Official reprint from UpToDate®
www.uptodate.com ©2017 UpToDate, Inc. and/or its affiliates. All Rights Reserved.

Hematologic manifestations of HIV infection: Thrombocytopenia and coagulation abnormalities

Timothy J Friel, MD
David T Scadden, MD
Section Editor
Lawrence LK Leung, MD
Deputy Editor
Jennifer S Tirnauer, MD


Shortly after the first description of the acquired immunodeficiency syndrome (AIDS), cytopenias of all major blood cell lines were increasingly recognized among patients infected with the human immunodeficiency virus (HIV). In one early series of patients with AIDS, anemia was noted in approximately 70 percent, lymphopenia in 70 percent, neutropenia in 50 percent, and thrombocytopenia in 40 percent [1]. Data from a large European cohort demonstrated a 3.2 percent prevalence of HIV infection among individuals presenting with unexplained thrombocytopenia or leukopenia lasting for more than four weeks [2].

The incidence of the various cytopenias correlates directly with the degree of immunosuppression. However, isolated abnormalities, particularly thrombocytopenia, may be encountered as the initial presentation of HIV infection. As a result, HIV infection should be considered in the assessment of patients presenting with any type of cytopenia.

The causes and treatment of thrombocytopenia and coagulation abnormalities in patients with HIV infection will be reviewed here [3]. Similar issues regarding anemia, neutropenia, and lymphopenia are discussed separately. (See "Hematologic manifestations of HIV infection: Anemia" and "Hematologic manifestations of HIV infection: Neutropenia" and "Techniques and interpretation of measurement of the CD4 cell count in HIV-infected patients".)


Overview — Thrombocytopenia was a common finding in individuals infected with HIV in the era prior to the use of potent antiretroviral therapy (ART), affecting approximately 40 percent of patients during the course of their illness [1]. In the context of widespread potent ART, the incidence of thrombocytopenia is far lower, diagnosed in only 0.6 percent of 5290 HIV infected individuals at the BC Centre for Excellence in HIV/AIDS [4].

HIV-associated thrombocytopenia occurs in patients from all major risk groups, including those exposed via homosexual or heterosexual contact, injection drug use, and blood product transfusion.

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: Sep 2017. | This topic last updated: Oct 18, 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 ©2017 UpToDate, Inc.
  1. Morris L, Distenfeld A, Amorosi E, Karpatkin S. Autoimmune thrombocytopenic purpura in homosexual men. Ann Intern Med 1982; 96:714.
  2. Sullivan AK, Raben D, Reekie J, et al. Feasibility and effectiveness of indicator condition-guided testing for HIV: results from HIDES I (HIV indicator diseases across Europe study). PLoS One 2013; 8:e52845.
  3. Karpatkin S, Nardi M, Green D. Platelet and coagulation defects associated with HIV-1-infection. Thromb Haemost 2002; 88:389.
  4. Ambler KL, Vickars LM, Leger CS, et al. Clinical Features, Treatment, and Outcome of HIV-Associated Immune Thrombocytopenia in the HAART Era. Adv Hematol 2012; 2012:910954.
  5. Sloand EM, Klein HG, Banks SM, et al. Epidemiology of thrombocytopenia in HIV infection. Eur J Haematol 1992; 48:168.
  6. Søgaard OS, Lohse N, Østergaard L, et al. Morbidity and risk of subsequent diagnosis of HIV: a population based case control study identifying indicator diseases for HIV infection. PLoS One 2012; 7:e32538.
  7. Lai SW, Lin HF, Lin CL, Liao KF. Immune thrombocytopenic purpura might be an early hematologic manifestation of undiagnosed human immunodeficiency virus infection. Intern Emerg Med 2017; 12:157.
  8. Galli M, Musicco M, Gervasoni C, et al. No evidence of a higher risk of progression to AIDS in patients with HIV-1-related severe thrombocytopenia. J Acquir Immune Defic Syndr Hum Retrovirol 1996; 12:268.
  9. Wandt H, Frank M, Ehninger G, et al. Safety and cost effectiveness of a 10 x 10(9)/L trigger for prophylactic platelet transfusions compared with the traditional 20 x 10(9)/L trigger: a prospective comparative trial in 105 patients with acute myeloid leukemia. Blood 1998; 91:3601.
  10. Vannappagari V, Nkhoma ET, Atashili J, et al. Prevalence, severity, and duration of thrombocytopenia among HIV patients in the era of highly active antiretroviral therapy. Platelets 2011; 22:611.
