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

Acquired TTP: Initial treatment

James N George, MD
Adam Cuker, MD, MS
Section Editor
Lawrence LK Leung, MD
Deputy Editor
Jennifer S Tirnauer, MD


Classification of thrombotic thrombocytopenic purpura (TTP) and related syndromes such as hemolytic uremic syndrome (HUS) is evolving. We now use TTP to refer to the thrombotic microangiopathy (TMA) caused by severely reduced activity of the von Willebrand factor-cleaving protease ADAMTS13. We divide TTP into acquired and hereditary syndromes, due to an autoantibody against ADAMTS13 and ADAMTS13 gene mutations, respectively. TTP is characterized by small-vessel platelet-rich thrombi, thrombocytopenia, and microangiopathic hemolytic anemia. In addition, some patients may have neurologic abnormalities, mild renal insufficiency, and low-grade fever.

Acquired autoimmune TTP is a medical emergency that is almost always fatal if appropriate treatment is not initiated promptly; with appropriate treatment, survival rates of up to 90 percent are possible.

This topic reviews our approach to the initial therapy for children and adults with acquired (autoimmune) TTP, defined by severe ADAMTS13 deficiency (activity level usually <10 percent) caused by an autoantibody.

The following aspects of care for individuals with acquired TTP are discussed in detail separately:

Clinical manifestations and diagnosis – (see "Acquired TTP: Clinical manifestations and diagnosis")

To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information on subscription options, click below on the option that best describes you:

