Download PDF
Semin Thromb Hemost 2020; 46(03): 289-301
DOI: 10.1055/s-0040-1708541
Review Article

Immune-Mediated Thrombotic Thrombocytopenic Purpura: A Narrative Review of Diagnosis and Treatment in Adults

Richard Blennerhassett
1   Sydney Medical School, University of Sydney, Sydney, Australia
2   Department of Haematology, Royal North Shore Hospital, Sydney, Australia
,
Jennifer Curnow
1   Sydney Medical School, University of Sydney, Sydney, Australia
3   Sydney Centres for Thrombosis and Haemostasis, Sydney, Australia
4   Department of Haematology, Westmead Hospital, Western Sydney Local Health District (WSLHD), Sydney, Australia
,
Leonardo Pasalic
1   Sydney Medical School, University of Sydney, Sydney, Australia
3   Sydney Centres for Thrombosis and Haemostasis, Sydney, Australia
5   Department of Haematology, Institute of Clinical Pathology and Medical Research, NSW Health Pathology, Westmead Hospital, Westmead, NSW, Australia
› Author Affiliations
› Further Information
    Permissions and Reprints

Abstract

Immune-mediated thrombotic thrombocytopenic purpura (iTTP) is a rare and potentially lethal disease characterized by fragmentary hemolysis, moderate-to-severe thrombocytopenia, end-organ dysfunction, and severely reduced ADAMTS13 levels (< 10%). Survival in iTTP has improved significantly since the introduction of plasma exchange as standard therapy combined with immune suppression to address the underlying pathophysiology. A host of challenges remain including prompt recognition of the disease, treatment of the end-organ effects of the disease, improving the early mortality rate, significantly reducing the relapse rate as well as addressing refractory disease. Discussed in this narrative review of iTTP are the recent measures aimed at addressing these issues, including improvements in clinical prediction models, postremission maintenance approaches with early retreatment as well as the development of novel therapies.

Keywords

thrombocytopenic purpura - thrombotic microangiopathy - ADAMTS13 - plasma exchange


Publication History

Publication Date:
07 April 2020 (online)

© 2020. Thieme. All rights reserved.

Thieme Medical Publishers, Inc.
333 Seventh Avenue, 18th Floor, New York, NY 10001, USA

 

