Erworbene thrombotisch-thrombozytopenische Purpura – Entwicklung einer autoimmunen Erkankung

Zeitschrift: Hämostaseologie
ISSN: 0720-9355
Thema:

Thrombotic microangiopathies

DOI: http://dx.doi.org/10.5482/HAMO-12-12-0023
Ausgabe: Hefte von 2013 (Vol. 33): Heft 2 2013 (77-188)
Seiten: 121-130

  1. Abbas AK, Lichtman AH. Introduction to the immune system. In: Schmitt W (ed). Basic Immunology: Saunders Elsevier 2011, p. 1-22
  2. Diamant E, Melamed D. Class switch recombination in B lymphopoiesis: a potential pathway for B cell autoimmunity. Autoimmun Rev 2004; 3: 464-469. DOI:10.1016/j.autrev.2004.03.008
  3. Burnet FM. Immunological recognition of self. Science 1961; 133: 307-311. DOI:10.1126/science.133.3449.307
  4. Pike BL, Boyd AW, Nossal GJ. Clonal anergy: the universally anergic B lymphocyte. Proc Natl Acad Sci USA 1982; 79: 2013-2017. DOI:10.1073/pnas.79.6.2013
  5. Jerne NK. Towards a network theory of the immune system. Annales d’ Immunologie 1974; 125: 373-389.
  6. Curotto de Lafaille MA, Lafaille JJ. Natural and adaptive foxp3+ regulatory T cells: more of the same or a division of labor? Immunity 2009; 30: 626-635. DOI:10.1016/j.immuni.2009.05.002
  7. Edwards JC, Cambridge G, Abrahams VM. Do self-perpetuating B lymphocytes drive human autoimmune disease? Immunology 1999; 97: 188-196. DOI:10.1046/j.1365-2567.1999.00772.x
  8. Tisch R, Wang B. Dysrulation of T cell peripheral tolerance in type 1 diabetes. Adv Immunol 2008; 100: 125-149.
  9. Edwards JC, Cambridge G. B-cell targeting in rheumatoid arthritis and other autoimmune diseases. Nat Rev Immunol 2006; 6: 394-403. DOI:10.1038/nri1838
  10. Foreman AL, Van de Water J, Gougeon ML, Gershwin ME. B cells in autoimmune diseases: insights from analyses of immunoglobulin variable (Ig V) gene usage. Autoimmun Rev 2007; 6: 387-401. DOI:10.1016/j.autrev.2006.12.005
  11. Moake JL, Rudy CK, Troll JH et al. Unusually large plasma factor VIII:von Willebrand factor multimers in chronic relapsing thrombotic thrombocytopenic purpura. N Engl J Med 1982; 307: 1432-1435. DOI:10.1056/NEJM198212023072306
  12. Ferrari S, Mudde GC, Rieger M et al. IgG subclass distribution of anti-ADAMTS13 antibodies in patients with acquired thrombotic thrombocytopenic purpura. J Thromb Haemost 2009; 7: 1703-1710. DOI:10.1111/j.1538-7836.2009.03568.x
  13. Pos W, Sorvillo N, Fijnheer R et al. Residues Arg568 and Phe592 contribute to an antigenic surface for anti-ADAMTS13 antibodies in the spacer domain. Haematologica 2011; 96: 1670-1677. DOI:10.3324/haematol.2010.036327
  14. Bettoni G, Palla R, Valsecchi C et al. ADAMTS- 13 activity and autoantibodies classes and subclasses as prognostic predictors in acquired thrombotic thrombocytopenic purpura. J Thromb Haemost 2012; 10: 1556-1565. DOI:10.1111/j.1538-7836.2012.04808.x