Subscribers log in here

Literature review current through: Nov 2017. | This topic last updated: Nov 06, 2017.
The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of this website is governed by the UpToDate Terms of Use ©2017 UpToDate, Inc.
  1. Vesely SK, George JN, Lämmle B, et al. ADAMTS13 activity in thrombotic thrombocytopenic purpura-hemolytic uremic syndrome: relation to presenting features and clinical outcomes in a prospective cohort of 142 patients. Blood 2003; 102:60.
  2. Amorosi EL, Ultmann JE. Thrombotic thrombocytopenic purpura: Report of 16 cases and review of the literature. Medicine (Baltimore) 1966; 45:139.
  3. 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.
  4. von Baeyer H. Plasmapheresis in thrombotic microangiopathy-associated syndromes: review of outcome data derived from clinical trials and open studies. Ther Apher 2002; 6:320.
  5. George JN. How I treat patients with thrombotic thrombocytopenic purpura: 2010. Blood 2010; 116:4060.
  6. Scully M, Hunt BJ, Benjamin S, et al. Guidelines on the diagnosis and management of thrombotic thrombocytopenic purpura and other thrombotic microangiopathies. Br J Haematol 2012; 158:323.
  7. Wyllie BF, Garg AX, Macnab J, et al. Thrombotic thrombocytopenic purpura/haemolytic uraemic syndrome: a new index predicting response to plasma exchange. Br J Haematol 2006; 132:204.
  8. Michael M, Elliott EJ, Ridley GF, et al. Interventions for haemolytic uraemic syndrome and thrombotic thrombocytopenic purpura. Cochrane Database Syst Rev 2009; :CD003595.
  9. Kremer Hovinga JA, Vesely SK, Terrell DR, et al. Survival and relapse in patients with thrombotic thrombocytopenic purpura. Blood 2010; 115:1500.
  10. Som S, Deford CC, Kaiser ML, et al. Decreasing frequency of plasma exchange complications in patients treated for thrombotic thrombocytopenic purpura-hemolytic uremic syndrome, 1996 to 2011. Transfusion 2012; 52:2525.
  11. Shah N, Rutherford C, Matevosyan K, et al. Role of ADAMTS13 in the management of thrombotic microangiopathies including thrombotic thrombocytopenic purpura (TTP). Br J Haematol 2013; 163:514.
  12. George JN. ADAMTS13: what it does, how it works, and why it's important. Transfusion 2009; 49:196.
  13. Bell WR, Braine HG, Ness PM, Kickler TS. Improved survival in thrombotic thrombocytopenic purpura-hemolytic uremic syndrome. Clinical experience in 108 patients. N Engl J Med 1991; 325:398.
  14. Pene F, Vigneau C, Auburtin M, et al. Outcome of severe adult thrombotic microangiopathies in the intensive care unit. Intensive Care Med 2005; 31:71.
  15. Zheng XL, Kaufman RM, Goodnough LT, Sadler JE. Effect of plasma exchange on plasma ADAMTS13 metalloprotease activity, inhibitor level, and clinical outcome in patients with idiopathic and nonidiopathic thrombotic thrombocytopenic purpura. Blood 2004; 103:4043.
  16. Moake JL. Thrombotic microangiopathies. N Engl J Med 2002; 347:589.
  17. Byrnes JJ, Moake JL, Klug P, Periman P. Effectiveness of the cryosupernatant fraction of plasma in the treatment of refractory thrombotic thrombocytopenic purpura. Am J Hematol 1990; 34:169.
  18. Blombery P, Scully M. Management of thrombotic thrombocytopenic purpura: current perspectives. J Blood Med 2014; 5:15.
  19. Zeigler ZR, Shadduck RK, Gryn JF, et al. Cryoprecipitate poor plasma does not improve early response in primary adult thrombotic thrombocytopenic purpura (TTP). J Clin Apher 2001; 16:19.
  20. Rock G, Anderson D, Clark W, et al. Does cryosupernatant plasma improve outcome in thrombotic thrombocytopenic purpura? No answer yet. Br J Haematol 2005; 129:79.
  21. Blackall DP, Uhl L, Spitalnik SL, Transfusion Practices Committee. Cryoprecipitate-reduced plasma:rationale for use and efficacy in the treatment of thrombotic thrombocytopenic purpura. Transfusion 2001; 41:840.
  22. Rock G, Shumak KH, Sutton DM, et al. Cryosupernatant as replacement fluid for plasma exchange in thrombotic thrombocytopenic purpura. Members of the Canadian Apheresis Group. Br J Haematol 1996; 94:383.
  23. Raife TJ, Friedman KD, Dwyre DM. The pathogenicity of von Willebrand factor in thrombotic thrombocytopenic purpura: reconsideration of treatment with cryopoor plasma. Transfusion 2006; 46:74.
  24. Toussaint-Hacquard M, Coppo P, Soudant M, et al. Type of plasma preparation used for plasma exchange and clinical outcome of adult patients with acquired idiopathic thrombotic thrombocytopenic purpura: a French retrospective multicenter cohort study. Transfusion 2015; 55:2445.
