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Diagnostic and treatment guidelines for thrombotic thrombocytopenic purpura (TTP) 2017 in Japan

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Abstract

Thrombotic thrombocytopenic purpura (TTP) can rapidly progress into a life-threatening condition, thus the importance of appropriate diagnosis and treatment cannot be overstated. Until recently, TTP has mainly been diagnosed by clinical findings such as thrombocytopenia and non-immune hemolytic anemia. In addition to these clinical findings, however, reduced activity of a disintegrin-like and metalloprotease with thrombospondin type 1 motif 13 (ADAMTS13) below 10% has been accepted internationally as a diagnostic criterion for TTP. In the present guidelines, we have taken all of these criteria into consideration. TTP is classified as acquired if the patient is positive for anti-ADAMTS13 autoantibodies, and as congenital if ADAMTS13 gene abnormalities are detected. Fresh-frozen plasma (FFP) transfusion is performed in patients with congenital TTP to supplement ADAMTS13. Plasma exchange therapy using FFP is conducted in patients with acquired TTP to supplement ADAMTS13 and remove anti-ADAMTS13 autoantibodies. To suppress autoantibody production, corticosteroid therapy may be administered in conjunction with plasma exchange. Recent reports show that the monoclonal anti-CD-20 antibody rituximab is effective in patients with refractory or relapsed TTP.

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References

  1. Moake JL. Thrombotic thrombocytopenic purpura: the systemic clumping “plague”. Annu Rev Med. 2002;53:75–88.

    Article  CAS  PubMed  Google Scholar 

  2. Furlan M, Robles R, Galbusera M, Remuzzi G, Kyrle PA, Brenner B, et al. von Willebrand factor-cleaving protease in thrombotic thrombocytopenic purpura and the hemolytic-uremic syndrome. N Engl J Med. 1998;339:1578–84.

    Article  CAS  PubMed  Google Scholar 

  3. Tsai HM, Lian EC. Antibodies to von Willebrand factor-cleaving protease in acute thrombotic thrombocytopenic purpura. N Engl J Med. 1998;339:1585–94.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. George JN, Nester CM. Syndromes of thrombotic microangiopathy. N Engl J Med. 2014;371:1847–8.

    Article  PubMed  Google Scholar 

  5. Levy GG, Nichols WC, Lian EC, Foroud T, McClintick JN, McGee BM, et al. Mutations in a member of the ADAMTS gene family cause thrombotic thrombocytopenic purpura. Nature. 2001;413:488–94.

    Article  CAS  PubMed  Google Scholar 

  6. Kokame K, Matsumoto M, Soejima K, Yagi H, Ishizashi H, Funato M, et al. Mutations and common polymorphisms in ADAMTS13 gene responsible for von Willebrand factor-cleaving protease activity. Proc Natl Acad Sci USA. 2002;99:11902–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Zheng X, Chung D, Takayama TK, Majerus EM, Sadler JE, Fujikawa K. Structure of von Willebrand factor-cleaving protease (ADAMTS13), a metalloprotease involved in thrombotic thrombocytopenic purpura. J Biol Chem. 2001;276:41059–63.

    Article  CAS  PubMed  Google Scholar 

  8. Von Furlan M. Willebrand factor: molecular size and functional activity. Ann Hematol. 1996;72:341–8.

    Article  Google Scholar 

  9. Savage B, Saldivar E, Ruggeri ZM. Initiation of platelet adhesion by arrest onto fibrinogen or translocation on von Willebrand factor. Cell. 1996;84:289–97.

    Article  CAS  PubMed  Google Scholar 

  10. Furlan M, Robles R, Lammle B. Partial purification and characterization of a protease from human plasma cleaving von Willebrand factor to fragments produced by in vivo proteolysis. Blood. 1996;87:4223–34.

    CAS  PubMed  Google Scholar 

  11. Tsai HM. Physiologic cleavage of von Willebrand factor by a plasma protease is dependent on its conformation and requires calcium ion. Blood. 1996;87:4235–44.