  15. Stone JH, Zen Y, Deshpande V. IgG4-related disease. N Engl J Med 2012; 366: 539-551. DOI:10.1056/NEJMra1104650
  16. Ferrari S, Scheiflinger F, Rieger M 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: 2815-2822.
  17. Rieger M, Mannucci PM, Kremer Hovinga JA et al. ADAMTS13 autoantibodies in patients with thrombotic microangiopathies and other immunomediated diseases. Blood 2005; 106: 1262-1267. DOI:10.1182/blood-2004-11-4490
  18. Knöbl P. Unraveling the immunologic response in thrombotic thrombocytopenic purpura. J Thromb Haemost 2006; 4: 2352-2354. DOI:10.1111/j.1538-7836.2006.02180.x
  19. Froehlich-Zahnd R, George JN, Vesely SK et al. Evidence for a role of anti-ADAMTS13 autoantibodies despite normal ADAMTS13 activity in recurrent thrombotic thrombocytopenic purpura. Haematologica 2012; 97: 297-303. DOI:10.3324/haematol.2011.051433
  20. Levy GG, Nichols WC, Lian EC et al. Mutations in a member of the ADAMTS gene family cause thrombotic thrombocytopenic purpura. Nature 2001; 413: 488-494. DOI:10.1038/35097008
  21. Luken BM, Turenhout EA, Hulstein JJ et al. The spacer domain of ADAMTS13 contains a major binding site for antibodies in patients with thrombotic thrombocytopenic purpura. Thromb Haemost 2005; 93: 267-274.
  22. Zheng XL, Wu H, Shang D et al. Multiple domains of ADAMTS13 are targeted by autoantibodies against ADAMTS13 in patients with acquired idiopathic thrombotic thrombocytopenic purpura. Haematologica 2010; 95: 1555-1562. DOI:10.3324/haematol.2009.019299
  23. Klaus C, Plaimauer B, Studt JD et al. Epitope mapping of ADAMTS13 autoantibodies in acquired thrombotic thrombocytopenic purpura. Blood 2004; 103: 4514-4519. DOI:10.1182/blood-2003-12-4165
  24. Yamaguchi Y, Moriki T, Igari A et al. Epitope analysis of autoantibodies to ADAMTS13 in patients with acquired thrombotic thrombocytopenic purpura. Thromb Res 2011; 128: 169-173. DOI:10.1016/j.thromres.2011.03.010
  25. Schaller M, Bigler C, Danner D et al. Autoantibodies against C1q in systemic lupus erythematosus are antigen-driven. J Immunol 2009; 183: 8225-8231. DOI:10.4049/jimmunol.0902642
  26. Schaller M, Burton DR, Ditzel HJ. Autoantibodies to GPI in rheumatoid arthritis: linkage between an animal model and human disease. Nat Immunol 2001; 2: 746-753. DOI:10.1038/90696
  27. Luken BM, Turenhout EA, Kaijen PH et al. Amino acid regions 572-579 and 657-666 of the spacer domain of ADAMTS13 provide a common antigenic core required for binding of antibodies in patients with acquired TTP. Thromb Haemost 2006; 96: 295-301.
  28. Pos W, Luken BM, Kremer Hovinga JA et al. VH1-69 germline encoded antibodies directed towards ADAMTS13 in patients with acquired thrombotic thrombocytopenic purpura. J Thromb Haemost 2009; 7: 421-428. DOI:10.1111/j.1538-7836.2008.03250.x
  29. Siegel DL. Translational applications of antibody phage display. Immunol Res 2008; 42: 118-131. DOI:10.1007/s12026-008-8044-y
  30. Pos W, Crawley JT, Fijnheer R et al. An autoantibody epitope comprising residues R660, Y661, and Y665 in the ADAMTS13 spacer domain identifies a binding site for the A2 domain of VWF. Blood 2010; 115: 1640-1649. DOI:10.1182/blood-2009-06-229203
  31. Jin SY, Skipwith CG, Zheng XL. Amino acid residues Arg(659), Arg(660), and Tyr(661) in the spacer domain of ADAMTS13 are critical for cleavage of von Willebrand factor. Blood 2010; 115: 2300-2310. DOI:10.1182/blood-2009-07-235101
  32. Akiyama M, Takeda S, Kokame K et al. Crystal structures of the noncatalytic domains of ADAMTS13 reveal multiple discontinuous exosites for von Willebrand factor. Proc Natl Acad Sci USA 2009; 106: 19274-19279. DOI:10.1073/pnas.0909755106
