Current and Future Perspectives on ADAMTS13 and Thrombotic Thrombocytopenic Purpura

Elien Roose; Bérangère S. Joly

doi:10.1055/a-1171-0473

Hämostaseologie, Table of Contents

Hamostaseologie 2020; 40(03): 322-336
DOI: 10.1055/a-1171-0473

Review Article

Georg Thieme Verlag KG Stuttgart · New York

Current and Future Perspectives on ADAMTS13 and Thrombotic Thrombocytopenic Purpura

Elien Roose

¹Laboratory for Thrombosis Research, IRF Life Sciences, KU Leuven Campus Kulak Kortrijk, Kortrijk, Belgium

,

Bérangère S. Joly

²Service d'Hématologie Biologique, Hôpital Lariboisière, and EA3518, Institut de Recherche Saint-Louis, Hôpital Saint Louis, AP-HP.Nord, Université de Paris, Paris, France

› Author Affiliations

Abstract

Thrombotic thrombocytopenic purpura (TTP) is a rare, relapsing, and life-threatening disorder with an annual incidence of 10 cases per million people. TTP is a thrombotic microangiopathy characterized by severe thrombocytopenia, microangiopathic hemolytic anemia, and organ ischemia. The disease is caused by a severe deficiency of the enzyme ADAMTS13 (a disintegrin and metalloprotease with thrombospondin type 1 repeats, member 13), which can either be acquired, mainly by autoantibodies targeting ADAMTS13, or congenital due to mutations in the ADAMTS13 gene. Thanks to the establishment of national registries worldwide, fundamental and translational research, major advances have been made on the diagnosis, treatment, and fundamental understanding of TTP, since the description of the first TTP case almost 100 years ago. The introduction of therapeutic plasma exchange in the 1970s has significantly improved patient survival, but novel diagnostic assays, targeted treatments (rituximab, caplacizumab, recombinant ADAMTS13), and the unraveling of both ADAMTS13 function and TTP pathophysiology should help to further improve the patients' quality of life. However, differential diagnosis of TTP remains challenging and still a lot of questions remain unanswered to completely understand this rare and devastating disease.

