Management of coagulation abnormalities in liver disease

Expert Review of Gastroenterology and Hepatology

Volumn 9, Issue 1, 2015, Pages 103-114

  Potze, Wilma ^a   Porte, Robert J ^b   Lisman, Ton ^a,b  

^a UNIVERSITY MEDICAL CENTER GRONINGEN   (Netherlands)

^b UNIVERSITY OF GRONINGEN   (Netherlands)

Author keywords

anticoagulants; bleeding; bleeding management; coagulation; coagulation tests; hemostasis; liver disease; thrombin generation; thrombosis; thrombosis management

Indexed keywords

AMINOCAPROIC ACID; ANTIBIOTIC AGENT; ANTIFIBRINOLYTIC AGENT; ANTIVITAMIN K; APIXABAN; APROTININ; BLOOD CLOTTING FACTOR 10; BLOOD CLOTTING FACTOR 11; BLOOD CLOTTING FACTOR 5; BLOOD CLOTTING FACTOR 7; BLOOD CLOTTING FACTOR 8; BLOOD CLOTTING FACTOR 9; DABIGATRAN; DESMOPRESSIN; ELTROMBOPAG; FIBRINOGEN; FRESH FROZEN PLASMA; HEPARIN; HEPARIN DERIVATIVE; LOW MOLECULAR WEIGHT HEPARIN; PROTEIN C; PROTEIN S; PROTHROMBIN; PROTHROMBIN COMPLEX; RECOMBINANT BLOOD CLOTTING FACTOR 7A; RIVAROXABAN; THROMBOCYTE CONCENTRATE; TRANEXAMIC ACID; UNINDEXED DRUG; VON WILLEBRAND FACTOR; COAGULATING AGENT; FIBRINOLYTIC AGENT;

ABSENCE OF SIDE EFFECTS; ACUTE LIVER FAILURE; ANTIBIOTIC PROPHYLAXIS; ANTICOAGULATION; BACTERIAL INFECTION; BLEEDING; BLEEDING TENDENCY; BLOOD CLOTTING DISORDER; BLOOD TRANSFUSION; DRUG EFFECT; DRUG EFFICACY; DRUG SAFETY; DRUG WITHDRAWAL; ERYTHROCYTE TRANSFUSION; FIBRINOLYSIS; HEMOSTASIS; HUMAN; LABORATORY TEST; LIVER CIRRHOSIS; LIVER DISEASE; PARTIAL THROMBOPLASTIN TIME; PORTAL HYPERTENSION; PORTAL VEIN THROMBOSIS; PROTHROMBIN TIME; REVIEW; THERAPY EFFECT; THROMBOCYTE DYSFUNCTION; THROMBOCYTE TRANSFUSION; THROMBOCYTOPENIA; THROMBOELASTOGRAPHY; THROMBOEMBOLISM; THROMBOSIS; TRANSFUSION RELATED ACUTE LUNG INJURY; UNSPECIFIED SIDE EFFECT; UPPER GASTROINTESTINAL BLEEDING; VEIN THROMBOSIS; ANIMAL; BLOOD; BLOOD CLOTTING; BLOOD CLOTTING TEST; COMPLICATION; DRUG EFFECTS; HEMORRHAGE; LIVER DISEASES; PREDICTIVE VALUE; RISK FACTOR; TREATMENT OUTCOME;

ANIMALS; BLOOD COAGULATION; BLOOD COAGULATION TESTS; BLOOD TRANSFUSION; COAGULANTS; FIBRINOLYSIS; FIBRINOLYTIC AGENTS; HEMORRHAGE; HUMANS; LIVER DISEASES; PREDICTIVE VALUE OF TESTS; RISK FACTORS; THROMBOSIS; TREATMENT OUTCOME;

EID: 84918794509     PISSN: 17474124     EISSN: 17474132     Source Type: Journal    
DOI: 10.1586/17474124.2014.934673     Document Type: Review

References (108)