  • References

  • 1 Scully M, Cataland S, Coppo P. et al; International Working Group for Thrombotic Thrombocytopenic Purpura. Consensus on the standardization of terminology in thrombotic thrombocytopenic purpura and related thrombotic microangiopathies. J Thromb Haemost 2017; 15 (02) 312-322
    Google Scholar
  • 2 Moschcowitz E. An acute febrile pleiochromic anemia with hyaline thrombosis of the terminal arterioles and capillaries; an undescribed disease. JAMA Intern Med 1925; 36 (01) 89-93
    Google Scholar
  • 3 Rubinstein MA, Kagan BM, MacGillviray MH, Merliss R, Sacks H. Unusual remission in a case of thrombotic thrombocytopenic purpura syndrome following fresh blood exchange transfusions. Ann Intern Med 1959; 51 (06) 1409-1419
    Google Scholar
  • 4 Marcus AJ. Moschcowitz revisited. N Engl J Med 1982; 307 (23) 1447-1448
    Google Scholar
  • 5 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 (06) 398-403
    Google Scholar
  • 6 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
    Google Scholar
  • 7 Tsai H-M, Lian EC-Y. Antibodies to von Willebrand factor-cleaving protease in acute thrombotic thrombocytopenic purpura. N Engl J Med 1998; 339 (22) 1585-1594
    Google Scholar
  • 8 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
    Google Scholar
  • 9 Crawley JT, 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
    Google Scholar
  • 10 Joly BS, Coppo P, Veyradier A. An update on pathogenesis and diagnosis of thrombotic thrombocytopenic purpura. Expert Rev Hematol 2019; 12 (06) 383-395
    Google Scholar
  • 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 (23) 1432-1435
    Google Scholar
  • 12 Dent JA, Berkowitz SD, Ware J, Kasper CK, Ruggeri ZM. Identification of a cleavage site directing the immunochemical detection of molecular abnormalities in type IIA von Willebrand factor. Proc Natl Acad Sci U S A 1990; 87 (16) 6306-6310
    Google Scholar
  • 13 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
    Google Scholar
  • 14 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. Thromb Haemost 1999; 81 (01) 8-13
    Google Scholar
  • 15 Zheng XL. Structure-function and regulation of ADAMTS-13 protease. J Thromb Haemost 2013; 11 (Suppl. 01) 11-23
    Google Scholar
  • 16 Arya M, Anvari B, Romo GM. et al. Ultralarge multimers of von Willebrand factor form spontaneous high-strength bonds with the platelet glycoprotein Ib-IX complex: studies using optical tweezers. Blood 2002; 99 (11) 3971-3977
    Google Scholar
  • 17 Roose E, Schelpe AS, Joly BS. et al. An open conformation of ADAMTS-13 is a hallmark of acute acquired thrombotic thrombocytopenic purpura. J Thromb Haemost 2018; 16 (02) 378-388
    Google Scholar
  • 18 Amorosi EL, Ultmann JE. Thrombotic thrombocytopenic purpura: report of 16 cases and review of the literature. Medicine (Baltimore) 1966; 45 (02) 139-160
    Google Scholar
  • 19 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
    Google Scholar
  • 20 Matsumoto M, Bennett CL, Isonishi A. et al. Acquired idiopathic ADAMTS13 activity deficient thrombotic thrombocytopenic purpura in a population from Japan. PLoS One 2012; 7 (03) e33029
    Google Scholar
  • 21 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
    Google Scholar
  • 22 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
    Google Scholar
  • 23 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
    Google Scholar
  • 24 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
    Google Scholar
  • 25 Bendapudi PK, Li A, Hamdan A. et al. Derivation and prospective validation of a predictive score for the rapid diagnosis of thrombotic thrombocytopenic purpura: the plasmic score. Blood 2014; 124 (21) 231-231
    Google Scholar
  • 26 Bentley MJ, Wilson AR, Rodgers GM. Performance of a clinical prediction score for thrombotic thrombocytopenic purpura in an independent cohort. Vox Sang 2013; 105 (04) 313-318
    Google Scholar
  • 27 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
    Google Scholar
  • 28 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
    Google Scholar
  • 29 Favaloro EJ, Grispo L, Exner T, Koutts J. Development of a simple collagen based ELISA assay aids in the diagnosis of, and permits sensitive discrimination between type I and type II, von Willebrand's disease. Blood Coagul Fibrinolysis 1991; 2 (02) 285-291
    Google Scholar
  • 30 Starke R, Machin S, Scully M, Purdy G, Mackie I. The clinical utility of ADAMTS13 activity, antigen and autoantibody assays in thrombotic thrombocytopenic purpura. Br J Haematol 2007; 136 (04) 649-655
    Google Scholar
  • 31 Meyer SC, Sulzer I, Lämmle B, Kremer Hovinga JA. Hyperbilirubinemia interferes with ADAMTS-13 activity measurement by FRETS-VWF73 assay: diagnostic relevance in patients suffering from acute thrombotic microangiopathies. J Thromb Haemost 2007; 5 (04) 866-867