Keywords

ADAMTS13 - thrombotic thrombocytopenic purpura - treatment - diagnosis

Full Text

References

References
1 Scully M, Yarranton H, Liesner R. , et al. Regional UK TTP registry: correlation with laboratory ADAMTS 13 analysis and clinical features. Br J Haematol 2008; 142 (05) 819-826
2 Kremer Hovinga JA, Vesely SK, Terrell DR, Lämmle B, George JN. Survival and relapse in patients with thrombotic thrombocytopenic purpura. Blood 2010; 115 (08) 1500-1511 , quiz 1662
3 Fujimura Y, Matsumoto M. Registry of 919 patients with thrombotic microangiopathies across Japan: database of Nara Medical University during 1998-2008. Intern Med 2010; 49 (01) 7-15
4 Jang MJ, Chong SY, Kim IH. , et al. Clinical features of severe acquired ADAMTS13 deficiency in thrombotic thrombocytopenic purpura: the Korean TTP registry experience. Int J Hematol 2011; 93 (02) 163-169
5 Deford CC, Reese JA, Schwartz LH. , et al. Multiple major morbidities and increased mortality during long-term follow-up after recovery from thrombotic thrombocytopenic purpura. Blood 2013; 122 (12) 2023-2029 , quiz 2142
6 George JN, Nester CM. Syndromes of thrombotic microangiopathy. N Engl J Med 2014; 371 (07) 654-666
7 Mariotte E, Azoulay E, Galicier L. , et al; French Reference Center for Thrombotic Microangiopathies. Epidemiology and pathophysiology of adulthood-onset thrombotic microangiopathy with severe ADAMTS13 deficiency (thrombotic thrombocytopenic purpura): a cross-sectional analysis of the French national registry for thrombotic microangiopathy. Lancet Haematol 2016; 3 (05) e237-e245
8 Joly BS, Stepanian A, Leblanc T. , et al; French Reference Center for Thrombotic Microangiopathies. Child-onset and adolescent-onset acquired thrombotic thrombocytopenic purpura with severe ADAMTS13 deficiency: a cohort study of the French national registry for thrombotic microangiopathy. Lancet Haematol 2016; 3 (11) e537-e546
9 Blombery P, Kivivali L, Pepperell D. , et al; TTP Registry Steering Committee. Diagnosis and management of thrombotic thrombocytopenic purpura (TTP) in Australia: findings from the first 5 years of the Australian TTP/thrombotic microangiopathy registry. Intern Med J 2016; 46 (01) 71-79
10 George JN, Al-Nouri ZL. Diagnostic and therapeutic challenges in the thrombotic thrombocytopenic purpura and hemolytic uremic syndromes. Hematology (Am Soc Hematol Educ Program) 2012; 2012: 604-609
11 Moschcowitz E. An acute febrile pleiochromic anemia with hyaline thrombosis of the terminal arterioles and capillaries: an undescribed disease. Arch Intern Med 1925; 36: 89-93
12 Furlan M, Robles R, Lämmle 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 (10) 4223-4234
13 Tsai HM. Physiologic cleavage of von Willebrand factor by a plasma protease is dependent on its conformation and requires calcium ion. Blood 1996; 87 (10) 4235-4244
14 Furlan M, Robles R, Solenthaler M, Wassmer M, Sandoz P, Lämmle B. Deficient activity of von Willebrand factor-cleaving protease in chronic relapsing thrombotic thrombocytopenic purpura. Blood 1997; 89 (09) 3097-3103
15 Levy GG, Nichols WC, Lian EC. , et al. Mutations in a member of the ADAMTS gene family cause thrombotic thrombocytopenic purpura. Nature 2001; 413 (6855): 488-494
16 Gerritsen HE, Robles R, Lämmle B, Furlan M. Partial amino acid sequence of purified von Willebrand factor-cleaving protease. Blood 2001; 98 (06) 1654-1661
17 Fujikawa K, Suzuki H, McMullen B, Chung D. Purification of human von Willebrand factor-cleaving protease and its identification as a new member of the metalloproteinase family. Blood 2001; 98 (06) 1662-1666
18 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 (44) 41059-41063
19 Soejima K, Mimura N, Hirashima M. , et al. A novel human metalloprotease synthesized in the liver and secreted into the blood: possibly, the von Willebrand factor-cleaving protease?. J Biochem 2001; 130 (04) 475-480
20 Lotta LA, Mariani M, Consonni D. , et al. Different clinical severity of first episodes and recurrences of thrombotic thrombocytopenic purpura. Br J Haematol 2010; 151 (05) 488-494
21 Reese JA, Muthurajah DS, Kremer Hovinga JA, Vesely SK, Terrell DR, George JN. Children and adults with thrombotic thrombocytopenic purpura associated with severe, acquired Adamts13 deficiency: comparison of incidence, demographic and clinical features. Pediatr Blood Cancer 2013; 60 (10) 1676-1682
22 Joly BS, Boisseau P, Roose E. , et al; French Reference Center for Thrombotic Microangiopathies. ADAMTS13 gene mutations influence ADAMTS13 conformation and disease age-onset in the French cohort of Upshaw-Schulman syndrome. ThrombHaemost 2018; 118 (11) 1902-1917
23 Mancini I, Pontiggia S, Palla R. , et al; Italian Group of TTP Investigators. Clinical and laboratory features of patients with acquired thrombotic thrombocytopenic purpura: fourteen years of the Milan TTP registry. ThrombHaemost 2019; 119 (05) 695-704
24 Furlan M, Robles R, Morselli B, Sandoz P, Lämmle B. Recovery and half-life of von Willebrand factor-cleaving protease after plasma therapy in patients with thrombotic thrombocytopenic purpura. ThrombHaemost 1999; 81 (01) 8-13
25 Zhou W, Inada M, Lee T-P. , et al. ADAMTS13 is expressed in hepatic stellate cells. Lab Invest 2005; 85 (06) 780-788
26 Uemura M, Tatsumi K, Matsumoto M. , et al. Localization of ADAMTS13 to the stellate cells of human liver. Blood 2005; 106 (03) 922-924
27 Muia J, Zhu J, Gupta G. , et al. Allosteric activation of ADAMTS13 by von Willebrand factor. Proc Natl Acad Sci U S A 2014; 111 (52) 18584-18589
28 Crawley JTB, de Groot R, Xiang Y, Luken BM, Lane DA. Unraveling the scissile bond: how ADAMTS13 recognizes and cleaves von Willebrand factor. Blood 2011; 118 (12) 3212-3221
