenschr 1948; 26 (37–38) 577-583
• 23 Ganter MT, Hofer CK. Coagulation monitoring: current techniques and clinical use of viscoelastic point-of-care coagulation devices. Anesth Analg 2008; 106 (5) 1366-1375
• 24 Whiting D, DiNardo JA. TEG and ROTEM: technology and clinical applications. Am J Hematol 2014; 89 (2) 228-232
• 25 Coakley M, Reddy K, Mackie I, Mallett S. Transfusion triggers in orthotopic liver transplantation: a comparison of the thromboelastometry analyzer, the thromboelastogram, and conventional coagulation tests. J Cardiothorac Vasc Anesth 2006; 20 (4) 548-553
• 26 Kitchen DP, Kitchen S, Jennings I, Woods T, Walker I. Quality assurance and quality control of thrombelastography and rotational Thromboelastometry: the UK NEQAS for blood coagulation experience. Semin Thromb Hemost 2010; 36 (7) 757-763
• 27 Karon BS. Why is everyone so excited about thromboelastrography (TEG)?. Clin Chim Acta 2014; 436: 143-148
• 28 Roullet S, Pillot J, Freyburger G , et al. Rotation thromboelastometry detects thrombocytopenia and hypofibrinogenaemia during orthotopic liver transplantation. Br J Anaesth 2010; 104 (4) 422-428
• 29 Nascimento B, Al Mahoos M, Callum J , et al. Vitamin K-dependent coagulation factor deficiency in trauma: a comparative analysis between international normalized ratio and thromboelastography. Transfusion 2012; 52 (1) 7-13
• 30 Esch JS, Jurk K, Knoefel WT , et al. Platelet activation and increased tissue factor expression on monocytes in reperfusion injury following orthotopic liver transplantation. Platelets 2010; 21 (5) 348-359
• 31 Rautou PE, Vion AC, Luyendyk JP, Mackman N. Circulating microparticle tissue factor activity is increased in patients with cirrhosis. Hepatology 2014; 60 (5) 1793-1795
• 32 Fries D, Haas T, Klingler A , et al. Efficacy of fibrinogen and prothrombin complex concentrate used to reverse dilutional coagulopathy—a porcine model. Br J Anaesth 2006; 97 (4) 460-467
• 33 Alexander DC, Butt WW, Best JD, Donath SM, Monagle PT, Shekerdemian LS. Correlation of thromboelastography with standard tests of anticoagulation in paediatric patients receiving extracorporeal life support. Thromb Res 2010; 125 (5) 387-392
• 34 Gunduz E, Akay OM, Bal C, Gulbas Z. Can thrombelastography be a new tool to assess bleeding risk in patients with idiopathic thrombocytopenic purpura?. Platelets 2011; 22 (7) 516-520
• 35 Kim WH, Park JB, Jung CW, Kim GS. Rebalanced hemostasis in patients with idiopathic thrombocytopenic purpura. Platelets 2015; 26 (1) 38-42
• 36 Görlinger K, Dirkmann D, Hanke AA , et al. First-line therapy with coagulation factor concentrates combined with point-of-care coagulation testing is associated with decreased allogeneic blood transfusion in cardiovascular surgery: a retrospective, single-center cohort study. Anesthesiology 2011; 115 (6) 1179-1191
• 37 Fenger-Eriksen C, Moore GW, Rangarajan S, Ingerslev J, Sørensen B. Fibrinogen estimates are influenced by methods of measurement and hemodilution with colloid plasma expanders. Transfusion 2010; 50 (12) 2571-2576
• 38 Molinaro RJ, Szlam F, Levy JH, Fantz CR, Tanaka KA. Low plasma fibrinogen levels with the Clauss method during anticoagulation with bivalirudin. Anesthesiology 2008; 109 (1) 160-161
• 39 Harr JN, Moore EE, Ghasabyan A , et al. Functional fibrinogen assay indicates that fibrinogen is critical in correcting abnormal clot strength following trauma. Shock 2013; 39 (1) 45-49
• 40 Haase N, Ostrowski SR, Wetterslev J , et al. Thromboelastography in patients with severe sepsis: a prospective cohort study. Intensive Care Med 2015; 41 (1) 77-85
• 41 Yang Lu S, Tanaka KA, Abuelkasem E, Planinsic RM, Sakai T. Clinical applicability of rapid thrombelastography and functional fibrinogen thrombelastography to adult liver transplantation. Liver Transpl 2014; 20 (9) 1097-1105
