Seminars in Hematology
Volume 46 , Pages S44-S58 , January 2009

Therapeutic Approaches to Secondary Immune Thrombocytopenic Purpura

  • James B. Bussel

      Affiliations

    • Corresponding Author InformationAddress correspondence to James B. Bussel, MD, Platelet Disorders Center, Division of Pediatric Hematology-Oncology, Weill Cornell Medical College of Cornell University, 525 E 68th St, P-695, New York, NY 10021

References 

  1. McMillan R. Chronic idiopathic thrombocytopenic purpura. N Engl J Med. 1981;304:1135–1147
  2. Kelton JG, Gibbons S. Autoimmune platelet destruction: idiopathic thrombocytopenic purpura. Semin Thromb Hemost. 1982;8:83–104
  3. Psaila B, Bussel JB. Immune thrombocytopenic purpura. Hematol Oncol Clin North Am. 2007;21:743–759
  4. Ballem PJ, Segal GM, Stratton JR, Gernsheimer T, Adamson JW, Slichter SJ. Mechanisms of thrombocytopenia in chronic autoimmune thrombocytopenic purpura (Evidence of both impaired platelet production and increased platelet clearance). J Clin Invest. 1987;80:33–40
  5. Olsson B, Andersson PO, Jernas M, Jacobsson S, Carlsson B, Carlsson LM, et al. T-cell-mediated cytotoxicity toward platelets in chronic idiopathic thrombocytopenic purpura. Nat Med. 2003;9:1123–1124
  6. Sayeh E, Sterling K, Speck E, Freedman J, Semple JW. IgG antiplatelet immunity is dependent on an early innate natural killer cell-derived interferon-gamma response that is regulated by CD8+ T cells. Blood. 2004;103:2705–2709
  7. Panitsas FP, Theodoropoulou M, Kouraklis A, et al. Adult chronic idiopathic thrombocytopenic purpura (ITP) is the manifestation of a type-1 polarized immune response. Blood. 2004;103:2645–2647
  8. Cines DB, Bussel JB. How I treat idiopathic thrombocytopenic purpura (ITP). Blood. 2005;106:2244–2251
  9. 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;88:3–40
  10. 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;120:574–596
  11. Mazzucconi MG, Fazi P, Bernasconi S, et al. Therapy with high-dose dexamethasone (HD-DXM) in previously untreated patients affected by idiopathic thrombocytopenic purpura: a GIMEMA experience. Blood. 2007;109:1401–1407
  12. Cines DB, McMillan R. Management of adult idiopathic thrombocytopenic purpura. Annu Rev Med. 2005;56:425–442
  13. Boruchov DM, Gururangan S, Driscoll MC, Bussel JB. Multiagent induction and maintenance therapy for patients with refractory immune thrombocytopenic purpura (ITP). Blood. 2007;110:3526–3531
  14. Siragam V, Crow AR, Brinc D, Song S, Freedman J, Lazarus AH. Intravenous immunoglobulin ameliorates ITP via activating Fc gamma receptors on dendritic cells. Nat Med. 2006;12:688–692
  15. Hansen RJ, Balthasar JP. Intravenous immunoglobulin mediates an increase in anti-platelet antibody clearance via the FcRn receptor. Thromb Haemost. 2002;88:898–899
  16. Scaradavou A, Woo B, Woloski BM, Cunningham-Rundles S, Ettinger LJ, Aledort LM, et al. Intravenous anti-D treatment of immune thrombocytopenic purpura: experience in 272 patients. Blood. 1997;89:2689–2700
  17. Bussel JB, Graziano JN, Kimberly RP, Pahwa S, Aledort LM. Intravenous anti-D treatment of immune thrombocytopenic purpura: analysis of efficacy, toxicity, and mechanism of effect. Blood. 1991;77:1884–1893
  18. Newman GC, Novoa MV, Fodero EM, Lesser ML, Woloski BM, Bussel JB. A dose of 75 microg/kg/d of i.v. anti-D increases the platelet count more rapidly and for a longer period of time than 50 microg/kg/d in adults with immune thrombocytopenic purpura. Br J Haematol. 2001;112:1076–1078
  19. Gaines AR. Acute onset hemoglobinemia and/or hemoglobinuria and sequelae following Rh(o)(D) immune globulin intravenous administration in immune thrombocytopenic purpura patients. Blood. 2000;95:2523–2529
  20. Gaines AR. Disseminated intravascular coagulation associated with acute hemoglobinemia or hemoglobinuria following Rh(0)(D) immune globulin intravenous administration for immune thrombocytopenic purpura. Blood. 2005;106:1532–1537
  21. Tarantino MD, Bussel JB, Cines DB, et al. A closer look at intravascular hemolysis (IVH) following intravenous anti-D for immune thrombocytopenic purpura (ITP). Blood. 2007;109:5527
  22. Sandler SG, Mallory D, Trimble J, Nance ST. Intravenous anti-D treatment for immune thrombocytopenic purpura. Blood. 1998;91:2624–2625
  23. Scaradavou A, Cunningham-Rundles S, Ho JL, Folman C, Doo H, Bussel JB. 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;82:335–341
  24. Pestka S, Langer JA, Zoon KC, Samuel CE. Interferons and their actions. Annu Rev Biochem. 1987;56:727–777
  25. Pfeffer LM, Dinarello CA, Herberman RB, et al. Biological properties of recombinant alpha-interferons: 40th anniversary of the discovery of interferons. Cancer Res. 1998;58:2489–2499
