Seminars in Hematology
Volume 47, Issue 3 , Pages 266-273 , July 2010

Use of Thrombopoietic Agents for the Thrombocytopenia of Liver Disease

  • Hans L. Tillmann

      Affiliations

    • Corresponding Author InformationCorresponding author: Hans L. Tillmann, MD, Assistant Professor of Medicine, Duke Clinical Research Institute, Duke University Medical Center, PO Box 17969, Durham, NC 27715-7969
    • ,
  • John G. McHutchison

References 

  1. Gressner OA, Weiskirchen R, Gressner AM. Biomarkers of liver fibrosis: clinical translation of molecular pathogenesis or based on liver-dependent malfunction tests. Clin Chim Acta. 2007;381:107–113
  2. Bashour FN, Teran JC, Mullen KD. Prevalence of peripheral blood cytopenias (hypersplenism) in patients with nonalcoholic chronic liver disease. Am J Gastroenterol. 2000;95:2936–2939
  3. 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
  4. Peck-Radosavljevic M. Review article: coagulation disorders in chronic liver disease. Aliment Pharmacol Ther. 2007;26(Suppl 1):21–28
  5. Jelkmann W. The role of the liver in the production of thrombopoietin compared with erythropoietin. Eur J Gastroenterol Hepatol. 2001;13:791–801
  6. Tripodi A, Caldwell SH, Hoffman M, Trotter JF, Sanyal AJ. Review article: the prothrombin time test as a measure of bleeding risk and prognosis in liver disease. Aliment Pharmacol Ther. 2007;26:141–148
  7. Tessari P. Protein metabolism in liver cirrhosis: from albumin to muscle myofibrils. Curr Opin Clin Nutr Metab Care. 2003;6:79–85
  8. Nagamine T, Ohtuka T, Takehara K, Arai T, Takagi H, Mori M. Thrombocytopenia associated with hepatitis C viral infection. J Hepatol. 1996;24:135–140
  9. García-Suárez J, Burgaleta C, Hernanz N, Albarran F, Tobaruela P, Alvarez-Mon M. HCV-associated thrombocytopenia: clinical characteristics and platelet response after recombinant alpha2b-interferon therapy. Br J Haematol. 2000;110:98–103
  10. Doi T, Homma H, Mezawa S, et al. Mechanisms for increment of platelet associated IgG and platelet surface IgG and their implications in immune thrombocytopenia associated with chronic viral liver disease. Hepatol Res. 2002;24:23
  11. Sanjo A, Satoi J, Ohnishi A, Maruno J, Fukata M, Suzuki N. Role of elevated platelet-associated immunoglobulin G and hypersplenism in thrombocytopenia of chronic liver diseases. J Gastroenterol Hepatol. 2003;18:638–644
  12. Kuter DJ. New drugs for familiar therapeutic targets: thrombopoietin receptor agonists and immune thrombocytopenic purpura. Eur J Haematol Suppl. 2008;69:9–18
  13. Shearer MJ. Vitamin K in parenteral nutrition. Gastroenterology. 2009;137(Suppl):S105–S118
  14. Wada H, Usui M, Sakuragawa N. Hemostatic abnormalities and liver diseases. Semin Thromb Hemost. 2008;34:772–778
  15. Tripodi A, Primignani M, Chantarangkul V, et al. Thrombin generation in patients with cirrhosis: the role of platelets. Hepatology. 2006;44:440–445
  16. 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
  17. 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;51:682–689
  18. Murata S, Hashimoto I, Nakano Y, Myronovych A, Watanabe M, Ohkohchi N. Single administration of thrombopoietin prevents progression of liver fibrosis and promotes liver regeneration after partial hepatectomy in cirrhotic rats. Ann Surg. 2008;248:821–828
  19. Myronovych A, Murata S, Chiba M, et al. Role of platelets on liver regeneration after 90% hepatectomy in mice. J Hepatol. 2008;49:363–372
  20. Shimabukuro R, Kawanaka H, Tomikawa M, et al. Effect of thrombopoietin on platelet counts and liver regeneration after partial hepatectomy in a rat model. Surg Today. 2009;39:1054–1059
  21. Alkozai EM, Nijsten MW, de Jong KP, et al. Immediate postoperative low platelet count is associated with delayed liver function recovery after partial liver resection. Ann Surg. 2010;251:300–306
  22. Lesurtel M, Graf R, Aleil B, et al. Platelet-derived serotonin mediates liver regeneration. Science. 2006;312:104–107
