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

Immune thrombocytopenia (ITP) in adults: Clinical manifestations and diagnosis

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


Primary immune thrombocytopenia (ITP, also called idiopathic thrombocytopenic purpura, immune thrombocytopenic purpura) is an acquired thrombocytopenia caused by autoantibodies against platelet antigens. It is one of the more common causes of thrombocytopenia in otherwise asymptomatic adults.

Major diagnostic concerns in an adult with suspected ITP are distinguishing ITP from other causes of thrombocytopenia, which often have a similar presentation but may require completely different management approaches, and determining whether the ITP is primary or secondary to an underlying condition that might also benefit from treatment.

The lack of a sensitive or specific diagnostic test for ITP, and large number of other potential causes of thrombocytopenia, some of which may be overlooked (eg, drug-induced, congenital platelet disorder), also contribute to the challenges in diagnosing ITP.

Here we discuss the clinical manifestations and diagnosis of primary ITP in adults, as well as the differential diagnosis of ITP and causes of "secondary ITP" due to other conditions.

Other issues are discussed in separate topic reviews:

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: Aug 22, 2016.
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. Rodeghiero F, Stasi R, Gernsheimer T, et al. Standardization of terminology, definitions and outcome criteria in immune thrombocytopenic purpura of adults and children: report from an international working group. Blood 2009; 113:2386.
  2. Cines DB, Blanchette VS. Immune thrombocytopenic purpura. N Engl J Med 2002; 346:995.
  3. Michel M, Lee K, Piette JC, et al. Platelet autoantibodies and lupus-associated thrombocytopenia. Br J Haematol 2002; 119:354.
  4. Kuwana M, Kaburaki J, Okazaki Y, et al. Two types of autoantibody-mediated thrombocytopenia in patients with systemic lupus erythematosus. Rheumatology (Oxford) 2006; 45:851.
  5. Nugent D, McMillan R, Nichol JL, Slichter SJ. Pathogenesis of chronic immune thrombocytopenia: increased platelet destruction and/or decreased platelet production. Br J Haematol 2009; 146:585.
  6. Toltl LJ, Arnold DM. Pathophysiology and management of chronic immune thrombocytopenia: focusing on what matters. Br J Haematol 2011; 152:52.
  7. Cines DB, Bussel JB, Liebman HA, Luning Prak ET. The ITP syndrome: pathogenic and clinical diversity. Blood 2009; 113:6511.
  8. Cooper N, Bussel J. The pathogenesis of immune thrombocytopaenic purpura. Br J Haematol 2006; 133:364.
  9. Sood R, Wong W, Gotlib J, et al. Gene expression and pathway analysis of immune thrombocytopenic purpura. Br J Haematol 2008; 140:99.
  10. DiMaggio D, Anderson A, Bussel JB. Cytomegalovirus can make immune thrombocytopenic purpura refractory. Br J Haematol 2009; 146:104.
  11. Wright JF, Blanchette VS, Wang H, et al. Characterization of platelet-reactive antibodies in children with varicella-associated acute immune thrombocytopenic purpura (ITP). Br J Haematol 1996; 95:145.
  12. Chiao EY, Engels EA, Kramer JR, et al. Risk of immune thrombocytopenic purpura and autoimmune hemolytic anemia among 120 908 US veterans with hepatitis C virus infection. Arch Intern Med 2009; 169:357.
  13. Zhang W, Nardi MA, Borkowsky W, et al. Role of molecular mimicry of hepatitis C virus protein with platelet GPIIIa in hepatitis C-related immunologic thrombocytopenia. Blood 2009; 113:4086.
  14. Semple JW, Aslam R, Kim M, et al. Platelet-bound lipopolysaccharide enhances Fc receptor-mediated phagocytosis of IgG-opsonized platelets. Blood 2007; 109:4803.
  15. Stasi R, Provan D. Helicobacter pylori and Chronic ITP. Hematology Am Soc Hematol Educ Program 2008; :206.
  16. Mahévas M, Chiche L, Uzunhan Y, et al. Association of sarcoidosis and immune thrombocytopenia: presentation and outcome in a series of 20 patients. Medicine (Baltimore) 2011; 90:269.
  17. Cines DB, Liebman H, Stasi R. Pathobiology of secondary immune thrombocytopenia. Semin Hematol 2009; 46:S2.