  25. Mintz PD, Neff A, MacKenzie M, et al. A randomized, controlled Phase III trial of therapeutic plasma exchange with fresh-frozen plasma (FFP) prepared with amotosalen and ultraviolet A light compared to untreated FFP in thrombotic thrombocytopenic purpura. Transfusion 2006; 46:1693.
  26. Moake J, Chintagumpala M, Turner N, et al. Solvent/detergent-treated plasma suppresses shear-induced platelet aggregation and prevents episodes of thrombotic thrombocytopenic purpura. Blood 1994; 84:490.
  27. Horowitz MS, Pehta JC. SD Plasma in TTP and coagulation factor deficiencies for which no concentrates are available. Vox Sang 1998; 74 Suppl 1:231.
  28. Evans G, Llewelyn C, Luddington R, et al. Solvent/detergent fresh frozen plasma as primary treatment of acute thrombotic thrombocytopenic purpura. Clin Lab Haematol 1999; 21:119.
  29. Harrison CN, Lawrie AS, Iqbal A, et al. Plasma exchange with solvent/detergent-treated plasma of resistant thrombotic thrombocytopenic purpura. Br J Haematol 1996; 94:756.
  30. Pehta JC. Clinical studies with solvent detergent-treated products. Transfus Med Rev 1996; 10:303.
  31. Flamholz R, Jeon HR, Baron JM, Baron BW. Study of three patients with thrombotic thrombocytopenic purpura exchanged with solvent/detergent-treated plasma: is its decreased protein S activity clinically related to their development of deep venous thromboses? J Clin Apher 2000; 15:169.
  32. Yarranton H, Cohen H, Pavord SR, et al. Venous thromboembolism associated with the management of acute thrombotic thrombocytopenic purpura. Br J Haematol 2003; 121:778.
  33. Rock G, Yousef H, Neurath D, Lu M. ADAMTS-13 in fresh, stored, and solvent/detergent-treated plasma. Transfusion 2006; 46:1261.
  34. Scott EA, Puca KE, Pietz BC, et al. Comparison and stability of ADAMTS13 activity in therapeutic plasma products. Transfusion 2007; 47:120.
  35. George JN. Clinical practice. Thrombotic thrombocytopenic purpura. N Engl J Med 2006; 354:1927.
  36. Coppo P, Bussel A, Charrier S, et al. High-dose plasma infusion versus plasma exchange as early treatment of thrombotic thrombocytopenic purpura/hemolytic-uremic syndrome. Medicine (Baltimore) 2003; 82:27.
  37. Novitzky N, Jacobs P, Rosenstrauch W. The treatment of thrombotic thrombocytopenic purpura: plasma infusion or exchange? Br J Haematol 1994; 87:317.
  38. Allford SL, Hunt BJ, Rose P, et al. Guidelines on the diagnosis and management of the thrombotic microangiopathic haemolytic anaemias. Br J Haematol 2003; 120:556.
  39. Balduini CL, Gugliotta L, Luppi M, et al. High versus standard dose methylprednisolone in the acute phase of idiopathic thrombotic thrombocytopenic purpura: a randomized study. Ann Hematol 2010; 89:591.
  40. Lim W, Vesely SK, George JN. The role of rituximab in the management of patients with acquired thrombotic thrombocytopenic purpura. Blood 2015; 125:1526.
  41. Uhl L, Kiss JE, Malynn E, et al. Rituximab for thrombotic thrombocytopenic purpura: lessons from the STAR trial. Transfusion 2017; 57:2532.
  42. George JN, Woodson RD, Kiss JE, et al. Rituximab therapy for thrombotic thrombocytopenic purpura: a proposed study of the Transfusion Medicine/Hemostasis Clinical Trials Network with a systematic review of rituximab therapy for immune-mediated disorders. J Clin Apher 2006; 21:49.
  43. Kiss JE. Randomized clinical trials in thrombotic thrombocytopenic purpura: where do we go from here? Transfusion 2006; 46:1659.
  44. Clinical trials.gov identifier: NCT00799773. www.clinicaltrials.gov/ct2/results?term=NCT00799773 (Accessed on January 09, 2009).
  45. Westwood JP, Thomas M, Alwan F, et al. Rituximab prophylaxis to prevent thrombotic thrombocytopenic purpura relapse: Outcome and evaluation of dosing regimens. Blood Advances 2017; 1:1159.
  46. Scully M, McDonald V, Cavenagh J, et al. A phase 2 study of the safety and efficacy of rituximab with plasma exchange in acute acquired thrombotic thrombocytopenic purpura. Blood 2011; 118:1746.
  47. Page EE, Kremer Hovinga JA, Terrell DR, et al. Rituximab reduces risk for relapse in patients with thrombotic thrombocytopenic purpura. Blood 2016; 127:3092.
  48. Westwood JP, Webster H, McGuckin S, et al. Rituximab for thrombotic thrombocytopenic purpura: benefit of early administration during acute episodes and use of prophylaxis to prevent relapse. J Thromb Haemost 2013; 11:481.
