Seminars in Hematology
Volume 46 , Pages S15-S25 , January 2009

Therapeutic Strategies for Hepatitis- and Other Infection-Related Immune Thrombocytopenias

  • Roberto Stasi

      Affiliations

    • Corresponding Author InformationAddress correspondence to Roberto Stasi, MD, Department of Medical Sciences, Ospedale “Regina Apostolorum,” Via San Francesco, 50, 00041 Albano Laziale, Italy

References 

  1. Stasi R, Evangelista ML, Stipa E, Buccisano F, Venditti A, Amadori S. Idiopathic thrombocytopenic purpura: current concepts in pathophysiology and management. Thromb Haemost. 2008;99:4–13
  2. Liebman H. Other immune thrombocytopenias. Semin Hematol. 2007;44:S24–S34
  3. Liebman HA, Stasi R. Secondary immune thrombocytopenic purpura. Curr Opin Hematol. 2007;14:557–573
  4. Blanchette V, Bolton-Maggs P. Childhood immune thrombocytopenic purpura: diagnosis and management. Pediatr Clin North Am. 2008;55:393–420
  5. Craxi A, Laffi G, Zignego AL. Hepatitis C virus (HCV) infection: a systemic disease. Mol Aspects Med. 2008;29:85–95
  6. Nguyen TT, Sedghi-Vaziri A, Wilkes LB, Mondala T, Pockros PJ, Lindsay KL, et al. Fluctuations in viral load (HCV RNA) are relatively insignificant in untreated patients with chronic HCV infection. J Viral Hepat. 1996;3:75–78
  7. Seeff LB. Natural history of chronic hepatitis C. Hepatology. 2002;36:S35–S46
  8. Palekar NA, Harrison SA. Extrahepatic manifestations of hepatitis C. South Med J. 2005;98:1019–1023
  9. Pyrsopoulos NT, Reddy KR. Extrahepatic manifestations of chronic viral hepatitis. Curr Gastroenterol Rep. 2001;3:71–78
  10. Shepard CW, Finelli L, Alter MJ. Global epidemiology of hepatitis C virus infection. Lancet Infect Dis. 2005;5:558–567
  11. Armstrong GL, Wasley A, Simard EP, McQuillan GM, Kuhnert WL, Alter MJ. The prevalence of hepatitis C virus infection in the United States, 1999 through 2002. Ann Intern Med. 2006;144:705–714
  12. Sulkowski MS. Management of the hematologic complications of hepatitis C therapy. Clin Liver Dis. 2005;9:601–616
  13. 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
  14. Rajan SK, Espina BM, Liebman HA. Hepatitis C virus-related thrombocytopenia: clinical and laboratory characteristics compared with chronic immune thrombocytopenic purpura. Br J Haematol. 2005;129:818–824
  15. Pockros PJ, Duchini A, McMillan R, Nyberg LM, McHutchison J, Viernes E. Immune thrombocytopenic purpura in patients with chronic hepatitis C virus infection. Am J Gastroenterol. 2002;97:2040–2045
  16. 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
  17. Garcia-Suarez 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
  18. Zhang L, Li H, Zhao H, Ji L, Yang R. Hepatitis C virus-related adult chronic idiopathic thrombocytopenic purpura: experience from a single Chinese center. Eur J Haematol. 2003;70:196–197
  19. Pivetti S, Novarino A, Merico F, Bertero MT, Brunetto MR, Bonino F, et al. High prevalence of autoimmune phenomena in hepatitis C virus antibody positive patients with lymphoproliferative and connective tissue disorders. Br J Haematol. 1996;95:204–211
  20. Sakuraya M, Murakami H, Uchiumi H, Hatsumi N, Akiba T, Yokohama A, et al. Steroid-refractory chronic idiopathic thrombocytopenic purpura associated with hepatitis C virus infection. Eur J Haematol. 2002;68:49–53
