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

Drug-induced immune thrombocytopenia

James N George, MD
Donald M Arnold, MD, MSc
Section Editor
Lawrence LK Leung, MD
Deputy Editor
Jennifer S Tirnauer, MD


Unexplained thrombocytopenia is a common clinical problem, and the possibility of drug-induced thrombocytopenia must be considered, especially in hospitalized patients. Drugs can cause thrombocytopenia by several mechanisms including direct bone marrow or other organ toxicity.

This topic review discusses drug-induced immune thrombocytopenia (DITP), in which the mechanism involves antibody-mediated platelet destruction caused by exposure to a drug that leads to isolated thrombocytopenia (without anemia or leukopenia). The "drug" in this context may be a prescribed medication (or its metabolite), over-the-counter medicine, herbal supplement, food, beverage, or other substance.

The unique thrombocytopenic drug reaction caused by heparin (heparin-induced thrombocytopenia [HIT], which we do not consider to be a form of DITP) is reviewed as a separate topic. (See "Clinical presentation and diagnosis of heparin-induced thrombocytopenia".)

General approaches to evaluating patients with thrombocytopenia in various settings are presented separately:

Neonates – (See "Causes of neonatal thrombocytopenia".)

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: Nov 2017. | This topic last updated: Apr 26, 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. Aster RH, Curtis BR, McFarland JG, Bougie DW. Drug-induced immune thrombocytopenia: pathogenesis, diagnosis, and management. J Thromb Haemost 2009; 7:911.
  2. Aster RH, Bougie DW. Drug-induced immune thrombocytopenia. N Engl J Med 2007; 357:580.
  3. Arnold DM, Nazi I, Warkentin TE, et al. Approach to the diagnosis and management of drug-induced immune thrombocytopenia. Transfus Med Rev 2013; 27:137.
  4. Bougie DW, Wilker PR, Aster RH. Patients with quinine-induced immune thrombocytopenia have both "drug-dependent" and "drug-specific" antibodies. Blood 2006; 108:922.
  5. Zhu J, Zhu J, Bougie DW, et al. Structural basis for quinine-dependent antibody binding to platelet integrin αIIbβ3. Blood 2015; 126:2138.
  6. Bougie DW, Peterson J, Rasmussen M, Aster RH. Mechanism of quinine-dependent monoclonal antibody binding to platelet glycoprotein IIb/IIIa. Blood 2015; 126:2146.
  7. Burgess JK, Lopez JA, Berndt MC, et al. Quinine-dependent antibodies bind a restricted set of epitopes on the glycoprotein Ib-IX complex: characterization of the epitopes. Blood 1998; 92:2366.
  8. Curtis BR, McFarland JG, Wu GG, et al. Antibodies in sulfonamide-induced immune thrombocytopenia recognize calcium-dependent epitopes on the glycoprotein IIb/IIIa complex. Blood 1994; 84:176.
  9. Reese JA, Li X, Hauben M, et al. Identifying drugs that cause acute thrombocytopenia: an analysis using 3 distinct methods. Blood 2010; 116:2127.
  10. Christie DJ, Weber RW, Mullen PC, et al. Structural features of the quinidine and quinine molecules necessary for binding of drug-induced antibodies to human platelets. J Lab Clin Med 1984; 104:730.
  11. Curtis BR, Kaliszewski J, Marques MB, et al. Immune-mediated thrombocytopenia resulting from sensitivity to oxaliplatin. Am J Hematol 2006; 81:193.
  12. Mirtsching BC, George JN, Aster RH, Curtis BR. Irinotecan-induced immune thrombocytopenia. Am J Med Sci 2014; 347:167.
  13. Cuker A, Coles AJ, Sullivan H, et al. A distinctive form of immune thrombocytopenia in a phase 2 study of alemtuzumab for the treatment of relapsing-remitting multiple sclerosis. Blood 2011; 118:6299.
  14. Mantadakis E, Farmaki E, Buchanan GR. Thrombocytopenic purpura after measles-mumps-rubella vaccination: a systematic review of the literature and guidance for management. J Pediatr 2010; 156:623.
