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Causes of thrombotic thrombocytopenic purpura-hemolytic uremic syndrome in adults

INTRODUCTION

The term thrombotic thrombocytopenic purpura-hemolytic uremic syndrome (TTP-HUS) describes acute syndromes with abnormalities in multiple organ systems (table 1). Although these syndromes have multiple different etiologies, different demographics, different responses to treatment, and different prognoses, their presenting features are similar in many patients: thrombocytopenia and microangiopathic hemolytic anemia without another apparent cause and, in many patients, neurologic and/or renal abnormalities [1,2].

  • In some patients, neurologic abnormalities are dominant and acute renal failure is minimal or not present; these patients are considered by some to represent classical or "idiopathic" TTP, typically associated with severe ADAMTS13 deficiency.
  • In other patients, acute renal failure is dominant and neurologic abnormalities are minimal or absent; these patients are considered by some to represent HUS. However, some patients present with both severe neurologic abnormalities, such as seizures and coma, and acute renal failure, making this distinction difficult.
  • Some patients may have thrombocytopenia and microangiopathic hemolytic anemia with no neurologic or renal abnormalities. For example, over half of patients with severe ADAMTS13 deficiency have no or minimal neurologic or renal abnormalities (table 2).

Therefore, when these patients are initially evaluated, they can best be described by the comprehensive term TTP-HUS. An additional justification for the use of the term TTP-HUS is that the pathologic changes in patients described as having TTP or HUS are identical and the initial treatment of all adult patients is the same: plasma exchange [1,2]. (See 'Evolution of disease definitions' below.)

As a result, these syndromes in adults will be considered together and referred to as TTP-HUS; the one exception is “typical” childhood HUS following an episode of abdominal pain and diarrhea that is often bloody, due most often to Shiga toxin-producing enterohemorrhagic Escherichia coli (table 1) [1,2]. This syndrome of children has the important difference that plasma exchange treatment is not a standard initial treatment.

The causes of TTP-HUS will be discussed here. The clinical manifestations, diagnosis, and treatment of TTP-HUS are discussed separately. (See "Diagnosis of thrombotic thrombocytopenic purpura-hemolytic uremic syndrome in adults" and "Treatment and prognosis of thrombotic thrombocytopenic purpura-hemolytic uremic syndromes in adults".)

                                    

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Literature review current through: Apr 2013. | This topic last updated: Apr 12, 2013.
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References
Top
  1. George JN. Clinical practice. Thrombotic thrombocytopenic purpura. N Engl J Med 2006; 354:1927.
  2. George JN. How I treat patients with thrombotic thrombocytopenic purpura: 2010. Blood 2010; 116:4060.
  3. Moschowitz E. An acute febrile pleiochromic anemia with hyaline thrombosis of the terminal arterioles and capillaries. Arch Intern Med 1925; 36:89.
  4. Amorosi E, Ultmann J. Thrombotic thrombocytopenic purpura: Report of 16 cases and review of the literature. Medicine 1966; 45:139.
  5. Rock GA, Shumak KH, Buskard NA, et al. Comparison of plasma exchange with plasma infusion in the treatment of thrombotic thrombocytopenic purpura. Canadian Apheresis Study Group. N Engl J Med 1991; 325:393.
  6. Clark WF, Garg AX, Blake PG, et al. Effect of awareness of a randomized controlled trial on use of experimental therapy. JAMA 2003; 290:1351.
  7. Laszik ZG, Silva FG. Hemolytic-uremic syndrome, thrombotic thrombocytopenic purpura, and systemic sclerosis (systemic scleroderma). In: Heptinstall's Pathology of the Kidney, 5th ed, Jennett JC, Olson JL, Schwartz MM, Silva FG (Eds), Lippincott-Raven, Philadelphia 1998. p.1003.
  8. GASSER C, GAUTIER E, STECK A, et al. [Hemolytic-uremic syndrome: bilateral necrosis of the renal cortex in acute acquired hemolytic anemia]. Schweiz Med Wochenschr 1955; 85:905.
  9. Karmali MA, Steele BT, Petric M, Lim C. Sporadic cases of haemolytic-uraemic syndrome associated with faecal cytotoxin and cytotoxin-producing Escherichia coli in stools. Lancet 1983; 1:619.
  10. Tarr PI, Gordon CA, Chandler WL. Shiga-toxin-producing Escherichia coli and haemolytic uraemic syndrome. Lancet 2005; 365:1073.