  11. Marks KM, Clarke RM, Bussel JB, et al. Risk factors for thrombocytopenia in HIV-infected persons in the era of potent antiretroviral therapy. J Acquir Immune Defic Syndr 2009; 52:595.
  12. Firnhaber C, Smeaton L, Saukila N, et al. Comparisons of anemia, thrombocytopenia, and neutropenia at initiation of HIV antiretroviral therapy in Africa, Asia, and the Americas. Int J Infect Dis 2010; 14:e1088.
  13. Ehmann WC, Rabkin CS, Eyster ME, Goedert JJ. Thrombocytopenia in HIV-infected and uninfected hemophiliacs. Multicenter Hemophilia Cohort study. Am J Hematol 1997; 54:296.
  14. Peltier JY, Lambin P, Doinel C, et al. Frequency and prognostic importance of thrombocytopenia in symptom-free HIV-infected individuals: a 5-year prospective study. AIDS 1991; 5:381.
  15. Glatt AE, Anand A. Thrombocytopenia in patients infected with human immunodeficiency virus: treatment update. Clin Infect Dis 1995; 21:415.
  16. Ballem PJ, Belzberg A, Devine DV, et al. Kinetic studies of the mechanism of thrombocytopenia in patients with human immunodeficiency virus infection. N Engl J Med 1992; 327:1779.
  17. Cole JL, Marzec UM, Gunthel CJ, et al. Ineffective platelet production in thrombocytopenic human immunodeficiency virus-infected patients. Blood 1998; 91:3239.
  18. 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.
  19. Bettaieb A, Oksenhendler E, Fromont P, et al. Immunochemical analysis of platelet autoantibodies in HIV-related thrombocytopenic purpura: a study of 68 patients. Br J Haematol 1989; 73:241.
  20. Karpatkin S, Nardi M, Lennette ET, et al. Anti-human immunodeficiency virus type 1 antibody complexes on platelets of seropositive thrombocytopenic homosexuals and narcotic addicts. Proc Natl Acad Sci U S A 1988; 85:9763.
  21. Bettaieb A, Fromont P, Louache F, et al. Presence of cross-reactive antibody between human immunodeficiency virus (HIV) and platelet glycoproteins in HIV-related immune thrombocytopenic purpura. Blood 1992; 80:162.
  22. Karpatkin S, Nardi M. Autoimmune anti-HIV-1gp120 antibody with antiidiotype-like activity in sera and immune complexes of HIV-1-related immunologic thrombocytopenia. J Clin Invest 1992; 89:356.
  23. Nardi M, Tomlinson S, Greco MA, Karpatkin S. Complement-independent, peroxide-induced antibody lysis of platelets in HIV-1-related immune thrombocytopenia. Cell 2001; 106:551.
  24. Koefoed K, Ditzel HJ. Identification of talin head domain as an immunodominant epitope of the antiplatelet antibody response in patients with HIV-1-associated thrombocytopenia. Blood 2004; 104:4054.
  25. Gonzalez-Conejero R, Rivera J, Rosillo MC, et al. Association of autoantibodies against platelet glycoproteins Ib/IX and IIb/IIIa, and platelet-reactive anti-HIV antibodies in thrombocytopenic narcotic addicts. Br J Haematol 1996; 93:464.
  26. Bettaieb A, Oksenhendler E, Duedari N, Bierling P. Cross-reactive antibodies between HIV-gp120 and platelet gpIIIa (CD61) in HIV-related immune thrombocytopenic purpura. Clin Exp Immunol 1996; 103:19.
  27. Nardi M, Karpatkin S. Antiidiotype antibody against platelet anti-GPIIIa contributes to the regulation of thrombocytopenia in HIV-1-ITP patients. J Exp Med 2000; 191:2093.
  28. Li Z, Nardi MA, Karpatkin S. Role of molecular mimicry to HIV-1 peptides in HIV-1-related immunologic thrombocytopenia. Blood 2005; 106:572.
  29. Bender BS, Frank MM, Lawley TJ, et al. Defective reticuloendothelial system Fc-receptor function in patients with acquired immunodeficiency syndrome. J Infect Dis 1985; 152:409.
  30. Grossetête B, Viard JP, Lehuen A, et al. Impaired Fc alpha receptor expression is linked to increased immunoglobulin A levels and disease progression in HIV-1-infected patients. AIDS 1995; 9:229.
  31. Zucker-Franklin D, Cao YZ. Megakaryocytes of human immunodeficiency virus-infected individuals express viral RNA. Proc Natl Acad Sci U S A 1989; 86:5595.
  32. Louache F, Bettaieb A, Henri A, et al. Infection of megakaryocytes by human immunodeficiency virus in seropositive patients with immune thrombocytopenic purpura. Blood 1991; 78:1697.