    CAS  PubMed  Google Scholar 

  12. Kokame K, Matsumoto M, Fujimura Y, Miyata T. VWF73, a region from D1596 to R1668 of von Willebrand factor, provides a minimal substrate for ADAMTS-13. Blood. 2004;103:607–12.

    Article  CAS  PubMed  Google Scholar 

  13. Kokame K, Nobe Y, Kokubo Y, Okayama A, Miyata T. FRETS-VWF73, a first fluorogenic substrate for ADAMTS13 assay. Br J Haematol. 2005;129:93–100.

    Article  CAS  PubMed  Google Scholar 

  14. Kato S, Matsumoto M, Matsuyama T, Isonishi A, Hiura H, Fujimura Y. Novel monoclonal antibody-based enzyme immunoassay for determining plasma levels of ADAMTS13 activity. Transfusion. 2006;46:1444–52.

    Article  CAS  PubMed  Google Scholar 

  15. Scheiflinger F, Knobl P, Trattner B, Plaimauer B, Mohr G, Dockal M, et al. Nonneutralizing IgM and IgG antibodies to von Willebrand factor-cleaving protease (ADAMTS-13) in a patient with thrombotic thrombocytopenic purpura. Blood. 2003;102:3241–3.

    Article  CAS  PubMed  Google Scholar 

  16. Ferrari S, Scheiflinger F, Rieger M, Mudde G, Wolf M, Coppo P, et al. Prognostic value of anti-ADAMTS 13 antibody features (Ig isotype, titer, and inhibitory effect) in a cohort of 35 adult French patients undergoing a first episode of thrombotic microangiopathy with undetectable ADAMTS 13 activity. Blood. 2007;109:2815–22.

    CAS  PubMed  Google Scholar 

  17. Kasper CK, Pool JG. Letter: measurement of mild factor VIII inhibitors in Bethesda units. Thromb Diath Haemorrh. 1975;34:875–6.

    CAS  PubMed  Google Scholar 

  18. Kremer Hovinga JA, Vesely SK, Terrell DR, Lämmle B, George JN. Survival and relapse in patients with thrombotic thrombocytopenic purpura. Blood. 2010;115:1500–11.

    Article  PubMed  Google Scholar 

  19. Matsumoto M, Bennett CL, Isonishi A, Qureshi Z, Hori Y, Hayakawa M, et al. Acquired Idiopathic ADAMTS13 Activity Deficient Thrombotic Thrombocytopenic Purpura in a Population from Japan. PLoS One. 2012;7:e33029.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Moschcowitz E. Hyaline Thrombosis of the terminal arterioles and capillaries: a hitherto undescribed disease. Proc N Y Pathol Soc. 1924;24:21–4.

    Google Scholar 

  21. Amorosi EL, Ultmann JE. Thrombotic thrombocytopenic purpura: report of 16 cases and review of the literature. Medicine. 1966;45:139–59.

    Article  Google Scholar 

  22. Rock GA, Shumak KH, Buskard NA, Blanchette VS, Kelton JG, Nair RC, 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;325:393–7.

    Article  CAS  PubMed  Google Scholar 

  23. Singer K, Bornstein FP, Wile SA. Thrombotic thrombocytopenic purpura; hemorrhagic diathesis with generalized platelet thromboses. Blood. 1947;2:542–54.

    CAS  PubMed  Google Scholar 

  24. Moake JL, Rudy CK, Troll JH, Weinstein MJ, Colannino NM, Azocar J, et al. Unusually large plasma factor VIII: von Willebrand factor multimers in chronic relapsing thrombotic thrombocytopenic purpura. N Engl J Med. 1982;307:1432–5.

    Article  CAS  PubMed  Google Scholar 

  25. Asada Y, Sumiyoshi A, Hayashi T, Suzumiya J, Kaketani K. Immunohistochemistry of vascular lesion in thrombotic thrombocytopenic purpura, with special reference to factor VIII related antigen. Thromb Res. 1985;38:469–79.