  11. Frank C, Werber D, Cramer JP, et al. Epidemic profile of Shiga-toxin-producing Escherichia coli O104:H4 outbreak in Germany. N Engl J Med 2011; 365:1771.
  12. Sallée M, Daniel L, Piercecchi MD, et al. Myocardial infarction is a complication of factor H-associated atypical HUS. Nephrol Dial Transplant 2010; 25:2028.
  13. Hertig A, Ridel C, Rondeau E. [Hemolytic uremic syndrome in adults]. Nephrol Ther 2010; 6:258.
  14. Noris M, Caprioli J, Bresin E, et al. Relative role of genetic complement abnormalities in sporadic and familial aHUS and their impact on clinical phenotype. Clin J Am Soc Nephrol 2010; 5:1844.
  15. Loirat C, Frémeaux-Bacchi V. Atypical hemolytic uremic syndrome. Orphanet J Rare Dis 2011; 6:60.
  16. Noris M, Remuzzi G. Atypical hemolytic-uremic syndrome. N Engl J Med 2009; 361:1676.
  17. Terrell DR, Williams LA, Vesely SK, et al. The incidence of thrombotic thrombocytopenic purpura-hemolytic uremic syndrome: all patients, idiopathic patients, and patients with severe ADAMTS-13 deficiency. J Thromb Haemost 2005; 3:1432.
  18. Kremer Hovinga JA, Vesely SK, Terrell DR, et al. Survival and relapse in patients with thrombotic thrombocytopenic purpura. Blood 2010; 115:1500.
  19. Coppo P, Bengoufa D, Veyradier A, et al. Severe ADAMTS13 deficiency in adult idiopathic thrombotic microangiopathies defines a subset of patients characterized by various autoimmune manifestations, lower platelet count, and mild renal involvement. Medicine (Baltimore) 2004; 83:233.
  20. Terrell DR, Motto DG, Kremer Hovinga JA, et al. Blood group O and black race are independent risk factors for thrombotic thrombocytopenic purpura associated with severe ADAMTS13 deficiency. Transfusion 2011; 51:2237.
  21. Subramanya A, Houghton D, Watnick S. Steroid-responsive idiopathic glomerular capillary endotheliosis: case report and literature review. Am J Kidney Dis 2005; 45:1090.
  22. Furlan M, Robles R, Galbusera M, et al. von Willebrand factor-cleaving protease in thrombotic thrombocytopenic purpura and the hemolytic-uremic syndrome. N Engl J Med 1998; 339:1578.
  23. Tsai HM, Lian EC. Antibodies to von Willebrand factor-cleaving protease in acute thrombotic thrombocytopenic purpura. N Engl J Med 1998; 339:1585.
  24. Levy GG, Nichols WC, Lian EC, et al. Mutations in a member of the ADAMTS gene family cause thrombotic thrombocytopenic purpura. Nature 2001; 413:488.
  25. Kremer Hovinga JA, Studt JD, Lämmle B. The von Willebrand factor-cleaving protease (ADAMTS-13) and the diagnosis of thrombotic thrombocytopenic purpura (TTP). Pathophysiol Haemost Thromb 2003; 33:417.
  26. Camilleri RS, Scully M, Thomas M, et al. A phenotype-genotype correlation of ADAMTS13 mutations in congenital thrombotic thrombocytopenic purpura patients treated in the United Kingdom. J Thromb Haemost 2012; 10:1792.
  27. Sadler JE. Von Willebrand factor, ADAMTS13, and thrombotic thrombocytopenic purpura. Blood 2008; 112:11.
  28. Furlan M, Lämmle B. Aetiology and pathogenesis of thrombotic thrombocytopenic purpura and haemolytic uraemic syndrome: the role of von Willebrand factor-cleaving protease. Best Pract Res Clin Haematol 2001; 14:437.
  29. Banno F, Kokame K, Okuda T, et al. Complete deficiency in ADAMTS13 is prothrombotic, but it alone is not sufficient to cause thrombotic thrombocytopenic purpura. Blood 2006; 107:3161.
  30. Motto DG, Chauhan AK, Zhu G, et al. Shigatoxin triggers thrombotic thrombocytopenic purpura in genetically susceptible ADAMTS13-deficient mice. J Clin Invest 2005; 115:2752.