29 Dong JF, Moake JL, Nolasco L. , et al. ADAMTS-13 rapidly cleaves newly secreted ultralarge von Willebrand factor multimers on the endothelial surface under flowing conditions. Blood 2002; 100 (12) 4033-4039
30 Zanardelli S, Chion AC, Groot E. , et al. A novel binding site for ADAMTS13 constitutively exposed on the surface of globular VWF. Blood 2009; 114 (13) 2819-2828
31 Zhang X, Halvorsen K, Zhang C-Z, Wong WP, Springer TA. Mechanoenzymatic cleavage of the ultralarge vascular protein von Willebrand factor. Science 2009; 324 (5932): 1330-1334
32 South K, Luken BM, Crawley JTB. , et al. Conformational activation of ADAMTS13. Proc Natl Acad Sci U S A 2014; 111 (52) 18578-18583
33 Deforche L, Roose E, Vandenbulcke A. , et al. Linker regions and flexibility around the metalloprotease domain account for conformational activation of ADAMTS-13. J ThrombHaemost 2015; 13 (11) 2063-2075
34 Wagner DD, Olmsted JB, Marder VJ. Immunolocalization of von Willebrand protein in Weibel-Palade bodies of human endothelial cells. J Cell Biol 1982; 95 (01) 355-360
35 Cramer EM, Meyer D, le Menn R, Breton-Gorius J. Eccentric localization of von Willebrand factor in an internal structure of platelet alpha-granule resembling that of Weibel-Palade bodies. Blood 1985; 66 (03) 710-713
36 Petri A, Kim HJ, Xu Y. , et al. Crystal structure and substrate-induced activation of ADAMTS13. Nat Commun 2019; 10 (01) 3781
37 Sadler JE. What's new in the diagnosis and pathophysiology of thrombotic thrombocytopenic purpura. Hematology (Am Soc Hematol Educ Program) 2015; 2015 (01) 631-636
38 Tsai H-M, Lian EC. Antibodies to von Willebrand factor-cleaving protease in acute thrombotic thrombocytopenic purpura. N Engl J Med 1998; 339 (22) 1585-1594
39 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 (22) 1578-1584
40 Moake JL. Thrombotic microangiopathies. N Engl J Med 2002; 347 (08) 589-600
41 Kokame K, Matsumoto M, Soejima K. , et al. Mutations and common polymorphisms in ADAMTS13 gene responsible for von Willebrand factor-cleaving protease activity. Proc Natl Acad Sci U S A 2002; 99 (18) 11902-11907
42 Schneppenheim R, Budde U, Oyen F. , et al. von Willebrand factor cleaving protease and ADAMTS13 mutations in childhood TTP. Blood 2003; 101 (05) 1845-1850
43 Veyradier A, Lavergne JM, Ribba AS. , et al. Ten candidate ADAMTS13 mutations in six French families with congenital thrombotic thrombocytopenic purpura (Upshaw-Schulman syndrome). J ThrombHaemost 2004; 2 (03) 424-429
44 Matsumoto M, Kokame K, Soejima K. , et al. Molecular characterization of ADAMTS13 gene mutations in Japanese patients with Upshaw-Schulman syndrome. Blood 2004; 103 (04) 1305-1310
45 van Dorland HA, Taleghani MM, Sakai K. , et al; Hereditary TTP Registry. The International Hereditary Thrombotic Thrombocytopenic Purpura Registry: key findings at enrollment until 2017. Haematologica 2019; 104 (10) 2107-2115
46 Tsai HM, Rice L, Sarode R, Chow TW, Moake JL. Antibody inhibitors to von Willebrand factor metalloproteinase and increased binding of von Willebrand factor to platelets in ticlopidine-associated thrombotic thrombocytopenic purpura. Ann Intern Med 2000; 132 (10) 794-799
47 Jacob S, Dunn BL, Qureshi ZP. , et al. Ticlopidine-, clopidogrel-, and prasugrel-associated thrombotic thrombocytopenic purpura: a 20-year review from the Southern Network on Adverse Reactions (SONAR). SeminThrombHemost 2012; 38 (08) 845-853
48 Bennett CL, Jacob S, Dunn BL. , et al. Ticlopidine-associated ADAMTS13 activity deficient thrombotic thrombocytopenic purpura in 22 persons in Japan: a report from the Southern Network on Adverse Reactions (SONAR). Br J Haematol 2013; 161 (06) 896-898
49 Coppo P, Veyradier A. Current management and therapeutical perspectives in thrombotic thrombocytopenic purpura. Presse Med 2012; 41 (3, Pt 2): e163-e176
50 Martino S, Jamme M, Deligny C. , et al; French Reference Center for Thrombotic Microangiopathies. Thrombotic thrombocytopenic purpura in Black people: impact of ethnicity on survival and genetic risk factors. PLoS One 2016; 11 (07) e0156679
51 Coppo P, Busson M, Veyradier A. , et al; French Reference Centre for Thrombotic Microangiopathies. HLA-DRB1*11: a strong risk factor for acquired severe ADAMTS13 deficiency-related idiopathic thrombotic thrombocytopenic purpura in Caucasians. J ThrombHaemost 2010; 8 (04) 856-859
52 Scully M, Brown J, Patel R, McDonald V, Brown CJ, Machin S. Human leukocyte antigen association in idiopathic thrombotic thrombocytopenic purpura: evidence for an immunogenetic link. J ThrombHaemost 2010; 8 (02) 257-262
53 John M-L, 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 (04) 507-510
54 Mancini I, Ricaño-Ponce I, Pappalardo E. , et al; Italian Group of TTP Investigators. Immunochip analysis identifies novel susceptibility loci in the human leukocyte antigen region for acquired thrombotic thrombocytopenic purpura. J ThrombHaemost 2016; 14 (12) 2356-2367
55 Sorvillo N, van Haren SD, Kaijen PH. , et al. Preferential HLA-DRB1*11-dependent presentation of CUB2-derived peptides by ADAMTS13-pulsed dendritic cells. Blood 2013; 121 (17) 3502-3510
56 Verbij FC, Turksma AW, de Heij F. , et al. CD4+ T cells from patients with acquired thrombotic thrombocytopenic purpura recognize CUB2 domain-derived peptides. Blood 2016; 127 (12) 1606-1609
57 Pos W, Luken BM, Sorvillo N, Kremer Hovinga JA, Voorberg J. Humoral immune response to ADAMTS13 in acquired thrombotic thrombocytopenic purpura. J ThrombHaemost 2011; 9 (07) 1285-1291
58 Verbij FC, Fijnheer R, Voorberg J, Sorvillo N. Acquired TTP: ADAMTS13 meets the immune system. Blood Rev 2014; 28 (06) 227-234