  33. Chelucci C, Federico M, Guerriero R, et al. Productive human immunodeficiency virus-1 infection of purified megakaryocytic progenitors/precursors and maturing megakaryocytes. Blood 1998; 91:1225.
  34. Bahner I, Kearns K, Coutinho S, et al. Infection of human marrow stroma by human immunodeficiency virus-1 (HIV-1) is both required and sufficient for HIV-1-induced hematopoietic suppression in vitro: demonstration by gene modification of primary human stroma. Blood 1997; 90:1787.
  35. Moses A, Nelson J, Bagby GC Jr. The influence of human immunodeficiency virus-1 on hematopoiesis. Blood 1998; 91:1479.
  36. Zauli G, Catani L, Gibellini D, et al. Impaired survival of bone marrow GPIIb/IIa+ megakaryocytic cells as an additional pathogenetic mechanism of HIV-1-related thrombocytopenia. Br J Haematol 1996; 92:711.
  37. Thompson GR 3rd, Lawrence VA, Crawford GE. HIV infection increases the risk of heparin-induced thrombocytopenia. Clin Infect Dis 2007; 45:1393.
  38. Manji F, Wilson E, Mahe E, et al. Acute HIV infection presenting as hemophagocytic lymphohistiocytosis: case report and review of the literature. BMC Infect Dis 2017; 17:633.
  39. Toltl LJ, Arnold DM. Pathophysiology and management of chronic immune thrombocytopenia: focusing on what matters. Br J Haematol 2011; 152:52.
  40. Ananworanich J, Phanuphak N, Nuesch R, et al. Recurring thrombocytopenia associated with structured treatment interruption in patients with human immunodeficiency virus infection. Clin Infect Dis 2003; 37:723.
  41. Bouldouyre MA, Charreau I, Marchou B, et al. Incidence and risk factors of thrombocytopenia in patients receiving intermittent antiretroviral therapy: a substudy of the ANRS 106-window trial. J Acquir Immune Defic Syndr 2009; 52:531.
  42. Imaz A, Olmo M, Peñaranda M, et al. Short-term and long-term clinical and immunological consequences of stopping antiretroviral therapy in HIV-infected patients with preserved immune function. Antivir Ther 2013; 18:125.
  43. Zidovudine for the treatment of thrombocytopenia associated with human immunodeficiency virus (HIV). A prospective study. The Swiss Group for Clinical Studies on the Acquired Immunodeficiency Syndrome (AIDS). Ann Intern Med 1988; 109:718.
  44. Oksenhendler E, Bierling P, Ferchal F, et al. Zidovudine for thrombocytopenic purpura related to human immunodeficiency virus (HIV) infection. Ann Intern Med 1989; 110:365.
  45. 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.
  46. Maness LJ, Blair DC, Newman N, Coyle TE. Elevation of platelet counts associated with indinavir treatment in human immunodeficiency virus-infected patients. Clin Infect Dis 1998; 26:207.
  47. Arranz Caso JA, Sanchez Mingo C, Garcia Tena J. Effect of highly active antiretroviral therapy on thrombocytopenia in patients with HIV infection. N Engl J Med 1999; 341:1239.
  48. 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.
  49. Choi SY, Kim I, Kim NJ, et al. Hematological manifestations of human immunodeficiency virus infection and the effect of highly active anti-retroviral therapy on cytopenia. Korean J Hematol 2011; 46:253.
  50. Abrams DI, Kiprov DD, Goedert JJ, et al. Antibodies to human T-lymphotropic virus type III and development of the acquired immunodeficiency syndrome in homosexual men presenting with immune thrombocytopenia. Ann Intern Med 1986; 104:47.
  51. Pollak AN, Janinis J, Green D. Successful intravenous immune globulin therapy for human immunodeficiency virus-associated thrombocytopenia. Arch Intern Med 1988; 148:695.
  52. Godeau B, Lesage S, Divine M, et al. Treatment of adult chronic autoimmune thrombocytopenic purpura with repeated high-dose intravenous immunoglobulin. Blood 1993; 82:1415.
  53. Holzman RS, Walsh CM, Karpatkin S. Risk for the acquired immunodeficiency syndrome among thrombocytopenic and nonthrombocytopenic homosexual men seropositive for the human immunodeficiency virus. Ann Intern Med 1987; 106:383.
  54. Ware RE, Zimmerman SA. Anti-D: mechanisms of action. Semin Hematol 1998; 35:14.
  55. Oksenhendler E, Bierling P, Brossard Y, et al. Anti-RH immunoglobulin therapy for human immunodeficiency virus-related immune thrombocytopenic purpura. Blood 1988; 71:1499.