  31. Feys HB, Roodt J, Vandeputte N, et al. Thrombotic thrombocytopenic purpura directly linked with ADAMTS13 inhibition in the baboon (Papio ursinus). Blood 2010; 116:2005.
  32. Klaus C, Plaimauer B, Studt JD, et al. Epitope mapping of ADAMTS13 autoantibodies in acquired thrombotic thrombocytopenic purpura. Blood 2004; 103:4514.
  33. Pos W, Luken BM, Sorvillo N, et al. Humoral immune response to ADAMTS13 in acquired thrombotic thrombocytopenic purpura. J Thromb Haemost 2011; 9:1285.
  34. Coppo P, Busson M, Veyradier A, et al. HLA-DRB1*11: a strong risk factor for acquired severe ADAMTS13 deficiency-related idiopathic thrombotic thrombocytopenic purpura in Caucasians. J Thromb Haemost 2010; 8:856.
  35. Varadi K, Schreiner J, Plaimauer B, et al. ADAMTS13 autoantibody detection by quantitative immunoblotting. Blood 2003; 102:1932.
  36. Plaimauer B, Kremer Hovinga JA, Juno C, et al. Recombinant ADAMTS13 normalizes von Willebrand factor-cleaving activity in plasma of acquired TTP patients by overriding inhibitory antibodies. J Thromb Haemost 2011; 9:936.
  37. Schiviz A, Wuersch K, Piskernik C, et al. A new mouse model mimicking thrombotic thrombocytopenic purpura: correction of symptoms by recombinant human ADAMTS13. Blood 2012; 119:6128.
  38. Bianchi V, Robles R, Alberio L, et al. Von Willebrand factor-cleaving protease (ADAMTS13) in thrombocytopenic disorders: a severely deficient activity is specific for thrombotic thrombocytopenic purpura. Blood 2002; 100:710.
  39. Ono T, Mimuro J, Madoiwa S, et al. Severe secondary deficiency of von Willebrand factor-cleaving protease (ADAMTS13) in patients with sepsis-induced disseminated intravascular coagulation: its correlation with development of renal failure. Blood 2006; 107:528.
  40. Nguyen TC, Liu A, Liu L, et al. Acquired ADAMTS-13 deficiency in pediatric patients with severe sepsis. Haematologica 2007; 92:121.
  41. Uemura M, Fujimura Y, Matsumoto M, et al. Comprehensive analysis of ADAMTS13 in patients with liver cirrhosis. Thromb Haemost 2008; 99:1019.
  42. George JN. Clinical insights from observations on ADAMTS13 deficiency in liver cirrhosis. Thromb Haemost 2008; 99:987.
  43. Mannucci PM, Canciani MT, Forza I, et al. Changes in health and disease of the metalloprotease that cleaves von Willebrand factor. Blood 2001; 98:2730.
  44. Reiter RA, Knöbl P, Varadi K, Turecek PL. Changes in von Willebrand factor-cleaving protease (ADAMTS13) activity after infusion of desmopressin. Blood 2003; 101:946.
  45. Mannucci PM, Capoferri C, Canciani MT. Plasma levels of von Willebrand factor regulate ADAMTS-13, its major cleaving protease. Br J Haematol 2004; 126:213.
  46. Mannucci PM, Parolari A, Canciani MT, et al. Opposite changes of ADAMTS-13 and von Willebrand factor after cardiac surgery. J Thromb Haemost 2005; 3:397.
  47. Swisher KK, Doan JT, Vesely SK, et al. Pancreatitis preceding acute episodes of thrombotic thrombocytopenic purpura-hemolytic uremic syndrome: report of five patients with a systematic review of published reports. Haematologica 2007; 92:936.
  48. Sánchez-Luceros A, Farías CE, Amaral MM, et al. von Willebrand factor-cleaving protease (ADAMTS13) activity in normal non-pregnant women, pregnant and post-delivery women. Thromb Haemost 2004; 92:1320.
  49. Furlan M, Robles R, Morselli B, et al. Recovery and half-life of von Willebrand factor-cleaving protease after plasma therapy in patients with thrombotic thrombocytopenic purpura. Thromb Haemost 1999; 81:8.
  50. Eremina V, Jefferson JA, Kowalewska J, et al. VEGF inhibition and renal thrombotic microangiopathy. N Engl J Med 2008; 358:1129.
  51. Ridolfi RL, Bell WR. Thrombotic thrombocytopenic purpura. Report of 25 cases and review of the literature. Medicine (Baltimore) 1981; 60:413.