59 Soejima K, Matsumoto M, Kokame K. , et al. ADAMTS-13 cysteine-rich/spacer domains are functionally essential for von Willebrand factor cleavage. Blood 2003; 102 (09) 3232-3237
60 Klaus C, Plaimauer B, Studt JD. , et al. Epitope mapping of ADAMTS13 autoantibodies in acquired thrombotic thrombocytopenic purpura. Blood 2004; 103 (12) 4514-4519
61 Luken BM, Turenhout EAM, Hulstein JJJ, Van Mourik JA, Fijnheer R, Voorberg J. The spacer domain of ADAMTS13 contains a major binding site for antibodies in patients with thrombotic thrombocytopenic purpura. ThrombHaemost 2005; 93 (02) 267-274
62 Zheng XL, Wu HM, 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 (09) 1555-1562
63 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 (02) 169-173
64 Thomas MR, de Groot R, Scully MA, Crawley JTB. Pathogenicity of anti-ADAMTS13 autoantibodies in acquired thrombotic thrombocytopenic purpura. EBioMedicine 2015; 2 (08) 942-952
65 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 (11) 1670-1677
66 Grillberger R, Casina VC, Turecek PL, Zheng XL, Rottensteiner H, Scheiflinger F. Anti-ADAMTS13 IgG autoantibodies present in healthy individuals share linear epitopes with those in patients with thrombotic thrombocytopenic purpura. Haematologica 2014; 99 (04) e58-e60
67 Scheiflinger F, Knöbl P, Trattner B. , 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 (09) 3241-3243
68 Rieger M, Mannucci PM, Kremer Hovinga JA. , et al. ADAMTS13 autoantibodies in patients with thrombotic microangiopathies and other immunomediated diseases. Blood 2005; 106 (04) 1262-1267
69 Feys HB, Liu F, Dong N. , et al. ADAMTS-13 plasma level determination uncovers antigen absence in acquired thrombotic thrombocytopenic purpura and ethnic differences. J ThrombHaemost 2006; 4 (05) 955-962
70 Roose E, Schelpe AS, Joly BS. , et al. An open conformation of ADAMTS-13 is a hallmark of acute acquired thrombotic thrombocytopenic purpura. J ThrombHaemost 2018; 16 (02) 378-388
71 Roose E, Schelpe AS, Tellier E. , et al. Open ADAMTS13, induced by antibodies, is a biomarker for subclinical immune-mediated thrombotic thrombocytopenic purpura. Blood 2020 Doi: 10.1182/blood.2019004221
72 Ferrari S, Scheiflinger F, Rieger M. , et al; French Clinical and Biological Network on Adult Thrombotic Microangiopathies. 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 (07) 2815-2822
73 Ferrari S, Mudde GC, Rieger M, Veyradier A, Kremer Hovinga JA, Scheiflinger F. IgG subclass distribution of anti-ADAMTS13 antibodies in patients with acquired thrombotic thrombocytopenic purpura. J ThrombHaemost 2009; 7 (10) 1703-1710
74 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 ThrombHaemost 2012; 10 (08) 1556-1565
75 Hrdinová J, D'Angelo S, Graça NAG. , et al. Dissecting the pathophysiology of immune thrombotic thrombocytopenic purpura: interplay between genes and environmental triggers. Haematologica 2018; 103 (07) 1099-1109
76 Luken BM, Kaijen PHP, 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 ThrombHaemost 2006; 4 (11) 2355-2364
77 Siegel DL. Translational applications of antibody phage display. Immunol Res 2008; 42 (1–3): 118-131
78 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 ThrombHaemost 2009; 7 (03) 421-428
79 Schaller M, Vogel M, Kentouche K, Lämmle B, Kremer Hovinga JA. The splenic autoimmune response to ADAMTS13 in thrombotic thrombocytopenic purpura contains recurrent antigen-binding CDR3 motifs. Blood 2014; 124 (23) 3469-3479
80 Ostertag EM, Kacir S, Thiboutot M. , et al. ADAMTS13 autoantibodies cloned from patients with acquired thrombotic thrombocytopenic purpura: 1. Structural and functional characterization in vitro. Transfusion 2016; 56 (07) 1763-1774
81 Roose E, Vidarsson G, Kangro K. , et al. Anti-ADAMTS13 autoantibodies against cryptic epitopes in immune-mediated thrombotic thrombocytopenic purpura. ThrombHaemost 2018; 118 (10) 1729-1742
82 Lotta LA, Valsecchi C, Pontiggia S. , et al. Measurement and prevalence of circulating ADAMTS13-specific immune complexes in autoimmune thrombotic thrombocytopenic purpura. J ThrombHaemost 2014; 12 (03) 329-336
83 Ferrari S, Palavra K, Gruber B. , et al. Persistence of circulating ADAMTS13-specific immune complexes in patients with acquired thrombotic thrombocytopenic purpura. Haematologica 2014; 99 (04) 779-787
84 Mancini I, Ferrari B, Valsecchi C. , et al; Italian Group of TTP Investigators. ADAMTS13-specific circulating immune complexes as potential predictors of relapse in patients with acquired thrombotic thrombocytopenic purpura. Eur J Intern Med 2017; 39 (04) 79-83
85 Westwood J-P, Langley K, Heelas E, Machin SJ, Scully M. Complement and cytokine response in acute thrombotic thrombocytopenic purpura. Br J Haematol 2014; 164 (06) 858-866
86 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 ThrombHaemost 2012; 10 (01) 156-158
87 Kremer Hovinga JA, George JN. Hereditary thrombotic thrombocytopenic purpura. N Engl J Med 2019; 381 (17) 1653-1662
88 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 (01) 943-957
89 Upshaw Jr JD. Congenital deficiency of a factor in normal plasma that reverses microangiopathic hemolysis and thrombocytopenia. N Engl J Med 1978; 298 (24) 1350-1352
90 Alwan F, Vendramin C, Liesner R. , et al. Characterization and treatment of congenital thrombotic thrombocytopenic purpura. Blood 2019; 133 (15) 1644-1651
91 Ferrari B, Cairo A, Pagliari MT, Mancini I, Arcudi S, Peyvandi F. Risk of diagnostic delay in congenital thrombotic thrombocytopenic purpura. J ThrombHaemost 2019; 17 (04) 666-669
92 Scully M. Hereditary thrombotic thrombocytopenic purpura. Haematologica 2019; 104 (10) 1916-1918
93 Lotta LA, Garagiola I, Palla R, Cairo A, Peyvandi F. ADAMTS13 mutations and polymorphisms in congenital thrombotic thrombocytopenic purpura. Hum Mutat 2010; 31 (01) 11-19