  21. Pawlotsky JM, Bouvier M, Fromont P, Deforges L, Duval J, Dhumeaux D, et al. Hepatitis C virus infection and autoimmune thrombocytopenic purpura. J Hepatol. 1995;23:635–639
  22. Hernandez F, Blanquer A, Linares M, Lopez A, Tarin F, Cervero A. Autoimmune thrombocytopenia associated with hepatitis C virus infection. Acta Haematol. 1998;99:217–220
  23. Ramos-Casals M, Garcia-Carrasco M, Lopez-Medrano F, et al. Severe autoimmune cytopenias in treatment-naive hepatitis C virus infection: clinical description of 35 cases. Medicine (Baltimore). 2003;82:87–96
  24. Rajan S, Liebman HA. Treatment of hepatitis C related thrombocytopenia with interferon alpha. Am J Hematol. 2001;68:202–209
  25. Iga D, Tomimatsu M, Endo H, Ohkawa S, Yamada O. Improvement of thrombocytopenia with disappearance of HCV RNA in patients treated by interferon-alpha therapy: possible etiology of HCV-associated immune thrombocytopenia. Eur J Haematol. 2005;75:417–423
  26. 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
  27. 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
  28. Morris L, Distenfeld A, Amorosi E, Karpatkin S. Autoimmune thrombocytopenic purpura in homosexual men. Ann Intern Med. 1982;96:714–717
  29. Ratnoff OD, Menitove JE, Aster RH, Lederman MM. Coincident classic hemophilia and “idiopathic” thrombocytopenic purpura in patients under treatment with concentrates of antihemophilic factor (factor VIII). N Engl J Med. 1983;308:439–442
  30. Walsh CM, Nardi MA, Karpatkin S. On the mechanism of thrombocytopenic purpura in sexually active homosexual men. N Engl J Med. 1984;311:635–639
  31. Walsh C, Krigel R, Lennette E, Karpatkin S. Thrombocytopenia in homosexual patients (Prognosis, response to therapy, and prevalence of antibody to the retrovirus associated with the acquired immunodeficiency syndrome). Ann Intern Med. 1985;103:542–545
  32. UNAIDS. AIDS epidemic update: December 2007. http://data.unaids.org/pub/EPISlides/2007/2007_epiupdate_en.pdfAccessed September 19, 2008
  33. The Henry J. Kaiser Family Foundation. Fact sheet: The HIV/AIDS epidemic in the United States. HIV/AIDS policy fact sheet. http://www.kff.org/hivaids/upload/3029-08.pdfAccessed September 19, 2008
  34. Kaslow RA, Phair JP, Friedman HB, et al. Infection with the human immunodeficiency virus: clinical manifestations and their relationship to immune deficiency (A report from the Multicenter AIDS Cohort Study). Ann Intern Med. 1987;107:474–480
  35. Sloand EM, Klein HG, Banks SM, Vareldzis B, Merritt S, Pierce P. Epidemiology of thrombocytopenia in HIV infection. Eur J Haematol. 1992;48:168–172
  36. Rossi G, Gorla R, Stellini R, et al. Prevalence, clinical, and laboratory features of thrombocytopenia among HIV-infected individuals. AIDS Res Hum Retroviruses. 1990;6:261–269
  37. Peltier JY, Lambin P, Doinel C, Courouce AM, Rouger P, Lefrere JJ. Frequency and prognostic importance of thrombocytopenia in symptom-free HIV-infected individuals: a 5-year prospective study. AIDS. 1991;5:381–384
  38. Mientjes GH, van Ameijden EJ, Mulder JW, van den Hoek JA, Coutinho RA, von dem Borne AE. Prevalence of thrombocytopenia in HIV-infected and non-HIV infected drug users and homosexual men. Br J Haematol. 1992;82:615–619
  39. Sullivan PS, Hanson DL, Chu SY, Jones JL, Ciesielski CA. Surveillance for thrombocytopenia in persons infected with HIV: results from the multistate Adult and Adolescent Spectrum of Disease Project. J Acquir Immune Defic Syndr Hum Retrovirol. 1997;14:374–379