1. Lisman T, Leebeek FW, de Groot PG. Haemostatic abnormalities. in patients with liver disease. J Hepatol 2002;37(2):280-7
2. Lisman T, Porte RJ. Rebalanced hemostasis in patients with liver disease: evidence and clinical consequences. Blood 2010;116(6): 878-85
3. Lisman T, Bakhtiari K, Pereboom IT, et al. Normal to increased thrombin generation in patients undergoing liver transplantation Despite prolonged conventional coagulation tests. J Hepatol 2010;52(3):355-61
4. Massicotte L, Denault AY, Beaulieu D, et al. Transfusion rate for 500 consecutive liver transplantations: experience of one liver transplantation center. Transplantation 2012;93(12):1276-81
5. Dzik WH. Predicting hemorrhage using preoperative coagulation screening assays. Curr Hematol Rep 2004;3(5):324-30
6. Dzik W, Rao A. Why do physicians request fresh frozen plasma?. Transfusion 2004; 44(9):1393-4
7. Lisman T, Caldwell SH, Burroughs AK, et al. Hemostasis and thrombosis in patients with liver disease: the ups and downs. J Hepatol 2010;53(2):362-71
8. Northup PG, Sundaram V, Fallon MB, et al. Hypercoagulation and thrombophilia in liver disease. J Thromb Haemost 2008; 6(1):2-9
9. Tripodi A, Anstee QM, Sogaard KK, et al. Hypercoagulability in cirrhosis: causes and consequences. J Thromb Haemost 2011; 9(9):1713-23
10. Caldwell SH, Hoffman M, Lisman T, et al. Coagulation Disorders and hemostasis in liver disease: pathophysiology and critical assessment of current management. Hepatology 2006;44(4):1039-46
11. Lisman T, Leebeek FW. Hemostatic alterations in liver disease: a review on pathophysiology, clinical consequences, and treatment. Dig Surg 2007;24(4):250-8
12. Northup PG, McMahon MM, Ruhl AP, et al. Coagulopathy does not fully protect hospitalized cirrhosis patients from peripheral venous thromboembolism. Am J Gastroenterol 2006;101(7):1524-8.quiz 1680
13. Caldwell S, Shah N. The prothrombin time-derived international normalized ratio: great for Warfarin, fair for prognosis and bad for liver-bleeding risk. Liver Int 2008; 28(10):1325-7
14. Northup PG, Caldwell SH. Coagulation in liver disease: a guide for the clinician. Clin Gastroenterol Hepatol 2013;11(9):1064-74
15. Aster RH. Pooling of platelets in the spleen: role in the pathogenesis of "hypersplenic" thrombocytopenia. J Clin Invest 1966; 45(5):645-57
16. Kajihara M, Kato S, Okazaki Y, et al. A role of autoantibody-mediated platelet destruction in thrombocytopenia in patients with cirrhosis. Hepatology 2003;37(6): 1267-76
17. Goulis J, Chau TN, Jordan S, et al. Thrombopoietin concentrations are low in patients with cirrhosis and thrombocytopenia and are restored after orthotopic liver transplantation. Gut 1999;44(5):754-8
18. Ikura Y, Ohsawa M, Okada M, et al. The significance of platelet consumption in the development of thrombocytopenia in patients with cirrhosis. Am J Med Sci 2013; 346(3):199-203
19. Lisman T, Bongers TN, Adelmeijer J, et al Elevated Levels of von Willebrand Factor in Cirrhosis Support Platelet Adhesion Despite Reduced Functional Capacity. Hepatology 2006;44(1):53-61
20. La Mura V, Reverter JC, Flores-Arroyo A, et al. Von Willebrand factor levels predict clinical outcome in patients with cirrhosis and portal hypertension. Gut 2011;60(8): 1133-8
21. Ferlitsch M, Reiberger T, Hoke M, et al. von Willebrand factor as new noninvasive predictor of portal hypertension, decompensation and mortality in patients with liver cirrhosis. Hepatology 2012;56(4): 1439-47
22. Lisman T, Adelmeijer J, de Groot PG, et al. No evidence for an intrinsic platelet defect in patients with liver cirrhosis-studies under flow conditions. J Thromb Haemost 2006; 4(9):2070-2
