IMMUNE THROMBOTIC THROMBOCYTOPENIC PURPURA: PATHOPHYSIOLOGY, DIAGNOSIS AND OPEN ISSUES
Main Article Content
Keywords
rituximab, Caplacizumab, thrombotic thrombocytopenic purpura
Abstract
Immune thrombotic thrombocytopenic purpura (iTTP) is a life-threatening thrombotic microangiopathy characterized by microangiopathic hemolytic anemia, thrombocytopenia, and ischemic end organ injury due to microvascular platelet-rich thrombi. iTTP pathophysiology is based on a severe ADAMTS13 deficiency, the specific von Willebrand factor (vWF)-cleaving protease, due to anti-ADAMTS13 autoantibodies. Early diagnosis and treatment reduce the mortality. Front-line therapy includes daily plasma exchange (PEX) with fresh frozen plasma replacement and immunosuppression with corticosteroids. Caplacizumab is recently added to the front-line therapy. Caplacizumab is a nanobody that binds to the A1 domain of vWF, blocking the interaction of ultra-large vWF multimers with the platelet, and thereby preventing the formation of platelet-rich thrombi. Caplacizumab reduces mortality due to ischemic events, refractoriness and exacerbations after PEX discontinuation. Until now, the criteria for response to treatment mainly took into account the normalization of platelet count and discontinuation of PEX, now with the use of caplacizumab, leading to rapid normalization of platelet count, it has been necessary to redefine the response criteria, taking into account also the underlying autoimmune disease. Monitoring of ADAMTS13 activity is important to identify cases with low value of activity (<10IU/L), requiring the optimization of immunosuppressive therapy with addition of rituximab. Rituximab is effective in patients with refractory disease or relapsing disease, currently the use of rituximab has expanded, both in front line treatment, and during follow-up as pre-emptive approach. Some patients do not achieve an ADAMTS13 remission following the acute phase despite steroids and rituximab treatment, requiring an individualized immunosuppressive approach to prevent clinical relapse. In iTTP, there is an increased risk of venous thrombotic events (VTEs) as well as arterial thrombotic events and most occur after platelet normalization. Until now, there is no consensus on the use of pharmacological thromboprophylaxis in patients on caplacizumab, because the drug is known to increase bleeding-risk.
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References
1. Moschcowitz, E. Hyaline Thrombosis of the Terminal Arterioles and Capillaries: A Hitherto Undescribed Disease. Proc. N. Y. Pathol. Soc. 1924, 24, 21–24
2. Scully, M.; Yarranton, H.; Liesner, R.; Cavenagh, J.; Hunt, B.; Benjamin, S.; Bevan, D.; Mackie, I.; Machin, S. Regional UK TTP registry: Correlation with laboratory ADAMTS 13 analysis and clinical features. Br. J. Haematol. 2008, 142, 819–826.
3. Mariotte, E.; Azoulay, E.; Galicier, L.; Rondeau, E.; Zouiti, F.; Boisseau, P.; Poullin, P.; de Maistre, E.; Provôt, F.; Delmas, Y.; et al. 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, e237–e245.
4. Amorosi EL, Ultmann JE. Thrombotic thrombocytopenic Purpura: report of 16 cases and review of the literature. Medicine 1966;45:139–60.
5. George JN, Nester CM. Syndromes of thrombotic microangiopathy. N Engl J Med. 2014 Aug 14;371(7):654-66.
6. 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.
7. South K, Luken BM, Crawley JTB, et al. Conformational activation of ADAMTS13. Proc Natl Acad Sci USA. 2014;111(52):18578–18583.
8. Muia J, Zhu J, Gupta G, et al. Allosteric activation of ADAMTS13 by von Willebrand factor. Proc Natl Acad Sci USA. 2014;111 (52):18584–18589.
9. Deforche L, Roose E, Vandenbulcke A, et al. Linker regions and flexibility around the metalloprotease domain account for conformational activation of ADAMTS-13. J Thromb Haemost JTH.2015;13(11):2063–2075.
10. Crawley JTB, de Groot R, Xiang Y, et al. Unraveling the scissile bond: how ADAMTS13 recognizes and cleaves von Willebrand factor. Blood. 2011;118(12):3212–3221
11. Sadler JE What’s new in the diagnosis and pathophysiology of thrombotic thrombocytopenic purpura. Hematol Educ Program Am Soc Hematol Am Soc Hematol Educ Program. 2015;2015:631–636
12. 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.