    Google Scholar
  • 32 Muia J, Gao W, Haberichter SL. et al. An optimized fluorogenic ADAMTS13 assay with increased sensitivity for the investigation of patients with thrombotic thrombocytopenic purpura. J Thromb Haemost 2013; 11 (08) 1511-1518
    Google Scholar
  • 33 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
    Google Scholar
  • 34 Jin M, Cataland S, Bissell M, Wu HM. A rapid test for the diagnosis of thrombotic thrombocytopenic purpura using surface enhanced laser desorption/ionization time-of-flight (SELDI-TOF)-mass spectrometry. J Thromb Haemost 2006; 4 (02) 333-338
    Google Scholar
  • 35 Binder NB, Griffiths M, Vetr H. A rapid and simple assay for the determination of Adamts-13 activity. Blood 2016; 128 (22) 1399-1399
    Google Scholar
  • 36 Favresse J, Lardinois B, Chatelain B, Jacqmin H, Mullier F. Evaluation of the fully automated HemosIL Acustar ADAMTS13 activity assay. Thromb Haemost 2018; 118 (05) 942-944
    Google Scholar
  • 37 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
    Google Scholar
  • 38 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
    Google Scholar
  • 39 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
    Google Scholar
  • 40 Thomas MR, Robinson S, Scully MA. How we manage thrombotic microangiopathies in pregnancy. Br J Haematol 2016; 173 (06) 821-830
    Google Scholar
  • 41 Scully M, Hunt BJ, Benjamin S. et al; British Committee for Standards in Haematology. Guidelines on the diagnosis and management of thrombotic thrombocytopenic purpura and other thrombotic microangiopathies. Br J Haematol 2012; 158 (03) 323-335
    Google Scholar
  • 42 Joly BS, Coppo P, Veyradier A. Thrombotic thrombocytopenic purpura. Blood 2017; 129 (21) 2836-2846
    Google Scholar
  • 43 Fox LC, Cohney SJ, Kausman JY. et al. Consensus opinion on diagnosis and management of thrombotic microangiopathy in Australia and New Zealand. Intern Med J 2018; 48 (06) 624-636
    Google Scholar
  • 44 Dervenoulas J, Tsirigotis P, Bollas G. et al. Thrombotic thrombocytopenic purpura/hemolytic uremic syndrome (TTP/HUS): treatment outcome, relapses, prognostic factors. A single-center experience of 48 cases. Ann Hematol 2000; 79 (02) 66-72
    Google Scholar
  • 45 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
    Google Scholar
  • 46 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 (10) 2445-2451
    Google Scholar
  • 47 Zeigler ZR, Shadduck RK, Gryn JF. et al; North American TTP Group. Cryoprecipitate poor plasma does not improve early response in primary adult thrombotic thrombocytopenic purpura (TTP). J Clin Apher 2001; 16 (01) 19-22
    Google Scholar
  • 48 Rock G, Anderson D, Clark W. et al; Canadian Apheresis Group; Canadian Association of Apheresis Nurses. Does cryosupernatant plasma improve outcome in thrombotic thrombocytopenic purpura? No answer yet. Br J Haematol 2005; 129 (01) 79-86
    Google Scholar
  • 49 Rock G, Yousef H, Neurath D, Lu M. ADAMTS-13 in fresh, stored, and solvent/detergent-treated plasma. Transfusion 2006; 46 (07) 1261-1262
    Google Scholar
  • 50 Scott EA, Puca KE, Pietz BC, Duchateau BK, Friedman KD. Comparison and stability of ADAMTS13 activity in therapeutic plasma products. Transfusion 2007; 47 (01) 120-125
    Google Scholar
  • 51 Howard MA, Williams LA, Terrell DR, Duvall D, Vesely SK, George JN. Complications of plasma exchange in patients treated for clinically suspected thrombotic thrombocytopenic purpura-hemolytic uremic syndrome. Transfusion 2006; 46 (01) 154-156
    Google Scholar
  • 52 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
    Google Scholar
  • 53 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
    Google Scholar
  • 54 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
    Google Scholar
  • 55 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
    Google Scholar
  • 56 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
    Google Scholar
  • 57 Lim W, Vesely SK, George JN. The role of rituximab in the management of patients with acquired thrombotic thrombocytopenic purpura. Blood 2015; 125 (10) 1526-1531
    Google Scholar
  • 58 Westwood JP, Webster H, McGuckin S, McDonald V, Machin SJ, Scully M. Rituximab for thrombotic thrombocytopenic purpura: benefit of early administration during acute episodes and use of prophylaxis to prevent relapse. J Thromb Haemost 2013; 11 (03) 481-490
    Google Scholar
  • 59 Page EE, Kremer Hovinga JA, Terrell DR, Vesely SK, George JN. Rituximab reduces risk for relapse in patients with thrombotic thrombocytopenic purpura. Blood 2016; 127 (24) 3092-3094
    Google Scholar
  • 60 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
    Google Scholar
  • 61 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
    Google Scholar