  15. Lai CC, Sheng WH, Wang JT, et al. Safety and efficacy of high-dose daptomycin as salvage therapy for severe gram-positive bacterial sepsis in hospitalized adult patients. BMC Infect Dis 2013; 13:66.
  16. Gerson SL, Kaplan SL, Bruss JB, et al. Hematologic effects of linezolid: summary of clinical experience. Antimicrob Agents Chemother 2002; 46:2723.
  17. Munster P, Marchion D, Bicaku E, et al. Clinical and biological effects of valproic acid as a histone deacetylase inhibitor on tumor and surrogate tissues: phase I/II trial of valproic acid and epirubicin/FEC. Clin Cancer Res 2009; 15:2488.
  18. Gentilini G, Curtis BR, Aster RH. An antibody from a patient with ranitidine-induced thrombocytopenia recognizes a site on glycoprotein IX that is a favored target for drug-induced antibodies. Blood 1998; 92:2359.
  19. Burgess JK, Lopez JA, Gaudry LE, Chong BH. Rifampicin-dependent antibodies bind a similar or identical epitope to glycoprotein IX-specific quinine-dependent antibodies. Blood 2000; 95:1988.
  20. Pereira J, Hidalgo P, Ocqueteau M, et al. Glycoprotein Ib/IX complex is the target in rifampicin-induced immune thrombocytopenia. Br J Haematol 2000; 110:907.
  21. Kroll H, Sun QH, Santoso S. Platelet endothelial cell adhesion molecule-1 (PECAM-1) is a target glycoprotein in drug-induced thrombocytopenia. Blood 2000; 96:1409.
  22. George JN, Raskob GE, Shah SR, et al. Drug-induced thrombocytopenia: a systematic review of published case reports. Ann Intern Med 1998; 129:886.
  23. Pedersen-Bjergaard U, Andersen M, Hansen PB. Drug-induced thrombocytopenia: clinical data on 309 cases and the effect of corticosteroid therapy. Eur J Clin Pharmacol 1997; 52:183.
  24. Pedersen-Bjergaard U, Andersen M, Hansen PB. Drug-specific characteristics of thrombocytopenia caused by non-cytotoxic drugs. Eur J Clin Pharmacol 1998; 54:701.
  25. Von Drygalski A, Curtis BR, Bougie DW, et al. Vancomycin-induced immune thrombocytopenia. N Engl J Med 2007; 356:904.
  26. Kaufman DW, Kelly JP, Johannes CB, et al. Acute thrombocytopenic purpura in relation to the use of drugs. Blood 1993; 82:2714.
  27. Pedersen-Bjergaard U, Andersen M, Hansen PB. Thrombocytopenia induced by noncytotoxic drugs in Denmark 1968-91. J Intern Med 1996; 239:509.
  28. ten Berg MJ, Huisman A, Souverein PC, et al. Drug-induced thrombocytopenia: a population study. Drug Saf 2006; 29:713.
  29. Patel N, VanDeWall H, Tristani L, et al. A comparative evaluation of adverse platelet outcomes among Veterans' Affairs patients receiving linezolid or vancomycin. J Antimicrob Chemother 2012; 67:727.
  30. Search on "Drug-induced thrombocytopenia". www.ouhsc.edu/platelets (Accessed on February 06, 2016).
  31. Nguyen L, Reese JA, George JN. Drug-induced thrombocytopenia. An updated systematic review, 2010. Drug Saf 2011; .:.
  32. Arnold DM, Kukaswadia S, Nazi I, et al. A systematic evaluation of laboratory testing for drug-induced immune thrombocytopenia. J Thromb Haemost 2013; 11:169.
  33. George JN, Aster RH. Drug-induced thrombocytopenia: pathogenesis, evaluation, and management. Hematology Am Soc Hematol Educ Program 2009; :153.
  34. Reese JA, Nguyen LP, Buchanan GR, et al. Drug-induced thrombocytopenia in children. Pediatr Blood Cancer 2013; 60:1975.
  35. Rousan TA, Aldoss IT, Cowley BD Jr, et al. Recurrent acute thrombocytopenia in the hospitalized patient: sepsis, DIC, HIT, or antibiotic-induced thrombocytopenia. Am J Hematol 2010; 85:71.
  36. Curtis BR, Divgi A, Garritty M, Aster RH. Delayed thrombocytopenia after treatment with abciximab: a distinct clinical entity associated with the immune response to the drug. J Thromb Haemost 2004; 2:985.
  37. O'Donnell E, Shepherd C, Neff A. Immune thrombocytopenia from vancomycin in orthopedic cement. Am J Hematol 2007; 82:1122.
  38. Warkentin TE. Drug-induced immune-mediated thrombocytopenia--from purpura to thrombosis. N Engl J Med 2007; 356:891.