13. Réti, M.; Farkas, P.; Csuka, D.; Rázsó, K.; Schlammadinger, Á.; Udvardy, M.L.; Madách, K.; Domján, G.; Bereczki, C.; Reusz, G.S.; et al. Complement activation in thrombotic thrombocytopenic purpura. J. Thromb. Haemost. 2012, 791-8
14. Turner, N.; Sartain, S.; Moake, J. Ultralarge von Willebrand factor-induced platelet clumping and activation of the alternative complement pathway in thrombotic thrombocytopenic purpura and the hemolytic-uremic syndromes. Hematol. Oncol. Clin. N.Am. 2015, 29, 509–524
15. Miyata, T.; Fan, X. A second hit for TMA. Blood 2012, 120, 1152–1154
16. Scheiflinger, F.; Knöbl, P.; Trattner, B.; Plaimauer, B.; Mohr, G.; Dockal, M.; Dorner, F.; Rieger, M. Nonneutralizing IgM and IgG antibodies to von Willebrand factor-cleaving protease (ADAMTS-13) in a patient with thrombotic thrombocytopenic purpura. Blood 2003, 102, 3241–3243.
17. Rieger, M.; Mannucci, P.M.; Kremer Hovinga, J.A.; Herzog, A.; Gerstenbauer, G.; Konetschny, C.; Zimmermann, K.; Scharrer,I.; Peyvandi, F.; Galbusera, M.; et al. ADAMTS13 autoantibodies in patients with thrombotic microangiopathies and other immunomediated diseases. Blood 2005, 106, 1262–1267
18. Thomas, M.R.; de Groot, R.; Scully, M.A.; Crawley, J.T. Pathogenicity of Anti-ADAMTS13 Autoantibodies in Acquired Thrombotic Thrombocytopenic Purpura. EBioMedicine 2015, 2, 942–952
19. Zheng, X.L.; Wu, H.M.; Shang, D.; Falls, E.; Skipwith, C.G.; Cataland, S.R.; Bennett, C.L.; Kwaan, H.C. Multiple domains of ADAMTS13 are targeted by autoantibodies against ADAMTS13 in patients with acquired idiopathic thrombotic thrombocytopenic purpura. Haematologica 2010, 95, 1555–1562.
20. Yamaguchi, Y.; Moriki, T.; Igari, A.; Nakagawa, T.; Wada, H.; Matsumoto, M.; Fujimura, Y.; Murata, M. Epitope analysis ofautoantibodies to ADAMTS13 in patients with acquired thrombotic thrombocytopenic purpura. Thromb. Res. 2011, 128, 169–173.
21. Verbij FC, Fijnheer R, Voorberg J, et al. Acquired TTP: ADAMTS13 meets the immune system. Blood Rev. 2014;28(6):227–234
22. Ferrari, S.; Scheiflinger, F.; Rieger, M.; Mudde, G.; Wolf, M.; Coppo, P.; Girma, J.P.; Azoulay, E.; Brun-Buisson, C.; Fakhouri, F.; 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.
23. Ferrari, S.; Mudde, G.C.; Rieger, M.; Veyradier, A.; Kremer Hovinga, J.A.; Scheiflinger, F. IgG subclass distribution of antiADAMTS13 antibodies in patients with acquired thrombotic thrombocytopenic purpura. J. Thromb. Haemost. 2009, 7, 1703–1710.
24. Bettoni, G.; Palla, R.; Valsecchi, C.; Consonni, D.; Lotta, L.A.; Trisolini, S.M.; Mancini, I.; Musallam, K.M.; Rosendaal, F.R.; Peyvandi, F. ADAMTS-13 activity and autoantibodies classes and subclasses as prognostic predictors in acquired thrombotic thrombocytopenic purpura. J. Thromb. Haemost. 2012, 10, 1556–1565.
25. Kosugi, N.; Tsurutani, Y.; Isonishi, A.; Hori, Y.; Matsumoto, M.; Fujimura, Y. Influenza A infection triggers thrombotic thrombocytopenic purpura by producing the anti-ADAMTS13 IgG inhibitor. Intern. Med. 2010, 49, 689–693.
26. Franchini, M. Thrombotic thrombocytopenic purpura: Proposal of a new pathogenic mechanism involving Helicobacter pylori infection. Med. Hypotheses 2005, 65, 1128–1131.
27. Talebi, T.; Fernandez-Castro, G.; Montero, A.J.; Stefanovic, A.; Lian, E. A case of severe thrombotic thrombocytopenic purpura with concomitant Legionella pneumonia: Review of pathogenesis and treatment. Am. J. Ther. 2011, 18, e180–e185.