    Article  CAS  PubMed  Google Scholar 

  26. Veyradier A, Obert B, Houllier A, Meyer D, Girma JP. Specific von Willebrand factor-cleaving protease in thrombotic microangiopathies: a study of 111 cases. Blood. 2001;98:1765–72.

    Article  CAS  PubMed  Google Scholar 

  27. Vesely SK, George JN, Lämmle B, Studt JD, Alberio L, El-Harake MA, 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;102:60–8.

    Article  CAS  PubMed  Google Scholar 

  28. Matsumoto M, Yagi H, Ishizashi H, Wada H, Fujimura Y. The Japanese experience with thrombotic thrombocytopenic purpura-hemolytic uremic syndrome. Semin Hematol. 2004;41:68–74.

    Article  PubMed  Google Scholar 

  29. Scully M, Cataland S, Coppo P, de la Rubia J, Friedman KD, Kremer Hovinga J, et al. Consensus on the standardization of terminology in thrombotic thrombocytopenic purpura and related thrombotic microangiopathies. J Thromb Haemost. 2017;15:312–22.

    Article  CAS  PubMed  Google Scholar 

  30. Terrell DR, Williams LA, Vesely SK, Lammle B, Hovinga JA, George JN. The incidence of thrombotic thrombocytopenic purpura-hemolytic uremic syndrome: all patients, idiopathic patients, and patients with severe ADAMTS-13 deficiency. J Thromb Haemost. 2005;3:1432–6.

    Article  CAS  PubMed  Google Scholar 

  31. Scully M, Yarranton H, Liesner R, Cavenagh J, Hunt B, Benjamin S, et al. Regional UK TTP registry: correlation with laboratory ADAMTS 13 analysis and clinical features. Br J Haematol. 2008;142:819–26.

    Article  PubMed  Google Scholar 

  32. 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;103:4043–9.

    Article  CAS  PubMed  Google Scholar 

  33. Coppo P, Bengoufa D, Veyradier A, Wolf M, Bussel A, Millot GA, 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;83:233–44.

    Article  CAS  Google Scholar 

  34. Scully M, Hunt BJ, Benjamin S, Liesner R, Rose P, Peyvandi F, et al. Guidelines on the diagnosis and management of thrombotic thrombocytopenic purpura and other thrombotic microangiopathies. Br J Haematol. 2012;158:323–35.

    Article  PubMed  Google Scholar 

  35. Zini G, d’Onofrio G, Briggs C, Erber W, Jou JM, Lee SH, et al. ICSH recommendations for identification, diagnostic value, and quantitation of schistocytes. Int J Lab Hematol. 2012;34:107–16.

    Article  CAS  PubMed  Google Scholar 

  36. Kato H, Nangaku M, Hataya H, Sawai T, Ashida A, Fujimaru R, et al. Clinical guides for atypical hemolytic uremic syndrome in Japan. Clin Exp Nephrol. 2016;20:536–43.

    Article  CAS  PubMed  Google Scholar 

  37. Sibai BM, Ramadan MK, Usta I, Salama M, Mercer BM, Friedman SA. Maternal morbidity and mortality in 442 pregnancies with hemolysis, elevated liver enzymes, and low platelets (HELLP syndrome). Am J Obstet Gynecol. 1993;169:1000–6.

    Article  CAS  PubMed  Google Scholar 

  38. Pereira A, Mazzara R, Monteagudo J, Sanz C, Puig L, Martinez A, et al. Thrombotic thrombocytopenic purpura/hemolytic uremic syndrome: a multivariate analysis of factors predicting the response to plasma exchange. Ann Hematol. 1995;70:319–23.

    Article  CAS  PubMed  Google Scholar 

  39. Balduini CL, Gugliotta L, Luppi M, Laurenti L, Klersy C, Pieresca C, et al. High versus standard dose methylprednisolone in the acute phase of idiopathic thrombotic thrombocytopenic purpura: a randomized study. Ann Hematol. 2010;89:591–6.