  33. Tao Z, Peng Y, Nolasco L et al. Recombinant CUB-1 domain polypeptide inhibits the cleavage of ULVWF strings by ADAMTS13 under flow conditions. Blood 2005; 106: 4139-4145. DOI:10.1182/blood-2005-05-2029
  34. Tao Z, Wang Y, Choi H et al. Cleavage of ultralarge multimers of von Willebrand factor by C-terminal-truncated mutants of ADAMTS-13 under flow. Blood 2005; 106: 141-143. DOI:10.1182/blood-2004-11-4188
  35. Zhang P, Pan W, Rux AH et al. The cooperative activity between the carboxyl-terminal TSP1 repeats and the CUB domains of ADAMTS13 is crucial for recognition of von Willebrand factor under flow. Blood 2007; 110: 1887-1894. DOI:10.1182/blood-2007-04-083329
  36. Banno F, Chauhan AK, Kokame K et al. The distal carboxyl-terminal domains of ADAMTS13 are required for regulation of in vivo thrombus formation. Blood 2009; 113: 5323-5329. DOI:10.1182/blood-2008-07-169359
  37. Vomund AN, Majerus EM. ADAMTS13 bound to endothelial cells exhibits enhanced cleavage of von Willebrand factor. J Biol Chem 2009; 284: 30925-30932. DOI:10.1074/jbc.M109.000927
  38. Luken BM, Kaijen PH, Turenhout EA et al. Multiple B-cell clones producing antibodies directed to the spacer and disintegrin/thrombospondin type-1 repeat 1 (TSP1) of ADAMTS13 in a patient with acquired thrombotic thrombocytopenic purpura. J Thromb Haemost 2006; 4: 2355-2364. DOI:10.1111/j.1538-7836.2006.02164.x
  39. Ferrari S, Knöbl P, Kolovratova V et al. Inverse correlation of free and immune complex-sequestered anti-ADAMTS13 antibodies in a patient with acquired thrombotic thrombocytopenic purpura. J Thromb Haemost 2012; 10: 156-158. DOI:10.1111/j.1538-7836.2011.04548.x
  40. Scully M, McDonald V, Cavenagh J et al. A phase II study of the safety and efficacy of rituximab with plasma exchange in acute acquired thrombotic thrombocytopenic purpura. Blood 2011; 118: 1746-1753. DOI:10.1182/blood-2011-03-341131
  41. Iioka F, Shimomura D, Ishii T et al. Short- and long-term effects of rituximab for the treatment of thrombotic thrombocytopenic purpura: four case reports. Int J Hematol 2012; 96: 506-512. DOI:10.1007/s12185-012-1162-2
  42. George JN. Corticosteroids and rituximab as adjunctive treatments for thrombotic thrombocytopenic purpura. Am J of Hematol 2012; 87 (Suppl 1): S88-S91. DOI:10.1002/ajh.23126
  43. Tun NM, Villani GM. Efficacy of rituximab in acute refractory or chronic relapsing non-familial idiopathic thrombotic thrombocytopenic purpura: a systematic review with pooled data analysis. J Thromb Thrombolysis 2012; 34: 347-359. DOI:10.1007/s11239-012-0723-9
  44. Yassa SK, Blessios G, Marinides G, Venuto RC. Anti-CD20 monoclonal antibody (rituximab) for life-threatening hemolytic-uremic syndrome. Clin Transplant 2005; 19: 423-426. DOI:10.1111/j.1399-0012.2005.00334.x
  45. Yomtovian R, Niklinski W, Silver B et al. Rituximab for chronic recurring thrombotic thrombocytopenic purpura: a case report and review of the literature. Br J Haematol 2004; 124: 787-795. DOI:10.1111/j.1365-2141.2004.04836.x
  46. Zheng X, Pallera AM, Goodnough LT et al. Remission of chronic thrombotic thrombocytopenic purpura after treatment with cyclophosphamide and rituximab. Ann Intern Med 2003; 138: 105-108. DOI:10.7326/0003-4819-138-2-200301210-00011
  47. Ahmad A, Aggarwal A, Sharma D et al. Rituximab for treatment of refractory/relapsing thrombotic thrombocytopenic purpura (TTP). Am J Hematol 2004; 77: 171-176. DOI:10.1002/ajh.20166
  48. Uchida J, Hamaguchi Y, Oliver JA et al. The innate mononuclear phagocyte network depletes B lymphocytes through Fc receptor dependent mechanisms during anti-CD20 antibody immunotherapy. J Exp Med 2004; 199: 1659-1669. DOI:10.1084/jem.20040119
  49. Di Gaetano N, Cittera E, Nota R et al. Complement activation determines the therapeutic activity of rituximab in vivo. J Immunol 2003; 171: 1581-1587.
