Smarter Decisions,
Better Care

UpToDate synthesizes the most recent medical information into evidence-based practical recommendations clinicians trust to make the right point of care decisions.

  • Rigorous editorial process: Evidence-based treatment recommendations
  • World-Renowned physician authors: over 5,100 physician authors around the globe
  • Innovative technology: integrates into the workflow; access from EMRs

For more information, click below.


Subscribers log in here


Related articles

Clinical manifestations and diagnosis of immune thrombocytopenia (ITP) in adults

INTRODUCTION

Immune thrombocytopenia (also called idiopathic thrombocytopenic purpura, immune thrombocytopenic purpura, ITP) is an acquired disorder. There are only two criteria required in order to make this diagnosis [1-6]:

  • Isolated thrombocytopenia is present. The rest of the complete blood count, including an examination of the peripheral blood smear, is entirely normal, unless other coincidental abnormalities are present, such as iron deficiency.
  • Clinically apparent associated conditions (eg, systemic lupus erythematosus, antiphospholipid syndrome, chronic lymphocytic leukemia) are not present. Patients with these associated conditions are described as having "secondary immune thrombocytopenia" [7]. Also, drugs, including herbal remedies and quinine-containing beverages that may cause thrombocytopenia are NOT apparent etiologies.

The clinical manifestations, diagnosis, and differential diagnosis of ITP will be reviewed here. The treatment and prognosis of this disorder and the clinical manifestations, diagnosis, treatment, and prognosis of childhood ITP are discussed separately. (See "Treatment and prognosis of immune thrombocytopenia (ITP) in adults" and "Immune thrombocytopenia (ITP) in children: Clinical manifestations and diagnosis".)

PATHOGENESIS

The pathogenesis of ITP is related to a combination of increased platelet destruction along with inhibition of megakaryocyte platelet production via the production of specific IgG autoantibodies by the patient's B cells, most often directed against platelet membrane glycoproteins such as GPIIb/IIIa [2,8-11].

Inciting events — The etiology of ITP is unclear, but is thought to include genetic as well as acquired factors [7,12,13].

                             