28. Yagita, M.; Uemura, M.; Nakamura, T.; Kunitomi, A.; Matsumoto, M.; Fujimura, Y. Development of ADAMTS13 inhibitor in apatient with hepatitis C virus-related liver cirrhosis causes thrombotic thrombocytopenic purpura. J. Hepatol. 2005, 42, 420–421.
29. Gunther, K.; Garizio, D.; Nesara, P. ADAMTS13 activity and the presence of acquired inhibitors in human immunodeficiency virus-related thrombotic thrombocytopenic purpura. Transfusion 2007, 47, 1710–1716.
30. Lotta, L.A.; Valsecchi, C.; Pontiggia, S.; Mancini, I.; Cannavò, A.; Artoni, A.; Mikovic, D.; Meloni, G.; Peyvandi, F. Measurement and prevalence of circulating ADAMTS13-specific immune complexes in autoimmune thrombotic thrombocytopenic purpura. J. Thromb. Haemost. 2014, 12, 329–336.
31. Ferrari, S.; Palavra, K.; Gruber, B.; Kremer Hovinga, J.A.; Knöbl, P.; Caron, C.; Cromwell, C.; Aledort, L.; Plaimauer, B.;Turecek, P.L.; et al. Persistence of circulating ADAMTS13-specific immune complexes in patients with acquired thrombotic thrombocytopenic purpura. Haematologica 2014, 99, 779–787.
32. Mancini, I.; Ferrari, B.; Valsecchi, C.; Pontiggia, S.; Fornili, M.; Biganzoli, E.; Peyvandi, F.; Investigators, I.G.o.T. ADAMTS13- specific circulating immune complexes as potential predictors of relapse in patients with acquired thrombotic thrombocytopenic purpura. Eur. J. Intern. Med. 2017, 39, 79–83
33. Westwood, J.P.; Langley, K.; Heelas, E.; Machin, S.J.; Scully, M. Complement and cytokine response in acute Thrombotic Thrombocytopenic Purpura. Br. J. Haematol. 2014, 164, 858–866
34. Jang, M.J.; Chong, S.Y.; Kim, I.H.; Kim, J.H.; Jung, C.W.; Kim, J.Y.; Park, J.C.; Lee, S.M.; Kim, Y.K.; Lee, J.E.; et al. Clinical features of severe acquired ADAMTS13 deficiency in thrombotic thrombocytopenic purpura: The Korean TTP registry experience. Int. J.Hematol. 2011, 93, 163–169.
35. Benhamou, Y.; Boelle, P.Y.; Baudin, B.; Ederhy, S.; Gras, J.; Galicier, L.; Azoulay, E.; Provôt, F.; Maury, E.; Pène, F.; et al. Cardiac troponin-I on diagnosis predicts early death and refractoriness in acquired thrombotic thrombocytopenic purpura. Experience of the French Thrombotic Microangiopathies Reference Center. J. Thromb. Haemost. 2015, 13, 293–302
36. Vesely, S.K.; George, J.N.; Lämmle, B.; Studt, J.D.; Alberio, L.; El-Harake, M.A.; Raskob, G.E. 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, 60–68.
37. Bell WR, Braine HG, Ness PM, Kickler TS. Improved survival in thrombotic thrombocytopenic purpura-hemolytic uremic syndrome. Clinical experience in 108 patients. N Engl J Med 1991;325:398–403.
38. Mackie I, Mancini I, Muia J, Kremer Hovinga J, Nair S, Machin S, Baker R. International Council for Standardization in Haematology (ICSH) recommendations for laboratory measurement of ADAMTS13. Int J Lab Hematol. 2020 Dec;42(6):685-696.
39. Coppo P, Schwarzinger M, Buffet M, Wynckel A, Clabault K, Presne C, et al. Predictive features of severe acquired ADAMTS13 deficiency in idiopathic thrombotic microangiopathies: the French TMA reference center experience. PLoS One 2010;5:e10208
40. Bendapudi P.K., Hurwitz S., Fry A., Marques M.B., Waldo S.W., Li A. Derivation and external validation of the PLASMIC score for rapid assessment of adults with thrombotic microangiopathies: a cohort study. Lancet Haematol. 2017;4:157–164.