23. Basili S, Raparelli V, Riggio O, et al. NADPH oxidase-mediated platelet isoprostane over-production in cirrhotic patients: implication for platelet activation. Liver Int 2011;31(10):1533-40
24. 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):2105-11
25. Hollestelle MJ, Geertzen HG, Straatsburg IH, et al. Factor VIII expression in liver disease. Thromb Haemost 2004; 91(2):267-75
26. Hollestelle MJ, Poyck PP, Hollestelle JM, et al. Extra-hepatic factor VIII expression in porcine fulminant hepatic failure. J Thromb Haemost 2005;3(10):2274-80
27. Martinez J, MacDonald KA, Palascak JE. The role of sialic acid in the dysfibrinogenemia associated with liver disease: distribution of sialic acid on the constituent chains. Blood 1983;61(6): 1196-202
28. Castoldi E, Simioni P, Tormene D, et al. Hereditary and acquired protein S deficiencies are associated with low TFPI levels in plasma. J Thromb Haemost 2010; 8(2):294-300
29. Potze W, Arshad F, Adelmeijer J, et al. Decreased tissue factor pathway inhibitor (TFPI)-dependent anticoagulant capacity in patients with cirrhosis who have decreased protein S but normal TFPI plasma levels. Br J Haematol 2013;162(6):819-26
30. Tripodi A, Primignani M, Lemma L, et al. Evidence that low protein C contributes to the procoagulant imbalance in cirrhosis. J Hepatol 2013;59(2):265-70
31. Tripodi A, Primignani M, Lemma L, et al. Detection of the imbalance of procoagulant versus anticoagulant factors in cirrhosis by a simple laboratory method. Hepatology 2010;52(1):249-55
32. Lisman T, Leebeek FW, Mosnier LO, et al. Thrombin-Activatable fibrinolysis inhibitor deficiency in cirrhosis is not associated with increased plasma fibrinolysis. Gastroenterology 2001;121(1):131-9
33. Stein SF, Harker LA. Kinetic and functional studies of platelets, fibrinogen, and plasminogen in patients with hepatic cirrhosis. J Lab Clin Med 1982;99(2): 217-30
34. Pernambuco JR, Langley PG, Hughes RD, et al. Activation of the fibrinolytic system in patients with fulminant liver failure. Hepatology 1993;18(6):1350-6
35. Leebeek FW, Kluft C, Knot EA, et al. A shift in balance between profibrinolytic and antifibrinolytic factors causes enhanced fibrinolysis in cirrhosis. Gastroenterology 1991;101(5):1382-90
36. Noris M, Remuzzi G. Uremic bleeding: closing the circle after 30 years of controversies?. Blood 1999;94(8):2569-74
37. Thalheimer U, Triantos CK, Samonakis DN, et al. Infection, coagulation, and variceal bleeding in cirrhosis. Gut 2005;54(4):556-63
38. van Der Poll T, Buller HR, ten Cate H, et al. Activation of coagulation after administration of tumor necrosis factor to normal subjects. N Engl J Med 1990; 322(23):1622-7
39. Logan TF, Virji MA, Gooding WE, et al. The pathogenesis of disseminated intravascular coagulation in sepsis. JAMA 1994;271(6):427-8
40. Aird WC. The role of the endothelium in severe sepsis and multiple organ Dysfunction syndrome. Blood 2003;101(10):3765-77
41. Bernard B, Grange JD, Khac EN, et al. Antibiotic prophylaxis for the prevention of bacterial infections in cirrhotic patients with gastrointestinal bleeding: a meta-Analysis. Hepatology 1999;29(6):1655-61
42. Mucino-Bermejo J, Carrillo-Esper R, Uribe M, Mendez-Sanchez N. Coagulation abnormalities in the cirrhotic patient. Ann Hepatol 2013;12(5):713-24
43. Garcia-Tsao G, Bosch J. Management of varices and variceal hemorrhage in cirrhosis. N Engl J Med 2010;362(9):823-32
44. Turon F, Casu S, Hernandez-Gea V, Garcia-Pagan JC. Variceal and other portal hypertension related bleeding. Best Pract Res Clin Gastroenterol 2013;27(5):649-64
45. Villa E, Camma C, Marietta M, et al. Enoxaparin prevents portal vein thrombosis and liver decompensation in patients with advanced cirrhosis. Gastroenterology 2012; 143(5):1253-60.e1-4
