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Coagulopathy in liver disease

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The liver plays a central role in hemostasis, as it is the site of synthesis of clotting factors, coagulation inhibitors, and fibrinolytic proteins. The most common coagulation disturbances occurring in liver disease include thrombocytopenia and impaired humoral coagulation. Therapy’s overall goal is not to achieve complete correction of laboratory value abnormalities but to gain hemostasis. Therapy with vitamin K may be a useful option in patients with increased prothrombin time due to vitamin K deficiency; in patients with malnutrition; in patients using antibiotics; and in patients with cholestatic liver disease, particularly prior to invasive procedures. Infusion of fresh frozen plasma is more often effective and is recommended in patients with liver disease before invasive procedures or surgery, as such patients require transient correction in their prothrombin time. Therapy with plasma exchange may be considered in patients who cannot be treated with fresh frozen plasma due to volume overload risk. In patients with severe coagulopathy and hypofibrinogenemia, cryoprecipitate therapy is ideal. Therapy with prothrombin-complex concentrate is seldom pursued in patients with liver disease due to high risk of thrombotic complications. Transfusions of platelets are appropriate for patients with thrombocytopenia (< 50,000/mm3) associated with active bleeding or before invasive procedures in which a short-term platelet count increase is noted. Trial with desmopressin may be considered before invasive procedures in patients with liver disease and with refractory and prolonged bleeding time. Recombinant activated factor VIIa administration is suggested for patients with significantly prolonged prothrombin time and contraindications to fresh frozen plasma therapy; however, this is expensive. Thrombopoietin and interleukin-11 are currently investigational for patients with thrombocytopenia of chronic liver disease. Liver transplantation completely restores impaired coagulation abnormalities and is the ultimate intervention that corrects coagulopathy of advanced liver disease and liver failure.

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References and Recommended Reading

  1. Kujovich JL: Hemostatic defects in end stage liver disease. Crit Care Clin 2005, 21:563–587.

    Article  PubMed  Google Scholar 

  2. Trotter JF: Coagulation abnormalities in patients who have liver disease. Clin Liver Dis 2006, 10:665–678, x-xi.

    Article  PubMed  Google Scholar 

  3. Braunwald E, Fauci AS, Kasper D, et al.: Harrison’s Principles of Internal Medicine, edn 15. New York: McGraw-Hill; 2001.

    Google Scholar 

  4. Aref S, Mabed M, Selim T, et al.: Thrombopoietin (TPO) levels in hepatic patients with thrombocytopenia. Hematology 2004, 9:351–356.

    Article  PubMed  CAS  Google Scholar 

  5. Koruk M, Onuk MD, Akcay F, et al.: Serum thrombopoietin levels in patients with chronic hepatitis and liver cirrhosis, and its relationship with circulating thrombocytes counts. Hepatogastroenterology 2002, 49:1645–1648.

    PubMed  CAS  Google Scholar 

  6. Peck-Radosavljevic M: Thrombocytopenia in liver disease. Can J Gastroenterol 2000, 14(Suppl D):60D–66D.

    PubMed  Google Scholar 

  7. Kim WR, Brown RS, Jr, Terrault NA, et al.: Burden of liver disease in the United States: summary of a workshop. Hepatology 2002, 36:227–242.

    Article  PubMed  Google Scholar 

  8. Amitrano L, Guardascione MA, Brancaccio V, et al.: Coagulation disorders in liver disease. Semin Liver Dis 2002, 22:83–96.

    Article  PubMed  CAS  Google Scholar 

  9. Lisman T, Leebeek FW, de Groot PG: Haemostatic abnormalities in patients with liver disease. J Hepatol 2002, 37:280–287.

    Article  PubMed  CAS  Google Scholar 

  10. Beers M, Berkow R: The Merck Manual of Diagnosis and Therapy, edn 17. Whitehouse Station, NJ: Merck & Co., Inc.; 1999.

    Google Scholar 

  11. Kelly DA, Tuddenham EG: Haemostatic problems in liver disease. Gut 1986, 27:339–349.

    Article  PubMed  CAS  Google Scholar 

  12. Hellstern P, Muntean W, Schramm W, et al.: Practical guidelines for the clinical use of plasma. Thromb Res 2002, 107(Suppl 1):S53–S57.

    Article  PubMed  CAS  Google Scholar 

  13. Phillips JR, Angulo P, Petterson T, et al.: Fat-soluble vitamin levels in patients with primary biliary cirrhosis. Am J Gastroenterol 2001, 96:2745–2750.

    Article  PubMed  CAS  Google Scholar 

  14. Pereira SP, Rowbotham D, Fitt S, et al.: Pharmacokinetics and efficacy of oral versus intravenous mixed-micellar phylloquinone (vitamin K1) in severe acute liver disease. J Hepatol 2005, 42:365–370.

    Article  PubMed  CAS  Google Scholar 

  15. Pereira SP, Williams R: Adverse events associated with vitamin K1: results of a worldwide postmarketing surveillance programme. Pharmacoepidemiol Drug Saf 1998, 7:173–182.

    Article  PubMed  CAS  Google Scholar 

  16. 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, 126:11–28.

    Article  PubMed  CAS  Google Scholar 

  17. Senzolo M, Burra P, Cholongitas E, et al.: New insights into the coagulopathy of liver disease and liver transplantation. World J Gastroenterol 2006, 12:7725–7736.

    PubMed  CAS  Google Scholar 

  18. Mueller MM, Bomke B, Seifried E: Fresh frozen plasma in patients with disseminated intravascular coagulation or in patients with liver diseases. Thromb Res 2002, 107(Suppl 1):S9–S17.

