European Journal of Internal Medicine
Volume 21, Issue 2 , Pages 65-69 , April 2010

The coagulopathy of chronic liver disease: Is there a causal relationship with bleeding? No

  • Armando Tripodi

      Affiliations

    • Corresponding Author InformationVia Pace 9, 20122-Milano, Italy. Tel.: +39 02 503 20725; fax: +39 02 503 20 723.

References 

  1. Gainnini EG, Savarino G. Thrombocytopenia in liver disease. Curr Opin Hematol. 2008;15:473–480
  2. Rubin MH, Weston MJ, Langley PG, et al. Platelet function in chronic liver disease: relationship to disease severity. Dig Dis Sci. 1979;24:197–202
  3. 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;24:1137–1142
  4. Thomas DP, Ream VJ, Stuart RK. Platelet aggregation in patients with Laennec's cirrhosis of the liver. N Engl J Med. 1967;276:1344–1348
  5. Ballard HS, Marcus AJ. Platelet aggregation in portal cirrhosis. Arch Intern Med. 1976;136:316–319
  6. Laffi G, La Villa G, Pinzani M, et al. Altered renal and platelet arachidonic acid metabolism in cirrhosis. Gastroenterology. 1986;90:274–282
  7. 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;8:1620–1626
  8. Laffi G, Daskalopoulos G, Kronborg I, et al. Effects of sulindac and ibuprofen in patients with cirrhosis and ascites. An explanation for the renal-sparing effect of sulindac. Gastroenterology. 1986;90:182–187
  9. Laffi G, Marra F, Failli P, et al. Defective signal transduction in platelets from cirrhotics is associated with increased cyclic nucleotides. Gastroenterology. 1993;105:148–156
  10. Laffi G, Marra F, Gresele P, et al. Evidence for a storage pool defect in platelets from cirrhotic patients with defective aggregation. Gastroenterology. 1992;103:641–646
  11. Ordinas A, Maragall S, Castillo R, et al. A glycoprotein I defect in the platelets of three patients with severe cirrhosis of the liver. Thromb Res. 1978;13:297–302
  12. Violi F, Leo R, Vezza E, et al. Bleeding time in patients with cirrhosis: relation with degree of liver failure and clotting abnormalities. C.A.L.C. Group. Coagulation Abnormalities in Cirrhosis Study Group. J Hepatol. 1994;20:531–536
  13. Boberg KM, Brosstad F, Egeland T, et al. Is a prolonged bleeding time associated with an increased risk of hemorrhage after liver biopsy?. Thromb Haemost. 1999;81:378–381
  14. Mannucci PM, Vicente V, Vianello L, et al. Controlled trial of desmopressin in liver cirrhosis and other conditions associated with a prolonged bleeding time. Blood. 1986;67:1148–1153
  15. Burroughs AK, Matthews K, Qadiri M, et al. Desmopressin and bleeding time in patients with cirrhosis. Br Med J. 1985;291:1377–1381
  16. Cattaneo M, Tenconi PM, Alberca I, et al. Subcutaneous desmopressin (DDAVP) shortens the prolonged bleeding time in patients with liver cirrhosis. Thromb Haemost. 1990;64:358–360
  17. de Franchis R, Arcidiacono PG, Carpinelli L, et al. Randomized controlled trial of desmopressin plus terlipressin vs. terlipressin alone for the treatment of acute variceal hemorrhage in cirrhotic patients: a multicenter, double-blind study. New Italian Endoscopic Club. Hepatology. 1993;18:1102–1107
  18. 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
  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;44:53–61
  20. Rockey DC, Caldwell SH, Goodman ZD, et al. American Association for the Study of Liver Diseases. Liver biopsy. Hepatology. 2009;49:1017–1044
  21. Newland A. Thrombopoietin receptor agonists in the treatment of thrombocytopenia. Curr Opin Hematol. 2009;16:357–364
  22. Tripodi A, Primignani M, Chantarangkul V, et al. An imbalance of pro- vs anti-coagulation factors in plasma from patients with cirrhosis. Gastroenterology. 2009;137:2105–2111
  23. Tripodi A, Chantarangkul V, Mannucci PM. Acquired coagulation disorders: revisited using global coagulation/anticoagulation testing. Br J Haematol. 2009;147:77–82
  24. Boks AL, Brommer EJ, Schalm SW, van Vliet HH. Hemostasis and fibrinolysis in severe liver failure and their relation to hemorrhage. Hepatology. 1986;6:79–86
  25. Hemker HC, Giesen P, Al Dieri R, et al. Calibrated automated thrombin generation measurement in clotting plasma. Pathophysiol Haemost Thromb. 2003;33:4–15