• 42 Thalheimer U, Triantos CK, Samonakis DN , et al. A comparison of kaolin-activated versus nonkaolin-activated thromboelastography in native and citrated blood. Blood Coagul Fibrinolysis 2008; 19 (6) 495-501
• 43 Kleinegris MC, Bos MH, Roest M , et al. Cirrhosis patients have a coagulopathy that is associated with decreased clot formation capacity. J Thromb Haemost 2014; 12 (10) 1647-1657
• 44 Rockey DC, Caldwell SH, Goodman ZD, Nelson RC, Smith AD ; American Association for the Study of Liver Diseases. Liver biopsy. Hepatology 2009; 49 (3) 1017-1044
• 45 Herbstreit F, Winter EM, Peters J, Hartmann M. Monitoring of haemostasis in liver transplantation: comparison of laboratory based and point of care tests. Anaesthesia 2010; 65 (1) 44-49
• 46 Afdhal NH, Giannini EG, Tayyab G , et al; ELEVATE Study Group. Eltrombopag before procedures in patients with cirrhosis and thrombocytopenia. N Engl J Med 2012; 367 (8) 716-724
• 47 Lisman T, Porte RJ. Eltrombopag before procedures in patients with cirrhosis and thrombocytopenia. N Engl J Med 2012; 367 (21) 2055-2056
• 48 Tripodi A, Primignani M, Chantarangkul V , et al. Global hemostasis tests in patients with cirrhosis before and after prophylactic platelet transfusion. Liver Int 2013; 33 (3) 362-367
• 49 Weeder PD, Porte RJ, Lisman T. Hemostasis in liver disease: implications of new concepts for perioperative management. Transfus Med Rev 2014; 28 (3) 107-113
• 50 Coppell JA, Thalheimer U, Zambruni A , et al. The effects of unfractionated heparin, low molecular weight heparin and danaparoid on the thromboelastogram (TEG): an in-vitro comparison of standard and heparinase-modified TEGs with conventional coagulation assays. Blood Coagul Fibrinolysis 2006; 17 (2) 97-104
• 51 White H, Sosnowski K, Bird R, Jones M, Solano C. The utility of thromboelastography in monitoring low molecular weight heparin therapy in the coronary care unit. Blood Coagul Fibrinolysis 2012; 23 (4) 304-310
• 52 McKee RF, Hodson S, Dawes J, Garden OJ, Carter DC. Plasma concentrations of endogenous heparinoids in portal hypertension. Gut 1992; 33 (11) 1549-1552
• 53 Nelson A, Berkestedt I, Schmidtchen A, Ljunggren L, Bodelsson M. Increased levels of glycosaminoglycans during septic shock: relation to mortality and the antibacterial actions of plasma. Shock 2008; 30 (6) 623-627
• 54 Ostrowski SR, Johansson PI. Endothelial glycocalyx degradation induces endogenous heparinization in patients with severe injury and early traumatic coagulopathy. J Trauma Acute Care Surg 2012; 73 (1) 60-66
• 55 Kettner SC, Gonano C, Seebach F , et al. Endogenous heparin-like substances significantly impair coagulation in patients undergoing orthotopic liver transplantation. Anesth Analg 1998; 86 (4) 691-695
• 56 Montalto P, Vlachogiannakos J, Cox DJ, Pastacaldi S, Patch D, Burroughs AK. Bacterial infection in cirrhosis impairs coagulation by a heparin effect: a prospective study. J Hepatol 2002; 37 (4) 463-470
• 57 Papatheodoridis GV, Patch D, Webster GJ, Brooker J, Barnes E, Burroughs AK. Infection and hemostasis in decompensated cirrhosis: a prospective study using thrombelastography. Hepatology 1999; 29 (4) 1085-1090
• 58 Thalheimer U, Triantos C, Samonakis D , et al. Endogenous heparinoids in acute variceal bleeding. Gut 2005; 54 (2) 310-311
• 59 Chau TN, Chan YW, Patch D, Tokunaga S, Greenslade L, Burroughs AK. Thrombelastographic changes and early rebleeding in cirrhotic patients with variceal bleeding. Gut 1998; 43 (2) 267-271
• 60 Triantos C, Louvros E, Kalafateli M , et al. Endogenous heparinoids detected by anti-Xa activity are present in blood during acute variceal bleeding in cirrhosis. A prospective study. J Gastrointestin Liver Dis 2014; 23 (2) 187-194