  50. Teeling JL, French RR, Cragg MS et al. Characterization of new human CD20 monoclonal antibodies with potent cytolytic activity against non-Hodgkin lymphomas. Blood 2004; 104: 1793-1800. DOI:10.1182/blood-2004-01-0039
  51. Gong Q, Ou Q, Ye S et al. Importance of cellular microenvironment and circulatory dynamics in B cell immunotherapy. J Immunol 2005; 174: 817-826.
  52. Caramazza D, Quintini G, Abbene I et al. Rituximab for managing relapsing or refractory patients with idiopathic thrombotic thrombocytopenic purpura-haemolytic uraemic syndrome. Blood Transfusion 2010; 8: 203-210.
  53. 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: 104-111. DOI:10.1097/CCM.0b013e31822e9d66
  54. Rehnberg M, Amu S, Tarkowski A et al. Short- and long-term effects of anti-CD20 treatment on B cell ontogeny in bone marrow of patients with rheumatoid arthritis. Arthritis Res Ther 2009; 11: R123. DOI:10.1186/ar2789
  55. Yoshida T, Mei H, Dorner T et al. Memory B and memory plasma cells. Immunol Rev 2010; 237: 117-139. DOI:10.1111/j.1600-065X.2010.00938.x
  56. Popa C, Leandro MJ, Cambridge G, Edwards JC. Repeated B lymphocyte depletion with rituximab in rheumatoid arthritis over 7 yrs. Rheumatology (Oxford) 2007; 46: 626-630. DOI:10.1093/rheumatology/kel393
  57. Vallerskog T, Gunnarsson I, Widhe M et al. Treatment with rituximab affects both the cellular and the humoral arm of the immune system in patients with SLE. Clin Immunol 2007; 122: 62-74. DOI:10.1016/j.clim.2006.08.016
  58. Mamani-Matsuda M, Cosma A, Weller S et al. The human spleen is a major reservoir for long-lived vaccinia virus-specific memory B cells. Blood 2008; 111: 4653-4659. DOI:10.1182/blood-2007-11-123844
  59. Dunn-Walters DK, Isaacson PG, Spencer J. Analysis of mutations in immunoglobulin heavy chain variable region genes of microdissected marginal zone (MGZ) B cells suggests that the MGZ of human spleen is a reservoir of memory B cells. J Exp Med 1995; 182: 559-566. DOI:10.1084/jem.182.2.559
  60. Aqui NA, Stein SH, Konkle BA et al. Role of splenectomy in patients with refractory or relapsed thrombotic thrombocytopenic purpura. J Clin Apher 2003; 18: 51-54. DOI:10.1002/jca.10053
  61. Kappers-Klunne MC, Wijermans P, Fijnheer R et al. Splenectomy for the treatment of thrombotic thrombocytopenic purpura. Br J Haematol 2005; 130: 768-776. DOI:10.1111/j.1365-2141.2005.05681.x
  62. Kremer Hovinga JA, Vesely SK, Terrell DR et al. Survival and relapse in patients with thrombotic thrombocytopenic purpura. Blood 2010; 115: 1500-1511. DOI:10.1182/blood-2009-09-243790
  63. Dorner T, Kaufmann J, Wegener WA et al. Initial clinical trial of epratuzumab (humanized anti-CD22 antibody) for immunotherapy of s ystemic lupus erythematosus. Arthritis Res Ther 2006; 8: R74. DOI:10.1186/ar1942
  64. Dorner T, Shock A, Smith KG. CD22 and autoimmune disease. Int Rev Immunol 2012; 31: 363-738. DOI:10.3109/08830185.2012.709890
  65. Vallera DA, Todhunter DA, Kuroki DW et al. A bispecific recombinant immunotoxin, DT2219, targeting human CD19 and CD22 receptors in a mouse xenograft model of B-cell leukemia / lymphoma. Clin Cancer Res 2005; 11: 3879-3888. DOI:10.1158/1078-0432.CCR-04-2290
  66. Mackay F, Sierro F, Grey ST, Gordon TP. The BAFF/APRIL system: an important player in systemic rheumatic diseases. Curr Dir Autoimmun 2005; 8: 243-265.