46. Shah NL, Northup PG, Caldwell SH. A clinical survey of bleeding, thrombosis, and blood product use in Decompensated cirrhosis patients. Ann Hepatol 2012;11(5): 686-90
47. Targher G, Chonchol M, Miele L, et al. Nonalcoholic fatty liver disease as a contributor to hypercoagulation and thrombophilia in the metabolic syndrome. Semin Thromb Hemost 2009;35(3):277-87
48. Caldwell S, Northup PG. Bleeding complication with liver biopsy: is it predictable?. Clin Gastroenterol Hepatol 2010;8(10):826-9
49. Tripodi A, Salerno F, Chantarangkul V, et al. Evidence of normal thrombin generation in cirrhosis despite abnormal conventional coagulation tests. Hepatology 2005;41(3):553-8
50. Gatt A, Riddell A, Calvaruso V, et al. Enhanced thrombin generation in patients with cirrhosis-induced coagulopathy. J Thromb Haemost 2010;8(9):1994-2000
51. Lisman T, Bakhtiari K, Adelmeijer J, et al. Intact thrombin generation and decreased fibrinolytic capacity in patients with acute liver injury or acute liver failure. J Thromb Haemost 2012;10(7):1312-19
52. 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): 103-7
53. Stravitz RT, Kramer AH, Davern T, et al. Acute Liver Failure Study Group. Intensive care of patients with acute liver failure: recommendations of the U.S. Crit Care Med 2007;35(11):2498-508
54. Boks AL, Brommer EJ, Schalm SW, Van Vliet HH. Hemostasis and fibrinolysis in severe liver failure and their relation to hemorrhage. Hepatology 1986;6(1):79-86
55. Hron G, Kollars M, Binder BR, et al. Identification of patients at low risk for recurrent venous thromboembolism by measuring thrombin generation. JAMA 2006;296(4):397-402
56. Besser M, Baglin C, Luddington R, et al. High rate of unprovoked recurrent venous thrombosis is associated with high thrombin-generating potential in a prospective cohort study. J Thromb Haemost 2008;6(10):1720-5
57. Tripodi A, Legnani C, Chantarangkul V, et al. High thrombin generation measured in the presence of thrombomodulin is associated with an increased risk of recurrent venous thromboembolism. J Thromb Haemost 2008;6(8):1327-33
58. van Veen JJ, Gatt A, Makris M. Thrombin generation testing in routine clinical practice: are we there yet?. Br J Haematol 2008;142(6):889-903
59. Mallett SV, Chowdary P, Burroughs AK. Clinical utility of viscoelastic tests of coagulation in patients with liver disease. Liver Int 2013;33(7):961-74
60. Stravitz RT. Potential applications of thromboelastography in patients with acute and chronic liver disease. Gastroenterol Hepatol (N Y) 2012;8(8):513-20
61. Salooja N, Perry DJ. Thrombelastography. Blood Coagul Fibrinolysis 2001;12(5): 327-37
62. Stanworth SJ, Hyde CJ, Murphy MF. Evidence for indications of fresh frozen plasma. Transfus Clin Biol 2007;14(6): 551-6
63. Tinmouth A. Evidence for a rationale use of frozen plasma for the treatment and prevention of bleeding. Transfus Apher Sci 2012;46(3):293-8
64. Afdhal NH, Giannini EG, Tayyab G, et al. Eltrombopag before procedures in patients with cirrhosis and thrombocytopenia. N Engl J Med 2012;367(8):716-24
65. O'Shaughnessy DF, Atterbury C, Bolton Maggs P, et al. Guidelines for the use of fresh-frozen plasma, cryoprecipitate and cryosupernatant. Br J Haematol 2004; 126(1):11-28
66. Stanca CM, Montazem AH, Lawal A, et al. Intranasal desmopressin versus blood transfusion in cirrhotic patients with coagulopathy undergoing dental extraction: a randomized controlled trial. J Oral Maxillofac Surg 2010;68(1):138-43
67. Youssef WI, Salazar F, Dasarathy S, et al. Role of fresh frozen plasma infusion in correction of coagulopathy of chronic liver disease: a dual phase study. Am J Gastroenterol 2003;98(6):1391-4