• 61 Thalheimer U, Triantos C, Samonakis D, Patch D, Burroughs AK. Heparin effect on thromboelastography after transjugular intrahepatic portosystemic shunt procedure. Scand J Gastroenterol 2009; 44 (12) 1463-1470
• 62 Northup PG. Hypercoagulation in liver disease. Clin Liver Dis 2009; 13 (1) 109-116
• 63 Tsochatzis EA, Senzolo M, Germani G, Gatt A, Burroughs AK. Systematic review: portal vein thrombosis in cirrhosis. Aliment Pharmacol Ther 2010; 31 (3) 366-374
• 64 Hoekstra J, Janssen HL. Vascular liver disorders (II): portal vein thrombosis. Neth J Med 2009; 67 (2) 46-53
• 65 Tripodi A, Primignani M, Chantarangkul V , et al. An imbalance of pro- vs anti-coagulation factors in plasma from patients with cirrhosis. Gastroenterology 2009; 137 (6) 2105-2111
• 66 Tripodi A, Anstee QM, Sogaard KK, Primignani M, Valla DC. Hypercoagulability in cirrhosis: causes and consequences. J Thromb Haemost 2011; 9 (9) 1713-1723
• 67 Pihusch R, Rank A, Göhring P, Pihusch M, Hiller E, Beuers U. Platelet function rather than plasmatic coagulation explains hypercoagulable state in cholestatic liver disease. J Hepatol 2002; 37 (5) 548-555
• 68 Hickman IJ, Sullivan CM, Flight S , et al. Altered clot kinetics in patients with non-alcoholic fatty liver disease. Ann Hepatol 2009; 8 (4) 331-338
• 69 Cakir T, Cingi A, Yeğen C. Coagulation dynamics and platelet functions in obstructive jaundiced patients. J Gastroenterol Hepatol 2009; 24 (5) 748-751
• 70 McCrath DJ, Cerboni E, Frumento RJ, Hirsh AL, Bennett-Guerrero E. Thromboelastography maximum amplitude predicts postoperative thrombotic complications including myocardial infarction. Anesth Analg 2005; 100 (6) 1576-1583
• 71 Toukh M, Siemens DR, Black A , et al. Thromboelastography identifies hypercoagulablilty and predicts thromboembolic complications in patients with prostate cancer. Thromb Res 2014; 133 (1) 88-95
• 72 Dai Y, Lee A, Critchley LAH, White PF. Does thromboelastography predict postoperative thromboembolic events? A systematic review of the literature. Anesth Analg 2009; 108 (3) 734-742
• 73 Munoz SJ, Rajender Reddy K, Lee W ; Acute Liver Failure Study Group. The coagulopathy of acute liver failure and implications for intracranial pressure monitoring. Neurocrit Care 2008; 9 (1) 103-107
• 74 Stravitz RT, Lisman T, Luketic VA , et al. Minimal effects of acute liver injury/acute liver failure on hemostasis as assessed by thromboelastography. J Hepatol 2012; 56 (1) 129-136
• 75 Agarwal B, Wright G, Gatt A , et al. Evaluation of coagulation abnormalities in acute liver failure. J Hepatol 2012; 57 (4) 780-786
• 76 Herriman DJ, Mallett S. A comparison of baseline international normalised ratio (INR) and thromboelastography (TEG) R times, and transfusion requirements for patients with fulminant hepatic failure undergoing orthotopic liver transplant (OLT). Liver Transpl 2011; 17 (6) S120
• 77 Agarwal S, Senzolo M, Melikian C, Burroughs A, Mallett SV. The prevalence of a heparin-like effect shown on the thromboelastograph in patients undergoing liver transplantation. Liver Transpl 2008; 14 (6) 855-860
• 78 Senzolo M, Riddell A, Tuddenham E, Burroughs AK. Endogenous heparinoids contribute to coagulopathy in patients with liver disease. J Hepatol 2008; 48 (2) 371-372 , author reply 372–373
• 79 Massicotte L, Lenis S, Thibeault L, Sassine MP, Seal RF, Roy A. Reduction of blood product transfusions during liver transplantation. Can J Anaesth 2005; 52 (5) 545-546
• 80 Ozier Y, Pessione F, Samain E, Courtois F ; French Study Group on Blood Transfusion in Liver Transplantation. Institutional variability in transfusion practice for liver transplantation. Anesth Analg 2003; 97 (3) 671-679
• 81 Schumann R. Intraoperative resource utilization in anesthesia for liver transplantation in the United States: a survey. Anesth Analg 2003; 97 (1) 21-28 table of contents.