  52. Davis AK, Makar RS, Stowell CP, et al. ADAMTS13 binds to CD36: a potential mechanism for platelet and endothelial localization of ADAMTS13. Transfusion 2009; 49:206.
  53. Wright JF, Wang H, Hornstein A, et al. Characterization of platelet glycoproteins and platelet/endothelial cell antibodies in patients with thrombotic thrombocytopenic purpura. Br J Haematol 1999; 107:546.
  54. Tandon NN, Rock G, Jamieson GA. Anti-CD36 antibodies in thrombotic thrombocytopenic purpura. Br J Haematol 1994; 88:816.
  55. Schultz DR, Arnold PI, Jy W, et al. Anti-CD36 autoantibodies in thrombotic thrombocytopenic purpura and other thrombotic disorders: identification of an 85 kD form of CD36 as a target antigen. Br J Haematol 1998; 103:849.
  56. George JN. ADAMTS13: what it does, how it works, and why it's important. Transfusion 2009; 49:196.
  57. Bergstein JM, Riley M, Bang NU. Role of plasminogen-activator inhibitor type 1 in the pathogenesis and outcome of the hemolytic uremic syndrome. N Engl J Med 1992; 327:755.
  58. Chandler WL, Jelacic S, Boster DR, et al. Prothrombotic coagulation abnormalities preceding the hemolytic-uremic syndrome. N Engl J Med 2002; 346:23.
  59. Fakhouri F, Roumenina L, Provot F, et al. Pregnancy-associated hemolytic uremic syndrome revisited in the era of complement gene mutations. J Am Soc Nephrol 2010; 21:859.
  60. Scully M, Brown J, Patel R, et al. Human leukocyte antigen association in idiopathic thrombotic thrombocytopenic purpura: evidence for an immunogenetic link. J Thromb Haemost 2010; 8:257.
  61. John ML, Scharrer I. Autoimmune disorders in patients with idiopathic thrombotic thrombocytopenic purpura. Hamostaseologie 2012; 32 Suppl 1:S86.
  62. Boyer A, Chadda K, Salah A, Bonmarchand G. Thrombotic microangiopathy: an atypical cause of acute renal failure in patients with acute pancreatitis. Intensive Care Med 2004; 30:1235.
  63. Talwalkar JA, Ruymann FW, Marcoux P, Farraye FA. Recurrent thrombotic thrombocytopenic purpura (TTP) as a complication of acute relapsing pancreatitis. Dig Dis Sci 2002; 47:1096.
  64. Upshaw JD Jr. Congenital deficiency of a factor in normal plasma that reverses microangiopathic hemolysis and thrombocytopenia. N Engl J Med 1978; 298:1350.
  65. McDonald V, Laffan M, Benjamin S, et al. Thrombotic thrombocytopenic purpura precipitated by acute pancreatitis: a report of seven cases from a regional UK TTP registry. Br J Haematol 2009; 144:430.
  66. Park YA, Schultz EF, Hay SN, Brecher ME. Thrombotic thrombocytopenic purpura and urinary tract infections: is there a connection? Am J Clin Pathol 2011; 135:85.
  67. Bernardo A, Ball C, Nolasco L, et al. Effects of inflammatory cytokines on the release and cleavage of the endothelial cell-derived ultralarge von Willebrand factor multimers under flow. Blood 2004; 104:100.
  68. George JN. The association of pregnancy with thrombotic thrombocytopenic purpura-hemolytic uremic syndrome. Curr Opin Hematol 2003; 10:339.
  69. Kovacs MJ, Roddy J, Grégoire S, et al. Thrombotic thrombocytopenic purpura following hemorrhagic colitis due to Escherichia coli O157:H7. Am J Med 1990; 88:177.
  70. Gervasoni C, Ridolfo AL, Vaccarezza M, et al. Thrombotic microangiopathy in patients with acquired immunodeficiency syndrome before and during the era of introduction of highly active antiretroviral therapy. Clin Infect Dis 2002; 35:1534.
  71. Becker S, Fusco G, Fusco J, et al. HIV-associated thrombotic microangiopathy in the era of highly active antiretroviral therapy: an observational study. Clin Infect Dis 2004; 39 Suppl 5:S267.
  72. Alpers CE. Light at the end of the TUNEL: HIV-associated thrombotic microangiopathy. Kidney Int 2003; 63:385.
  73. Weiner NJ, Goodman JW, Kimmel PL. The HIV-associated renal diseases: current insight into pathogenesis and treatment. Kidney Int 2003; 63:1618.