  18. Semple JW. T cell and cytokine abnormalities in patients with autoimmune thrombocytopenic purpura. Transfus Apher Sci 2003; 28:237.
  19. Olsson B, Andersson PO, Jernås M, et al. T-cell-mediated cytotoxicity toward platelets in chronic idiopathic thrombocytopenic purpura. Nat Med 2003; 9:1123.
  20. Coopamah MD, Garvey MB, Freedman J, Semple JW. Cellular immune mechanisms in autoimmune thrombocytopenic purpura: An update. Transfus Med Rev 2003; 17:69.
  21. Liu B, Zhao H, Poon MC, et al. Abnormality of CD4(+)CD25(+) regulatory T cells in idiopathic thrombocytopenic purpura. Eur J Haematol 2007; 78:139.
  22. Guo C, Chu X, Shi Y, et al. Correction of Th1-dominant cytokine profiles by high-dose dexamethasone in patients with chronic idiopathic thrombocytopenic purpura. J Clin Immunol 2007; 27:557.
  23. Sakakura M, Wada H, Tawara I, et al. Reduced Cd4+Cd25+ T cells in patients with idiopathic thrombocytopenic purpura. Thromb Res 2007; 120:187.
  24. Ling Y, Cao X, Yu Z, Ruan C. Circulating dendritic cells subsets and CD4+Foxp3+ regulatory T cells in adult patients with chronic ITP before and after treatment with high-dose dexamethasome. Eur J Haematol 2007; 79:310.
  25. Stasi R, Cooper N, Del Poeta G, et al. Analysis of regulatory T-cell changes in patients with idiopathic thrombocytopenic purpura receiving B cell-depleting therapy with rituximab. Blood 2008; 112:1147.
  26. Yu J, Heck S, Patel V, et al. Defective circulating CD25 regulatory T cells in patients with chronic immune thrombocytopenic purpura. Blood 2008; 112:1325.
  27. Audia S, Samson M, Guy J, et al. Immunologic effects of rituximab on the human spleen in immune thrombocytopenia. Blood 2011; 118:4394.
  28. Ustun C, Dainer P, Hendricks L, et al. Association of breast cancer and immune thrombocytopenic purpura. South Med J 2002; 95:1335.
  29. Peffault de Latour R, Des Guetz G, Laurence V, et al. Breast cancer associated with idiopathic thrombocytopenic purpura: a single center series of 10 cases. Am J Clin Oncol 2004; 27:333.
  30. Tfayli A, Vesely SK, George JN. Occurrence of immune thrombocytopenic purpura in patients with nonhematologic cancers: a systematic review of clinical evidence from case reports. Community Oncology 2008; 5:260.
  31. Khasraw M, Baron-Hay S. Immune thrombocytopenic purpura (ITP) and breast cancer. Does adjuvant therapy for breast cancer improve platelet counts in ITP? Ann Oncol 2009; 20:1282.
  32. Sukati H, Watson HG, Urbaniak SJ, Barker RN. Mapping helper T-cell epitopes on platelet membrane glycoprotein IIIa in chronic autoimmune thrombocytopenic purpura. Blood 2007; 109:4528.
  33. Patel VL, Schwartz J, Bussel JB. The effect of anti-CD40 ligand in immune thrombocytopenic purpura. Br J Haematol 2008; 141:545.
  34. Chong BH. Primary immune thrombocytopenia: understanding pathogenesis is the key to better treatments. J Thromb Haemost 2009; 7:319.
  35. Kuwana M, Okazaki Y, Ikeda Y. Splenic macrophages maintain the anti-platelet autoimmune response via uptake of opsonized platelets in patients with immune thrombocytopenic purpura. J Thromb Haemost 2009; 7:322.
  36. British Committee for Standards in Haematology General Haematology Task Force. Guidelines for the investigation and management of idiopathic thrombocytopenic purpura in adults, children and in pregnancy. Br J Haematol 2003; 120:574.
  37. George JN, el-Harake MA, Raskob GE. Chronic idiopathic thrombocytopenic purpura. N Engl J Med 1994; 331:1207.
  38. Fabris F, Scandellari R, Ruzzon E, et al. Platelet-associated autoantibodies as detected by a solid-phase modified antigen capture ELISA test (MACE) are a useful prognostic factor in idiopathic thrombocytopenic purpura. Blood 2004; 103:4562.
  39. Frederiksen H, Schmidt K. The incidence of idiopathic thrombocytopenic purpura in adults increases with age. Blood 1999; 94:909.
  40. Terrell DR, Beebe LA, Vesely SK, et al. The incidence of immune thrombocytopenic purpura in children and adults: A critical review of published reports. Am J Hematol 2010; 85:174.
  41. Harari A, Petitpierre S, Vallelian F, Pantaleo G. Skewed representation of functionally distinct populations of virus-specific CD4 T cells in HIV-1-infected subjects with progressive disease: changes after antiretroviral therapy. Blood 2004; 103:966.