  40. Burbano X, Miguez MJ, Lecusay R, et al. Thrombocytopenia in HIV-infected drug users in the HAART era. Platelets. 2001;12:456–461
  41. Landonio G, Galli M, Nosari A, et al. HIV-related severe thrombocytopenia in intravenous drug users: prevalence, response to therapy in a medium-term follow-up, and pathogenetic evaluation. AIDS. 1990;4:29–34
  42. Ciernik IF, Cone RW, Fehr J, Weber R. Impaired liver function and retroviral activity are risk factors contributing to HIV-associated thrombocytopenia (Swiss HIV Cohort Study). AIDS. 1999;13:1913–1920
  43. Quan CM, Krajden M, Grigoriew GA, Salit IE. Hepatitis C virus infection in patients infected with the human immunodeficiency virus. Clin Infect Dis. 1993;17:117–119
  44. Quaranta JF, Delaney SR, Alleman S, Cassuto JP, Dellamonica P, Allain JP. Prevalence of antibody to hepatitis C virus (HCV) in HIV-1-infected patients (nice SEROCO cohort). J Med Virol. 1994;42:29–32
  45. Berhane K, Karim R, Cohen MH, et al. Impact of highly active antiretroviral therapy on anemia and relationship between anemia and survival in a large cohort of HIV-infected women: Women's Interagency HIV Study. J Acquir Immune Defic Syndr. 2004;37:1245–1252
  46. Levine AM, Karim R, Mack W, et al. Neutropenia in human immunodeficiency virus infection: data from the women's interagency HIV study. Arch Intern Med. 2006;166:405–410
  47. Karpatkin S. Autoimmune thrombocytopenias. Autoimmunity. 2004;37:363–368
  48. Ragni MV, Bontempo FA, Myers DJ, Kiss JE, Oral A. Hemorrhagic sequelae of immune thrombocytopenic purpura in human immunodeficiency virus-infected hemophiliacs. Blood. 1990;75:1267–1272
  49. Finazzi G, Mannucci PM, Lazzarin A, et al. Low incidence of bleeding from HIV-related thrombocytopenia in drug addicts and hemophiliacs: implications for therapeutic strategies. Eur J Haematol. 1990;45:82–85
  50. Yetgin S, Demir H, Arslan D, Unal S, Kocak N. Autoimmune thrombocytopenic purpura and Helicobacter pylori infection effectivity during childhood. Am J Hematol. 2005;78:318
  51. Murphy MF, Metcalfe P, Waters AH, Carne CA, Weller IV, Linch DC, et al. Incidence and mechanism of neutropenia and thrombocytopenia in patients with human immunodeficiency virus infection. Br J Haematol. 1987;66:337–340
  52. Landonio G, Nosari A, Spinelli F, Vigorelli R, Caggese L, Schlacht I. HIV-related thrombocytopenia: four different clinical subsets. Haematologica. 1992;77:398–401
  53. Servais J, Nkoghe D, Schmit JC, et al. HIV-associated hematologic disorders are correlated with plasma viral load and improve under highly active antiretroviral therapy. J Acquir Immune Defic Syndr. 2001;28:221–225
  54. Landonio G, Cinque P, Nosari A, et al. Comparison of two dose regimens of zidovudine in an open, randomized, multicentre study for severe HIV-related thrombocytopenia. AIDS. 1993;7:209–212
  55. Oksenhendler E, Bierling P, Ferchal F, Clauvel JP, Seligmann M. Zidovudine for thrombocytopenic purpura related to human immunodeficiency virus (HIV) infection. Ann Intern Med. 1989;110:365–368
  56. Cinque P, Landonio G, Lazzarin A, et al. Long-term treatment with zidovudine in patients with human immunodeficiency virus (HIV)-associated thrombocytopenia: modes of response and correlation with markers of HIV replication. Eur J Haematol. 1993;50:17–21