  74. Moore RD. Schistocytosis and a thrombotic microangiopathy-like syndrome in hospitalized HIV-infected patients. Am J Hematol 1999; 60:116.
  75. Benjamin M, Terrell DR, Vesely SK, et al. Frequency and significance of HIV infection among patients diagnosed with thrombotic thrombocytopenic purpura. Clin Infect Dis 2009; 48:1129.
  76. Hart D, Sayer R, Miller R, et al. Human immunodeficiency virus associated thrombotic thrombocytopenic purpura--favourable outcome with plasma exchange and prompt initiation of highly active antiretroviral therapy. Br J Haematol 2011; 153:515.
  77. Begue R, Dennehy PH, Peter G. Hemolytic uremic syndrome associated with Streptococcus pneumoniae. N Engl J Med 1991; 325:133.
  78. Centers for Disease Control and Prevention (CDC). Thrombotic thrombocytopenic purpura (TTP)-like illness associated with intravenous Opana ER abuse--Tennessee, 2012. MMWR Morb Mortal Wkly Rep 2013; 62:1.
  79. Kojouri K, Vesely SK, George JN. Quinine-associated thrombotic thrombocytopenic purpura-hemolytic uremic syndrome: frequency, clinical features, and long-term outcomes. Ann Intern Med 2001; 135:1047.
  80. Maguire RB, Stroncek DF, Campbell AC. Recurrent pancytopenia, coagulopathy, and renal failure associated with multiple quinine-dependent antibodies. Ann Intern Med 1993; 119:215.
  81. Gottschall JL, Neahring B, McFarland JG, et al. Quinine-induced immune thrombocytopenia with hemolytic uremic syndrome: clinical and serological findings in nine patients and review of literature. Am J Hematol 1994; 47:283.
  82. Stroncek DF, Vercellotti GM, Hammerschmidt DE, et al. Characterization of multiple quinine-dependent antibodies in a patient with episodic hemolytic uremic syndrome and immune agranulocytosis. Blood 1992; 80:241.
  83. Aster RA, et al. Experience of the BloodCenter of Wisconsin, Milwaukee.
  84. Lesesne JB, Rothschild N, Erickson B, et al. Cancer-associated hemolytic-uremic syndrome: analysis of 85 cases from a national registry. J Clin Oncol 1989; 7:781.
  85. Groff JA, Kozak M, Boehmer JP, et al. Endotheliopathy: a continuum of hemolytic uremic syndrome due to mitomycin therapy. Am J Kidney Dis 1997; 29:280.
  86. Jackson AM, Rose BD, Graff LG, et al. Thrombotic microangiopathy and renal failure associated with antineoplastic chemotherapy. Ann Intern Med 1984; 101:41.
  87. Canpolat C, Pearson P, Jaffe N. Cisplatin-associated hemolytic uremic syndrome. Cancer 1994; 74:3059.
  88. Zupancic M, Shah PC, Shah-Khan F. Gemcitabine-associated thrombotic thrombocytopenic purpura. Lancet Oncol 2007; 8:634.
  89. Roy V, Rizvi MA, Vesely SK, George JN. Thrombotic thrombocytopenic purpura-like syndromes following bone marrow transplantation: an analysis of associated conditions and clinical outcomes. Bone Marrow Transplant 2001; 27:641.
  90. George JN, Li X, McMinn JR, et al. Thrombotic thrombocytopenic purpura-hemolytic uremic syndrome following allogeneic HPC transplantation: a diagnostic dilemma. Transfusion 2004; 44:294.
  91. Humphreys BD, Sharman JP, Henderson JM, et al. Gemcitabine-associated thrombotic microangiopathy. Cancer 2004; 100:2664.
  92. Izzedine H, Isnard-Bagnis C, Launay-Vacher V, et al. Gemcitabine-induced thrombotic microangiopathy: a systematic review. Nephrol Dial Transplant 2006; 21:3038.
  93. Glezerman I, Kris MG, Miller V, et al. Gemcitabine nephrotoxicity and hemolytic uremic syndrome: report of 29 cases from a single institution. Clin Nephrol 2009; 71:130.
  94. Gore EM, Jones BS, Marques MB. Is therapeutic plasma exchange indicated for patients with gemcitabine-induced hemolytic uremic syndrome? J Clin Apher 2009; 24:209.