    Article  CAS  PubMed  Google Scholar 

  40. Holst LB, Haase N, Wetterslev J, Wernerman J, Guttormsen AB, Karlsson S, et al. Lower versus higher hemoglobin threshold for transfusion in septic shock. N Engl J Med. 2014;371:1381–91.

    Article  PubMed  Google Scholar 

  41. Hebert PC, Wells G, Blajchman MA, Marshall J, Martin C, Pagliarello G, et al. A multicenter, randomized, controlled clinical trial of transfusion requirements in critical care. Transfusion Requirements in Critical Care Investigators, Canadian Critical Care Trials Group. N Engl J Med. 1999;340:409–17.

    Article  CAS  PubMed  Google Scholar 

  42. Benhamou Y, Baudel JL, Wynckel A, Galicier L, Azoulay E, Provot F, et al. Are platelet transfusions harmful in acquired thrombotic thrombocytopenic purpura at the acute phase? Experience of the French thrombotic microangiopathies reference center. Am J Hematol. 2015;90:E127–9.

    Article  PubMed  Google Scholar 

  43. Kumar A, Mhaskar R, Grossman BJ, Kaufman RM, Tobian AA, Kleinman S, et al. Platelet transfusion: a systematic review of the clinical evidence. Transfusion. 2015;55:1116–27.

    Article  PubMed  Google Scholar 

  44. Miyakawa Y, Imada K, Ichinohe T, Nishio K, Abe T, Murata M, et al. Efficacy and safety of rituximab in Japanese patients with acquired thrombotic thrombocytopenic purpura refractory to conventional therapy. Int J Hematol. 2016;104:228–35.

    Article  CAS  PubMed  Google Scholar 

  45. Isonishi A, Bennett CL, Plaimauer B, Scheiflinger F, Matsumoto M, Fujimura Y. Poor responder to plasma exchange therapy in acquired thrombotic thrombocytopenic purpura is associated with ADAMTS13 inhibitor boosting: visualization of an ADAMTS13 inhibitor complex and its proteolytic clearance from plasma. Transfusion. 2015;55:2321–30.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Scully M, McDonald V, Cavenagh J, Hunt BJ, Longair I, Cohen H, et al. A phase 2 study of the safety and efficacy of rituximab with plasma exchange in acute acquired thrombotic thrombocytopenic purpura. Blood. 2011;118:1746–53.

    Article  CAS  PubMed  Google Scholar 

  47. Froissart A, Buffet M, Veyradier A, Poullin P, Provôt F, Malot S, 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;40:104–11.

    Article  CAS  PubMed  Google Scholar 

  48. Beloncle F, Buffet M, Coindre JP, Munoz-Bongrand N, Malot S, Pene F, et al. Splenectomy and/or cyclophosphamide as salvage therapies in thrombotic thrombocytopenic purpura: the French TMA Reference Center experience. Transfusion. 2012;52:2436–44.

    Article  PubMed  Google Scholar 

  49. Ziman A, Mitri M, Klapper E, Pepkowitz SH, Goldfinger D. Combination vincristine and plasma exchange as initial therapy in patients with thrombotic thrombocytopenic purpura: one institution’s experience and review of the literature. Transfusion. 2005;45:41–9.

    Article  CAS  PubMed  Google Scholar 

  50. Nosari A, Redaelli R, Caimi TM, Mostarda G, Morra E. Cyclosporine therapy in refractory/relapsed patients with thrombotic thrombocytopenic purpura. Am J Hematol. 2009;84:313–4.

    Article  PubMed  Google Scholar 

  51. Kappers-Klunne MC, Wijermans P, Fijnheer R, Croockewit AJ, van der Holt B, de Wolf JT, et al. Splenectomy for the treatment of thrombotic thrombocytopenic purpura. Br J Haematol. 2005;130:768–76.

    Article  CAS  PubMed  Google Scholar 

  52. Kawano N, Yokota-Ikeda N, Yoshida S, Kuriyama T, Yamashita K, Sugio Y, et al. Therapeutic modality of 11 patients with TTP in a single institution in Miyazaki from 2000 to 2011. Intern Med. 2013;52:1883–91.