  26. Proctor SJ, Jackson G, Carey P, et al. Improvement of platelet counts in steroid-unresponsive idiopathic immune thrombocytopenic purpura after short-course therapy with recombinant alpha 2b interferon. Blood. 1989;74:1894–1897
  27. Dubbeld P, Hillen HF, Schouten HC. Interferon treatment of refractory idiopathic thrombocytopenic purpura (ITP). Eur J Haematol. 1994;52:233–235
  28. Cohn RJ, Schwyzer R, Hesseling PB, Poole JE, Naidoo J, Van Heerden C. Alpha-interferon therapy for severe chronic idiopathic thrombocytopenic purpura in children. Am J Hematol. 1993;43:246–250
  29. Behrenbeck U, Riedel F, Rieger CH. Increase in platelet count following short course therapy with recombinant alpha-2b-interferon in immune thrombocytopenic purpura in childhood. Pediatr Allergy Immunol. 1993;4:10–12
  30. Northfelt DW, Kaplan LD, Abrams DI. Continuous, low-dose therapy with interferon-alpha for human immunodeficiency virus (HIV)-related immune thrombocytopenic purpura. Am J Hematol. 1991;38:238–239
  31. Stellini R, Rossi G, Paraninfo G. Interferon therapy in intravenous drug users with HIV-associated idiopathic thrombocytopenic purpura. Haematologica. 1992;77:418–420
  32. Vianelli N, Catani L, Gugliotta L, et al. Recombinant alpha-interferon 2b in the treatment of HIV-related thrombocytopenia. AIDS. 1993;7:823–827
  33. Rossi E, Damasio E, Terragna A, Mazzarello G, Spriano M, Anselmo M. HIV-related thrombocytopenia: a therapeutical update. Haematologica. 1991;76:141–149
  34. Fabris F, Sgarabotto D, Zanon E, Francavilla F, Zaggia F, Cadrobbi P, et al. The effect of a single course of alpha-2B-interferon in patients with HIV-related and chronic idiopathic immune thrombocytopenia. Autoimmunity. 1993;14:175–179
  35. Shrestha R, McKinley C, Bilir BM, Everson GT. Possible idiopathic thrombocytopenic purpura associated with natural alpha interferon therapy for chronic hepatitis C infection. Am J Gastroenterol. 1995;90:1146–1147
  36. Medeiros BC, Seligman PA, Everson GT, Forman LM. Possible autoimmune thrombocytopenia associated with pegylated interferon-alpha2a plus ribavarin treatment for hepatitis C. J Clin Gastroenterol. 2004;38:84–86
  37. Arimura K, Arima N, Ohtsubo H, et al. Severe autoimmune thrombocytopenic purpura during interferon-alpha therapy for chronic myelogenous leukemia. Acta Haematol. 2004;112:217–218
  38. Sekreta CM, Baker DE. Interferon alfa therapy in adults with chronic idiopathic thrombocytopenic purpura. Ann Pharmacother. 1996;30:1176–1179
  39. Crossley AR, Dickinson AM, Proctor SJ, Calvert JE. Effects of interferon-alpha therapy on immune parameters in immune thrombocytopenic purpura. Autoimmunity. 1996;24:81–100
  40. Vianelli N, Galli M, de Vivo A, et al. Efficacy and safety of splenectomy in immune thrombocytopenic purpura: long-term results of 402 cases. Haematologica. 2005;90:72–77
  41. Stasi R, Stipa E, Masi M, et al. Long-term observation of 208 adults with chronic idiopathic thrombocytopenic purpura. Am J Med. 1995;98:436–442
  42. Schwartz J, Leber MD, Gillis S, Giunta A, Eldor A, Bussel JB. Long term follow-up after splenectomy performed for immune thrombocytopenic purpura (ITP). Am J Hematol. 2003;72:94–98
  43. Kojouri K, Vesely SK, Terrell DR, George JN. Splenectomy for adult patients with idiopathic thrombocytopenic purpura: a systematic review to assess long-term platelet count responses, prediction of response, and surgical complications. Blood. 2004;104:2623–2634
  44. Centers for Disease Control and Prevention. Recommendations of the Advisory Committee on Immunization Practices: use of vaccines and immune globulins in persons with altered immunocompetence. MMWR. 1993;42:1–11
  45. Davidson RN, Wall RA. Prevention and management of infections in patients without a spleen. Clin Microbiol Infect. 2001;7:657–660
  46. Marcaccio MJ. Laparoscopic splenectomy in chronic idiopathic thrombocytopenic purpura. Semin Hematol. 2000;37:267–274
  47. Fabris F, Tassan T, Ramon R, et al. Age as the major predictive factor of long-term response to splenectomy in immune thrombocytopenic purpura. Br J Haematol. 2001;112:637–640
  48. Bussel J. Treatment of immune thrombocytopenic purpura in adults. Semin Hematol. 2006;43:S3–S10
  49. Stasi R, Pagano A, Stipa E, Amadori S. Rituximab chimeric anti-CD20 monoclonal antibody treatment for adults with chronic idiopathic thrombocytopenic purpura. Blood. 2001;98:952–957
  50. Cooper N, Stasi R, Cunningham-Rundles S, Feuerstein MA, Leonard JP, Amadori S, et al. The efficacy and safety of B-cell depletion with anti-CD20 monoclonal antibody in adults with chronic immune thrombocytopenic purpura. Br J Haematol. 2004;125:232–239
  51. Bussel J. Treatment of immune thrombocytopenic purpura in adults. Semin Hematol. 2006;43:S3–S10