  57. Aboulafia DM, Bundow D, Waide S, Bennet C, Kerr D. Initial observations on the efficacy of highly active antiretroviral therapy in the treatment of HIV-associated autoimmune thrombocytopenia. Am J Med Sci. 2000;320:117–123
  58. Carbonara S, Fiorentino G, Serio G, et al. Response of severe HIV-associated thrombocytopenia to highly active antiretroviral therapy including protease inhibitors. J Infect. 2001;42:251–256
  59. Miguez MJ, Burbano X, Archer H, Shor-Posner G. Limited impact of highly active antiretroviral therapy in thrombocytopenia. J Acquir Immune Defic Syndr. 2002;30:260–261
  60. Schacter LP, Rozencweig M, Beltangady M, et al. Effects of therapy with didanosine on hematologic parameters in patients with advanced human immunodeficiency virus disease. Blood. 1992;80:2969–2976
  61. Nasti G, Errante D, Tirelli U. Successful treatment of HIV-1-related, zidovudine resistant, thrombocytopenia with didanosine. Am J Hematol. 1997;55:118–119
  62. Marroni M, Gresele P, Landonio G, et al. Interferon-alpha is effective in the treatment of HIV-1-related, severe, zidovudine-resistant thrombocytopenia (A prospective, placebo-controlled, double-blind trial). Ann Intern Med. 1994;121:423–429
  63. Northfelt DW, Charlebois ED, Mirda MI, Child C, Kaplan LD, Abrams DI. Continuous low-dose interferon-alpha therapy for HIV-related immune thrombocytopenic purpura. J Acquir Immune Defic Syndr Hum Retrovirol. 1995;8:45–50
  64. Oksenhendler E, Bierling P, Farcet JP, Rabian C, Seligmann M, Clauvel JP. Response to therapy in 37 patients with HIV-related thrombocytopenic purpura. Br J Haematol. 1987;66:491–495
  65. Oksenhendler E, Bierling P, Chevret S, Delfraissy JF, Laurian Y, Clauvel JP, et al. Splenectomy is safe and effective in human immunodeficiency virus-related immune thrombocytopenia. Blood. 1993;82:29–32
  66. Scaradavou A, Woo B, Woloski BM, Cunningham-Rundles S, Ettinger LJ, Aledort LM, et al. Intravenous anti-D treatment of immune thrombocytopenic purpura: experience in 272 patients. Blood. 1997;89:2689–2700
  67. Najean Y, Rain JD. The mechanism of thrombocytopenia in patients with HIV infection. J Lab Clin Med. 1994;123:415–420
  68. Leissinger CA, Andes WA. Role of splenectomy in the management of hemophilic patients with human immunodeficiency virus-associated immunopathic thrombocytopenic purpura. Am J Hematol. 1992;40:207–209
  69. Marroni M, Sinnone MS, Landonio G, Aristei C, Boschetti E, Lazzarin A, et al. Splenic irradiation versus splenectomy for severe, refractory HIV-related thrombocytopenia: effects on platelet counts and immunological status. AIDS. 2000;14:1664–1667
  70. Andersen LP. Colonization and infection by Helicobacter pylori in humans. Helicobacter. 2007;12(Suppl 2):12–15
  71. Suerbaum S, Michetti P. Helicobacter pylori infection. N Engl J Med. 2002;347:1175–1186
  72. Logan RP, Walker MM. ABC of the upper gastrointestinal tract: epidemiology and diagnosis of Helicobacter pylori infection. BMJ. 2001;323:920–922
  73. Graham DY, Kimura K, Shimoyama T, Takemoto T. Helicobacter pylori infection in Japan: current status and future options. Eur J Gastroenterol Hepatol. 1994;6(Suppl 1):S1–S4
  74. Russo A, Eboli M, Pizzetti P, et al. Determinants of Helicobacter pylori seroprevalence among Italian blood donors. Eur J Gastroenterol Hepatol. 1999;11:867–873