    Article  PubMed  Google Scholar 

  53. Peyvandi F, Lavoretano S, Palla R, Feys HB, Vanhoorelbeke K, Battaglioli T, et al. ADAMTS13 and anti-ADAMTS13 antibodies as markers for recurrence of acquired thrombotic thrombocytopenic purpura during remission. Haematologica. 2008;93:232–9.

    Article  CAS  PubMed  Google Scholar 

  54. Dacie JV, Mollison PL, Richardson N, Selwyn JG, Shapiro L. Atypical congenital haemolytic anaemia. Q J Med. 1953;22:79–98.

    CAS  PubMed  Google Scholar 

  55. Schulman I, Pierce M, Lukens A, Currimbhoy Z. Studies on thrombopoiesis. I. A factor in normal human plasma required for platelet production; chronic thrombocytopenia due to its deficiency. Blood. 1960;16:943–57.

    CAS  PubMed  Google Scholar 

  56. Upshaw JD Jr. Congenital deficiency of a factor in normal plasma that reverses microangiopathic hemolysis and thrombocytopenia. N Engl J Med. 1978;298:1350–2.

    Article  PubMed  Google Scholar 

  57. Rennard S, Abe S. Decreased cold-insoluble globulin in congenital thrombocytopenia (Upshaw-Schulman syndrome). N Engl J Med. 1979;300:368.

    CAS  PubMed  Google Scholar 

  58. Furlan M, Robles R, Solenthaler M, Wassmer M, Sandoz P, Lammle B. Deficient activity of von Willebrand factor-cleaving protease in chronic relapsing thrombotic thrombocytopenic purpura. Blood. 1997;89:3097–103.

    CAS  PubMed  Google Scholar 

  59. Kinoshita S, Yoshioka A, Park YD, Shizashi H, Konno M, Funato M, et al. Upshaw-Schulman syndrome revisited: a concept of congenital thrombotic thrombocytopenic purpura. Int J Hematol. 2001;74:101–8.

    Article  CAS  PubMed  Google Scholar 

  60. Sadler JE. What’s new in the diagnosis and pathophysiology of thrombotic thrombocytopenic purpura. Hematol Am Soc Hematol Educ Progr. 2015;2015:631–6.

    Google Scholar 

  61. Mansouri Taleghani M, von Krogh AS, Fujimura Y, George JN, Hrachovinova I, Knobl PN, et al. Hereditary thrombotic thrombocytopenic purpura and the hereditary TTP registry. Hamostaseologie. 2013;33:138–43.

    Article  CAS  PubMed  Google Scholar 

  62. Kokame K, Kokubo Y, Miyata T. Polymorphisms and mutations of ADAMTS13 in the Japanese population and estimation of the number of patients with Upshaw-Schulman syndrome. J Thromb Haemost. 2011;9:1654–6.

    Article  CAS  PubMed  Google Scholar 

  63. Fujimura Y, Kokame K, Yagi H, Isonishi A, Matsumoto M, Miyata T. Hereditary deficiency of ADAMTS13 activity: Upshaw-Schulman syndrome. In: Rodgers MD, editor. ADAMTS13. Switzerland: Springer; 2015. p. 73–90.

    Google Scholar 

  64. Fujimura Y, Matsumoto M, Kokame K, Isonishi A, Soejima K, Akiyama N, et al. Pregnancy-induced thrombocytopenia and TTP, and the risk of fetal death, in Upshaw-Schulman syndrome: a series of 15 pregnancies in 9 genotyped patients. Br J Haematol. 2009;144:742–54.

    Article  CAS  PubMed  Google Scholar 

  65. Taguchi F, Yagi H, Matsumoto M, Sadamura S, Isonishi A, Soejima K, et al. The homozygous p. C1024R- ADAMTS13 gene mutation links to a late-onset phenotype of Upshaw-Schulman syndrome in Japan. Thromb Haemost. 2012;107:1003–5.