94 Fujimura Y, Matsumoto M, Isonishi A. , et al. Natural history of Upshaw-Schulman syndrome based on ADAMTS13 gene analysis in Japan. J ThrombHaemost 2011; 9 (01) (Suppl. 01) 283-301
95 Kremer Hovinga JA, Heeb SR, Skowronska M, Schaller M. Pathophysiology of thrombotic thrombocytopenic purpura and hemolytic uremic syndrome. J ThrombHaemost 2018; 16 (04) 618-629
96 Plaimauer B, Fuhrmann J, Mohr G. , et al. Modulation of ADAMTS13 secretion and specific activity by a combination of common amino acid polymorphisms and a missense mutation. Blood 2006; 107 (01) 118-125
97 Scully MA, Machin SJ. Berend Houwen Memorial Lecture: ISLH Las Vegas May 2009: the pathogenesis and management of thrombotic microangiopathies. Int J Lab Hematol 2009; 31 (03) 268-276
98 Donadelli R, Banterla F, Galbusera M. , et al; International Registry of Recurrent and Familial HUS/TTP. In-vitro and in-vivo consequences of mutations in the von Willebrand factor cleaving protease ADAMTS13 in thrombotic thrombocytopenic purpura. ThrombHaemost 2006; 96 (04) 454-464
99 Fujimura Y, Lämmle B, Tanabe S. , et al. Patent ductus arteriosus generates neonatal hemolytic jaundice with thrombocytopenia in Upshaw-Schulman syndrome. Blood Adv 2019; 3 (21) 3191-3195
100 Camilleri RS, Cohen H, Mackie IJ. , et al. Prevalence of the ADAMTS-13 missense mutation R1060W in late onset adult thrombotic thrombocytopenic purpura. J ThrombHaemost 2008; 6 (02) 331-338
101 Moatti-Cohen M, Garrec C, Wolf M. , et al; French Reference Center for Thrombotic Microangiopathies. Unexpected frequency of Upshaw-Schulman syndrome in pregnancy-onset thrombotic thrombocytopenic purpura. Blood 2012; 119 (24) 5888-5897
102 Kremer Hovinga JA, Coppo P, Lämmle B, Moake JL, Miyata T, Vanhoorelbeke K. Thrombotic thrombocytopenic purpura. Nat Rev Dis Primers 2017; 3: 17020
103 Hughes C, McEwan JR, Longair I. , et al. Cardiac involvement in acute thrombotic thrombocytopenic purpura: association with troponin T and IgG antibodies to ADAMTS 13. J ThrombHaemost 2009; 7 (04) 529-536
104 Benhamou Y, Boelle PY, Baudin B. , et al; Reference Center for Thrombotic Microangiopathies. Cardiac troponin-I on diagnosis predicts early death and refractoriness in acquired thrombotic thrombocytopenic purpura. Experience of the French Thrombotic Microangiopathies Reference Center. J ThrombHaemost 2015; 13 (02) 293-302
105 Joly BS, Coppo P, Veyradier A. Thrombotic thrombocytopenic purpura. Blood 2017; 129 (21) 2836-2846
106 Prevel R, Roubaud-Baudron C, Gourlain S. , et al. Immune thrombotic thrombocytopenic purpura in older patients: prognosis and long-term survival. Blood 2019; 134 (24) 2209-2217
107 Agosti P, Mancini I, Artoni A. , et al; Italian Group of TTP Investigators. The features of acquired thrombotic thrombocytopenic purpura occurring at advanced age. Thromb Res 2020; 187 (03) 197-201
108 Coppo P, Schwarzinger M, Buffet M. , et al; French Reference Center for Thrombotic Microangiopathies. Predictive features of severe acquired ADAMTS13 deficiency in idiopathic thrombotic microangiopathies: the French TMA reference center experience. PLoS One 2010; 5 (04) e10208
109 Bendapudi PK, Hurwitz S, Fry A. , et al. Derivation and external validation of the PLASMIC score for rapid assessment of adults with thrombotic microangiopathies: a cohort study. Lancet Haematol 2017; 4 (04) e157-e164
110 Gerritsen HE, Turecek PL, Schwarz HP, Lämmle B, Furlan M. Assay of von Willebrand factor (vWF)-cleaving protease based on decreased collagen binding affinity of degraded vWF: a tool for the diagnosis of thrombotic thrombocytopenic purpura (TTP). ThrombHaemost 1999; 82 (05) 1386-1389
111 Obert B, Tout H, Veyradier A, Fressinaud E, Meyer D, Girma JP. Estimation of the von Willebrand factor-cleaving protease in plasma using monoclonal antibodies to vWF. ThrombHaemost 1999; 82 (05) 1382-1385
112 Kokame K, Nobe Y, Kokubo Y, Okayama A, Miyata T. FRETS-VWF73, a first fluorogenic substrate for ADAMTS13 assay. Br J Haematol 2005; 129 (01) 93-100
113 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 (08) 1444-1452
114 Palla R, Valsecchi C, Bajetta M, Spreafico M, De Cristofaro R, Peyvandi F. Evaluation of assay methods to measure plasma ADAMTS13 activity in thrombotic microangiopathies. ThrombHaemost 2011; 105 (02) 381-385
115 Masias C, Cataland SR. The role of ADAMTS13 testing in the diagnosis and management of thrombotic microangiopathies and thrombosis. Blood 2018; 132 (09) 903-910
116 Hubbard AR, Heath AB, Kremer Hovinga JA. ; Subcommittee on von Willebrand Factor. Establishment of the WHO 1st International Standard ADAMTS13, plasma (12/252): communication from the SSC of the ISTH. J ThrombHaemost 2015; 13 (06) 1151-1153
117 Peyvandi F, Palla R, Lotta LA, Mackie I, Scully MA, Machin SJ. ADAMTS-13 assays in thrombotic thrombocytopenic purpura. J ThrombHaemost 2010; 8 (04) 631-640
118 Thouzeau S, Capdenat S, Stépanian A, Coppo P, Veyradier A. Evaluation of a commercial assay for ADAMTS13 activity measurement. ThrombHaemost 2013; 110 (04) 852-853
119 Joly B, Stepanian A, Hajage D. , et al. Evaluation of a chromogenic commercial assay using VWF-73 peptide for ADAMTS13 activity measurement. Thromb Res 2014; 134 (05) 1074-1080
120 Thomas W, Cutler JA, Moore GW, McDonald V, Hunt BJ. The utility of a fast turnaround ADAMTS13 activity in the diagnosis and exclusion of thrombotic thrombocytopenic purpura. Br J Haematol 2019; 184 (06) 1026-1032
121 Valsecchi C, Mirabet M, Mancini I. , et al. Evaluation of a new, rapid, fully automated assay for the measurement of ADAMTS13 activity. ThrombHaemost 2019; 119 (11) 1767-1772