  52. Bennett CM, Rogers ZR, Kinnamon DD, et al. Prospective phase 1/2 study of rituximab in childhood and adolescent chronic immune thrombocytopenic purpura. Blood. 2006;107:2639–2642
  53. Wang J, Wiley JM, Luddy R, Greenberg J, Feuerstein MA, Bussel JB. Chronic immune thrombocytopenic purpura in children: assessment of rituximab treatment. J Pediatr. 2005;146:217–221
  54. McHutchison JG, Dusheiko G, Shiffman ML, et al. Eltrombopag for thrombocytopenia in patients with cirrhosis associated with hepatitis C. N Engl J Med. 2007;357:2227–2236
  55. Li J, Yang C, Xia Y, Bertino A, Glaspy J, Roberts M, et al. Thrombocytopenia caused by the development of antibodies to thrombopoietin. Blood. 2001;98:3241–3248
  56. Basser RL, O'Flaherty E, Green M, et al. Development of pancytopenia with neutralizing antibodies to thrombopoietin after multicycle chemotherapy supported by megakaryocyte growth and development factor. Blood. 2002;99:2599–2602
  57. Andemariam B, Psaila B, Bussel JB. Novel thrombopoietic agents. Hematology Am Soc Hematol Educ Program. 2007;106–113
  58. Kuter DJ. New thrombopoietic growth factors. Blood. 2007;109:4607–4616
  59. Broudy VC, Lin NL. AMG531 stimulates megakaryopoiesis in vitro by binding to Mpl. Cytokine. 2004;25:52–60
  60. Bussel JB, Kuter DJ, George JN, et al. AMG 531, a thrombopoiesis-stimulating protein, for chronic ITP. N Engl J Med. 2006;355:1672–1681
  61. Newland A, Caulier MT, Kappers-Klunne M, et al. An open-label, unit dose-finding study of AMG 531, a novel thrombopoiesis-stimulating peptibody, in patients with immune thrombocytopenic purpura. Br J Haematol. 2006;135:547–553
  62. Newland A. Thrombopoietin mimetic agents in the management of immune thrombocytopenic purpura. Semin Hematol. 2007;44:S35–S45
  63. Bussel JB. Unknown. Blood. In press.
  64. Gernsheimer TB, Pullarkat V, Senecal FM, et al. Evaluation of AMG 531 efficacy in splenectomized patients with chronic immune thrombocytopenic purpura (ITP) in a randomized placebo-controlled phase 3 study [abstract 2]. Blood. 2007;110:8a
  65. Kuter DJ, Bussel JB, Senecal FM, et al. Evaluation of AMG 531 efficacy in nonsplenectomized patients with chronic immune thrombocytopenia purpura (ITP) in a randomized placebo-controlled phase 3 study [abstract 565]. Blood. 2007;110:173a
  66. Kuter D, Bussel J, George J, et al. Long-term dosing of AMG 531 in thrombocytopenic patients with immune thrombocytopenic purpura: 48-week update [abstract 476]. Blood. 2006;108:144a
  67. Kuter DJ, Bussel JB, Lyons RM, et al. Efficacy of romiplostim in patients with chronic immune thrombocytopenic purpura: a double-blind randomised controlled trial. Lancet. 2008;371:395–403
  68. Bussel JB, Cheng G, Saleh M, et al. Analysis of bleeding in patients with immune thrombocytopenic purpura (ITP): a randomized, double-blind, placebo-controlled trial of eltrombopag, an oral platelet growth factor [abstract 475]. Blood. 2006;108:144a
  69. Bussel JB, Cheng G, Saleh MN, et al. Eltrombopag for the treatment of chronic idiopathic thrombocytopenic purpura. N Engl J Med. 2007;357:2237–2247
  70. Bussel JB. Unknown. Lancet. In press.
  71. Desjardins RE, Tempel DL, Lucek R, Kuter DJ. Single and multiple oral doses of AKR-501 (YM477) increases the platelet count in healthy volunteers [abstract 477]. Blood. 2006;108:145a
  72. Gernsheimer T, McCrae KR. Immune thrombocytopenic purpura in pregnancy. Curr Opin Hematol. 2007;14:574–580
  73. McCrae KR. Thrombocytopenia in pregnancy: differential diagnosis, pathogenesis, and management. Blood Rev. 2003;17:7–14
  74. Gill KK, Kelton JG. Management of idiopathic thrombocytopenic purpura in pregnancy. Semin Hematol. 2000;37:275–289
  75. George JN, Raskob GE. Idiopathic thrombocytopenic purpura: diagnosis and management. Am J Med Sci. 1998;316:87–93
  76. Lescale KB, Eddleman KA, Cines DB, Samuels P, Lesser ML, McFarland JG, et al. Antiplatelet antibody testing in thrombocytopenic pregnant women. Am J Obstet Gynecol. 1996;174:1014–1018
  77. Boehlen F, Hohlfeld P, Extermann P, de Moerloose P. Maternal antiplatelet antibodies in predicting risk of neonatal thrombocytopenia. Obstet Gynecol. 1999;93:169–173
  78. Fujimura K, Harada Y, Fujimoto T, et al. Nationwide study of idiopathic thrombocytopenic purpura in pregnant women and the clinical influence on neonates. Int J Hematol. 2002;75:426–433
  79. Samuels P, Bussel JB, Braitman LE, Tomaski A, Druzin ML, Mennuti MT, et al. Estimation of the risk of thrombocytopenia in the offspring of pregnant women with presumed immune thrombocytopenic purpura. N Engl J Med. 1990;323:229–235
  80. Carmichael SL, Shaw GM, Ma C, Werler MM, Rasmussen SA, Lammer EJ. Maternal corticosteroid use and orofacial clefts. Am J Obstet Gynecol. 2007;197:585–587