  75. Rajantie J, Klemola T. Helicobacter pylori and idiopathic thrombocytopenic purpura in children. Blood. 2003;101:1660
  76. Hayashi H, Okuda M, Aoyagi N, Yoshiyama M, Miyashiro E, Kounami S, et al. Helicobacter pylori infection in children with chronic idiopathic thrombocytopenic purpura. Pediatr Int. 2005;47:292–295
  77. Jaing TH, Yang CP, Hung IJ, Chiu CH, Chang KW. Efficacy of Helicobacter pylori eradication on platelet recovery in children with chronic idiopathic thrombocytopenic purpura. Acta Paediatr. 2003;92:1153–1157
  78. Franchini M, Cruciani M, Mengoli C, Pizzolo G, Veneri D. Effect of Helicobacter pylori eradication on platelet count in idiopathic thrombocytopenic purpura: a systematic review and meta-analysis. J Antimicrob Chemother. 2007;60:237–246
  79. Michel M, Cooper N, Jean C, Frissora C, Bussel JB. Does Helicobater pylori initiate or perpetuate immune thrombocytopenic purpura?. Blood. 2004;103:890–896
  80. Stasi R, Rossi Z, Stipa E, Amadori S, Newland AC, Provan D. Helicobacter pylori eradication in the management of patients with idiopathic thrombocytopenic purpura. Am J Med. 2005;118:414–419
  81. Fukui O, Shimoya K, Shimizu T, Fukuda H, Wasada K, Murata Y. Helicobacter pylori infection and platelet counts during pregnancy. Int J Gynaecol Obstet. 2005;89:26–30
  82. Fujimura K, Kuwana M, Kurata Y, et al. Is eradication therapy useful as the first line of treatment in Helicobacter pylori-positive idiopathic thrombocytopenic purpura? (Analysis of 207 eradicated chronic ITP cases in Japan). Int J Hematol. 2005;81:162–168
  83. Suzuki T, Matsushima M, Masui A, et al. Effect of Helicobacter pylori eradication in patients with chronic idiopathic thrombocytopenic purpura—a randomized controlled trial. Am J Gastroenterol. 2005;100:1265–1270
  84. Inaba T, Mizuno M, Take S, et al. Eradication of Helicobacter pylori increases platelet count in patients with idiopathic thrombocytopenic purpura in Japan. Eur J Clin Invest. 2005;35:214–219
  85. Asahi A, Kuwana M, Suzuki H, Hibi T, Kawakami Y, Ikeda Y. Effects of a Helicobacter pylori eradication regimen on anti-platelet autoantibody response in infected and uninfected patients with idiopathic thrombocytopenic purpura. Haematologica. 2006;91:1436–1437
  86. Emilia G, Luppi M, Zucchini P, et al. Helicobacter pylori infection and chronic immune thrombocytopenic purpura: long-term results of bacterium eradication and association with bacterium virulence profiles. Blood. 2007;110:3833–3841
  87. Veneri D, De Matteis G, Solero P, et al. Analysis of B- and T-cell clonality and HLA class II alleles in patients with idiopathic thrombocytopenic purpura: correlation with Helicobacter pylori infection and response to eradication treatment. Platelets. 2005;16:307–311
  88. Jarque I, Andreu R, Llopis I, et al. Absence of platelet response after eradication of Helicobacter pylori infection in patients with chronic idiopathic thrombocytopenic purpura. Br J Haematol. 2001;115:1002–1003
  89. Ahn ER, Tiede MP, Jy W, Bidot CJ, Fontana V, Ahn YS. Platelet activation in Helicobacter pylori-associated idiopathic thrombocytopenic purpura: eradication reduces platelet activation but seldom improves platelet counts. Acta Haematol. 2006;116:19–24