  39. McMahon CM, Cuker A. Hospital-acquired thrombocytopenia. Hosp Pract (1995) 2014; 42:142.
  40. Llevadot J, Coulter SA, Giugliano RP. A practical approach to the diagnosis and management of thrombocytopenia associated with glycoprotein IIb/IIIa receptor inhibitors. J Thromb Thrombolysis 2000; 9:175.
  41. Huxtable LM, Tafreshi MJ, Rakkar AN. Frequency and management of thrombocytopenia with the glycoprotein IIb/IIIa receptor antagonists. Am J Cardiol 2006; 97:426.
  42. Berkowitz SD, Harrington RA, Rund MM, Tcheng JE. Acute profound thrombocytopenia after C7E3 Fab (abciximab) therapy. Circulation 1997; 95:809.
  43. Berkowitz SD, Sane DC, Sigmon KN, et al. Occurrence and clinical significance of thrombocytopenia in a population undergoing high-risk percutaneous coronary revascularization. Evaluation of c7E3 for the Prevention of Ischemic Complications (EPIC) Study Group. J Am Coll Cardiol 1998; 32:311.
  44. Dasgupta H, Blankenship JC, Wood GC, et al. Thrombocytopenia complicating treatment with intravenous glycoprotein IIb/IIIa receptor inhibitors: a pooled analysis. Am Heart J 2000; 140:206.
  45. Merlini PA, Rossi M, Menozzi A, et al. Thrombocytopenia caused by abciximab or tirofiban and its association with clinical outcome in patients undergoing coronary stenting. Circulation 2004; 109:2203.
  46. Sane DC, Damaraju LV, Topol EJ, et al. Occurrence and clinical significance of pseudothrombocytopenia during abciximab therapy. J Am Coll Cardiol 2000; 36:75.
  47. Bougie DW, Wilker PR, Wuitschick ED, et al. Acute thrombocytopenia after treatment with tirofiban or eptifibatide is associated with antibodies specific for ligand-occupied GPIIb/IIIa. Blood 2002; 100:2071.
  48. Billheimer JT, Dicker IB, Wynn R, et al. Evidence that thrombocytopenia observed in humans treated with orally bioavailable glycoprotein IIb/IIIa antagonists is immune mediated. Blood 2002; 99:3540.
  49. Peterson JA, Nelson TN, Kanack AJ, Aster RH. Fine specificity of drug-dependent antibodies reactive with a restricted domain of platelet GPIIIA. Blood 2008; 111:1234.
  50. Bougie DW, Rasmussen M, Zhu J, Aster RH. Antibodies causing thrombocytopenia in patients treated with RGD-mimetic platelet inhibitors recognize ligand-specific conformers of αIIb/β3 integrin. Blood 2012; 119:6317.
  51. Gao C, Boylan B, Bougie D, et al. Eptifibatide-induced thrombocytopenia and thrombosis in humans require FcgammaRIIa and the integrin beta3 cytoplasmic domain. J Clin Invest 2009; 119:504.
  52. Curtis BR, Swyers J, Divgi A, et al. Thrombocytopenia after second exposure to abciximab is caused by antibodies that recognize abciximab-coated platelets. Blood 2002; 99:2054.
  53. Platelet Glycoprotein IIb/IIIa in Unstable Angina: Receptor Suppression Using Integrilin Therapy (PURSUIT) Trial Investigators. Inhibition of platelet glycoprotein IIb/IIIa with eptifibatide in patients with acute coronary syndromes. N Engl J Med 1998; 339:436.
  54. Platelet Receptor Inhibition in Ischemic Syndrome Management (PRISM) Study Investigators. A comparison of aspirin plus tirofiban with aspirin plus heparin for unstable angina. N Engl J Med 1998; 338:1498.
  55. Royer DJ, George JN, Terrell DR. Thrombocytopenia as an adverse effect of complementary and alternative medicines, herbal remedies, nutritional supplements, foods, and beverages. Eur J Haematol 2010; 84:421.
  56. Azuno Y, Yaga K, Sasayama T, Kimoto K. Thrombocytopenia induced by Jui, a traditional Chinese herbal medicine. Lancet 1999; 354:304.
  57. Ohmori T, Nishii K, Hagihara A, et al. Acute thrombocytopenia induced by jui, a traditional herbal medicine. J Thromb Haemost 2004; 2:1479.
  58. Liles NW, Page EE, Liles AL, et al. Diversity and severity of adverse reactions to quinine: A systematic review. Am J Hematol 2016; 91:461.
  59. Arnold J, Ouwehand WH, Smith GA, Cohen H. A young woman with petechiae. Lancet 1998; 352:618.