  81. Ward MJ, Pauliny J, Lipper EG, Bussel JB. Long-term effects of fetal and neonatal alloimmune thrombocytopenia and its antenatal treatment on the medical and developmental outcomes of affected children. Am J Perinatol. 2006;23:487–492
  82. Webert KE, Mittal R, Sigouin C, Heddle NM, Kelton JG. A retrospective 11-year analysis of obstetric patients with idiopathic thrombocytopenic purpura. Blood. 2003;102:4306–4311
  83. Ajzenberg N, Dreyfus M, Kaplan C, Yvart J, Weill B, Tchernia G. Pregnancy-associated thrombocytopenia revisited: assessment and follow-up of 50 cases. Blood. 1998;92:4573–4580
  84. McCrae KR, Bussel JB, Mannucci PM, Remuzzi G, Cines DB. Platelets: an update on diagnosis and management of thrombocytopenic disorders. Hematology Am Soc Hematol Educ Program. 2001;282–305
  85. Michel M, Novoa MV, Bussel JB. Intravenous anti-D as a treatment for immune thrombocytopenic purpura (ITP) during pregnancy. Br J Haematol. 2003;123:142–146
  86. de Boer NK, Jarbandhan SV, de Graaf P, Mulder CJ, van Elburg RM, van Bodegraven AA. Azathioprine use during pregnancy: unexpected intrauterine exposure to metabolites. Am J Gastroenterol. 2006;101:1390–1392
  87. Kimby E, Sverrisdottir A, Elinder G. Safety of rituximab therapy during the first trimester of pregnancy: a case history. Eur J Haematol. 2004;72:292–295
  88. Herold M, Schnohr S, Bittrich H. Efficacy and safety of a combined rituximab chemotherapy during pregnancy. J Clin Oncol. 2001;19:34–39
  89. Klink DT, van Elburg RM, Schreurs MW, van Well GT. Rituximab administration in third trimester of pregnancy suppresses neonatal B-cell development. Clin Dev Immunol. 2008;271363
  90. Anglin BV, Rutherford C, Ramus R, Lieser M, Jones DB. Immune thrombocytopenic purpura during pregnancy: laparoscopic treatment. JSLS. 2001;5:63–67
  91. Griffiths J, Sia W, Shapiro AM, Tataryn I, Turner AR. Laparoscopic splenectomy for the treatment of refractory immune thrombocytopenia in pregnancy. J Obstet Gynaecol Can. 2005;27:771–774
  92. Bussel JB. Splenectomy-sparing strategies for the treatment and long-term maintenance of chronic idiopathic (immune) thrombocytopenic purpura. Semin Hematol. 2000;37:1–4
  93. Ahn YS, Harrington WJ. Treatment of idiopathic thrombocytopenic purpura (ITP). Annu Rev Med. 1977;28:299–309
  94. Nossent JC, Swaak AJ. Prevalence and significance of haematological abnormalities in patients with systemic lupus erythematosus. Q J Med. 1991;80:605–612
  95. Pistiner M, Wallace DJ, Nessim S, Metzger AL, Klinenberg JR. Lupus erythematosus in the 1980s: a survey of 570 patients. Semin Arthritis Rheum. 1991;21:55–64
  96. Cervera R, Khamashta MA, Font J, et al. Morbidity and mortality in systemic lupus erythematosus during a 10-year period: a comparison of early and late manifestations in a cohort of 1,000 patients. Medicine (Baltimore). 2003;82:299–308
  97. Chen JL, Huang XM, Zeng XJ, et al. [Hematological abnormalities in systemic lupus erythematosus and clinical significance thereof: comparative analysis of 236 cases]. Zhonghua Yi Xue Za Zhi. 2007;87:1330–1333
  98. Villamin CA, Navarra SV. Clinical manifestations and clinical syndromes of Filipino patients with systemic lupus erythematosus. Mod Rheumatol. 2008;18:161–164
  99. Cervera R, Asherson RA. Clinical and epidemiological aspects in the antiphospholipid syndrome. Immunobiology. 2003;207:5–11
  100. George JN, Vesely SK, James JA. Overlapping features of thrombotic thrombocytopenic purpura and systemic lupus erythematosus. South Med J. 2007;100:512–514
  101. Pluchinotta FR, Schiavo B, Vittadello F, Martini G, Perilongo G, Zulian F. Distinctive clinical features of pediatric systemic lupus erythematosus in three different age classes. Lupus. 2007;16:550–555
  102. Clark WF, Lewis ML, Cameron JS, Parsons V. Intrarenal platelet consumption in the diffuse proliferative nephritis of systemic lupus erythematosus. Clin Sci Mol Med. 1975;49:247–252
  103. Ziakas PD, Routsias JG, Giannouli S, Tasidou A, Tzioufas AG, Voulgarelis M. Suspects in the tale of lupus-associated thrombocytopenia. Clin Exp Immunol. 2006;145:71–80
  104. Gernsheimer T. Epidemiology and pathophysiology of immune thrombocytopenic purpura. Eur J Haematol. 2008;(Suppl):3–8
  105. Roach BA, Hutchinson GJ. Treatment of refractory, systemic lupus erythematosus-associated thrombocytopenia with intermittent low-dose intravenous cyclophosphamide. Arthritis Rheum. 1993;36:682–684
  106. West SG, Johnson SC. Danazol for the treatment of refractory autoimmune thrombocytopenia in systemic lupus erythematosus. Ann Intern Med. 1988;108:703–706
  107. ter Borg EJ, Kallenberg CG. Treatment of severe thrombocytopenia in systemic lupus erythematosus with intravenous gammaglobulin. Ann Rheum Dis. 1992;51:1149–1151
  108. Goebel KM, Gassel WD, Goebel FD. Evaluation of azathioprine in autoimmune thrombocytopenia and lupus erythematosus. Scand J Haematol. 1973;10:28–34