  56. Scaradavou A, Woo B, Woloski BM, et al. Intravenous anti-D treatment of immune thrombocytopenic purpura: experience in 272 patients. Blood 1997; 89:2689.
  57. Gringeri A, Cattaneo M, Santagostino E, Mannucci PM. Intramuscular anti-D immunoglobulins for home treatment of chronic immune thrombocytopenic purpura. Br J Haematol 1992; 80:337.
  58. Scaradavou A, Cunningham-Rundles S, Ho JL, et al. Superior effect of intravenous anti-D compared with IV gammaglobulin in the treatment of HIV-thrombocytopenia: results of a small, randomized prospective comparison. Am J Hematol 2007; 82:335.
  59. Durand JM, Lefèvre P, Hovette P, et al. Dapsone for thrombocytopenic purpura related to human immunodeficiency virus infection. Am J Med 1991; 90:675.
  60. Oksenhendler E, Bierling P, Farcet JP, et al. Response to therapy in 37 patients with HIV-related thrombocytopenic purpura. Br J Haematol 1987; 66:491.
  61. 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.
  62. Northfelt DW, Charlebois ED, Mirda MI, et al. Continuous low-dose interferon-alpha therapy for HIV-related immune thrombocytopenic purpura. J Acquir Immune Defic Syndr Hum Retrovirol 1995; 8:45.
  63. Mintzer DM, Real FX, Jovino L, Krown SE. Treatment of Kaposi's sarcoma and thrombocytopenia with vincristine in patients with the acquired immunodeficiency syndrome. Ann Intern Med 1985; 102:200.
  64. Oksenhendler E, Bierling P, Chevret S, et al. Splenectomy is safe and effective in human immunodeficiency virus-related immune thrombocytopenia. Blood 1993; 82:29.
  65. Barbui T, Cortelazzo S, Minetti B, et al. Does splenectomy enhance risk of AIDS in HIV-positive patients with chronic thrombocytopenia? Lancet 1987; 2:342.
  66. Kemeny MM, Cooke V, Melester TS, et al. Splenectomy in patients with AIDS and AIDS-related complex. AIDS 1993; 7:1063.
  67. Aboolian A, Ricci M, Shapiro K, et al. Surgical treatment of HIV-related immune thrombocytopenia. Int Surg 1999; 84:81.
  68. Lord RV, Coleman MJ, Milliken ST. Splenectomy for HIV-related immune thrombocytopenia: comparison with results of splenectomy for non-HIV immune thrombocytopenic purpura. Arch Surg 1998; 133:205.
  69. Antel KR, Panieri E, Novitzky N. Role of splenectomy for immune thrombocytopenic purpura (ITP) in the era of new second-line therapies and in the setting of a high prevalence of HIV-associated ITP. S Afr Med J 2015; 105:408.
  70. Needleman SW, Sorace J, Poussin-Rosillo H. Low-dose splenic irradiation in the treatment of autoimmune thrombocytopenia in HIV-infected patients. Ann Intern Med 1992; 116:310.
  71. Soum F, Trille JA, Auvergnat JC, et al. Low-dose splenic irradiation in the treatment of immune thrombocytopenia in HIV-infected patients. Int J Radiat Oncol Biol Phys 1998; 41:123.
  72. Blauth J, Fisher S, Henry D, Nichini F. The role of splenic irradiation in treating HIV-associated immune thrombocytopenia. Int J Radiat Oncol Biol Phys 1999; 45:457.
  73. Kowalczyk M, Rubinstein PG, Aboulafia DM. Initial Experience with the Use of Thrombopoetin Receptor Agonists in Patients with Refractory HIV-Associated Immune Thrombocytopenic Purpura: A Case Series. J Int Assoc Provid AIDS Care 2015; 14:211.
  74. Sullivan PS, Dworkin MS, Jones JL, Hooper WC. Epidemiology of thrombosis in HIV-infected individuals. The Adult/Adolescent Spectrum of HIV Disease Project. AIDS 2000; 14:321.
  75. Fultz SL, McGinnis KA, Skanderson M, et al. Association of venous thromboembolism with human immunodeficiency virus and mortality in veterans. Am J Med 2004; 116:420.
  76. Malek J, Rogers R, Kufera J, Hirshon JM. Venous thromboembolic disease in the HIV-infected patient. Am J Emerg Med 2011; 29:278.
  77. Jacobson MC, Dezube BJ, Aboulafia DM. Thrombotic complications in patients infected with HIV in the era of highly active antiretroviral therapy: a case series. Clin Infect Dis 2004; 39:1214.