  49. Sayani FA, Abrams CS. How I treat refractory thrombotic thrombocytopenic purpura. Blood 2015; 125:3860.
  50. Scully M, Cohen H, Cavenagh J, et al. Remission in acute refractory and relapsing thrombotic thrombocytopenic purpura following rituximab is associated with a reduction in IgG antibodies to ADAMTS-13. Br J Haematol 2007; 136:451.
  51. Froissart A, Buffet M, Veyradier A, et al. Efficacy and safety of first-line rituximab in severe, acquired thrombotic thrombocytopenic purpura with a suboptimal response to plasma exchange. Experience of the French Thrombotic Microangiopathies Reference Center. Crit Care Med 2012; 40:104.
  52. McDonald V, Manns K, Mackie IJ, et al. Rituximab pharmacokinetics during the management of acute idiopathic thrombotic thrombocytopenic purpura. J Thromb Haemost 2010; 8:1201.
  53. George JN. Measuring ADAMTS13 activity in patients with suspected thrombotic thrombocytopenic purpura: when, how, and why? Transfusion 2015; 55:11.
  54. Parekh HD, Reese JA, Cobb PW, George JN. Bone marrow necrosis discovered in a patient with suspected thrombotic thrombocytopenic purpura. Am J Hematol 2015; 90:264.
  55. Booth KK, Terrell DR, Vesely SK, George JN. Systemic infections mimicking thrombotic thrombocytopenic purpura. Am J Hematol 2011; 86:743.
  56. George JN. Systemic malignancies as a cause of unexpected microangiopathic hemolytic anemia and thrombocytopenia. Oncology (Williston Park) 2011; 25:908.
  57. Rizvi MA, Vesely SK, George JN, et al. Complications of plasma exchange in 71 consecutive patients treated for clinically suspected thrombotic thrombocytopenic purpura-hemolytic-uremic syndrome. Transfusion 2000; 40:896.
  58. McClain RS, Terrell DR, Vesely SK, George JN. Plasma exchange complications in patients treated for thrombotic thrombocytopenia purpura-hemolytic uremic syndrome: 2011 to 2014. Transfusion 2014; 54:3257.
  59. Apter AJ, Kaplan AA. An approach to immunologic reactions associated with plasma exchange. J Allergy Clin Immunol 1992; 90:119.
  60. Scully M, Gattens M, Khair K, Liesner R. The use of intermediate purity factor VIII concentrate BPL 8Y as prophylaxis and treatment in congenital thrombotic thrombocytopenic purpura. Br J Haematol 2006; 135:101.
  61. Peyvandi F, Mannucci PM, Valsecchi C, et al. ADAMTS13 content in plasma-derived factor VIII/von Willebrand factor concentrates. Am J Hematol 2013; 88:895.
  62. Naik S, Mahoney DH. Successful treatment of congenital TTP with a novel approach using plasma-derived factor VIII. J Pediatr Hematol Oncol 2013; 35:551.
  63. Goel R, Ness PM, Takemoto CM, et al. Platelet transfusions in platelet consumptive disorders are associated with arterial thrombosis and in-hospital mortality. Blood 2015; 125:1470.
  64. Swisher KK, Terrell DR, Vesely SK, et al. Clinical outcomes after platelet transfusions in patients with thrombotic thrombocytopenic purpura. Transfusion 2009; 49:873.
  65. Peyvandi F, Scully M, Kremer Hovinga JA, et al. Caplacizumab for Acquired Thrombotic Thrombocytopenic Purpura. N Engl J Med 2016; 374:511.
  66. Peyvandi F, Scully M, Kremer Hovinga JA, et al. Caplacizumab reduces the frequency of major thromboembolic events, exacerbations and death in patients with acquired thrombotic thrombocytopenic purpura. J Thromb Haemost 2017; 15:1448.
  67. https://www.clinicaltrials.gov/ct2/results?term=02553317 (Accessed on February 11, 2016).
  68. Scully M, Thomas M, Underwood M, et al. Thrombotic thrombocytopenic purpura and pregnancy: presentation, management, and subsequent pregnancy outcomes. Blood 2014; 124:211.
  69. Egerman RS, Witlin AG, Friedman SA, Sibai BM. Thrombotic thrombocytopenic purpura and hemolytic uremic syndrome in pregnancy: review of 11 cases. Am J Obstet Gynecol 1996; 175:950.
  70. Ezra Y, Rose M, Eldor A. Therapy and prevention of thrombotic thrombocytopenic purpura during pregnancy: a clinical study of 16 pregnancies. Am J Hematol 1996; 51:1.
  71. Wurzei JM. TTP lesions in placenta but not fetus. N Engl J Med 1979; 301:503.
  72. 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.
  73. Dabak V, Kuriakose P, Raman S. Successful management of a Jehovah's Witness with thrombotic thrombocytopenic purpura unwilling to be treated with therapeutic plasma exchange. J Clin Apher 2007; 22:330.