Subscribers log in here

To continue reading this article you must have access through your hospital or your group practice, log in to your personal subscription, or purchase a personal subscription. For more information, click below.
Literature review current through: May 2013. | This topic last updated: Apr 29, 2013.
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 ©2013 UpToDate, Inc.
References
Top
  1. 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.
  2. Cines DB, Blanchette VS. Immune thrombocytopenic purpura. N Engl J Med 2002; 346:995.
  3. 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.
  4. 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.
  5. Provan D, Stasi R, Newland AC, et al. International consensus report on the investigation and management of primary immune thrombocytopenia. Blood 2010; 115:168.
  6. 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.
  7. Cines DB, Bussel JB, Liebman HA, Luning Prak ET. The ITP syndrome: pathogenic and clinical diversity. Blood 2009; 113:6511.
  8. Michel M, Lee K, Piette JC, et al. Platelet autoantibodies and lupus-associated thrombocytopenia. Br J Haematol 2002; 119:354.
  9. 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.
  10. 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.
  11. Toltl LJ, Arnold DM. Pathophysiology and management of chronic immune thrombocytopenia: focusing on what matters. Br J Haematol 2011; 152:52.
  12. Cooper N, Bussel J. The pathogenesis of immune thrombocytopaenic purpura. Br J Haematol 2006; 133:364.
  13. Sood R, Wong W, Gotlib J, et al. Gene expression and pathway analysis of immune thrombocytopenic purpura. Br J Haematol 2008; 140:99.
  14. DiMaggio D, Anderson A, Bussel JB. Cytomegalovirus can make immune thrombocytopenic purpura refractory. Br J Haematol 2009; 146:104.
  15. 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.
  16. Cines DB, Liebman H, Stasi R. Pathobiology of secondary immune thrombocytopenia. Semin Hematol 2009; 46:S2.
  17. Ustun C, Dainer P, Hendricks L, et al. Association of breast cancer and immune thrombocytopenic purpura. South Med J 2002; 95:1335.
  18. 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.
  19. 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.
  20. 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.
  21. 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.
  22. Patel VL, Schwartz J, Bussel JB. The effect of anti-CD40 ligand in immune thrombocytopenic purpura. Br J Haematol 2008; 141:545.
  23. 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.
  24. Chong BH. Primary immune thrombocytopenia: understanding pathogenesis is the key to better treatments. J Thromb Haemost 2009; 7:319.
  25. Peerschke EI, Andemariam B, Yin W, Bussel JB. Complement activation on platelets correlates with a decrease in circulating immature platelets in patients with immune thrombocytopenic purpura. Br J Haematol 2010; 148:638.
  26. Stasi R, Del Poeta G, Stipa E, et al. Response to B-cell depleting therapy with rituximab reverts the abnormalities of T-cell subsets in patients with idiopathic thrombocytopenic purpura. Blood 2007; 110:2924.
  27. Semple JW. T cell and cytokine abnormalities in patients with autoimmune thrombocytopenic purpura. Transfus Apher Sci 2003; 28:237.
  28. Olsson B, Andersson PO, Jernås M, et al. T-cell-mediated cytotoxicity toward platelets in chronic idiopathic thrombocytopenic purpura. Nat Med 2003; 9:1123.
  29. Coopamah MD, Garvey MB, Freedman J, Semple JW. Cellular immune mechanisms in autoimmune thrombocytopenic purpura: An update. Transfus Med Rev 2003; 17:69.
  30. 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.
  31. 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.
  32. Sakakura M, Wada H, Tawara I, et al. Reduced Cd4+Cd25+ T cells in patients with idiopathic thrombocytopenic purpura. Thromb Res 2007; 120:187.
  33. 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.
  34. 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.
  35. 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.
  36. Audia S, Samson M, Guy J, et al. Immunologic effects of rituximab on the human spleen in immune thrombocytopenia. Blood 2011; 118:4394.
  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. Zeller B, Rajantie J, Hedlund-Treutiger I, et al. Childhood idiopathic thrombocytopenic purpura in the Nordic countries: epidemiology and predictors of chronic disease. Acta Paediatr 2005; 94:178.
  40. Frederiksen H, Schmidt K. The incidence of idiopathic thrombocytopenic purpura in adults increases with age. Blood 1999; 94:909.