122 Favresse J, Lardinois B, Chatelain B, Jacqmin H, Mullier F. Evaluation of the fully automated HemosILAcustar ADAMTS13 activity assay. ThrombHaemost 2018; 118 (05) 942-944
123 Moore GW, Meijer D, Griffiths M. , et al. A multi-center evaluation of TECHNOSCREEN^® ADAMTS-13 activity assay as a screening tool for detecting deficiency of ADAMTS-13. J ThrombHaemost 2020; (e-pub ahead of print)
124 Vendramin C, Thomas M, Westwood JP, Scully M. Bethesda assay for detecting inhibitory anti-ADAMTS13 antibodies in immune-mediated thrombotic thrombocytopenic purpura. TH Open 2018; 2 (03) e329-e333
125 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 (06) 1765-1772
126 Alwan F, Vendramin C, Vanhoorelbeke K. , et al. Presenting ADAMTS13 antibody and antigen levels predict prognosis in immune-mediated thrombotic thrombocytopenic purpura. Blood 2017; 130 (04) 466-471
127 Azoulay E, Bauer PR, Mariotte E. , et al; Nine-i Investigators. Expert statement on the ICU management of patients with thrombotic thrombocytopenic purpura. Intensive Care Med 2019; 45 (11) 1518-1539
128 Coppo P, Froissart A. ; French Reference Center for Thrombotic Microangiopathies. Treatment of thrombotic thrombocytopenic purpura beyond therapeutic plasma exchange. Hematology (Am Soc Hematol Educ Program) 2015; 2015 (01) 637-643
129 Joly BS, Vanhoorelbeke K, Veyradier A. Understanding therapeutic targets in thrombotic thrombocytopenic purpura. Intensive Care Med 2017; 43 (09) 1398-1400
130 Coppo P, Cuker A, George JN. Thrombotic thrombocytopenic purpura: Toward targeted therapy and precision medicine. Res PractThrombHaemost 2018; 3 (01) 26-37
131 Mazepa MA, Masias C, Chaturvedi S. How targeted therapy disrupts the treatment paradigm for acquired TTP: the risks, benefits, and unknowns. Blood 2019; 134 (05) 415-420
132 Tsai HM. Thrombotic thrombocytopenic purpura: beyond empiricism and plasma exchange. Am J Med 2019; 132 (09) 1032-1037
133 Rock GA, Shumak KH, Buskard NA. , et al; Canadian Apheresis Study Group. Comparison of plasma exchange with plasma infusion in the treatment of thrombotic thrombocytopenic purpura. N Engl J Med 1991; 325 (06) 393-397
134 Sayani FA, Abrams CS. How I treat refractory thrombotic thrombocytopenic purpura. Blood 2015; 125 (25) 3860-3867
135 Soucemarianadin M, Benhamou Y, Delmas Y. , et al. Twice-daily therapeutical plasma exchange-based salvage therapy in severe autoimmune thrombotic thrombocytopenic purpura: the French TMA Reference Center experience. Eur J Haematol 2016; 97 (02) 183-191
136 Balduini CL, Gugliotta L, Luppi M. , et al; Italian TTP Study Group. High versus standard dose methylprednisolone in the acute phase of idiopathic thrombotic thrombocytopenic purpura: a randomized study. Ann Hematol 2010; 89 (06) 591-596
137 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 (12) 2525-2532 , quiz 2524
138 Cataland SR, Kourlas PJ, Yang S. , et al. Cyclosporine or steroids as an adjunct to plasma exchange in the treatment of immune-mediated thrombotic thrombocytopenic purpura. Blood Adv 2017; 1 (23) 2075-2082
139 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 (03) 451-461
140 Jasti S, Coyle T, Gentile T, Rosales L, Poiesz B. Rituximab as an adjunct to plasma exchange in TTP: a report of 12 cases and review of literature. J Clin Apher 2008; 23 (05) 151-156
141 Ling HT, Field JJ, Blinder MA. Sustained response with rituximab in patients with thrombotic thrombocytopenic purpura: a report of 13 cases and review of the literature. Am J Hematol 2009; 84 (07) 418-421
142 Rubia J, Moscardó F, Gómez MJ. , et al; Grupo Español de Aféresis (GEA). Efficacy and safety of rituximab in adult patients with idiopathic relapsing or refractory thrombotic thrombocytopenic purpura: results of a Spanish multicenter study. Transfus Apheresis Sci 2010; 43 (03) 299-303
143 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 (07) 1746-1753
144 Froissart A, Buffet M, Veyradier A. , et al; French Thrombotic Microangiopathies Reference Center; Experience of the French Thrombotic Microangiopathies Reference Center. Efficacy and safety of first-line rituximab in severe, acquired thrombotic thrombocytopenic purpura with a suboptimal response to plasma exchange. Crit Care Med 2012; 40 (01) 104-111
145 Page EE, Kremer Hovinga JA, Terrell DR, Vesely SK, George JN. Clinical importance of ADAMTS13 activity during remission in patients with acquired thrombotic thrombocytopenic purpura. Blood 2016; 128 (17) 2175-2178
146 Benhamou Y, Paintaud G, Azoulay E. , et al; French Reference Center for Thrombotic Microangiopathies. Efficacy of a rituximab regimen based on B cell depletion in thrombotic thrombocytopenic purpura with suboptimal response to standard treatment: results of a phase II, multicenter noncomparative study. Am J Hematol 2016; 91 (12) 1246-1251
147 McDonald V, Manns K, Mackie IJ, Machin SJ, Scully MA. Rituximab pharmacokinetics during the management of acute idiopathic thrombotic thrombocytopenic purpura. J ThrombHaemost 2010; 8 (06) 1201-1208
148 Hie M, Gay J, Galicier L. , et al; French Thrombotic Microangiopathies Reference Centre. Preemptive rituximab infusions after remission efficiently prevent relapses in acquired thrombotic thrombocytopenic purpura. Blood 2014; 124 (02) 204-210
149 Froissart A, Veyradier A, Hié M, Benhamou Y, Coppo P. ; French Reference Center for Thrombotic Microangiopathies. Rituximab in autoimmune thrombotic thrombocytopenic purpura: a success story. Eur J Intern Med 2015; 26 (09) 659-665
150 Jestin M, Benhamou Y, Schelpe AS. , et al; French Thrombotic Microangiopathies Reference Center. Preemptive rituximab prevents long-term relapses in immune-mediated thrombotic thrombocytopenic purpura. Blood 2018; 132 (20) 2143-2153
