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Clinical manifestations and diagnosis of immune (idiopathic) thrombocytopenic purpura in adults

INTRODUCTION

Immune thrombocytopenic purpura (idiopathic thrombocytopenic purpura, ITP) is an acquired disorder. There are only two criteria required in order to make this diagnosis [1-3]:

  • Isolated thrombocytopenia is present. The rest of the complete blood count, including an examination of the peripheral blood smear, is entirely normal.
  • Clinically apparent associated conditions, drugs, or other agents that may cause thrombocytopenia are NOT present.

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. A short history of our understanding of ITP is available [4]. (See "Treatment and prognosis of immune (idiopathic) thrombocytopenic purpura in adults" and "Clinical manifestations and diagnosis of immune (idiopathic) thrombocytopenic purpura in children".)

Overall approaches to the patient with thrombocytopenia are presented separately. (See "Evaluation and management of thrombocytopenia by primary care physicians" and "Approach to the adult patient with thrombocytopenia" and "Clinical manifestations and evaluation of thrombocytopenia in children".)

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 [2,5-7].
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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. Guidelines for the investigation and management of idiopathic thrombocytopenic purpura in adults, children and in pregnancy. Br J Haematol 2003; 120:574.
  4. Imbach, P, Kuhne, T, Signer, E. Historical aspects and present knowledge of idiopathic thrombocytopenic purpura. Br J Haematol 2002; 119:894.
  5. Michel, M, Lee, K, Piette, JC, et al. Platelet autoantibodies and lupus-associated thrombocytopenia. Br J Haematol 2002; 119:354.
  6. 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.
  7. 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.
  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. Cines, DB, Bussel, JB, Liebman, HA, Luning Prak, ET. The ITP syndrome: pathogenic and clinical diversity. Blood 2009; 113:6511.
  11. Ustun, C, Dainer, P, Hendricks, L, et al. Association of breast cancer and immune thrombocytopenic purpura. South Med J 2002; 95:1335.
  12. 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.
  13. 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.
  14. 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.
  15. 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.
  16. Patel, VL, Schwartz, J, Bussel, JB. The effect of anti-CD40 ligand in immune thrombocytopenic purpura. Br J Haematol 2008; 141:545.
  17. 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.
  18. Chong, BH. Primary immune thrombocytopenia: understanding pathogenesis is the key to better treatments. J Thromb Haemost 2009; 7:319.
  19. 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.
  20. Semple, JW. T cell and cytokine abnormalities in patients with autoimmune thrombocytopenic purpura. Transfus Apher Sci 2003; 28:237.
  21. Olsson, B, Andersson, PO, Jernas, M, et al. T-cell-mediated cytotoxicity toward platelets in chronic idiopathic thrombocytopenic purpura. Nat Med 2003; 9:1123.
  22. Coopamah, MD, Garvey, MB, Freedman, J, Semple, JW. Cellular immune mechanisms in autoimmune thrombocytopenic purpura: An update. Transfus Med Rev 2003; 17:69.
  23. 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.
  24. 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.
  25. Sakakura, M, Wada, H, Tawara, I, et al. Reduced Cd4+Cd25+ T cells in patients with idiopathic thrombocytopenic purpura. Thromb Res 2007; 120:187.
  26. 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.
  27. 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; 112:927.
  28. 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.
  29. 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.
  30. George, JN, El-Harake, MA, Raskob, GE. Chronic idiopathic thrombocytopenic purpura. N Engl J Med 1994; 331:1207.
  31. 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.
  32. Frederiksen, H, Schmidt, K. The incidence of idiopathic thrombocytopenic purpura in adults increases with age. Blood 1999; 94:909.
  33. Portielje, JE, Westendorp, RG, Kluin-Nelemans, HC, Brand, A. Morbidity and mortality in adults with idiopathic thrombocytopenic purpura. Blood 2001; 97:2549.
  34. 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.
  35. Marieke Schoonen, W, Kucera, G, Coalson, J, et al. Epidemiology of immune thrombocytopenic purpura in the General Practice Research Database. Br J Haematol 2009; 145:235.
  36. Segal, JB, Powe, NR. Prevalence of immune thrombocytopenia: analyses of administrative data. J Thromb Haemost 2006; 4:2377.
  37. 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.
  38. Guthrie, TH, Brannan, DP, Prisant, LM. Idiopathic thrombocytopenic purpura in the older adult patient. Am J Med Sci 1988; 296:17.
  39. Lusher, JM, Iyer, R. Idiopathic thrombocytopenic purpura in children. Semin Thromb Hemost 1977; 3:175.
  40. Lusher, JM, Zuelzer, WW. Idiopathic thrombocytopenic purpura in childhood. J Pediatr 1966; 68:971.
  41. Wright, JF, Blanchette, VS, Wang, H, et al. Characterization of platelet-reactive antibodies in children with varicella-associated acute idiopathic thrombocytopenic purpura (ITP). Br J Haematol 1996; 95:145.