  109. Arnal C, Piette JC, Leone J, et al. Treatment of severe immune thrombocytopenia associated with systemic lupus erythematosus: 59 cases. J Rheumatol. 2002;29:75–83
  110. Garcia Hernandez FJ, Ocana Medina C, Gonzalez Leon R, Garrido Rasco R, Colorado Bonilla R, Castillo Palma MJ, et al. [Rituximab for treatment of patients with systemic autoimmune diseases]. Med Clin (Barc). 2007;128:458–462
  111. Lehembre S, Macario-Barrel A, Musette P, Carvalho P, Joly P. [Rituximab treatment for immune thrombocytopenia associated with systemic lupus erythematosus]. Ann Dermatol Venereol. 2006;133:53–55
  112. Ahn ER, Lander G, Bidot CJ, Jy W, Ahn YS. Long-term remission from life-threatening hypercoagulable state associated with lupus anticoagulant (LA) following rituximab therapy. Am J Hematol. 2005;78:127–129
  113. Kneitz C, Wilhelm M, Tony HP. Effective B cell depletion with rituximab in the treatment of autoimmune diseases. Immunobiology. 2002;206:519–527
  114. Harris EN, Gharavi AE, Asherson RA, Hughes GR. Antiphospholipid antibodies: a review. Eur J Rheumatol Inflamm. 1984;7:5–8
  115. Galli M, Luciani D, Bertolini G, Barbui T. Anti-beta 2-glycoprotein I, antiprothrombin antibodies, and the risk of thrombosis in the antiphospholipid syndrome. Blood. 2003;102:2717–2723
  116. Pullarkat V, Ngo M, Iqbal S, Espina B, Liebman HA. Detection of lupus anticoagulant identifies patients with autoimmune haemolytic anaemia at increased risk for venous thromboembolism. Br J Haematol. 2002;118:1166–1169
  117. Galli M, Luciani D, Bertolini G, Barbui T. Lupus anticoagulants are stronger risk factors for thrombosis than anticardiolipin antibodies in the antiphospholipid syndrome: a systematic review of the literature. Blood. 2003;101:1827–1832
  118. De Groot PG, Lutters B, Derksen RH, Lisman T, Meijers JC, Rosendaal FR. Lupus anticoagulants and the risk of a first episode of deep venous thrombosis. J Thromb Haemost. 2005;3:1993–1997
  119. Stasi R, Stipa E, Masi M, et al. Prevalence and clinical significance of elevated antiphospholipid antibodies in patients with idiopathic thrombocytopenic purpura. Blood. 1994;84:4203–4208
  120. Diz-Kucukkaya R, Hacihanefioglu A, Yenerel M, Turgut M, Keskin H, Nalcaci M, et al. Antiphospholipid antibodies and antiphospholipid syndrome in patients presenting with immune thrombocytopenic purpura: a prospective cohort study. Blood. 2001;98:1760–1764
  121. Dash S, Marwaha RK, Mohanty S. Lupus anticoagulant in immune thrombocytopenic purpura. Indian J Pediatr. 2004;71:505–507
  122. Miyakis S, Lockshin MD, Atsumi T, et al. International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS). J Thromb Haemost. 2006;4:295–306
  123. Galli M, Daldossi M, Barbui T. Anti-glycoprotein Ib/IX and IIb/IIIa antibodies in patients with antiphospholipid antibodies. Thromb Haemost. 1994;71:571–575
  124. Macchi L, Rispal P, Clofent-Sanchez G, Pellegrin JL, Nurden P, Leng B, et al. Anti-platelet antibodies in patients with systemic lupus erythematosus and the primary antiphospholipid antibody syndrome: their relationship with the observed thrombocytopenia. Br J Haematol. 1997;98:336–341
  125. Godeau B, Piette JC, Fromont P, Intrator L, Schaeffer A, Bierling P. Specific antiplatelet glycoprotein autoantibodies are associated with the thrombocytopenia of primary antiphospholipid syndrome. Br J Haematol. 1997;98:873–879
  126. Fabris F, Steffan A, Cordiano I, Borzini P, Luzzatto G, Randi ML, et al. Specific antiplatelet autoantibodies in patients with antiphospholipid antibodies and thrombocytopenia. Eur J Haematol. 1994;53:232–236
  127. Nojima J, Suehisa E, Kuratsune H, et al. Platelet activation induced by combined effects of anticardiolipin and lupus anticoagulant IgG antibodies in patients with systemic lupus erythematosus—possible association with thrombotic and thrombocytopenic complications. Thromb Haemost. 1999;81:436–441
  128. Alliot C, Messouak D, Albert F, Barrios M. Correction of thrombocytopenia with aspirin in the primary antiphospholipid syndrome. Am J Hematol. 2001;68:215
  129. Alarcon-Segovia D, Sanchez-Guerrero J. Correction of thrombocytopenia with small dose aspirin in the primary antiphospholipid syndrome. J Rheumatol. 1989;16:1359–1361
  130. Cohen MG, Lui SF. Multiple complications of the antiphospholipid syndrome with apparent response to aspirin therapy. J Rheumatol. 1992;19:803–806
  131. Gruel Y, Rupin A, Watier H, Vigier S, Bardos P, Leroy J. Anticardiolipin antibodies in heparin-associated thrombocytopenia. Thromb Res. 1992;67:601–606
  132. Arnout J. The pathogenesis of the antiphospholipid syndrome: a hypothesis based on parallelisms with heparin-induced thrombocytopenia. Thromb Haemost. 1996;75:536–541