  23. Balasubramanian S, Paulose CS. Induction of DNA synthesis in primary cultures of rat hepatocytes by serotonin: possible involvement of serotonin S2 receptor. Hepatology. 1998;27:62–66
  24. 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;27:1017–1029
  25. Aytac S, Turkay C, Bavbek N, Kosar A. Hemostasis and global fibrinolytic capacity in chronic liver disease. Blood Coagul Fibrinolysis. 2007;18:623–626
  26. Nagaoka MR, Kouyoumdjian M, Borges DR. Hepatic clearance of tissue-type plasminogen activator and plasma kallikrein in experimental liver fibrosis. Liver Int. 2003;23:476–483
  27. Herwald H, Mörgelin M, Dahlbäck B, Björck L. Interactions between surface proteins of Streptococcus pyogenes and coagulation factors modulate clotting of human plasma. J Thromb Haemost. 2003;1:284–291
  28. Poynard T, Marcellin P, Lee SS, et al. Randomised trial of interferon alpha2b plus ribavirin for 48 weeks or for 24 weeks versus interferon alpha2b plus placebo for 48 weeks for treatment of chronic infection with hepatitis C virus (International Hepatitis Interventional Therapy Group (IHIT)). Lancet. 1998;352:1426–1432
  29. Davis GL, Esteban-Mur R, Rustgi V, et al. Interferon alfa-2b alone or in combination with ribavirin for the treatment of relapse of chronic hepatitis C (International Hepatitis Interventional Therapy Group). N Engl J Med. 1998;339:1493–1499
  30. Trivedi HS, Trivedi M. Subnormal rise of erythropoietin in patients receiving interferon and ribavirin combination therapy for hepatitis C. J Clin Gastroenterol. 2004;38:595–598
  31. Kaupke CJ, Butler GC, Vaziri ND. Effect of recombinant human erythropoietin on platelet production in dialysis patients. J Am Soc Nephrol. 1993;3:1672–1679
  32. Shreiner DP, Levin J. The effects of hemorrhage, hypoxia, and a preparation of erythropoietin on thrombopoiesis. J Lab Clin Med. 1976;88:930–940
  33. Heathcote EJ, Shiffman ML, Cooksley WG, et al. Peginterferon alfa-2a in patients with chronic hepatitis C and cirrhosis. N Engl J Med. 2000;343:1673–1680
  34. McHutchison JG, Manns M, Patel K, et al. Adherence to combination therapy enhances sustained response in genotype-1-infected patients with chronic hepatitis C. Gastroenterology. 2002;123:1061–1069
  35. McHutchison JG, Everson GT, Gordon SC, et al. Telaprevir with peginterferon and ribavirin for chronic HCV genotype 1 infection. N Engl J Med. 2009;360:1827–1838
  36. Hézode C, Forestier N, Dusheiko G, et al. Telaprevir and peginterferon with or without ribavirin for chronic HCV infection. N Engl J Med. 2009;360:1839–1850
  37. Mederacke I, Wedemeyer H, Manns MP. Boceprevir, an NS3 serine protease inhibitor of hepatitis C virus, for the treatment of HCV infection. Curr Opin Invest Drugs. 2009;10:181–189
  38. Bogen SL, Pan W, Ruan S, et al. Toward the back-up of boceprevir (SCH 503034): discovery of new extended P4-capped ketoamide inhibitors of hepatitis C virus NS3 serine protease with improved potency and pharmacokinetic profiles. J Med Chem. 2009;52:3679–3688
  39. Sharma P, McDonald GB, Banaji M. The risk of bleeding after percutaneous liver biopsy: relation to platelet count. J Clin Gastroenterol. 1982;4:451–453
  40. Rebulla P. Trigger for platelet transfusion. Vox Sang. 2000;78(Suppl 2):179–182
  41. Mourtzoukou EG, Pappas G, Peppas G, Falagas ME. Vaccination of asplenic or hyposplenic adults. Br J Surg. 2008;95:273–280
  42. Kato M, Shimohashi N, Ouchi J, et al. Partial splenic embolization facilitates completion of interferon therapy in patients with chronic HCV infection and hypersplenism. J Gastroenterol. 2005;40:1076–1077
  43. Dienstag JL, McHutchison JG. American Gastroenterological Association technical review on the management of hepatitis C. Gastroenterology. 2006;130:231–264
  44. Ghany MG, Strader DB, Thomas DL, Seeff LB American Association for the Study of Liver Diseases. Diagnosis, management, and treatment of hepatitis C: an update. Hepatology. 2009;49:1335–1374