  67. Thompson JS, Bixler SA, Qian F et al. BAFF-R, a newly identified TNF receptor that specifically interacts with BAFF. Science 2001; 293: 2108-2111. DOI:10.1126/science.1061965
  68. Mackay F, Woodcock SA, Lawton P et al. Mice transgenic for BAFF develop lymphocytic disorders along with autoimmune manifestations. J Exp Med 1999; 190: 1697-1710. DOI:10.1084/jem.190.11.1697
  69. Gross JA, Dillon SR, Mudri S et al. TACI-Ig neutralizes molecules critical for B cell development and autoimmune disease. Impaired B cell maturation in mice lacking BLyS. Immunity 2001; 15: 289-302. DOI:10.1016/S1074-7613(01)00183-2
  70. Gross JA, Johnston J, Mudri S et al. TACI and BCMA are receptors for a TNF homologue implicated in B-cell autoimmune disease. Nature 2000; 404: 995-999. DOI:10.1038/35010115
  71. Lesley R, Xu Y, Kalled SL et al. Reduced competitiveness of autoantigen-engaged B cells due to increased dependence on BAFF. Immunity 2004; 20: 441-453. DOI:10.1016/S1074-7613(04)00079-2
  72. Stohl W, Hiepe F, Latinis KM et al. Belimumab reduces autoantibodies, normalizes low complement levels, and reduces select B cell populations in patients with systemic lupus erythematosus. Arthritis Rheum 2012; 64: 2328-2337. DOI:10.1002/art.34400
  73. Genovese MC, Becker JC, Schiff M et al. Abatacept for rheumatoid arthritis refractory to tumor necrosis factor alpha inhibition. N Engl J Med 2005; 353: 1114-1123. DOI:10.1056/NEJMoa050524
  74. Lindvall JM, Blomberg KE, Valiaho J et al. Bruton’s tyrosine kinase: cell biology, sequence conservation, mutation spectrum, siRNA modifications, and expression profiling. Immunol Rev 2005; 203: 200-215. DOI:10.1111/j.0105-2896.2005.00225.x
  75. Wong BR, Grossbard EB, Payan DG, Masuda ES. Targeting Syk as a treatment for allergic and autoimmune disorders. Expert Opin Investig Drugs 2004; 13: 743-762. DOI:10.1517/13543784.13.7.743
  76. Venanzi ES, Benoist C, Mathis D. Good riddance: Thymocyte clonal deletion prevents autoimmunity. Curr Opin Immunol 2004; 16: 197-202. DOI:10.1016/j.coi.2004.01.008
  77. Starr R, Hilton DJ. Defining control: regulation of dendritic cell activation and immune homeostasis by SOCS1. Immunity 2003; 19: 308-309. DOI:10.1016/S1074-7613(03)00243-7
  78. Sorvillo N, Pos W, van den Berg LM et al. The macrophage mannose receptor promotes uptake of ADAMTS13 by dendritic cells. Blood 2012; 119: 3828-3835. DOI:10.1182/blood-2011-09-377754
  79. 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. Thromb Heamost 2010; 8: 856-859. DOI:10.1111/j.1538-7836.2010.03772.x
  80. Pos W, Luken BM, Sorvillo N et al. Humoral immune response to ADAMTS13 in acquired TTP. J Thromb Heamost 2011; 9: 1285-1291. DOI:10.1111/j.1538-7836.2011.04307.x
  81. Mariani M, Cairo A, Palla R et al. B and T lymphocytes in acquired thrombotic thrombocytopenic purpura during disease remission. Thromb Res 2011; 128: 590-592. DOI:10.1016/j.thromres.2011.07.038
  82. Gambineri E, Torgerson TR, Ochs HD. Immune dysregulation, polyendocrinopathy, enteropathy, and X-linked inheritance (IPEX), a syndrome of systemic autoimmunity caused by mutations of FOXP3, a critical regulator of T-cell homeostasis. Curr Opin Rheumatol 2003; 15: 430-435. DOI:10.1097/00002281-200307000-00010