  95. Blake-Haskins JA, Lechleider RJ, Kreitman RJ. Thrombotic microangiopathy with targeted cancer agents. Clin Cancer Res 2011; 17:5858.
  96. Raife TJ, Lager DJ. Chronic thrombotic microangiopathy associated with antineoplastic therapy with minimal hematologic effects. Mayo Clin Proc 2002; 77:323.
  97. Ruutu T, Hermans J, Niederwieser D, et al. Thrombotic thrombocytopenic purpura after allogeneic stem cell transplantation: a survey of the European Group for Blood and Marrow Transplantation (EBMT). Br J Haematol 2002; 118:1112.
  98. Myers BD. Cyclosporine nephrotoxicity. Kidney Int 1986; 30:964.
  99. Beaufils H, de Groc F, Gubler MC, et al. Hemolytic uremic syndrome in patients with Behçet's disease treated with cyclosporin A: report of 2 cases. Clin Nephrol 1990; 34:157.
  100. Grace AA, Barradas MA, Mikhailidis DP, et al. Cyclosporine A enhances platelet aggregation. Kidney Int 1987; 32:889.
  101. Shulman H, Striker G, Deeg HJ, et al. Nephrotoxicity of cyclosporin A after allogeneic marrow transplantation: glomerular thromboses and tubular injury. N Engl J Med 1981; 305:1392.
  102. Holman MJ, Gonwa TA, Cooper B, et al. FK506-associated thrombotic thrombocytopenic purpura. Transplantation 1993; 55:205.
  103. Trimarchi HM, Truong LD, Brennan S, et al. FK506-associated thrombotic microangiopathy: report of two cases and review of the literature. Transplantation 1999; 67:539.
  104. Zarifian A, Meleg-Smith S, O'donovan R, et al. Cyclosporine-associated thrombotic microangiopathy in renal allografts. Kidney Int 1999; 55:2457.
  105. Abramowicz D, Pradier O, Marchant A, et al. Induction of thromboses within renal grafts by high-dose prophylactic OKT3. Lancet 1992; 339:777.
  106. Dlott JS, Danielson CF, Blue-Hnidy DE, McCarthy LJ. Drug-induced thrombotic thrombocytopenic purpura/hemolytic uremic syndrome: a concise review. Ther Apher Dial 2004; 8:102.
  107. Pradier O, Marchant A, Abramowicz D, et al. Procoagulant effect of the OKT3 monoclonal antibody: involvement of tumor necrosis factor. Kidney Int 1992; 42:1124.
  108. Leaf AN, Laubenstein LJ, Raphael B, et al. Thrombotic thrombocytopenic purpura associated with human immunodeficiency virus type 1 (HIV-1) infection. Ann Intern Med 1988; 109:194.
  109. Bennett CL, Davidson CJ, Raisch DW, et al. Thrombotic thrombocytopenic purpura associated with ticlopidine in the setting of coronary artery stents and stroke prevention. Arch Intern Med 1999; 159:2524.
  110. Steinhubl SR, Tan WA, Foody JM, Topol EJ. Incidence and clinical course of thrombotic thrombocytopenic purpura due to ticlopidine following coronary stenting. EPISTENT Investigators. Evaluation of Platelet IIb/IIIa Inhibitor for Stenting. JAMA 1999; 281:806.
  111. Bennett CL, Kim B, Zakarija A, et al. Two mechanistic pathways for thienopyridine-associated thrombotic thrombocytopenic purpura: a report from the SERF-TTP Research Group and the RADAR Project. J Am Coll Cardiol 2007; 50:1138.
  112. Bennett CL, Connors JM, Carwile JM, et al. Thrombotic thrombocytopenic purpura associated with clopidogrel. N Engl J Med 2000; 342:1773.
  113. Zakarija A, Bandarenko N, Pandey DK, et al. Clopidogrel-associated TTP: an update of pharmacovigilance efforts conducted by independent researchers, pharmaceutical suppliers, and the Food and Drug Administration. Stroke 2004; 35:533.
  114. Hankey GJ. Clopidogrel and thrombotic thrombocytopenic purpura. Lancet 2000; 356:269.
  115. Paradiso-Hardy FL, Papastergiou J, Lanctôt KL, Cohen EA. Thrombotic thrombocytopenic purpura associated with clopidogrel: further evaluation. Can J Cardiol 2002; 18:771.