  42. Abrahamson PE, Hall SA, Feudjo-Tepie M, et al. The incidence of idiopathic thrombocytopenic purpura among adults: a population-based study and literature review. Eur J Haematol 2009; 83:83.
  43. Terrell DR, Beebe LA, Neas BR, et al. Prevalence of primary immune thrombocytopenia in Oklahoma. Am J Hematol 2012; 87:848.
  44. Portielje JE, Westendorp RG, Kluin-Nelemans HC, Brand A. Morbidity and mortality in adults with idiopathic thrombocytopenic purpura. Blood 2001; 97:2549.
  45. 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.
  46. Moulis G, Palmaro A, Montastruc JL, et al. Epidemiology of incident immune thrombocytopenia: a nationwide population-based study in France. Blood 2014; 124:3308.
  47. Schoonen WM, Kucera G, Coalson J, et al. Epidemiology of immune thrombocytopenic purpura in the General Practice Research Database. Br J Haematol 2009; 145:235.
  48. Neunert C, Noroozi N, Norman G, et al. Severe bleeding events in adults and children with primary immune thrombocytopenia: a systematic review. J Thromb Haemost 2015; 13:457.
  49. Peng J, Friese P, Heilmann E, et al. Aged platelets have an impaired response to thrombin as quantitated by P-selectin expression. Blood 1994; 83:161.
  50. Terrell DR, Beebe LA, Vesely SK, et al. Determining a definite diagnosis of primary immune thrombocytopenia by medical record review. Am J Hematol 2012; 87:843.
  51. George JN, Woolf SH, Raskob GE, et al. Idiopathic thrombocytopenic purpura: a practice guideline developed by explicit methods for the American Society of Hematology. Blood 1996; 88:3.
  52. Provan D, Stasi R, Newland AC, et al. International consensus report on the investigation and management of primary immune thrombocytopenia. Blood 2010; 115:168.
  53. Neunert C, Lim W, Crowther M, et al. The American Society of Hematology 2011 evidence-based practice guideline for immune thrombocytopenia. Blood 2011; 117:4190.
  54. Cheung E, Liebman HA. Thyroid disease in patients with immune thrombocytopenia. Hematol Oncol Clin North Am 2009; 23:1251.
  55. Gupta R, Soupir CP, Johari V, Hasserjian RP. Myelodysplastic syndrome with isolated deletion of chromosome 20q: an indolent disease with minimal morphological dysplasia and frequent thrombocytopenic presentation. Br J Haematol 2007; 139:265.
  56. Jubelirer SJ, Harpold R. The role of the bone marrow examination in the diagnosis of immune thrombocytopenic purpura: case series and literature review. Clin Appl Thromb Hemost 2002; 8:73.
  57. Mahabir VK, Ross C, Popovic S, et al. A blinded study of bone marrow examinations in patients with primary immune thrombocytopenia. Eur J Haematol 2013; 90:121.
  58. McMillan R. The role of antiplatelet autoantibody assays in the diagnosis of immune thrombocytopenic purpura. Curr Hematol Rep 2005; 4:160.
  59. Raife TJ, Olson JD, Lentz SR. Platelet antibody testing in idiopathic thrombocytopenic purpura. Blood 1997; 89:1112.
  60. Lescale KB, Eddleman KA, Cines DB, et al. Antiplatelet antibody testing in thrombocytopenic pregnant women. Am J Obstet Gynecol 1996; 174:1014.
  61. Berchtold P, Müller D, Beardsley D, et al. International study to compare antigen-specific methods used for the measurement of antiplatelet autoantibodies. Br J Haematol 1997; 96:477.
  62. Davoren A, Bussel J, Curtis BR, et al. Prospective evaluation of a new platelet glycoprotein (GP)-specific assay (PakAuto) in the diagnosis of autoimmune thrombocytopenia (AITP). Am J Hematol 2005; 78:193.
  63. McMillan R, Wang L, Tani P. Prospective evaluation of the immunobead assay for the diagnosis of adult chronic immune thrombocytopenic purpura (ITP). J Thromb Haemost 2003; 1:485.
  64. Warner MN, Moore JC, Warkentin TE, et al. A prospective study of protein-specific assays used to investigate idiopathic thrombocytopenic purpura. Br J Haematol 1999; 104:442.
  65. George JN. Platelet immunoglobulin G: its significance for the evaluation of thrombocytopenia and for understanding the origin of alpha-granule proteins. Blood 1990; 76:859.
  66. Cines DB, Bussel JB. How I treat idiopathic thrombocytopenic purpura (ITP). Blood 2005; 106:2244.