68. Patel IJ, Davidson JC, Nikolic B, et al. Consensus guidelines for periprocedural management of coagulation status and hemostasis risk in percutaneous image-guided interventions. J Vasc Interv Radiol 2012;23(6):727-36
69. Giannini EG, Greco A, Marenco S, et al. Incidence of bleeding following invasive procedures in patients with thrombocytopenia and advanced liver disease. Clin Gastroenterol Hepatol 2010; 8(10):899-902.quiz e109
70. 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
71. Villanueva C, Colomo A, Bosch A, et al. Transfusion strategies for acute upper gastrointestinal bleeding. N Engl J Med 2013;368(1):11-21
72. Burroughs AK, Matthews K, Qadiri M, et al. Desmopressin and bleeding time in patients with cirrhosis. Br Med J (Clin Res Ed) 1985;291(6506):1377-81
73. Wong AY, Irwin MG, Hui TW, et al. Desmopressin Does not decrease blood loss and transfusion requirements in patients undergoing hepatectomy. Can J Anaesth 2003;50(1):14-20
74. Pivalizza EG, Warters RD, Gebhard R. Desmopressin before liver transplantation. Can J Anaesth 2003;50(7):748-9
75. Porte RJ, Molenaar IQ, Begliomini B, et al. Aprotinin and transfusion requirements in orthotopic liver transplantation: a multicentre randomised double-blind study. EMSALT Study Group. Lancet 2000;355(9212):1303-9
76. Boylan JF, Klinck JR, Sandler AN, et al. Tranexamic acid reduces blood loss, transfusion requirements, and coagulation factor use in primary orthotopic liver transplantation. Anesthesiology 1996;85(5): 1043-8
77. Gurusamy KS, Pissanou T, Pikhart H, et al. Methods to decrease blood loss and transfusion requirements for liver transplantation. Cochrane Database Syst Rev 2011(12):CD009052
78. Ramsay MA. Con: antifibrinolytics are not safe and effective in patients undergoing liver transplantation. J Cardiothorac Vasc Anesth 2006;20(6):891-3
79. Clinicaltrials.gov. Available from: www. clinicaltrials.gov/ct2/show/NCT01658124
80. Hendriks HG, Meijer K, de Wolf JT, et al. Reduced transfusion requirements by recombinant factor VIIa in orthotopic liver transplantation: a pilot study. Transplantation 2001;71(3):402-5
81. Planinsic RM, van Der Meer J, Testa G, et al. Safety and efficacy of a single bolus administration of recombinant factor VIIa in liver transplantation Due to chronic liver disease. Liver Transpl 2005;11(8):895-900
82. Lodge JP, Jonas S, Jones RM, et al. Efficacy and safety of repeated perioperative doses of recombinant factor VIIa in liver transplantation. Liver Transpl 2005;11(8): 9739
83. Bendtsen F, D'Amico G, Rusch E, et al. Effect of recombinant factor VIIa on outcome of acute variceal bleeding: an individual patient based meta-Analysis of two controlled trials. J Hepatol 2014. [Epub ahead of print
84. 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
85. Lisman T, Kamphuisen PW, Northup PG, Porte RJ. Established and new-generation antithrombotic drugs in patients with cirrhosis - Possibilities and caveats. J Hepatol 2013;59(2):358-66
86. Garcia-Fuster MJ, Abdilla N, Fabia MJ, et al. Venous thromboembolism and liver cirrhosis. Rev Esp Enferm Dig 2008;100(5): 259-62
87. Levi M, Hovingh GK, Cannegieter SC, et al. Bleeding in patients receiving vitamin K antagonists who would have been excluded from trials on which the indication for anticoagulation was based. Blood 2008; 111(9):4471-6
88. Amitrano L, Guardascione MA, Menchise A, et al. Safety and efficacy of anticoagulation therapy with low molecular weight heparin for portal vein thrombosis in patients with liver cirrhosis. J Clin Gastroenterol 2010; 44(6):448-51