  116. Feinberg JE, Hurwitz S, Cooper D, et al. A randomized, double-blind trial of valaciclovir prophylaxis for cytomegalovirus disease in patients with advanced human immunodeficiency virus infection. AIDS Clinical Trials Group Protocol 204/Glaxo Wellcome 123-014 International CMV Prophylaxis Study Group. J Infect Dis 1998; 177:48.
  117. Bell WR, Chulay JD, Feinberg JE. Manifestations resembling thrombotic microangiopathy in patients with advanced human immunodeficiency virus (HIV) disease in a cytomegalovirus prophylaxis trial (ACTG 204). Medicine (Baltimore) 1997; 76:369.
  118. George JN. Systemic malignancies as a cause of unexpected microangiopathic hemolytic anemia and thrombocytopenia. Oncology (Williston Park) 2011; 25:908.
  119. Vesely SK, Li X, McMinn JR, et al. Pregnancy outcomes after recovery from thrombotic thrombocytopenic purpura-hemolytic uremic syndrome. Transfusion 2004; 44:1149.
  120. Mokrzycki MH, Rickles FR, Kaplan AA, Kohn OF. Thrombotic thrombocytopenic purpura in pregnancy: successful treatment with plasma exchange. Case report and review of the literature. Blood Purif 1995; 13:271.
  121. Kincaid-Smith P, Fairley KF, Kloss M. Lupus anticoagulant associated with renal thrombotic microangiopathy and pregnancy-related renal failure. Q J Med 1988; 68:795.
  122. Nesher G, Hanna VE, Moore TL, et al. Thrombotic microangiographic hemolytic anemia in systemic lupus erythematosus. Semin Arthritis Rheum 1994; 24:165.
  123. Asherson RA, Cervera R, Piette JC, et al. Catastrophic antiphospholipid syndrome: clues to the pathogenesis from a series of 80 patients. Medicine (Baltimore) 2001; 80:355.
  124. Amoura Z, Costedoat-Chalumeau N, Veyradier A, et al. Thrombotic thrombocytopenic purpura with severe ADAMTS-13 deficiency in two patients with primary antiphospholipid syndrome. Arthritis Rheum 2004; 50:3260.
  125. Devinsky O, Petito CK, Alonso DR. Clinical and neuropathological findings in systemic lupus erythematosus: the role of vasculitis, heart emboli, and thrombotic thrombocytopenic purpura. Ann Neurol 1988; 23:380.
  126. Chang JC, Shipstone A, Llenado-Lee MA. Postoperative thrombotic thrombocytopenic purpura following cardiovascular surgeries. Am J Hematol 1996; 53:11.
  127. Pavlovsky M, Weinstein R. Thrombotic thrombocytopenic purpura following coronary artery bypass graft surgery: prospective observations of an emerging syndrome. J Clin Apher 1997; 12:159.
  128. Almehmi A, Malas A, Jubelirer SJ. Thrombotic thrombocytopenic purpura following cardiovascular surgery: a case report. W V Med J 2004; 100:64.
  129. Anstadt MP, Carwile JM, Guill CK, et al. Relapse of thrombotic thrombocytopenic purpura associated with decreased VWF cleaving activity. Am J Med Sci 2002; 323:281.
  130. Ho VT, Cutler C, Carter S, et al. Blood and marrow transplant clinical trials network toxicity committee consensus summary: thrombotic microangiopathy after hematopoietic stem cell transplantation. Biol Blood Marrow Transplant 2005; 11:571.
  131. Ruutu T, Barosi G, Benjamin RJ, et al. Diagnostic criteria for hematopoietic stem cell transplant-associated microangiopathy: results of a consensus process by an International Working Group. Haematologica 2007; 92:95.
  132. Kennedy GA, Bleakley S, Butler J, et al. Posttransplant thrombotic microangiopathy: sensitivity of proposed new diagnostic criteria. Transfusion 2009; 49:1884.
  133. Laskin BL, Goebel J, Davies SM, Jodele S. Small vessels, big trouble in the kidneys and beyond: hematopoietic stem cell transplantation-associated thrombotic microangiopathy. Blood 2011; 118:1452.
  134. Siami K, Kojouri K, Swisher KK, et al. Thrombotic microangiopathy after allogeneic hematopoietic stem cell transplantation: an autopsy study. Transplantation 2008; 85:22.
  135. Search on "TTP-HUS." www.ouhsc.edu/platelets (Accessed on January 30, 2012).