  45. Alvarez OA, Lopera GA, Patel V, Encarnacion CE, Palmaz JC, Lee M. Improvement of thrombocytopenia due to hypersplenism after transjugular intrahepatic portosystemic shunt placement in cirrhotic patients. Am J Gastroenterol. 1996;91:134–137
  46. Colombato L. The role of transjugular intrahepatic portosystemic shunt (TIPS) in the management of portal hypertension. J Clin Gastroenterol. 2007;41(Suppl 3):S344–S351
  47. McHutchison JG, Dusheiko G, Shiffman ML, et al. Eltrombopag for thrombocytopenia in patients with cirrhosis associated with hepatitis C. N Engl J Med. 2007;357:2227–2236
  48. http://clinicaltrials.gov/ct2/show/NCT00678587Accessed December 23, 2009
  49. http://www.nplate.com/patient/pdf/nplate_pi.pdfAccessed December 23, 2009
  50. http://www.promactacares.com/prescribing_information.pdfAccessed December 23, 2009
  51. Bussel JB, Cheng G, Saleh MN, et al. Eltrombopag for the treatment of chronic idiopathic thrombocytopenic purpura. N Engl J Med. 2007;357:2237–2247
  52. Wolber EM, Haase B, Jelkmann W. Thrombopoietin production in human hepatic cell cultures (HepG2) is resistant to IFN-alpha, IFN-beta, and IFN-gamma treatment. J Interferon Cytokine Res. 2002;22:1185–1189
  53. Yamane A, Nakamura T, Suzuki H, et al. Interferon-{alpha}2b-induced thrombocytopenia is caused by inhibition of platelet production but not proliferation and endomitosis in human megakaryocytes. Blood. 2008;112:542–550
  54. Vadhan-Raj S, Cohen V, Bueso-Ramos C. Thrombopoietic growth factors and cytokines. Curr Hematol Rep. 2005;4:137–144
  55. Brown JR, Demetri GD. Challenges in the development of platelet growth factors: low expectations for low counts. Curr Hematol Rep. 2002;1:110–118
  56. Smith JW, Longo DL, Alvord WG, et al. The effects of treatment with interleukin-1 alpha on platelet recovery after high-dose carboplatin. N Engl J Med. 1993;328:756–761
  57. http://www.wyeth.com/content/showlabeling.asp?id=500Accessed December 23, 2009
  58. Artz AS, Ershler WB, Rustgi V. Interleukin-11 for thrombocytopenia associated with hepatitis C. J Clin Gastroenterol. 2001;33:425–426
  59. Ghalib R, Levine C, Hassan M, et al. Recombinant human interleukin-11 improves thrombocytopenia in patients with cirrhosis. Hepatology. 2003;37:1165–1171
  60. Lawitz EJ, Hepburn MJ, Casey TJ. A pilot study of interleukin-11 in subjects with chronic hepatitis C and advanced liver disease nonresponsive to antiviral therapy. Am J Gastroenterol. 2004;99:2359–2364
  61. Fontana V, Dudkiewicz P, Jy W, Horstman L, Ahn YS. Interleukin-11 for treatment of hepatitis C-associated ITP. Acta Haematol. 2008;119:126–132
  62. NICE Technology Appraisal Guideline (August 2008). Pregnancy - routine anti-D prophylaxis for rhesus negative women (review of TA41). http://www.nice.org.uk/nicemedia/pdf/TA156Guidance.pdfAccessed December 19, 2009
  63. Ware RE, Zimmerman SA. Anti-D: mechanisms of action. Semin Hematol. 1998;35(Suppl 1):14–22
  64. WinRho®SDF prescribing information. http://www.baxter.com/products/biopharmaceuticals/downloads/winrhopi.pdfAccessed December 19, 2009
  65. http://rhophylac.com/pdf/PI%20Information%20Chart.pdfAccessed December 19, 2009
  66. de Almeida AJ, Campos-de-Magalhães M, Antonietti CL, et al. Autoimmune thrombocytopenia related to chronic hepatitis C virus infection. Hematology. 2009;14:49–58
  67. Bussel JB, Kuter DJ, Pullarkat V, Lyons RM, Guo M, Nichol JL. Safety and efficacy of long-term treatment with romiplostim in thrombocytopenic patients with chronic ITP. Blood. 2009;113:2161–2171

 Financial disclosures: H.L.T. has served as an adviser to Amgen concerning potential use of Nplate in liver disease. J.G.M. is an adviser and has received grant support from GSK in regard to their thrombopoeitic drug eltrombopag.

PII: S0037-1963(10)00059-4

doi: 10.1053/j.seminhematol.2010.04.003

Seminars in Hematology
Volume 47, Issue 3 , Pages 266-273 , July 2010

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