151 Falter T, Herold S, Weyer-Elberich V. , et al. Relapse rate in survivors of acute autoimmune thrombotic thrombocytopenic purpura treated with or without rituximab. ThrombHaemost 2018; 118 (10) 1743-1751
152 Stubbs MJ, Low R, McGuckin S. , et al. Comparison of rituximab originator (MabThera) to biosimilar (Truxima) in patients with immune-mediated thrombotic thrombocytopenic purpura. Br J Haematol 2019; 185 (05) 912-917
153 Sun L, Mack J, Li A. , et al. Predictors of relapse and efficacy of rituximab in immune thrombotic thrombocytopenic purpura. Blood Adv 2019; 3 (09) 1512-1518
154 Owattanapanich W, Wongprasert C, Rotchanapanya W, Owattanapanich N, Ruchutrakool T. Comparison of the long-term remission of rituximab and conventional treatment for acquired thrombotic thrombocytopenic purpura: a systematic review and meta-analysis. Clin Appl ThrombHemost 2019; 25: 1-8
155 Westwood JP, Thomas M, Alwan F. , et al. Rituximab prophylaxis to prevent thrombotic thrombocytopenic purpura relapse: outcome and evaluation of dosing regimens. Blood Adv 2017; 1 (15) 1159-1166
156 Zwicker JI, Muia J, Dolatshahi L. , et al; ART Investigators. Adjuvant low-dose rituximab and plasma exchange for acquired TTP. Blood 2019; 134 (13) 1106-1109
157 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 (01) 41-49
158 Ahmad HN, Thomas-Dewing RR, Hunt BJ. Mycophenolate mofetil in a case of relapsed, refractory thrombotic thrombocytopenic purpura. Eur J Haematol 2007; 78 (05) 449-452
159 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 (05) 313-314
160 Fioredda F, Cappelli E, Mariani A. , et al. Thrombotic thrombocytopenic purpura and defective apoptosis due to CASP8/10 mutations: the role of mycophenolate mofetil. Blood Adv 2019; 3 (21) 3432-3435
161 Patriquin CJ, Thomas MR, Dutt T. , et al. Bortezomib in the treatment of refractory thrombotic thrombocytopenic purpura. Br J Haematol 2016; 173 (05) 779-785
162 Shortt J, Oh DH, Opat SS. ADAMTS13 antibody depletion by bortezomib in thrombotic thrombocytopenic purpura. N Engl J Med 2013; 368 (01) 90-92
163 Kremer Hovinga JA, Studt JD, DemarmelsBiasiutti F. , et al. Splenectomy in relapsing and plasma-refractory acquired thrombotic thrombocytopenic purpura. Haematologica 2004; 89 (03) 320-324
164 Kappers-Klunne MC, Wijermans P, Fijnheer R. , et al. Splenectomy for the treatment of thrombotic thrombocytopenic purpura. Br J Haematol 2005; 130 (05) 768-776
165 Beloncle F, Buffet M, Coindre JP. , et al; Thrombotic Microangiopathies Reference Center. Splenectomy and/or cyclophosphamide as salvage therapies in thrombotic thrombocytopenic purpura: the French TMA Reference Center experience. Transfusion 2012; 52 (11) 2436-2444
166 Feys HB, Roodt J, Vandeputte N. , et al. Thrombotic thrombocytopenic purpura directly linked with ADAMTS13 inhibition in the baboon (Papioursinus). Blood 2010; 116 (12) 2005-2010
167 Callewaert F, Roodt J, Ulrichts H. , et al. Evaluation of efficacy and safety of the anti-VWF Nanobody ALX-0681 in a preclinical baboon model of acquired thrombotic thrombocytopenic purpura. Blood 2012; 120 (17) 3603-3610
168 Scully M, Cataland SR, Peyvandi F. , et al; HERCULES Investigators. Caplacizumabtreatment for acquired thrombotic thrombocytopenic purpura. N Engl J Med 2019; 380 (04) 335-346
169 Knoebl P, Cataland S, Peyvandi F. , et al. Efficacy and safety of open-labelcaplacizumab in patients with exacerbations of acquired thrombotic thrombocytopenic purpura in the HERCULES study. J ThrombHaemost 2020; 18 (02) 479-484
170 Veyradier A. Von Willebrand factor--a new target for TTP treatment?. N Engl J Med 2016; 374 (06) 583-585
171 Peyvandi F, Scully M, Kremer Hovinga JA. , et al; TITAN Investigators. Caplacizumab for acquired thrombotic thrombocytopenic purpura. N Engl J Med 2016; 374 (06) 511-522
172 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 ThrombHaemost 2017; 15 (07) 1448-1452
173 le Besnerais M, Veyradier A, Benhamou Y, Coppo P. Caplacizumab: a change in the paradigm of thrombotic thrombocytopenic purpura treatment. Expert Opin Biol Ther 2019; 19 (11) 1127-1134
174 Sargentini-Maier ML, De Decker P, Tersteeg C, Canvin J, Callewaert F, De Winter H. Clinical pharmacology of caplacizumab for the treatment of patients with acquired thrombotic thrombocytopenic purpura. Expert Rev Clin Pharmacol 2019; 12 (06) 537-545
175 Tersteeg C, Schiviz A, De Meyer SF. , et al. Potential for recombinant ADAMTS13 as an effective therapy for acquired thrombotic thrombocytopenic purpura. ArteriosclerThrombVasc Biol 2015; 35 (11) 2336-2342
176 Scully M, Knöbl P, Kentouche K. , et al. Recombinant ADAMTS-13: first-in-human pharmacokinetics and safety in congenital thrombotic thrombocytopenic purpura. Blood 2017; 130 (19) 2055-2063
177 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 ThrombHaemost 2011; 9 (05) 936-944
178 Plaimauer B, Schiviz A, Kaufmann S, Höllriegl W, Rottensteiner H, Scheiflinger F. Neutralization of inhibitory antibodies and restoration of therapeutic ADAMTS-13 activity levels in inhibitor-treated rats by the use of defined doses of recombinant ADAMTS-13. J ThrombHaemost 2015; 13 (11) 2053-2062
179 Chen J, Reheman A, Gushiken FC. , et al. N-acetylcysteine reduces the size and activity of von Willebrand factor in human plasma and mice. J Clin Invest 2011; 121 (02) 593-603
180 Turner N, Nolasco L, Moake J. Generation and breakdown of soluble ultralarge von Willebrand factor multimers. SeminThrombHemost 2012; 38 (01) 38-46
181 Li GW, Rambally S, Kamboj J. , et al. Treatment of refractory thrombotic thrombocytopenic purpura with N-acetylcysteine: a case report. Transfusion 2014; 54 (05) 1221-1224