    Article  PubMed  CAS  Google Scholar 

  19. 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, 98:1391–1394.

    Article  PubMed  Google Scholar 

  20. Wang YJ, He NH, Wang ZW, et al.: Assessment of the combined effect of plasma exchange and plasma perfusion on patients with severe hepatitis awaiting orthotopic liver transplantation. Int J Artif Organs 2004, 27:40–44.

    PubMed  Google Scholar 

  21. Singer AL, Olthoff KM, Kim H, et al.: Role of plasmapheresis in the management of acute hepatic failure in children. Ann Surg 2001, 234:418–424.

    Article  PubMed  CAS  Google Scholar 

  22. 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, 50:14–20.

    Article  PubMed  Google Scholar 

  23. Carless PA, Henry DA, Moxey AJ, et al.: Desmopressin for minimising perioperative allogeneic blood transfusion. Cochrane Database Syst Rev 2004, 1:CD001884.

  24. Franchini M: The use of desmopressin as a hemostatic agent: a concise review. Am J Hematol 2007, 82:731–735.

    Article  PubMed  CAS  Google Scholar 

  25. Tonda R, Galan AM, Pino M, et al.: Hemostatic effect of activated recombinant factor VII (rFVIIa) in liver disease: studies in an in vitro model. J Hepatol 2003, 39:954–959.

    Article  PubMed  CAS  Google Scholar 

  26. Shami VM, Caldwell SH, Hespenheide EE, et al.: Recombinant activated factor VII for coagulopathy in fulminant hepatic failure compared with conventional therapy. Liver Transpl 2003, 9:138–143.

    Article  PubMed  Google Scholar 

  27. Pavese P, Bonadona A, Beaubien J, et al.: FVIIa corrects the coagulopathy of fulminant hepatic failure but may be associated with thrombosis: a report of four cases. Can J Anaesth 2005, 52:26–29.

    PubMed  Google Scholar 

  28. Brown JB, Emerick KM, Brown DL, et al.: Recombinant factor VIIa improves coagulopathy caused by liver failure. J Pediatr Gastroenterol Nutr 2003, 37:268–272.

    Article  PubMed  CAS  Google Scholar 

  29. Jeffers L, Chalasani N, Balart L, et al.: Safety and efficacy of recombinant factor VIIa in patients with liver disease undergoing laparoscopic liver biopsy. Gastroenterology 2002, 123:118–126.

    Article  PubMed  CAS  Google Scholar 

  30. Anantharaju A, Mehta K, Mindikoglu AL, et al.: Use of activated recombinant human factor VII (rhFVIIa) for colonic polypectomies in patients with cirrhosis and coagulopathy. Dig Dis Sci 2003, 48:1414–1424.

    Article  PubMed  CAS  Google Scholar 

  31. Papatheodoridis GV, Chung S, Keshav S, et al.: Correction of both prothrombin time and primary haemostasis by recombinant factor VII during therapeutic alcohol injection of hepatocellular cancer in liver cirrhosis. J Hepatol 1999, 31:747–750.

    Article  PubMed  CAS  Google Scholar 

  32. Mindikoglu AL, Anantharaju A, Villanueva J, et al.: Pericardiocentesis and pancreatic aspiration needle biopsy in coagulopathic and thrombocytopenic cirrhotic patient. Chest 2003, 123:956–958.

    Article  PubMed  Google Scholar 

  33. Surudo T, Wojcicki M, Milkiewicz P, et al.: Rapid correction of prothrombin time after low-dose recombinant factor VIIA in patients undergoing orthotopic liver transplantation. Transplant Proc 2003, 35:2323–2325.

    Article  PubMed  CAS  Google Scholar 

  34. 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, 71:402–405.

    Article  PubMed  CAS  Google Scholar 

  35. 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, 11:895–900.

    Article  PubMed  Google Scholar 

  36. 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, 11:973–979.

    Article  PubMed  Google Scholar 

  37. Bosch J, Thabut D, Bendtsen F, et al.: Recombinant factor VIIa for upper gastrointestinal bleeding in patients with cirrhosis: a randomized, double-blind trial. Gastroenterology 2004, 127:1123–1130.

    Article  PubMed  CAS  Google Scholar 

  38. Cao ZX, Chen XP, Wu ZD: Effects of splenectomy in patients with cirrhosis undergoing hepatic resection for hepatocellular carcinoma. World J Gastroenterol 2003, 9:2460–2463.

    PubMed  Google Scholar 

  39. Wu CC, Cheng SB, Ho WM, et al.: Appraisal of concomitant splenectomy in liver resection for hepatocellular carcinoma in cirrhotic patients with hypersplenic thrombocytopenia. Surgery 2004, 136:660–668.

    Article  PubMed  Google Scholar 

  40. Kercher KW, Carbonell AM, Heniford BT, et al.: Laparoscopic splenectomy reverses thrombocytopenia in patients with hepatitis C cirrhosis and portal hypertension. J Gastrointest Surg 2004, 8:120–126.

    Article  PubMed  Google Scholar 

  41. N’Kontchou G, Seror O, Bourcier V, et al.: Partial splenic embolization in patients with cirrhosis: efficacy, tolerance and long-term outcome in 32 patients. Eur J Gastroenterol Hepatol 2005, 17:179–184.

    Article  PubMed  Google Scholar 

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Correspondence to K. Rajender Reddy.

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Blonski, W., Siropaides, T. & Reddy, K.R. Coagulopathy in liver disease. Curr Treat Options Gastro 10, 464–473 (2007). https://doi.org/10.1007/s11938-007-0046-7

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