  • 62 Zaja F, Battista ML, Pirrotta MT. et al. Lower dose rituximab is active in adults patients with idiopathic thrombocytopenic purpura. Haematologica 2008; 93 (06) 930-933
    Google Scholar
  • 63 McDonald V, Manns K, Mackie IJ, Machin SJ, Scully MA. Rituximab pharmacokinetics during the management of acute idiopathic thrombotic thrombocytopenic purpura. J Thromb Haemost 2010; 8 (06) 1201-1208
    Google Scholar
  • 64 Kremer Hovinga JA, Studt JD, Demarmels Biasiutti F. et al. Splenectomy in relapsing and plasma-refractory acquired thrombotic thrombocytopenic purpura. Haematologica 2004; 89 (03) 320-324
    Google Scholar
  • 65 Dubois L, Gray DK. Case series: splenectomy: does it still play a role in the management of thrombotic thrombocytopenic purpura?. Can J Surg 2010; 53 (05) 349-355
    Google Scholar
  • 66 Lombardi AM, Pasquale ID, Businaro MA. et al. Relapsing thrombotic thrombocytopenic purpura with low ADAMTS13 antigen levels: an indication for splenectomy?. Hematol Rep 2019; 11 (01) 7904
    Google Scholar
  • 67 Coppo P, Cuker A, George JN. Thrombotic thrombocytopenic purpura: toward targeted therapy and precision medicine. Res Pract Thromb Haemost 2018; 3 (01) 26-37
    Google Scholar
  • 68 Bartunek J, Barbato E, Heyndrickx G, Vanderheyden M, Wijns W, Holz JB. Novel antiplatelet agents: ALX-0081, a nanobody directed towards von Willebrand factor. J Cardiovasc Transl Res 2013; 6 (03) 355-363
    Google Scholar
  • 69 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
    Google Scholar
  • 70 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
    Google Scholar
  • 71 Scully M, Cataland SR, Peyvandi F. et al; HERCULES Investigators. Caplacizumab treatment for acquired thrombotic thrombocytopenic purpura. N Engl J Med 2019; 380 (04) 335-346
    Google Scholar
  • 72 FDA approved caplacizumab-yhdp. Accessed: January 6, 2019 at: https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approved-caplacizumab-yhdp
    Google Scholar
  • 73 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
    Google Scholar
  • 74 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
    Google Scholar
  • 75 Coppo P. French Reference Center for Thrombotic Microangiopathies. Treatment of autoimmune thrombotic thrombocytopenic purpura in the more severe forms. Transfus Apheresis Sci 2017; 56 (01) 52-56
    Google Scholar
  • 76 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
    Google Scholar
  • 77 Pandey MR, Vachhani P, Ontiveros EP. Remission of severe, relapsed, and refractory TTP after multiple cycles of bortezomib. Case Rep Hematol 2017; 2017: 9681832
    Google Scholar
  • 78 Shortt J, Oh DH, Opat SS. ADAMTS13 antibody depletion by bortezomib in thrombotic thrombocytopenic purpura. N Engl J Med 2013; 368 (01) 90-92
    Google Scholar
  • 79 van Balen T, Schreuder MF, de Jong H, van de Kar NC. Refractory thrombotic thrombocytopenic purpura in a 16-year-old girl: successful treatment with bortezomib. Eur J Haematol 2014; 92 (01) 80-82
    Google Scholar
  • 80 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
    Google Scholar
  • 81 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 (05) 936-944
    Google Scholar
  • 82 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
    Google Scholar
  • 83 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
    Google Scholar
  • 84 Mariani S, Trisolini SM, Capria S. et al. Acquired thrombotic thrombocytopenic purpura in a child: rituximab to prevent relapse. A pediatric report and literature review. Haematologica 2018; 103 (03) e138-e140
    Google Scholar
  • 85 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
    Google Scholar
  • 86 Saleem R, Rogers ZR, Neunert C, George JN. Maintenance rituximab for relapsing thrombotic thrombocytopenic purpura: a case report. Transfusion 2019; 59 (03) 921-926
    Google Scholar
  • 87 Bresin E, Gastoldi S, Daina E. et al. Rituximab as pre-emptive treatment in patients with thrombotic thrombocytopenic purpura and evidence of anti-ADAMTS13 autoantibodies. Thromb Haemost 2009; 101 (02) 233-238
    Google Scholar
  • 88 Tate C, Mollee P. Intravenous OxyContin-associated thrombotic microangiopathy treated successfully without plasma exchange. Med J Aust 2015; 202 (06) 330-331
    Google Scholar
  • 89 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
    Google Scholar
  • 90 Nguyen L, Li X, Duvall D, Terrell DR, Vesely SK, George JN. Twice-daily plasma exchange for patients with refractory thrombotic thrombocytopenic purpura: the experience of the Oklahoma Registry, 1989 through 2006. Transfusion 2008; 48 (02) 349-357
    Google Scholar
  • 91 Kremer Hovinga JA, Coppo P, Lämmle B, Moake JL, Miyata T, Vanhoorelbeke K. Thrombotic thrombocytopenic purpura. Nat Rev Dis Primers 2017; 3: 17020
    Google Scholar
  • 92 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
    Google Scholar