• 82 Steib A, Freys G, Lehmann C, Meyer C, Mahoudeau G. Intraoperative blood losses and transfusion requirements during adult liver transplantation remain difficult to predict. Can J Anaesth 2001; 48 (11) 1075-1079
• 83 McCluskey SA, Karkouti K, Wijeysundera DN , et al. Derivation of a risk index for the prediction of massive blood transfusion in liver transplantation. Liver Transpl 2006; 12 (11) 1584-1593
• 84 Massicotte L, Beaulieu D, Roy JD , et al. MELD score and blood product requirements during liver transplantation: no link. Transplantation 2009; 87 (11) 1689-1694
• 85 Massicotte L, Denault AY, Thibeault L, Hevesi Z, Nozza A, Roy A. Relationship between conventional coagulation tests and bleeding for 600 consecutive liver transplantations. Transplantation 2014; 98 (2) e13-e15
• 86 Lopez-Plaza I. Transfusion guidelines and liver transplantation: time for consensus. Liver Transpl 2007; 13 (12) 1630-1632
• 87 Massicotte L, Sassine MP, Lenis S, Seal RF, Roy A. Survival rate changes with transfusion of blood products during liver transplantation. Can J Anaesth 2005; 52 (2) 148-155
• 88 Trentino KM, Farmer SL, Swain SG , et al. Increased hospital costs associated with red blood cell transfusion. Transfusion 2014;
• 89 Trzebicki J, Flakiewicz E, Kosieradzki M , et al. The use of thromboelastometry in the assessment of hemostasis during orthotopic liver transplantation reduces the demand for blood products. Ann Transplant 2010; 15 (3) 19-24
• 90 Gorlinger K, Dirkmann D, Muller-Beissenhirtz H, Paul A, Hartmann M, Saner F. Thromboelastometry-based perioperative coagulation management in visceral surgery and liver transplantation: experience of 10 tears and 1105 LTX. Liver Transpl 2010; 16 (6) S86
• 91 Kozek-Langenecker SA, Afshari A, Albaladejo P , et al. Management of severe perioperative bleeding: guidelines from the European Society of Anaesthesiology. Eur J Anaesthesiol 2013; 30 (6) 270-382
• 92 Haas T, Spielmann N, Mauch J , et al. Comparison of thromboelastometry (ROTEM®) with standard plasmatic coagulation testing in paediatric surgery. Br J Anaesth 2012; 108 (1) 36-41
• 93 Kirchner C, Dirkmann D, Treckmann JW , et al. Coagulation management with factor concentrates in liver transplantation: a single-center experience. Transfusion 2014; 54 (10 Pt 2) 2760-2768
• 94 Larsen OH, Fenger-Eriksen C, Christiansen K, Ingerslev J, Sørensen B. Diagnostic performance and therapeutic consequence of thromboelastometry activated by kaolin versus a panel of specific reagents. Anesthesiology 2011; 115 (2) 294-302
• 95 Pereboom ITA, de Boer MT, Haagsma EB, Hendriks HGD, Lisman T, Porte RJ. Platelet transfusion during liver transplantation is associated with increased postoperative mortality due to acute lung injury. Anesth Analg 2009; 108 (4) 1083-1091
• 96 Schöchl H, Voelckel W, Maegele M, Kirchmair L, Schlimp CJ. Endogenous thrombin potential following hemostatic therapy with 4-factor prothrombin complex concentrate: a 7-day observational study of trauma patients. Crit Care 2014; 18 (4) R147
• 97 Arshad F, Ickx B, van Beem RT , et al. Prothrombin complex concentrate in the reduction of blood loss during orthotopic liver transplantation: PROTON-trial. BMC Surg 2013; 13: 22
• 98 Mannucci PM, Franchini M. Recombinant factor VIIa as haemostatic therapy in advanced liver disease. Blood Transfus 2013; 11 (4) 487-490
• 99 Ferraris VA, Brown JR, Despotis GJ , et al; Society of Thoracic Surgeons Blood Conservation Guideline Task Force; Society of Cardiovascular Anesthesiologists Special Task Force on Blood Transfusion; International Consortium for Evidence Based Perfusion. 2011 update to the Society of Thoracic Surgeons and the Society of Cardiovascular Anesthesiologists blood conservation clinical practice guidelines. Ann Thorac Surg 2011; 91 (3) 944-982