  42. 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.
  43. 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.
  44. 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.
  45. Semple, JW, Aslam, R, Kim, M, et al. Platelet-bound lipopolysaccharide enhances Fc receptor-mediated phagocytosis of IgG-opsonized platelets. Blood 2007; 109:4803.
  46. 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.
  47. 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.
  48. 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.
  49. Coles, AJ, Compston, DA, Selmaj, KW, et al. Alemtuzumab vs. Interferon beta-1a in early multiple sclerosis. N Engl J Med 2008; 359:1786.
  50. 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.
  51. 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.
  52. Lacey, JV, Penner, JA. Management of idiopathic thrombocytopenic purpura in the adult. Semin Thromb Hemost 1977; 3:160.
  53. McMillan, R. The role of antiplatelet autoantibody assays in the diagnosis of immune thrombocytopenic purpura. Curr Hematol Rep 2005; 4:160.
  54. Payne, BA, Pierre, RV. Pseudothrombocytopenia: a laboratory artifact with potentially serious consequences. Mayo Clin Proc 1984; 59:123.
  55. Savage, RA. Pseudoleukocytosis due to EDTA-induced platelet clumping. Am J Clin Pathol 1984; 81:317.
  56. Vicari, A, Banfi, G, Bonini, PA. EDTA-dependent pseudothrombocytopaenia: A 12-month epidemiological study. Scand J Clin Lab Invest 1988; 48:537.
  57. 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.
  58. Pegels, JG, Bruynes, ECE, Engelfriet, CP, von dem Borne, AE. Pseudothrombocytopenia: An immunologic study on platelet antibodies dependent on ethylene diamine tetra-acetate. Blood 1982; 59:157.
  59. 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.
  60. George, JN, Raskob, GE, Shah, SR, et al. Drug-induced Thrombocytopenia: A systematic review of published case reports. Ann Intern Med 1998; 129:886.
  61. Cines, DB, Bussel, JB. How I treat idiopathic thrombocytopenic purpura (ITP). Blood 2005; 106:2244.
  62. Najean, Y, Lecompte, T. Chronic pure thrombocytopenia in elderly patients: An aspect of the myelodysplastic syndrome. Cancer 1989; 64:2506.
  63. 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.
  64. Raife, TJ, Olson, JD, Lentz, SR. Platelet antibody testing in idiopathic thrombocytopenic purpura. Blood 1997; 89:1112.
  65. Lescale, KB, Eddleman, KA, Cines, DB, et al. Antiplatelet antibody testing in thrombocytopenic pregnant women. Am J Obstet Gynecol 1996; 174:1014.
  66. 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.
  67. 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.
  68. 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.
  69. 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.
  70. 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.
  71. 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.
  72. 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.
  73. 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.
  74. 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.
  75. 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.
  76. 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.
  77. Pierrot-Deseilligny Despujol, C, Michel, M, Khellaf, M, et al. Antiphospholipid antibodies in adults with immune thrombocytopenic purpura. Br J Haematol 2008; 142:638.
  78. Cunningham-Rundles, C. Hematologic complications of primary immune deficiencies. Blood Rev 2002; 16:61.
  79. 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.
  80. Diz-Kucukkaya, R, Hacihanefioglu, A, Yenerel, M, et al. Antiphospholipid antibodies and antiphospholipd syndrome in patients presenting with immune thrombocytopenic purpura: A prospective cohort study. Blood 2001; 98:1760.
  81. 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.
  82. 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.
  83. George, JN. Clinical practice. Thrombotic thrombocytopenic purpura. N Engl J Med 2006; 354:1927.
  84. Burrows, RF, Kelton, JG. Fetal thrombocytopenia and its relation to maternal thrombocytopenia. N Engl J Med 1993; 329:1463.
  85. Curtis, BR, McFarland, JG, Wu, G-G, et al. Antibodies in sulfonamide-induced immune thrombocytopenia recognize calcium-dependent epitopes on the glycoprotein IIb/IIIa Complex. Blood 1994; 84:176.
  86. Von Drygalski, A, Curtis, BR, Bougie, DW, et al. Vancomycin-induced immune thrombocytopenia. N Engl J Med 2007; 356:904.
  87. Aster, RH. Pooling of platelets in the spleen: role in the pathogenesis of "hypersplenic" thrombocytopenia. J Clin Invest 1966; 45:645.
  88. 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.
  89. 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.
  90. Najean, Y, Lecompte, T. Genetic thrombocytopenia with autosomal dominant transmission: A review of 54 cases. Br J Haematol 1990; 74:203.
  91. Mhawech, P, Saleem, A. Inherited giant platelet disorders. Classification and literature review. Am J Clin Pathol 2000; 113:176.
  92. Drachman, JG. Inherited thrombocytopenia: when a low platelet count does not mean ITP. Blood 2004; 103:390.
  93. Clare, NM, Montiel, MM, Lifschitz, MD, et al. Alport's syndrome associated with macrothrombopathic thrombocytopenia. Am J Clin Pathol 1979; 72:111.
  94. 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.
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