  26. Tripodi A, Salerno F, Chantarangkul V, et al. Evidence of normal thrombin generation in cirrhosis despite abnormal conventional coagulation tests. Hepatology. 2005;41:553–558
  27. Tripodi A, Primignani M, Chantarangkul V, et al. Thrombin generation in patients with cirrhosis: the role of platelets. Hepatology. 2006;44:440–445
  28. Bosch J, Thabut D, Bendtsen F, et al. for the European Study Group on rFVIIa in UGI Haemorrhage Recombinant factor VIIa for upper gastrointestinal bleeding in patients with cirrhosis: a randomized, double-blind trial. Gastroenterology. 2004;127:1123–1130
  29. Bosch J, Thabut D, Albillos A, et al. for the International Study Group on rFVIIa in UGI Hemorrhage Recombinant factor VIIa for variceal bleeding in patients with advanced cirrhosis: A randomized, controlled trial. Hepatology. 2008;47:1604–1614
  30. 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
  31. 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
  32. Caldwell SH, Hoffman M, Lisman T, et al. Coagulation disorders and hemostasis in liver disease: pathophysiology and critical assessment of current management. Hepatology. 2006;44:1039–1046
  33. Booth NA, Anderson JA, Bennett B. Plasminogen activators in alcoholic cirrhosis: demonstration of increased tissue type and urokinase type activator. J Clin Pathol. 1984;37:772–777
  34. Hersch SL, Kunelis T, Francio RB. The pathogenesis of accelerated fibrinolysis in liver cirrhosis: a critical role for tissue plasminogen activator inhibitor. Blood. 1987;69:1315–1319
  35. Tran-Thang C, Fasel-Felley J, Pralong G, et al. Plasminogen activators and plasminogen activator inhibitors in liver deficiencies caused by chronic alcoholism or infectious hepatitis. Thromb Haemost. 1989;62:651–653
  36. Marongiu F, Mamusa AM, Mameli C, et al. Alpha 2 Antiplasmin and disseminated intravascular coagulation in liver cirrhosis. Thromb Res. 1985;37:287–294
  37. Sinclair TS, Booth NA, Penman SM, et al. Protease inhibitors in liver disease. Scand J Gastroenterol. 1988;23:620–624
  38. Van Thiel DH, George M, Fareed J. Low levels of thrombin activatable fibrinolysis inhibitor (TAFI) in patients with chronic liver disease. Thromb Haemost. 2001;85:667–670
  39. Lisman T, Leebeek FW, Mosnier LO, et al. Thrombin-activatable fibrinolysis inhibitor deficiency in cirrhosis is not associated with increased plasma fibrinolysis. Gastroenterology. 2001;121:131–139
  40. Colucci M, Binetti BM, Branca MG, et al. Deficiency of thrombin activatable fibrinolysis inhibitor in cirrhosis is associated with increased plasma fibrinolysis. Hepatology. 2003;38:230–237
  41. Gunawan B, Runyon B. The efficacy and safety of έ-aminocaproic acid treatment in patients with cirrhosis and hyperfibrinolysis. Alim Pharm Ther. 2006;23:115–120
  42. Northup PG, McMahon MM, Ruhl AP, et al. Coagulopathy does not fully protect hospitalized cirrhosis patients from peripheral venous thromboembolism. Am J Gastroenterol. 2006;101:1524–1528
  43. Søgaard KK, Horváth-Puhó E, Grønbaek H, et al. Risk of venous thromboembolism in patients with liver disease: a nationwide population-based case-control study. Am J Gastroenterol. 2009;104:96–101
  44. Valla DC. Thrombosis and anticoagulation in liver disease. Hepatology. 2008;47:1384–1393
  45. Okuda K, Ohnishi K, Kimura K, et al. Incidence of portal vein thrombosis in liver cirrhosis. An angiographic study in 708 patients. Gastroenterology. 1985;89:279–286
  46. Francoz C, Belghiti J, Vilgrain V, et al. Splanchnic vein thrombosis in candidates for liver transplantation: usefulness of screening and anticoagulation. Gut. 2005;54:691–697
  47. Amitrano L, Brancaccio V, Guardascione MA, et al. Inherited coagulation disorders in cirrhotic patients with portal vein thrombosis. Hepatology. 2000;31:345–348
  48. Saliola M, Lorenzet R, Ferro D, et al. Enhanced expression of monocyte tissue factor in patients with liver cirrhosis. Gut. 1998;43:428–432
  49. 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;37:463–470

PII: S0953-6205(10)00020-8

doi: 10.1016/j.ejim.2010.02.001

European Journal of Internal Medicine
Volume 21, Issue 2 , Pages 65-69 , April 2010

Article Tools