• 100 Noval-Padillo JA, León-Justel A, Mellado-Miras P , et al. Introduction of fibrinogen in the treatment of hemostatic disorders during orthotopic liver transplantation: implications in the use of allogenic blood. Transplant Proc 2010; 42 (8) 2973-2974
• 101 Wang SC, Shieh JF, Chang KY , et al. Thromboelastography-guided transfusion decreases intraoperative blood transfusion during orthotopic liver transplantation: randomized clinical trial. Transplant Proc 2010; 42 (7) 2590-2593
• 102 Roullet S, Freyburger G, Cruc M , et al. Management of bleeding and transfusion during liver transplantation before and after the introduction of a ROTEM -based algorithm. Liver Transpl 2014;
• 103 Hevesi ZG, Lopukhin SY, Mezrich JD, Andrei AC, Lee M. Designated liver transplant anesthesia team reduces blood transfusion, need for mechanical ventilation, and duration of intensive care. Liver Transpl 2009; 15 (5) 460-465
• 104 Wang SC, Lin HT, Chang KY , et al. Use of higher thromboelastogram transfusion values is not associated with greater blood loss in liver transplant surgery. Liver Transpl 2012; 18 (10) 1254-1258
• 105 Ferro D, Celestini A, Violi F. Hyperfibrinolysis in liver disease. Clin Liver Dis 2009; 13 (1) 21-31
• 106 Porte RJ, Bontempo FA, Knot EA, Lewis JH, Kang YG, Starzl TE. Systemic effects of tissue plasminogen activator-associated fibrinolysis and its relation to thrombin generation in orthotopic liver transplantation. Transplantation 1989; 47 (6) 978-984
• 107 Homatas J, Wasantapruek S, Von Kaulla E, Von Kaulla KN, Eiseman B. Clotting abnormalities following orthotopic and heterotopic transplantation of marginally preserved pig livers. Acta Hepatosplenol 1971; 18 (1) 14-26
• 108 Porte RJ, Blauw E, Knot EA , et al. Role of the donor liver in the origin of platelet disorders and hyperfibrinolysis in liver transplantation. J Hepatol 1994; 21 (4) 592-600
• 109 Görlinger K. [Coagulation management during liver transplantation]. Hamostaseologie 2006; 26 (3) (Suppl. 01) S64-S76
• 110 Schofield N, Sugavanam A, Thompson K, Mallett SV. No increase in blood transfusions during liver transplantation since the withdrawal of aprotinin. Liver Transpl 2014; 20 (5) 584-590
• 111 Kang Y. Coagulation and liver transplantation. Transplant Proc 1993; 25 (2) 2001-2005
• 112 Kang Y. Thromboelastography in liver transplantation. Semin Thromb Hemost 1995; 21 (Suppl. 04) 34-44
• 113 Harding SA, Mallett SV, Peachey TD, Cox DJ. Use of heparinase modified thrombelastography in liver transplantation. Br J Anaesth 1997; 78 (2) 175-179
• 114 Bezeaud A, Denninger MH, Dondero F , et al. Hypercoagulability after partial liver resection. Thromb Haemost 2007; 98 (6) 1252-1256
• 115 Krzanicki D, Sugavanam A, Mallett S. Intraoperative hypercoagulability during liver transplantation as demonstrated by thromboelastography. Liver Transpl 2013; 19 (8) 852-861
• 116 Schöchl H, Solomon C, Schulz A , et al. Thromboelastometry (TEM) findings in disseminated intravascular coagulation in a pig model of endotoxinemia. Mol Med 2011; 17 (3-4) 266-272
• 117 Warnaar N, Molenaar IQ, Colquhoun SD , et al. Intraoperative pulmonary embolism and intracardiac thrombosis complicating liver transplantation: a systematic review. J Thromb Haemost 2008; 6 (2) 297-302
• 118 Xia VW, Ho JK, Nourmand H, Wray C, Busuttil RW, Steadman RH. Incidental intracardiac thromboemboli during liver transplantation: incidence, risk factors, and management. Liver Transpl 2010; 16 (12) 1421-1427
• 119 Lerner AB, Sundar E, Mahmood F, Sarge T, Hanto DW, Panzica PJ. Four cases of cardiopulmonary thromboembolism during liver transplantation without the use of antifibrinolytic drugs. Anesth Analg 2005; 101 (6) 1608-1612
• 120 Tripodi A, Mannucci PM. The coagulopathy of chronic liver disease. N Engl J Med 2011; 365 (2) 147-156