89. Intagliata N, Henry Z, Shah N, et al. Prophylactic anticoagulation for venous thromboembolism in hospitalized cirrhosis patients is not associated with high rates of gastrointestinal bleeding. Liver Int 2014; 34(1):26-32
90. Potze W, Arshad F, Adelmeijer J, et al. Differential in vitro inhibition of thrombin generation by anticoagulant drugs in plasma from patients with cirrhosis. PLoS One 2014;9(2):e88390
91. Senzolo M, Rodriguez-Castro KI, Rossetto V, et al. Increased anticoagulant response to low-molecular-weight heparin in plasma from patients with advanced cirrhosis. J Thromb Haemost 2012;10(9): 1823-9
92. Bechmann LP, Sichau M, Wichert M, et al. Low-molecular-weight heparin in patients with advanced cirrhosis. Liver Int 2011; 31(1):75-82
93. Lisman T, Porte RJ. Towards a rational use of low-molecular-weight heparin in patients with cirrhosis. Liver Int 2011;31(7):1063
94. Potze W, Arshad F, Adelmeijer J, et al. Routine coagulation assays underestimate levels of antithrombin-dependent drugs but not of direct anticoagulant drugs in plasma from patients with cirrhosis. Br J Haematol 2013;163(5):666-73
95. Schulman S, Crowther MA. How I treat with anticoagulants in 2012: new and old anticoagulants, and when and how to switch. Blood 2012;119(13):3016-23
96. Martinez M, Tandra A, Vuppalanchi R. Treatment of acute portal vein thrombosis by non-Traditional anticoagulation. Hepatology 2014. [Epub ahead of print
97. Intagliata N, Maitland H, Northup P, Caldwell S. Treating thrombosis in cirrhosis patients with new oral agents: ready or not?. Hepatology 2014. [Epub ahead of print
98. Feys HB, Canciani MT, Peyvandi F, et al. ADAMTS13 activity to antigen ratio in physiological and pathological conditions associated with an increased risk of thrombosis. Br J Haematol 2007;138(4): 534-40
99. Giannini EG, Savarino V. Thrombocytopenia in liver disease. Curr Opin Hematol 2008;15(5):473-80
100. Ordinas A, Escolar G, Cirera I, et al. Existence of a platelet-Adhesion Defect in patients with cirrhosis independent of hematocrit: studies under flow conditions. Hepatology 1996;24(5):1137-42
101. Laffi G, Cominelli F, Ruggiero M, et al. Altered platelet function in cirrhosis of the liver: impairment of inositol lipid and arachidonic acid metabolism in response to agonists. Hepatology 1988;8(6):1620-6
102. Laffi G, Marra F, Gresele P, et al. Evidence for a storage pool defect in platelets from cirrhotic patients with defective aggregation. Gastroenterology 1992;103(2):641-6
103. Desai K, Mistry P, Bagget C, et al. Inhibition of platelet aggregation by abnormal high density lipoprotein particles in plasma from patients with hepatic cirrhosis. Lancet 1989;1(8640):693-5
104. Escolar G, Cases A, Vinas M, et al. Evaluation of acquired platelet dysfunctions in uremic and cirrhotic patients using the platelet function analyzer (PFA-100): influence of hematocrit elevation. Haematologica 1999;84(7):614-19
105. Lisman T, Porte RJ. Pitfalls in assessing platelet activation status in patients with liver disease. Liver Int 2012;32(6):1027. author reply 1028
106. Violi F, Ferro D, Basili S, et al. Hyperfibrinolysis resulting from clotting activation in patients with different degrees of cirrhosis. The CALC Group. Coagulation Abnormalities in Liver Cirrhosis. Hepatology 1993;17(1):78-83
107. Colucci M, Binetti BM, Branca MG, et al. Deficiency of thrombin activatable fibrinolysis inhibitor in cirrhosis is associated with increased plasma fibrinolysis. Hepatology 2003;38(1):230-7
108. Hu KQ, Yu AS, Tiyyagura L, et al. Hyperfibrinolytic activity in hospitalized cirrhotic patients in a referral liver unit. Am J Gastroenterol 2001;96(5):1581-6