    Article  CAS  PubMed  Google Scholar 

  66. Matsumoto M, Kokame K, Soejima K, Miura M, Hayashi S, Fujii Y, et al. Molecular characterization of ADAMTS13 gene mutations in Japanese patients with Upshaw-Schulman syndrome. Blood. 2004;103:1305–10.

    Article  CAS  PubMed  Google Scholar 

  67. Fujimura Y, Matsumoto M, Isonishi A, Yagi H, Kokame K, Soejima K, et al. Natural history of Upshaw-Schulman syndrome based on ADAMTS13 gene analysis in Japan. J Thromb Haemost. 2011;9(Suppl 1):283–301.

    Article  CAS  PubMed  Google Scholar 

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Correspondence to Masanori Matsumoto.

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The following authors declare competing interests with respect to this article. Masanori Matsumoto: Received consultant/advisor fees from Baxalta, Alexion Pharma, Ablynx nv and Kainos Laboratories; lecture fees from Asahi Kasei Pharma, Chugai Pharmaceutical, Alexion Pharma, and Bayer Yakuhin; and research funds from Chugai Pharmaceutical, Bayer Yakuhin, and Baxalta. He has shared patent rights with Alfresa Pharma. Yoshihiro Fujimura: Is an employee of the Japanese Red Cross Kinki Block Blood Center. He also has shared patent rights with Alfresa Pharma. Hideo Wada: Received lecture fees from Alexion Pharma and research fund from Daiichi Sankyo. Koichi Kokame: Received patent royalties through National Cerebral and Cardiovascular Center from the Peptide Institute, Peptides International, Kainos Laboratories, SRL, Alfresa Pharma, and AnaSpec. Yoshitaka Miyakawa: Received consultant/advisor fees from Novartis Pharma, Kyowa Hakko Kirin, Kainos Laboratories, and Fujifilm; lecture fees from Novartis Pharma, Kyowa Hakko Kirin, Alexion Pharma, Chugai Pharmaceutical, Bayer Yakuhin, Daiichi Sankyo, Asahi Kasei Pharma, Kissei Pharmaceutical, Biogen, and Baxalta; manuscript fees from Terumo, Zenyaku Kogyo, and the Japan Blood Products Organization; and research funds from Alexion Pharma and Teijin Pharma. Yasunori Ueda: Received consultant/advisor fees from Ablynx nv and Kainos Laboratories; research found for clinical trial from Eli Lilly Japan, Sumitomo Dainippon Pharma, Celgene, Symbio Pharmaceutical, Astellas Pharma, Inc. and Eisai. Takanori Moriki: Is an employee at the Bank of Tokyo-Mitsubishi UFJ, Ltd. Medical Center, Head Office. Toshiyuki Miyata: Received consultant/advisor fees from Alexion Pharma and lecture fees from CSL Behring, LSI Medience, Alexion Pharma, Daiichi Sankyo, and Bayer Yakuhin. He also received patent royalties through National Cerebral and Cardiovascular Center from the Peptide Institute, Peptides International, Kainos Laboratories, SRL, Alfresa Pharma, and AnaSpec. Mitsuru Murata: Received consultant/advisor fees from Pfizer and Otsuka Pharmaceutical; lecture and related fees from Sekisui Medical, LSI Medience, Siemens Healthcare Diagnostics, Sumitomo Dainippon Pharma, Taisho Toyama Pharmaceutical, Tosoh Bioscience, Beckman Coulter, and Alexion Pharma; and research funds from Hitachi High-Technologies, Sanofi, Abbott Japan, Tosoh, and Shino-Test.

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The Japanese version of these guidelines was published in Jpn J Clin Hematol 2017;58:271–81.

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Matsumoto, M., Fujimura, Y., Wada, H. et al. Diagnostic and treatment guidelines for thrombotic thrombocytopenic purpura (TTP) 2017 in Japan. Int J Hematol 106, 3–15 (2017). https://doi.org/10.1007/s12185-017-2264-7

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