  90. Suvajdzic N, Stankovic B, Artiko V, et al. Helicobacter pylori eradication can induce platelet recovery in chronic idiopathic thrombocytopenic purpura. Platelets. 2006;17:227–230
  91. Estrada-Gomez RA, Parra-Ortega I, Martinez-Barreda C, Ruiz-Arguelles GJ. Helicobacter pylori infection and thrombocytopenia: a single-institution experience in Mexico. Rev Invest Clin. 2007;59:112–115
  92. Campuzano-Maya G. Proof of an association between Helicobacter pylori and idiopathic thrombocytopenic purpura in Latin America. Helicobacter. 2007;12:265–273
  93. Gasbarrini A, Franceschi F, Tartaglione R, Landolfi R, Pola P, Gasbarrini G. Regression of autoimmune thrombocytopenia after eradication of Helicobacter pylori. Lancet. 1998;352:878
  94. Kohda K, Kuga T, Kogawa K, et al. Effect of Helicobacter pylori eradication on platelet recovery in Japanese patients with chronic idiopathic thrombocytopenic purpura and secondary autoimmune thrombocytopenic purpura. Br J Haematol. 2002;118:584–588
  95. Hino M, Yamane T, Park K, et al. Platelet recovery after eradication of Helicobacter pylori in patients with idiopathic thrombocytopenic purpura. Ann Hematol. 2003;82:30–32
  96. Hashino S, Mori A, Suzuki S, et al. Platelet recovery in patients with idiopathic thrombocytopenic purpura after eradication of Helicobacter pylori. Int J Hematol. 2003;77:188–191
  97. Ando K, Shimamoto T, Tauchi T, et al. Can eradication therapy for Helicobacter pylori really improve the thrombocytopenia in idiopathic thrombocytopenic purpura? (Our experience and a literature review). Int J Hematol. 2003;77:239–244
  98. Takahashi T, Yujiri T, Shinohara K, et al. Molecular mimicry by Helicobacter pylori CagA protein may be involved in the pathogenesis of H. pylori-associated chronic idiopathic thrombocytopenic purpura. Br J Haematol. 2004;124:91–96
  99. Sato R, Murakami K, Watanabe K, et al. Effect of Helicobacter pylori eradication on platelet recovery in patients with chronic idiopathic thrombocytopenic purpura. Arch Intern Med. 2004;164:1904–1907
  100. Ando T, Tsuzuki T, Mizuno T, et al. Characteristics of Helicobacter pylori-induced gastritis and the effect of H. pylori eradication in patients with chronic idiopathic thrombocytopenic purpura. Helicobacter. 2004;9:443–452
  101. Nomura S, Inami N, Kanazawa S. The effects of Helicobacter pylori eradication on chemokine production in patients with immune thrombocytopenic purpura. Eur J Haematol. 2004;72:304–305
  102. Sayan O, Akyol Erikci A, Ozturk A. The efficacy of Helicobacter pylori eradication in the treatment of idiopathic thrombocytopenic purpura—the first study in Turkey. Acta Haematol. 2006;116:146–149
  103. Kodama M, Kitadai Y, Ito M, et al. Immune response to CagA protein is associated with improved platelet count after Helicobacter pylori eradication in patients with idiopathic thrombocytopenic purpura. Helicobacter. 2007;12:36–42
  104. Satake M, Nishikawa J, Fukagawa Y, et al. The long-term efficacy of Helicobacter pylori eradication therapy in patients with idiopathic thrombocytopenic purpura. J Gastroenterol Hepatol. 2007;22:2233–2237

 STATEMENT OF CONFLICT OF INTEREST: Roberto Stasi, MD, discloses the following: Honoraria: Amgen, GSK; Speakers’ Bureau: Amgen, GSK.

PII: S0037-1963(08)00205-9

doi: 10.1053/j.seminhematol.2008.12.006

Seminars in Hematology
Volume 46 , Pages S15-S25 , January 2009

Article Tools