  133. Galindo M, Khamashta MA, Hughes GR. Splenectomy for refractory thrombocytopenia in the antiphospholipid syndrome. Rheumatology (Oxford). 1999;38:848–853
  134. Delgado Alves J, Inanc M, Diz-Kucukkaya R, Grima B, Soromenho F, Isenberg DA. Thrombotic risk in patients submitted to splenectomy for systemic lupus erythematosus and antiphospholipid antibody syndrome-related thrombocytopenia. Eur J Intern Med. 2004;15:162–167
  135. Erdozain JG, Ruiz-Irastorza G, Egurbide MV, Aguirre C. Sustained response to rituximab of autoimmune hemolytic anemia associated with antiphospholipid syndrome. Haematologica. 2004;89:ECR34
  136. Rubenstein E, Arkfeld DG, Metyas S, Shinada S, Ehresmann S, Liebman HA. Rituximab treatment for resistant antiphospholipid syndrome. J Rheumatol. 2006;33:355–357
  137. Caldwell WG, Meikle M. Thyrotoxicosis complicated by thrombocytopenic purpura. Br Med J. 1953;2:976–977
  138. Hymes K, Blum M, Lackner H, Karpatkin S. Easy bruising, thrombocytopenia, and elevated platelet immunoglobulin G in Graves' disease and Hashimoto's thyroiditis. Ann Intern Med. 1981;94:27–30
  139. Altintas A, Pasa S, Cil T, Bayan K, Gokalp D, Ayyildiz O. Thyroid and celiac diseases autoantibodies in patients with adult chronic idiopathic thrombocytopenic purpura. Platelets. 2008;19:252–257
  140. Cordiano I, Betterle C, Spadaccino CA, Soini B, Girolami A, Fabris F. Autoimmune thrombocytopenia (AITP) and thyroid autoimmune disease (TAD): overlapping syndromes?. Clin Exp Immunol. 1998;113:373–378
  141. Panzer S, Haubenstock A, Minar E. Platelets in hyperthyroidism: studies on platelet counts, mean platelet volume, 111-indium-labeled platelet kinetics, and platelet-associated immunoglobulins G and M. J Clin Endocrinol Metab. 1990;70:491–496
  142. Stiegler G, Stohlawetz P, Brugger S, Jilma B, Vierhapper H, Hocker P, et al. Elevated numbers of reticulated platelets in hyperthyroidism: direct evidence for an increase of thrombopoiesis. Br J Haematol. 1998;101:656–658
  143. Pratt EL, Tarantino MD, Wagner D, Hirsch Pescovitz O, Bowyer S, Shapiro AD. Prevalence of elevated antithyroid antibodies and antinuclear antibodies in children with immune thrombocytopenic purpura. Am J Hematol. 2005;79:175–179
  144. Nabriski D, Ellis M, Ness-Abramof R, Shapiro M, Shenkman L. Autoimmune thyroid disease and antiphospholipid antibodies. Am J Hematol. 2000;64:73–75
  145. Adrouny A, Sandler RM, Carmel R. Variable presentation of thrombocytopenia in Graves' disease. Arch Intern Med. 1982;142:1460–1464
  146. Hofbauer LC, Spitzweg C, Schmauss S, Heufelder AE. Graves disease associated with autoimmune thrombocytopenic purpura. Arch Intern Med. 1997;157:1033–1036
  147. Sugimoto K, Sasaki M, Isobe Y, Tamayose K, Hieda M, Oshimi K. Improvement of idiopathic thrombocytopenic purpura by antithyroid therapy. Eur J Haematol. 2005;74:73–74
  148. Bowles KM, Turner GE, Wimperis JZ. Resolution of chronic severe refractory thrombocytopenia after treatment of hypothyroidism. J Clin Pathol. 2004;57:995–996
  149. Geha RS, Notarangelo LD, Casanova JL, Chapel H, Conley ME, Fischer A, et al. Primary immunodeficiency diseases: an update from the International Union of Immunological Societies Primary Immunodeficiency Diseases Classification Committee. J Allergy Clin Immunol. 2007;120:776–794
  150. Park MA, Li JT, Hagan JB, Maddox DE, Abraham RS. Common variable immunodeficiency: a new look at an old disease. Lancet. 2008;372:489–502
  151. Cunningham-Rundles C, Bodian C. Common variable immunodeficiency: clinical and immunological features of 248 patients. Clin Immunol. 1999;92:34–48
  152. Quinti I, Soresina A, Spadaro G, Martino S, Donnanno S, Agostini C, et al. Long-term follow-up and outcome of a large cohort of patients with common variable immunodeficiency. J Clin Immunol. 2007;27:308–316
  153. Michel M, Chanet V, Galicier L, Ruivard M, Levy Y, Hermine O, et al. Autoimmune thrombocytopenic purpura and common variable immunodeficiency: analysis of 21 cases and review of the literature. Medicine (Baltimore). 2004;83:254–263
  154. Wang J, Cunningham-Rundles C. Treatment and outcome of autoimmune hematologic disease in common variable immunodeficiency (CVID). J Autoimmun. 2005;25:57–62
  155. Cunningham-Rundles C. Autoimmune manifestations in common variable immunodeficiency. J Clin Immunol. 2008;28(Suppl 1):S42–S45
  156. Ramyar A, Aghamohammadi A, Moazzami K, Rezaei N, Yeganeh M, Cheraghi T, et al. Presence of idiopathic thrombocytopenic purpura and autoimmune hemolytic anemia in the patients with common variable immunodeficiency. Iran J Allergy Asthma Immunol. 2008;7:169–175
  157. Brouet JC, Chedeville A, Fermand JP, Royer B. Study of the B cell memory compartment in common variable immunodeficiencyResolution of chronic severe refractory thrombocytopenia after treatment of hypothyroidismd. Eur J Immunol. 2000;30:2516–2520