182 Rottenstreich A, Hochberg-Klein S, Rund D, Kalish Y. The role of N-acetylcysteine in the treatment of thrombotic thrombocytopenic purpura. J Thromb Thrombolysis 2016; 41 (04) 678-683
183 Tersteeg C, Roodt J, Van Rensburg WJ. , et al. N-Acetylcysteine in preclinical mouse and baboon models of thrombotic thrombocytopenic purpura. Blood 2017; 129 (08) 1030-1038
184 Hassan A, Iqbal M, George JN. Additional autoimmune disorders in patients with acquired autoimmune thrombotic thrombocytopenic purpura. Am J Hematol 2019; 94 (06) E172-E174
185 Jin M, Casper TC, Cataland SR. , et al. Relationship between ADAMTS13 activity in clinical remission and the risk of TTP relapse. Br J Haematol 2008; 141 (05) 651-658
186 Fuchs TA, Kremer Hovinga JA, Schatzberg D, Wagner DD, Lämmle B. Circulating DNA and myeloperoxidase indicate disease activity in patients with thrombotic microangiopathies. Blood 2012; 120 (06) 1157-1164
187 Jiménez-Alcázar M, Napirei M, Panda R. , et al. Impaired DNase1-mediated degradation of neutrophil extracellular traps is associated with acute thrombotic microangiopathies. J ThrombHaemost 2015; 13 (05) 732-742
188 Pillai VG, Bao J, Zander CB. , et al. Human neutrophil peptides inhibit cleavage of von Willebrand factor by ADAMTS13: a potential link of inflammation to TTP. Blood 2016; 128 (01) 110-119
189 Gilardin L, Delignat S, Peyron I. , et al. The ADAMTS13^1239-1253 peptide is a dominant HLA-DR1-restricted CD4⁺ T-cell epitope. Haematologica 2017; 102 (11) 1833-1841
190 Underwood MI, Thomas MR, Scully MA, Crawley JTB. Autoantibodies binding to “open” and “closed” ADAMTS13 in patients with acquired immune thrombotic thrombocytopenic purpura. Res PractThrombHaemost 2017; 1 (01) 255
191 Nowak AA, O'Brien HER, Henne P. , et al. ADAMTS-13 glycans and conformation-dependent activity. J ThrombHaemost 2017; 15 (06) 1155-1166
192 Smith MR. Rituximab (monoclonal anti-CD20 antibody): mechanisms of action and resistance. Oncogene 2003; 22 (47) 7359-7368
193 von Krogh AS, Quist-Paulsen P, Waage A. , et al. High prevalence of hereditary thrombotic thrombocytopenic purpura in central Norway: from clinical observation to evidence. J ThrombHaemost 2016; 14 (01) 73-82
194 Beauvais D, Venditti L, Chassin O. , et al. Inherited thrombotic thrombocytopenic purpura revealed by recurrent strokes in a male adult: case report and literature review. J Stroke Cerebrovasc Dis 2019; 28 (06) 1537-1539
195 Page EE, Kremer Hovinga JA, Terrell DR, Vesely SK, George JN. Thrombotic thrombocytopenic purpura: diagnostic criteria, clinical features, and long-term outcomes from 1995 through 2015. Blood Adv 2017; 1 (10) 590-600
196 Sadler JE. Pathophysiology of thrombotic thrombocytopenic purpura. Blood 2017; 130 (10) 1181-1188
197 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 (16) 3836-3843
198 Tersteeg C, de Maat S, De Meyer SF. , et al. Plasmin cleavage of von Willebrand factor as an emergency bypass for ADAMTS13 deficiency in thrombotic microangiopathy. Circulation 2014; 129 (12) 1320-1331
199 Shin Y, Miyake H, Togashi K, Hiratsuka R, Endou-Ohnishi K, Imamura Y. Proteolytic inactivation of ADAMTS13 by plasmin in human plasma: risk of thrombotic thrombocytopenic purpura. J Biochem 2018; 163 (05) 381-389
200 Stubbs MJ, Thomas M, Vendramin C. , et al. Administration of immunoglobulin G-degrading enzyme of Streptococcus pyogenes (IdeS) for persistent anti-ADAMTS13 antibodies in patients with thrombotic thrombocytopenic purpura in clinical remission. Br J Haematol 2019; 186 (01) 137-140
201 Trionfini P, Tomasoni S, Galbusera M. , et al. Adenoviral-mediated gene transfer restores plasma ADAMTS13 antigen and activity in ADAMTS13 knockout mice. Gene Ther 2009; 16 (11) 1373-1379
202 Niiya M, Endo M, Shang D. , et al. Correction of ADAMTS13 deficiency by in utero gene transfer of lentiviral vector encoding ADAMTS13 genes. Mol Ther 2009; 17 (01) 34-41
203 Laje P, Shang D, Cao W. , et al. Correction of murine ADAMTS13 deficiency by hematopoietic progenitor cell-mediated gene therapy. Blood 2009; 113 (10) 2172-2180
204 Verhenne S, Vandeputte N, Pareyn I. , et al. Long-term prevention of congenital thrombotic thrombocytopenic purpura in ADAMTS13 knockout mice by sleeping beauty transposon-mediated gene therapy. ArteriosclerThrombVasc Biol 2017; 37 (05) 836-844
205 Jin S-Y, Xiao J, Bao J, Zhou S, Wright JF, Zheng XL. AAV-mediated expression of an ADAMTS13 variant prevents shigatoxin-induced thrombotic thrombocytopenic purpura. Blood 2013; 121 (19) 3825-3829 , S1–S3
206 Itami H, Hara S, Matsumoto M. , et al. Complement activation associated with ADAMTS13 deficiency may contribute to the characteristic glomerular manifestations in Upshaw-Schulman syndrome. Thromb Res 2018; 170 (10) 148-155
207 Staley EM, Cao W, Pham HP. , et al. Clinical factors and biomarkers predict outcome in patients with immune-mediated thrombotic thrombocytopenic purpura. Haematologica 2019; 104 (01) 166-175
208 Zheng L, Zhang D, Cao W, Song WC, Zheng XL. Synergistic effects of ADAMTS13 deficiency and complement activation in pathogenesis of thrombotic microangiopathy. Blood 2019; 134 (13) 1095-1105
209 Wu TC, Yang S, Haven S. , et al. Complement activation and mortality during an acute episode of thrombotic thrombocytopenic purpura. J ThrombHaemost 2013; 11 (10) 1925-1927
210 Pos W, Crawley JTB, Fijnheer R, Voorberg J, Lane DA, Luken BM. 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 (08) 1640-1649
211 Graça NAG, Ercig B, Velásquez Pereira LC. , et al. Modifying ADAMTS13 to modulate binding of pathogenic autoantibodies of patients with acquired thrombotic thrombocytopenic purpura. Haematologica 2019; 104 (e-pub ahead of print)