Official reprint from UpToDate®
www.uptodate.com ©2018 UpToDate, Inc. and/or its affiliates. All Rights Reserved.

Hemostatic abnormalities in patients with liver disease

Neeral L Shah, MD
Nicolas Intagliata, MD
Section Editor
Lawrence LK Leung, MD
Deputy Editor
Jennifer S Tirnauer, MD


Individuals with liver disease have a variety of hemostatic abnormalities, resulting in "rebalanced" hemostasis. These changes increase risks of bleeding as well as thrombosis. They become especially important in patients with bleeding and thrombotic risks such as gastrointestinal varices and vascular stasis, respectively. Management may be particularly challenging in individuals who require invasive procedures or anticoagulant therapy.

This topic discusses the hemostatic abnormalities in patients with liver disease and our approach to common clinical problems, including the roles of plasma products and prohemostatic factors, and the risks, prevention, and management of peripheral venous thrombosis.

Diagnosis and management of portal vein thrombosis, liver injury, cirrhosis, and liver disease from alcohol use are discussed in separate topic reviews:

(See "Acute portal vein thrombosis in adults: Clinical manifestations, diagnosis, and management".)

(See "Chronic portal vein thrombosis in adults: Clinical manifestations, diagnosis, and management".)

To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information on subscription options, click below on the option that best describes you:

Subscribers log in here

Literature review current through: Dec 2017. | This topic last updated: Sep 13, 2017.
The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of this website is governed by the UpToDate Terms of Use ©2018 UpToDate, Inc.
  1. Northup PG, Caldwell SH. Coagulation in liver disease: a guide for the clinician. Clin Gastroenterol Hepatol 2013; 11:1064.
  2. Yates SG, Gavva C, Agrawal D, Sarode R. How do we transfuse blood components in cirrhotic patients undergoing gastrointestinal procedures? Transfusion 2016; 56:791.
  3. Marks PW. Hematologic manifestations of liver disease. Semin Hematol 2013; 50:216.
  4. Shah NL, Intagliata NM, Northup PG, et al. Procoagulant therapeutics in liver disease: a critique and clinical rationale. Nat Rev Gastroenterol Hepatol 2014; 11:675.
  5. Afdhal N, McHutchison J, Brown R, et al. Thrombocytopenia associated with chronic liver disease. J Hepatol 2008; 48:1000.
  6. Weeder PD, Porte RJ, Lisman T. Hemostasis in liver disease: implications of new concepts for perioperative management. Transfus Med Rev 2014; 28:107.
  7. Mallett SV, Chowdary P, Burroughs AK. Clinical utility of viscoelastic tests of coagulation in patients with liver disease. Liver Int 2013; 33:961.
  8. Delgado MG, Seijo S, Yepes I, et al. Efficacy and safety of anticoagulation on patients with cirrhosis and portal vein thrombosis. Clin Gastroenterol Hepatol 2012; 10:776.
  9. Qi X, Ren W, Guo X, Fan D. Epidemiology of venous thromboembolism in patients with liver diseases: a systematic review and meta-analysis. Intern Emerg Med 2015; 10:205.
  10. Saleh T, Matta F, Alali F, Stein PD. Venous thromboembolism with chronic liver disease. Am J Med 2011; 124:64.
  11. Dabbagh O, Oza A, Prakash S, et al. Coagulopathy does not protect against venous thromboembolism in hospitalized patients with chronic liver disease. Chest 2010; 137:1145.
  12. Tripodi A, Mannucci PM. The coagulopathy of chronic liver disease. N Engl J Med 2011; 365:147.
  13. Pandit TN, Sarode R. Blood component support in acquired coagulopathic conditions: is there a method to the madness? Am J Hematol 2012; 87 Suppl 1:S56.
  14. Tripodi A. Hemostasis abnormalities in cirrhosis. Curr Opin Hematol 2015; 22:406.
  15. Kalambokis GN, Oikonomou A, Christou L, et al. von Willebrand factor and procoagulant imbalance predict outcome in patients with cirrhosis and thrombocytopenia. J Hepatol 2016; 65:921.
  16. Wölpl A, Lattke H, Board PG, et al. Coagulation factor XIII A and B subunits in bone marrow and liver transplantation. Transplantation 1987; 43:151.
  17. Qamar AA, Grace ND, Groszmann RJ, et al. Incidence, prevalence, and clinical significance of abnormal hematologic indices in compensated cirrhosis. Clin Gastroenterol Hepatol 2009; 7:689.
  18. Bernard B, Grangé JD, Khac EN, et al. Antibiotic prophylaxis for the prevention of bacterial infections in cirrhotic patients with gastrointestinal bleeding: a meta-analysis. Hepatology 1999; 29:1655.
  19. Senzolo M, Coppell J, Cholongitas E, et al. The effects of glycosaminoglycans on coagulation: a thromboelastographic study. Blood Coagul Fibrinolysis 2007; 18:227.
  20. McKee RF, Hodson S, Dawes J, et al. Plasma concentrations of endogenous heparinoids in portal hypertension. Gut 1992; 33:1549.
  21. Kujovich JL. Hemostatic defects in end stage liver disease. Crit Care Clin 2005; 21:563.
  22. Ferro D, Celestini A, Violi F. Hyperfibrinolysis in liver disease. Clin Liver Dis 2009; 13:21.
  23. Bennani-Baiti N, Daw HA. Primary hyperfibrinolysis in liver disease: a critical review. Clin Adv Hematol Oncol 2011; 9:250.
  24. Nair GB, Lajin M, Muslimani A. A cirrhotic patient with spontaneous intramuscular hematoma due to primary hyperfibrinolysis. Clin Adv Hematol Oncol 2011; 9:249.
  25. Seested T, Appa RS, Christensen EI, et al. In vivo clearance and metabolism of recombinant activated factor VII (rFVIIa) and its complexes with plasma protease inhibitors in the liver. Thromb Res 2011; 127:356.
  26. Van Thiel DH, George M, Fareed J. Low levels of thrombin activatable fibrinolysis inhibitor (TAFI) in patients with chronic liver disease. Thromb Haemost 2001; 85:667.
  27. Agarwal S, Joyner KA Jr, Swaim MW. Ascites fluid as a possible origin for hyperfibrinolysis in advanced liver disease. Am J Gastroenterol 2000; 95:3218.
  28. Ferro D, Quintarelli C, Lattuada A, et al. High plasma levels of von Willebrand factor as a marker of endothelial perturbation in cirrhosis: relationship to endotoxemia. Hepatology 1996; 23:1377.
  29. Witters P, Freson K, Verslype C, et al. Review article: blood platelet number and function in chronic liver disease and cirrhosis. Aliment Pharmacol Ther 2008; 27:1017.
  30. 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; 26:554.
  31. Pihusch R, Rank A, Göhring P, et al. Platelet function rather than plasmatic coagulation explains hypercoagulable state in cholestatic liver disease. J Hepatol 2002; 37:548.
  32. Stine JG, Shah NL, Argo CK, et al. Increased risk of portal vein thrombosis in patients with cirrhosis due to nonalcoholic steatohepatitis. Liver Transpl 2015; 21:1016.
  33. 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; 124:132.
  34. Villa E, Cammà C, Marietta M, et al. Enoxaparin prevents portal vein thrombosis and liver decompensation in patients with advanced cirrhosis. Gastroenterology 2012; 143:1253.