  83. Kim CH. Molecular targets of FoxP3+ regulatory T cells. Mini Rev Med Chem 2007; 7: 1136-1143. DOI:10.2174/138955707782331731
  84. 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: 257-262. DOI:10.1111/j.1538-7836.2009.03692.x
  85. John ML, Hitzler W, Scharrer I. The role of human leukocyte antigens as predisposing and/or protective factors in patients with idiopathic thrombotic thrombocytopenic purpura. Ann Hematol 2012; 91: 507-510. DOI:10.1007/s00277-011-1384-z
  86. Studt JD, Hovinga JA, Radonic R et al. Familial acquired thrombotic thrombocytopenic purpura: ADAMTS13 inhibitory autoantibodies in identical twins. Blood 2004; 103: 4195-4197. DOI:10.1182/blood-2003-11-3888
  87. Cataland SR, Wu HM. Targeting the inhibitor of ADAMTS13 in thrombotic thrombocytopenic purpura. Expert Opin Pharmacothe 2007; 8: 437-444. DOI:10.1517/14656566.8.4.437
  88. Cataland SR, Jin M, Lin S et al. Effect of prophylactic cyclosporine therapy on ADAMTS13 biomarkers in patients with idiopathic thrombotic thrombocytopenic purpura. Am J Hematol 2008; 83: 911-915. DOI:10.1002/ajh.21281
  89. Cataland SR, Jin M, Ferketich AK et al. An evaluation of cyclosporin and corticosteroids individually as adjuncts to plasma exchange in the treatment of thrombotic thrombocytopenic purpura. Br J Haematol 2007; 136: 146-149. DOI:10.1111/j.1365-2141.2006.06384.x
  90. Van der Plas RM, Schiphorst ME, Huizinga EG et al. Von Willebrand factor proteolysis is deficient in classic, but not in bone marrow transplantation-associated, thrombotic thrombocytopenic purpura. Blood 1999; 93: 3798-3802.
  91. Peyvandi F, Siboni SM, Lambertenghi Deliliers D et al. Prospective study on the behaviour of the metalloprotease ADAMTS13 and of von Willebrand factor after bone marrow transplantation. Br J Haematol 2006; 134: 187-195. DOI:10.1111/j.1365-2141.2006.06126.x
  92. Kentouche K, Zintl F, Angerhaus D et al. Von Willebrand factor-cleaving protease (ADAMTS13) in the course of stem cell transplantation. Semin Thromb Hemost 2006; 32: 98-104. DOI:10.1055/s-2006-939765
  93. Hershko K, Simhadri V, Blaisdell A et al. Cyclosporin A impairs the secretion and activity of ADAMTS13. J Biol Chem 2012; 287: 44361-44371. DOI:10.1074/jbc.M112.383968
  94. Mathis D, Benoist C. A decade of AIRE. Nat Rev Immunol 2007; 7: 645-650. DOI:10.1038/nri2136
  95. Fuchs TA, Kremer Hovinga JA, Schatzberg D et al. Circulating DNA and myeloperoxidase indicate disease activity in patients with thrombotic microangiopathies. Blood 2012; 120: 1157-1164. DOI:10.1182/blood-2012-02-412197
  96. 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: 936-944. DOI:10.1111/j.1538-7836.2011.04224.x
  97. Jian C, Xiao J, Gong L et al. Gain-of-function ADAMTS13 variants that are resistant to autoantibodies against ADAMTS13 in patients with acquired thrombotic thrombocytopenic purpura. Blood 2012; 119: 3836-3843. DOI:10.1182/blood-2011-12-399501
  98. Coppo P, Veyradier A. Current management and therapeutical perspectives in thrombotic thrombocytopenic purpura. Presse Med 2012; 41: 163-176. DOI:10.1016/j.lpm.2011.10.024
  99. Kremer Hovinga JA, Voorberg J. Improving on nature: redesigning ADAMTS13. Blood 2012; 119: 3654-3655. DOI:10.1182/blood-2012-02-410431

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