  158. Agematsu K, Futatani T, Hokibara S, Kobayashi N, Takamoto M, Tsukada S, et al. Absence of memory B cells in patients with common variable immunodeficiency. Clin Immunol. 2002;103:34–42
  159. Warnatz K, Denz A, Drager R, Braun M, Groth C, Wolff-Vorbeck G, et al. Severe deficiency of switched memory B cells (CD27(+)IgM(-)IgD(-)) in subgroups of patients with common variable immunodeficiency: a new approach to classify a heterogeneous disease. Blood. 2002;99:1544–1551
  160. Piqueras B, Lavenu-Bombled C, Galicier L, Bergeron-van der CF, Mouthon L, Chevret S, et al. Common variable immunodeficiency patient classification based on impaired B cell memory differentiation correlates with clinical aspects. J Clin Immunol. 2003;23:385–400
  161. Wehr C, Kivioja T, Schmitt C, Ferry B, Witte T, Eren E, et al. The EUROclass trial: defining subgroups in common variable immunodeficiency. Blood. 2008;111:77–85
  162. Chapel H, Lucas M, Lee M, Bjorkander J, Webster D, Grimbacher B, et al. Common variable immunodeficiency disorders: division into distinct clinical phenotypes. Blood. 2008;112:277–286
  163. Ko J, Radigan L, Cunningham-Rundles C. Immune competence and switched memory B cells in common variable immunodeficiency. Clin Immunol. 2005;116:37–41
  164. Alachkar H, Taubenheim N, Haeney MR, Durandy A, Arkwright PD. Memory switched B cell percentage and not serum immunoglobulin concentration is associated with clinical complications in children and adults with specific antibody deficiency and common variable immunodeficiency. Clin Immunol. 2006;120:310–318
  165. Jiang H, Chess L. Regulation of immune responses by T cells. N Engl J Med. 2006;354:1166–1176
  166. Giovannetti A, Pierdominici M, Mazzetta F, Marziali M, Renzi C, Mileo AM, et al. Unravelling the complexity of T cell abnormalities in common variable immunodeficiency. J Immunol. 2007;178:3932–3943
  167. Fevang B, Yndestad A, Sandberg WJ, Holm AM, Muller F, Aukrust P, et al. Low numbers of regulatory T cells in common variable immunodeficiency: association with chronic inflammation in vivo. Clin Exp Immunol. 2007;147:521–525
  168. Casanova JL, Fieschi C, Zhang SY, Abel L. Revisiting human primary immunodeficiencies. J Intern Med. 2008;264:115–127
  169. Notarangelo LD, Sorensen R. Is it necessary to identify molecular defects in primary immunodeficiency disease?. J Allergy Clin Immunol. 2008;
  170. Zhang L, Radigan L, Salzer U, Behrens TW, Grimbacher B, Diaz G, et al. Transmembrane activator and calcium-modulating cyclophilin ligand interactor mutations in common variable immunodeficiency: clinical and immunologic outcomes in heterozygotes. J Allergy Clin Immunol. 2007;120:1178–1185
  171. Cunningham-Rundles C. Hematologic complications of primary immune deficiencies. Blood Rev. 2002;16:61–64
  172. Carbone J, Escudero A, Mayayo M, Ballesteros M, Perez-Corral A, Sanchez-Ramon S, et al. Partial response to anti-CD20 monoclonal antibody treatment of severe immune thrombocytopenic purpura in a patient with common variable immunodeficiency. Ann N Y Acad Sci. 2005;1051:666–671
  173. Mahevas M, Le PL, Salle V, Cevallos R, Smail A, Duhaut P, et al. Efficiency of rituximab in the treatment of autoimmune thrombocytopenic purpura associated with common variable immunodeficiency. Am J Hematol. 2006;81:645–646
  174. Evans RS, Takahashi K, Duane RT, Payne R, Liu C. Primary thrombocytopenic purpura and acquired hemolytic anemia; evidence for a common etiology. AMA Arch Intern Med. 1951;87:48–65
  175. Rabinowitz Y, Dameshek W. Systemic lupus erytematosus after “idiopathic” thrombocytopenic purpura: a review. Ann Intern Med. 1960;52:1–28
  176. Deleze M, Oria CV, Alarcon-Segovia D. Occurrence of both hemolytic anemia and thrombocytopenic purpura (Evans' syndrome) in systemic lupus erythematosus (Relationship to antiphospholipid antibodies). J Rheumatol. 1988;15:611–615
  177. Lavalle C, Hurtado R, Quezada JJ, Cabral A, Fraga A. Hemocytopenia as initial manifestation of systemic lupus erythematosus (Prognostic significance). Clin Rheumatol. 1983;2:227–232
  178. Teachey DT, Obzut DA, Axsom K, Choi JK, Goldsmith KC, Hall J, et al. Rapamycin improves lymphoproliferative disease in murine autoimmune lymphoproliferative syndrome (ALPS). Blood. 2006;108:1965–1971
  179. Norton A, Roberts I. Management of Evans syndrome. Br J Haematol. 2006;132:125–137
  180. Mathew P, Chen G, Wang W. Evans syndrome: results of a national survey. J Pediatr Hematol Oncol. 1997;19:433–437
  181. Scaradavou A, Bussel J. Evans syndrome (Results of a pilot study utilizing a multiagent treatment protocol). J Pediatr Hematol Oncol. 1995;17:290–295