  60. Achterbergh R, Vermeer HJ, Curtis BR, et al. Thrombocytopenia in a nutshell. Lancet 2012; 379:776.
  61. Kojouri K, Perdue JJ, Medina PJ, George JN. Occult quinine-induced thrombocytopenia. J Okla State Med Assoc 2000; 93:519.
  62. Reddy JC, Shuman MA, Aster RH. Quinine/quinidine-induced thrombocytopenia: a great imitator. Arch Intern Med 2004; 164:218.
  63. Neylon AJ, Saunders PW, Howard MR, et al. Clinically significant newly presenting autoimmune thrombocytopenic purpura in adults: a prospective study of a population-based cohort of 245 patients. Br J Haematol 2003; 122:966.
  64. http://www.fda.gov/ucm/groups/fdagov-public/@fdagov-bio-gen/documents/document/ucm350239.pdf.
  65. Höchtl T, Pachinger L, Unger G, et al. Antiplatelet drug induced isolated profound thrombocytopenia in interventional cardiology: a review based on individual case reports. J Thromb Thrombolysis 2007; 24:59.
  66. http://www.ouhsc.edu/platelets/ditp.html.
  67. Al-Nouri ZL, George JN. Drug-induced thrombocytopenia: an updated systematic review, 2012. Drug Saf 2012; 35:693.
  68. Nguyen L, Reese J, George JN. Drug-induced thrombocytopenia: an updated systematic review, 2010. Drug Saf 2011; 34:437.
  69. Swisher KK, Li X, Vesely SK, George JN. Drug-induced thrombocytopenia: an updated systematic review, 2008. Drug Saf 2009; 32:85.
  70. Li X, Swisher KK, Vesely SK, George JN. Drug-induced thrombocytopenia: an updated systematic review, 2006. Drug Saf 2007; 30:185.
  71. Rizvi MA, Kojouri K, George JN. Drug-induced thrombocytopenia: an updated systematic review. Ann Intern Med 2001; 134:346.
  72. Warkentin TE, Kelton JG. Temporal aspects of heparin-induced thrombocytopenia. N Engl J Med 2001; 344:1286.
  73. Bougie D, Aster R. Immune thrombocytopenia resulting from sensitivity to metabolites of naproxen and acetaminophen. Blood 2001; 97:3846.
  74. Bougie DW, Benito AI, Sanchez-Abarca LI, et al. Acute thrombocytopenia caused by sensitivity to the glucuronide conjugate of acetaminophen. Blood 2007; 109:3608.
  75. Scognamiglio F, Corso C, Madeo D, et al. Flow cytometry in the diagnosis of drug-induced thrombocytopenia: two illustrative cases. Am J Hematol 2008; 83:326.
  76. Leach MF, Cooper LK, AuBuchon JP. Detection of drug-dependent, platelet-reactive antibodies by solid-phase red cell adherence assays. Br J Haematol 1997; 97:755.
  77. Nieminen U, Kekomäki R. Quinidine-induced thrombocytopenic purpura: clinical presentation in relation to drug-dependent and drug-independent platelet antibodies. Br J Haematol 1992; 80:77.
  78. Tcheng JE, Kereiakes DJ, Lincoff AM, et al. Abciximab readministration: results of the ReoPro Readministration Registry. Circulation 2001; 104:870.
  79. Madan M, Kereiakes DJ, Hermiller JB, et al. Efficacy of abciximab readministration in coronary intervention. Am J Cardiol 2000; 85:435.
  80. Ray JB, Brereton WF, Nullet FR. Intravenous immune globulin for the treatment of presumed quinidine-induced thrombocytopenia. DICP 1990; 24:693.
  81. Kereiakes DJ, Essell JH, Abbottsmith CW, et al. Abciximab-associated profound thrombocytopenia: therapy with immunoglobulin and platelet transfusion. Am J Cardiol 1996; 78:1161.
  82. Greinacher A, Fuerll B, Zinke H, et al. Megakaryocyte impairment by eptifibatide-induced antibodies causes prolonged thrombocytopenia. Blood 2009; 114:1250.
  83. Coblyn JS, Weinblatt M, Holdsworth D, Glass D. Gold-induced thrombocytopenia. A clinical and immunogenetic study of twenty-three patients. Ann Intern Med 1981; 95:178.
  84. Adachi JD, Bensen WG, Kassam Y, et al. Gold induced thrombocytopenia: 12 cases and a review of the literature. Semin Arthritis Rheum 1987; 16:287.
  85. Garner SF, Campbell K, Metcalfe P, et al. Glycoprotein V: the predominant target antigen in gold-induced autoimmune thrombocytopenia. Blood 2002; 100:344.