  35. Sharara AI, Rockey DC. Gastroesophageal variceal hemorrhage. N Engl J Med 2001; 345:669.
  36. Shah NL, Northup PG, Caldwell SH. A clinical survey of bleeding, thrombosis, and blood product use in decompensated cirrhosis patients. Ann Hepatol 2012; 11:686.
  37. De Pietri L, Bianchini M, Montalti R, et al. Thrombelastography-guided blood product use before invasive procedures in cirrhosis with severe coagulopathy: A randomized, controlled trial. Hepatology 2016; 63:566.
  38. Intagliata NM, Caldwell SH, Porte RJ, Lisman T. Prediction of bleeding in cirrhosis patients: Is the forecast any clearer? Hepatology 2016; 64:989.
  39. Rai R, Nagral S, Nagral A. Surgery in a patient with liver disease. J Clin Exp Hepatol 2012; 2:238.
  40. Stellingwerff M, Brandsma A, Lisman T, Porte RJ. Prohemostatic interventions in liver surgery. Semin Thromb Hemost 2012; 38:244.
  41. Kor DJ, Stubbs JR, Gajic O. Perioperative coagulation management--fresh frozen plasma. Best Pract Res Clin Anaesthesiol 2010; 24:51.
  42. Ng VL. Liver disease, coagulation testing, and hemostasis. Clin Lab Med 2009; 29:265.
  43. Ewe K. Bleeding after liver biopsy does not correlate with indices of peripheral coagulation. Dig Dis Sci 1981; 26:388.
  44. Rockey DC, Caldwell SH, Goodman ZD, et al. Liver biopsy. Hepatology 2009; 49:1017.
  45. 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; 68:138.
  46. http://www.aasld.org/sites/default/files/guideline_documents/adultascitesenhanced.pdf (Accessed on July 15, 2015).
  47. Runyon BA, AASLD Practice Guidelines Committee. Management of adult patients with ascites due to cirrhosis: an update. Hepatology 2009; 49:2087.
  48. Bianchini M, De Pietri L, Villa E. Coagulopathy in liver diseases: complication or therapy? Dig Dis 2014; 32:609.
  49. Zocco MA, Di Stasio E, De Cristofaro R, et al. Thrombotic risk factors in patients with liver cirrhosis: correlation with MELD scoring system and portal vein thrombosis development. J Hepatol 2009; 51:682.
  50. Intagliata NM, Saad WE, Caldwell SH. Effects of restoring portal flow with anticoagulation and partial splenorenal shunt embolization. Hepatology 2015; 61:1088.
  51. Buresi M, Hull R, Coffin CS. Venous thromboembolism in cirrhosis: a review of the literature. Can J Gastroenterol 2012; 26:905.
  52. Fontana RJ. Prophylactic anticoagulation in cirrhotics: a paradox for prime time? Gastroenterology 2012; 143:1138.
  53. Qi X, Han G, Fan D. Management of portal vein thrombosis in liver cirrhosis. Nat Rev Gastroenterol Hepatol 2014; 11:435.
  54. Søgaard KK, Horváth-Puhó E, Montomoli J, et al. Cirrhosis is Associated with an Increased 30-Day Mortality After Venous Thromboembolism. Clin Transl Gastroenterol 2015; 6:e97.
  55. Ambrosino P, Tarantino L, Criscuolo L, et al. The risk of venous thromboembolism in patients with hepatitis C. A systematic review and meta-analysis. Thromb Haemost 2016; 116:958.
  56. Ambrosino P, Tarantino L, Di Minno G, et al. The risk of venous thromboembolism in patients with cirrhosis. A systematic review and meta-analysis. Thromb Haemost 2017; 117:139.
  57. Ali M, Ananthakrishnan AN, McGinley EL, Saeian K. Deep vein thrombosis and pulmonary embolism in hospitalized patients with cirrhosis: a nationwide analysis. Dig Dis Sci 2011; 56:2152.
  58. Ng KJ, Lee YK, Huang MY, et al. Risks of venous thromboembolism in patients with liver cirrhosis: a nationwide cohort study in Taiwan. J Thromb Haemost 2015; 13:206.
  59. Bogari H, Patanwala AE, Cosgrove R, Katz M. Risk-assessment and pharmacological prophylaxis of venous thromboembolism in hospitalized patients with chronic liver disease. Thromb Res 2014; 134:1220.
  60. Intagliata NM, Henry ZH, 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; 34:26.
  61. Shatzel J, Dulai PS, Harbin D, et al. Safety and efficacy of pharmacological thromboprophylaxis for hospitalized patients with cirrhosis: a single-center retrospective cohort study. J Thromb Haemost 2015; 13:1245.
  62. Intagliata NM, Maitland H, Northup PG, Caldwell SH. Treating thrombosis in cirrhosis patients with new oral agents: ready or not? Hepatology 2015; 61:738.
  63. Intagliata NM, Henry ZH, Maitland H, et al. Direct Oral Anticoagulants in Cirrhosis Patients Pose Similar Risks of Bleeding When Compared to Traditional Anticoagulation. Dig Dis Sci 2016; 61:1721.
  64. Hum J, Shatzel JJ, Jou JH, Deloughery TG. The efficacy and safety of direct oral anticoagulants vs traditional anticoagulants in cirrhosis. Eur J Haematol 2017; 98:393.
  65. Lisman T, Porte RJ. Towards a rational use of low-molecular-weight heparin in patients with cirrhosis. Liver Int 2011; 31:1063.
  66. Francoz C, Belghiti J, Vilgrain V, et al. Splanchnic vein thrombosis in candidates for liver transplantation: usefulness of screening and anticoagulation. Gut 2005; 54:691.
  67. 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; 44:448.
  68. Condat B, Pessione F, Helene Denninger M, et al. Recent portal or mesenteric venous thrombosis: increased recognition and frequent recanalization on anticoagulant therapy. Hepatology 2000; 32:466.
  69. 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; 10:1312.
  70. 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; 56:129.
  71. 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; 9:103.