  78. Saif MW, Bona R, Greenberg B. AIDS and thrombosis: retrospective study of 131 HIV-infected patients. AIDS Patient Care STDS 2001; 15:311.
  79. Klein SK, Slim EJ, de Kruif MD, et al. Is chronic HIV infection associated with venous thrombotic disease? A systematic review. Neth J Med 2005; 63:129.
  80. Ahonkhai AA, Gebo KA, Streiff MB, et al. Venous thromboembolism in patients with HIV/AIDS: a case-control study. J Acquir Immune Defic Syndr 2008; 48:310.
  81. Crum-Cianflone NF, Weekes J, Bavaro M. Review: thromboses among HIV-infected patients during the highly active antiretroviral therapy era. AIDS Patient Care STDS 2008; 22:771.
  82. Funderburg NT, Mayne E, Sieg SF, et al. Increased tissue factor expression on circulating monocytes in chronic HIV infection: relationship to in vivo coagulation and immune activation. Blood 2010; 115:161.
  83. Baker JV, Huppler Hullsiek K, Bradford RL, et al. Circulating levels of tissue factor microparticle procoagulant activity are reduced with antiretroviral therapy and are associated with persistent inflammation and coagulation activation among HIV-positive patients. J Acquir Immune Defic Syndr 2013; 63:367.
  84. Funderburg NT, Lederman MM. Coagulation and morbidity in treated HIV infection. Thromb Res 2014; 133 Suppl 1:S21.
  85. Stimmler MM, Quismorio FP Jr, McGehee WG, et al. Anticardiolipin antibodies in acquired immunodeficiency syndrome. Arch Intern Med 1989; 149:1833.
  86. Abuaf N, Laperche S, Rajoely B, et al. Autoantibodies to phospholipids and to the coagulation proteins in AIDS. Thromb Haemost 1997; 77:856.
  87. Martinez V, Diemert MC, Braibant M, et al. Anticardiolipin antibodies in HIV infection are independently associated with antibodies to the membrane proximal external region of gp41 and with cell-associated HIV DNA and immune activation. Clin Infect Dis 2009; 48:123.
  88. Abdollahi A, Morteza A. Serum concentrations of antiphospholipid and anticardiolipin antibodies are higher in HIV-infected women. Rheumatol Int 2012; 32:1927.
  89. Bloom EJ, Abrams DI, Rodgers G. Lupus anticoagulant in the acquired immunodeficiency syndrome. JAMA 1986; 256:491.
  90. Cohen AJ, Philips TM, Kessler CM. Circulating coagulation inhibitors in the acquired immunodeficiency syndrome. Ann Intern Med 1986; 104:175.
  91. Aboulafia DM, Mitsuyasu RT. Hematologic abnormalities in AIDS. Hematol Oncol Clin North Am 1991; 5:195.
  92. Saif MW, Greenberg B. HIV and thrombosis: a review. AIDS Patient Care STDS 2001; 15:15.
  93. Bissuel F, Berruyer M, Causse X, et al. Acquired protein S deficiency: correlation with advanced disease in HIV-1-infected patients. J Acquir Immune Defic Syndr 1992; 5:484.
  94. Erbe M, Rickerts V, Bauersachs RM, Lindhoff-Last E. Acquired protein C and protein S deficiency in HIV-infected patients. Clin Appl Thromb Hemost 2003; 9:325.
  95. Stahl CP, Wideman CS, Spira TJ, et al. Protein S deficiency in men with long-term human immunodeficiency virus infection. Blood 1993; 81:1801.
  96. Gris JC, Toulon P, Brun S, et al. The relationship between plasma microparticles, protein S and anticardiolipin antibodies in patients with human immunodeficiency virus infection. Thromb Haemost 1996; 76:38.
  97. Becker S, Fusco G, Fusco J, et al. HIV-associated thrombotic microangiopathy in the era of highly active antiretroviral therapy: an observational study. Clin Infect Dis 2004; 39 Suppl 5:S267.
  98. Benjamin M, Terrell DR, Vesely SK, et al. Frequency and significance of HIV infection among patients diagnosed with thrombotic thrombocytopenic purpura. Clin Infect Dis 2009; 48:1129.
  99. Novitzky N, Thomson J, Abrahams L, et al. Thrombotic thrombocytopenic purpura in patients with retroviral infection is highly responsive to plasma infusion therapy. Br J Haematol 2005; 128:373.
  100. Hart D, Sayer R, Miller R, et al. Human immunodeficiency virus associated thrombotic thrombocytopenic purpura--favourable outcome with plasma exchange and prompt initiation of highly active antiretroviral therapy. Br J Haematol 2011; 153:515.