  182. Seipelt G, Bohme A, Koschmieder S, Hoelzer D. Effective treatment with rituximab in a patient with refractory prolymphocytoid transformed B-chronic lymphocytic leukemia and Evans syndrome. Ann Hematol. 2001;80:170–173
  183. Zecca M, Nobili B, Ramenghi U, Perrotta S, Amendola G, Rosito P, et al. Rituximab for the treatment of refractory autoimmune hemolytic anemia in children. Blood. 2003;101:3857–3861
  184. Bader-Meunier B, Aladjidi N, Bellmann F, Monpoux F, Nelken B, Robert A, et al. Rituximab therapy for childhood Evans syndrome. Haematologica. 2007;92:1691–1694
  185. Kittaka K, Dobashi H, Baba N, Iseki K, Kameda T, Susaki K, et al. A case of Evans syndrome combined with systemic lupus erythematosus successfully treated with rituximab. Scand J Rheumatol. 2008;37:390–393
  186. George JN, Raskob GE, Shah SR, Rizvi MA, Hamilton SA, Osborne S, et al. Drug-induced thrombocytopenia: a systematic review of published case reports. Ann Intern Med. 1998;129:886–890
  187. Blackburn SC, Oliart AD, Garcia Rodriguez LA, Perez Gutthann S. Antiepileptics and blood dyscrasias: a cohort study. Pharmacotherapy. 1998;18:1277–1283
  188. Bessmertny O, Pham T. Antiepileptic hypersensitivity syndrome: clinicians beware and be aware. Curr Allergy Asthma Rep. 2002;2:34–39
  189. Bougie D, Aster R. Immune thrombocytopenia resulting from sensitivity to metabolites of naproxen and acetaminophen. Blood. 2001;97:3846–3850
  190. Aster RH, Bougie DW. Drug-induced immune thrombocytopenia. N Engl J Med. 2007;357:580–587
  191. Schmitt SK, Tomford JW. Quinine-induced pancytopenia and coagulopathy. Ann Intern Med. 1994;120:90–91
  192. Rhodes GR, Dixon RH, Silver D. Heparin induced thrombocytopenia with thrombotic and hemorrhagic manifestations. Surg Gynecol Obstet. 1973;136:409–416
  193. Kelton JG. The pathophysiology of heparin-induced thrombocytopenia: biological basis for treatment. Chest. 2005;127:9S–20S
  194. Warkentin TE, Greinacher A. Heparin-induced thrombocytopenia: recognition, treatment, and prevention: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest. 2004;126:311S–337S
  195. Warkentin TE, Sheppard JA, Sigouin CS, Kohlmann T, Eichler P, Greinacher A. Gender imbalance and risk factor interactions in heparin-induced thrombocytopenia. Blood. 2006;108:2937–2941
  196. Greinacher A, Farner B, Kroll H, Kohlmann T, Warkentin TE, Eichler P. Clinical features of heparin-induced thrombocytopenia including risk factors for thrombosis (A retrospective analysis of 408 patients). Thromb Haemost. 2005;94:132–135
  197. Cines DB, Bussel JB, McMillan RB, Zehnder JL. Congenital and acquired thrombocytopenia. Hematology Am Soc Hematol Educ Program. 2004;390–406
  198. Gettings EM, Brush KA, Van Cott EM, Hurford WE. Outcome of postoperative critically ill patients with heparin-induced thrombocytopenia: an observational retrospective case-control study. Crit Care. 2006;10:R161
  199. Oliveira GB, Crespo EM, Becker RC, Honeycutt EF, Abrams CS, Anstrom KJ, et al. Incidence and prognostic significance of thrombocytopenia in patients treated with prolonged heparin therapy. Arch Intern Med. 2008;168:94–102
  200. Warkentin TE, Greinacher A, Koster A, Lincoff AM. Treatment and prevention of heparin-induced thrombocytopenia: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest. 2008;133:340S–380S
  201. Pouplard C, Amiral J, Borg JY, Laporte-Simitsidis S, Delahousse B, Gruel Y. Decision analysis for use of platelet aggregation test, carbon 14-serotonin release assay, and heparin-platelet factor 4 enzyme-linked immunosorbent assay for diagnosis of heparin-induced thrombocytopenia. Am J Clin Pathol. 1999;111:700–706
  202. Hirsh J, Heddle N, Kelton JG. Treatment of heparin-induced thrombocytopenia: a critical review. Arch Intern Med. 2004;164:361–369
  203. Warkentin TE, Kelton JG. A 14-year study of heparin-induced thrombocytopenia. Am J Med. 1996;101:502–507
  204. Alsaleh KA, Al-Nasser SM, Bates SM, Patel A, Warkentin TE, Arnold DM. Delayed-onset HIT caused by low-molecular-weight heparin manifesting during fondaparinux prophylaxis. Am J Hematol. 2009;83:876–878
  205. Bartholomew JR. Transition to an oral anticoagulant in patients with heparin-induced thrombocytopenia. Chest. 2005;127:27S–34S
  206. Warkentin TE, Greinacher A. Heparin-induced thrombocytopenia and cardiac surgery. Ann Thorac Surg. 2003;76:2121–2131

 STATEMENT OF CONFLICT OF INTEREST: James B. Bussel, MD, discloses the following: Consultant/Advisory Board: Amgen, GSK, Ligand, Baxter; Speaker Programs: Baxter; Investigator: Amgen, GSK, Ligand, Biogenldec, Cangene, Genentech, Genzyme, Immunomedics, MGI Pharma, Sysmex; Stockholder (Spouse): Amgen, GSK.

PII: S0037-1963(08)00202-3

doi: 10.1053/j.seminhematol.2008.12.003

Seminars in Hematology
Volume 46 , Pages S44-S58 , January 2009

Article Tools