  41. Portielje JE, Westendorp RG, Kluin-Nelemans HC, Brand A. Morbidity and mortality in adults with idiopathic thrombocytopenic purpura. Blood 2001; 97:2549.
  42. 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.
  43. 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.
  44. Segal JB, Powe NR. Prevalence of immune thrombocytopenia: analyses of administrative data. J Thromb Haemost 2006; 4:2377.
  45. 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.
  46. Cortelazzo S, Finazzi G, Buelli M, et al. High risk of severe bleeding in aged patients with chronic idiopathic thrombocytopenic purpura. Blood 1991; 77:31.
  47. Guthrie TH Jr, Brannan DP, Prisant LM. Idiopathic thrombocytopenic purpura in the older adult patient. Am J Med Sci 1988; 296:17.
  48. Lusher JM, Iyer R. Idiopathic thrombocytopenic purpura in children. Semin Thromb Hemost 1977; 3:175.
  49. Lusher JM, Zuelzer WW. Idiopathic thrombocytopenic purpura in childhood. J Pediatr 1966; 68:971.
  50. 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.
  51. Ben-Yehuda D, Gillis S, Eldor A. Clinical and therapeutic experience in 712 Israeli patients with idiopathic thrombocytopenic purpura. Israeli ITP Study Group. Acta Haematol 1994; 91:1.
  52. 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.
  53. 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.
  54. Semple JW, Aslam R, Kim M, et al. Platelet-bound lipopolysaccharide enhances Fc receptor-mediated phagocytosis of IgG-opsonized platelets. Blood 2007; 109:4803.
  55. Elimelakh M, Dayton V, Park KS, et al. Red cell aplasia and autoimmune hemolytic anemia following immunosuppression with alemtuzumab, mycophenolate, and daclizumab in pancreas transplant recipients. Haematologica 2007; 92:1029.
  56. Otton SH, Turner DL, Frewin R, et al. Autoimmune thrombocytopenia after treatment with Campath 1H in a patient with chronic lymphocytic leukaemia. Br J Haematol 1999; 106:261.
  57. Haider I, Cahill M. Fatal thrombocytopaenia temporally related to the administration of alemtuzumab (MabCampath) for refractory CLL despite early discontinuation of therapy. Hematology 2004; 9:409.
  58. CAMMS223 Trial Investigators, Coles AJ, Compston DA, et al. Alemtuzumab vs. interferon beta-1a in early multiple sclerosis. N Engl J Med 2008; 359:1786.
  59. 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.
  60. 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.
  61. 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.
  62. Lacey JV, Penner JA. Management of idiopathic thrombocytopenic purpura in the adult. Semin Thromb Hemost 1977; 3:160.
  63. McMillan R. The role of antiplatelet autoantibody assays in the diagnosis of immune thrombocytopenic purpura. Curr Hematol Rep 2005; 4:160.
  64. Payne BA, Pierre RV. Pseudothrombocytopenia: a laboratory artifact with potentially serious consequences. Mayo Clin Proc 1984; 59:123.
  65. Savage RA. Pseudoleukocytosis due to EDTA-induced platelet clumping. Am J Clin Pathol 1984; 81:317.
  66. Vicari A, Banfi G, Bonini PA. EDTA-dependent pseudothrombocytopaenia: a 12-month epidemiological study. Scand J Clin Lab Invest 1988; 48:537.
  67. Garcia Suarez J, Calero MA, Ricard MP, et al. EDTA-dependent pseudothrombocytopenia in ambulatory patients: clinical characteristics and role of new automated cell-counting in its detection. Am J Hematol 1992; 39:146.
  68. Pegels JG, Bruynes EC, Engelfriet CP, von dem Borne AE. Pseudothrombocytopenia: an immunologic study on platelet antibodies dependent on ethylene diamine tetra-acetate. Blood 1982; 59:157.
  69. Lam YK, Wong WC, Wong KF. Autoimmune thrombocytopenic purpura with spuriously normal platelet count and 'punch-hole' red cells. Br J Haematol 2007; 139:172.
  70. George JN, Raskob GE, Shah SR, et al. Drug-induced thrombocytopenia: a systematic review of published case reports. Ann Intern Med 1998; 129:886.
  71. Cines DB, Bussel JB. How I treat idiopathic thrombocytopenic purpura (ITP). Blood 2005; 106:2244.
  72. Najean Y, Lecompte T. Chronic pure thrombocytopenia in elderly patients. An aspect of the myelodysplastic syndrome. Cancer 1989; 64:2506.
  73. Menke DM, Colon-Otero G, Cockerill KJ, et al. Refractory thrombocytopenia. A myelodysplastic syndrome that may mimic immune thrombocytopenic purpura. Am J Clin Pathol 1992; 98:502.
  74. Raife TJ, Olson JD, Lentz SR. Platelet antibody testing in idiopathic thrombocytopenic purpura. Blood 1997; 89:1112.
  75. Lescale KB, Eddleman KA, Cines DB, et al. Antiplatelet antibody testing in thrombocytopenic pregnant women. Am J Obstet Gynecol 1996; 174:1014.
  76. 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.
  77. 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.
  78. 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.
  79. 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.
  80. Brighton TA, Evans S, Castaldi PA, et al. Prospective evaluation of the clinical usefulness of an antigen-specific assay (MAIPA) in idiopathic thrombocytopenic purpura and other immune thrombocytopenias. Blood 1996; 88:194.
  81. Kuwana M, Okazaki Y, Kaburaki J, Ikeda Y. Detection of circulating B cells secreting platelet-specific autoantibody is useful in the diagnosis of autoimmune thrombocytopenia. Am J Med 2003; 114:322.
  82. Mestanza-Peralta M, Ariza-Ariza R, Cardiel MH, Alcocer-Varela J. Thrombocytopenic purpura as initial manifestation of systemic lupus erythematosus. J Rheumatol 1997; 24:867.
  83. Kurata Y, Miyagawa S, Kosugi S, et al. High-titer antinuclear antibodies, anti-SSA/Ro antibodies and anti-nuclear RNP antibodies in patients with idiopathic thrombocytopenic purpura. Thromb Haemost 1994; 71:184.
  84. Stasi R, Stipa E, Masi M, et al. Prevalence and clinical significance of elevated antiphospholipid antibodies in patients with idiopathic thrombocytopenic purpura. Blood 1994; 84:4203.
  85. Bidot CJ, Jy W, Horstman LL, et al. Antiphospholipid antibodies in immune thrombocytopenic purpura tend to emerge in exacerbation and decline in remission. Br J Haematol 2005; 128:366.
  86. Bidot CJ, Jy W, Horstman LL, et al. Antiphospholipid antibodies (APLA) in immune thrombocytopenic purpura (ITP) and antiphospholipid syndrome (APS). Am J Hematol 2006; 81:391.
  87. Pierrot-Deseilligny Despujol C, Michel M, Khellaf M, et al. Antiphospholipid antibodies in adults with immune thrombocytopenic purpura. Br J Haematol 2008; 142:638.
  88. Cunningham-Rundles C. Hematologic complications of primary immune deficiencies. Blood Rev 2002; 16:61.
  89. Michel M, Chanet V, Galicier L, et al. Autoimmune thrombocytopenic purpura and common variable immunodeficiency: analysis of 21 cases and review of the literature. Medicine (Baltimore) 2004; 83:254.
  90. Diz-Küçükkaya R, Hacihanefioğlu A, Yenerel M, et al. Antiphospholipid antibodies and antiphospholipid syndrome in patients presenting with immune thrombocytopenic purpura: a prospective cohort study. Blood 2001; 98:1760.
  91. 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.
  92. 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.
  93. George JN. Clinical practice. Thrombotic thrombocytopenic purpura. N Engl J Med 2006; 354:1927.
  94. Burrows RF, Kelton JG. Fetal thrombocytopenia and its relation to maternal thrombocytopenia. N Engl J Med 1993; 329:1463.
  95. 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.
  96. 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.
  97. Von Drygalski A, Curtis BR, Bougie DW, et al. Vancomycin-induced immune thrombocytopenia. N Engl J Med 2007; 356:904.
  98. Stasi R, Willis F, Shannon MS, Gordon-Smith EC. Infectious causes of chronic immune thrombocytopenia. Hematol Oncol Clin North Am 2009; 23:1275.
  99. Aster RH. Pooling of platelets in the spleen: role in the pathogenesis of "hypersplenic" thrombocytopenia. J Clin Invest 1966; 45:645.
  100. Peck-Radosavljevic M, Zacherl J, Meng YG, et al. Is inadequate thrombopoietin production a major cause of thrombocytopenia in cirrhosis of the liver? J Hepatol 1997; 27:127.
  101. Soupir CP, Vergilio JA, Kelly E, et al. Identification of del(20q) in a subset of patients diagnosed with idiopathic thrombocytopenic purpura. Br J Haematol 2009; 144:800.
  102. Najean Y, Lecompte T. Genetic thrombocytopenia with autosomal dominant transmission: a review of 54 cases. Br J Haematol 1990; 74:203.
  103. Mhawech P, Saleem A. Inherited giant platelet disorders. Classification and literature review. Am J Clin Pathol 2000; 113:176.
  104. Drachman JG. Inherited thrombocytopenia: when a low platelet count does not mean ITP. Blood 2004; 103:390.
  105. Noris P, Klersy C, Zecca M, et al. Platelet size distinguishes between inherited macrothrombocytopenias and immune thrombocytopenia. J Thromb Haemost 2009; 7:2131.
  106. Clare NM, Montiel MM, Lifschitz MD, Bannayan GA. Alport's syndrome associated with macrothrombopathic thrombocytopenia. Am J Clin Pathol 1979; 72:111.
  107. Seri M, Pecci A, Di Bari F, et al. MYH9-related disease: May-Hegglin anomaly, Sebastian syndrome, Fechtner syndrome, and Epstein syndrome are not distinct entities but represent a variable expression of a single illness. Medicine (Baltimore) 2003; 82:203.