41. Li A, Khalighi PR, Wu Q, Garcia DA. External validation of the PLASMIC score: a clinical prediction tool for thrombotic thrombocytopenic purpura diagnosis and treatment. J Thromb Haemost 2018;16:164–9
42. Paydary K, Banwell E, Tong J, Chen Y, Cuker A. Diagnostic accuracy of the PLASMIC score in patients with suspected thrombotic thrombocytopenic purpura: A systematic review and meta-analysis. Transfusion. 2020 Sep;60(9):2047-2057.
43. Zheng XL, Vesely SK, Cataland SR, Coppo P, Geldziler B, Iorio A, Matsumoto M, Mustafa RA, Pai M, Rock G, Russell L, Tarawneh R, Valdes J, Peyvandi F. ISTH guidelines for treatment of thrombotic thrombocytopenic purpura. J Thromb Haemost. 2020 Oct;18(10):2496-2502. doi: 10.1111/jth.15010. Epub 2020 Sep 11.
44. Rock, G.A.; Shumak, K.H.; Buskard, N.A.; Blanchette, V.S.; Kelton, J.G.; Nair, R.C.; Spasoff, R.A. Comparison of plasma exchange with plasma infusion in the treatment of thrombotic thrombocytopenic purpura. Canadian Apheresis Study Group. N. Engl. J.Med. 1991, 325, 393–397
45. Coppo P, Bussel A, Charrier S, Adrie C, Galicier L, Boulanger E, et al. High-dose plasma infusion versus plasma exchange as early treatment of thrombotic thrombocytopenic purpura/hemolytic-uremic syndrome. Medicine (Baltimore) 2003;82:27–38
46. Scully M, Hunt BJ, Benjamin S, Liesner R, Rose P, Peyvandi F, Cheung B, Machin SJ; British Committee for Standards in Haematology. Guidelines on the diagnosis and management of thrombotic thrombocytopenic purpura and other thrombotic microangiopathies. Br J Haematol. 2012 Aug;158(3):323-35.
47. Kathrin Eller, Paul Knoebel, Sevcan A. Bakkaloglu, Jan J. Menne, Paul T. Brinkkoetter, Leonie Grandt, Ursula Thiem, Paul Coppo, Marie Scully and Maria C. Haller. European renal best practice endorsement of guidelines for diagnosis and therapy of thrombotic thrombocytopenic purpura published by the International Society on thrombosis and Haemostasis. Nephrol Dial Transplant (2022) 37: 1229–1234
48. Balduini, C.L.; Gugliotta, L.; Luppi, M.; Laurenti, L.; Klersy, C.; Pieresca, C.; Quintini, G.; Iuliano, F.; Re, R.; Spedini, P.; et al. High versus standard dose methylprednisolone in the acute phase of idiopathic thrombotic thrombocytopenic purpura: A randomized study. Ann. Hematol. 2010, 89, 591–596
49. Callewaert F, Roodt J, Ulrichts H, Stohr T, van Rensburg WJ, Lamprecht S, 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; 120:3603–10.
50. Peyvandi F, Scully M, Kremer Hovinga JA, Cataland S, Knobl ¨ P, Wu H, et al. Caplacizumab for acquired thrombotic thrombocytopenic Purpura. N Engl J Med 2016; 374:511–22.
51. Scully M, Cataland SR, Peyvandi F, Coppo P, Knobl ¨ P, Kremer Hovinga JA, et al. Caplacizumab treatment for acquired thrombotic thrombocytopenic Purpura. N Engl J Med 2019; 380:335–46
52. Flora Peyvandi, Spero Cataland, Marie Scully, Paul Coppo, Paul Knoebl, Johanna A. Kremer Hovinga, Ara Metjian, Javier de la Rubia, Katerina Pavenski, Jessica Minkue Mi Edou, Hilde De Winter, Filip Callewaert; Caplacizumab prevents refractoriness and mortality in acquired thrombotic thrombocytopenic purpura: integrated analysis. Blood Adv 2021; 5 (8): 2137–2141.
53. Izquierdo CP, Mingot-Castellano ME, Fuentes AEK, García-Arroba Peinado J, Cid J, Jimenez MM, Valcarcel D, Gómez-Seguí I, de la Rubia J, Martin P, Goterris R, Hernández L, Tallón I, Varea S, Fernández M, García-Muñoz N, Vara M, Zarzoso MF, García-Candel F, Paciello ML, García-García I, Zalba S, Campuzano V, Gala JM, Estévez JV, Jiménez GM, López Lorenzo JL, Arias EG, Freiría C, Solé M, Ávila Idrovo LF, Hernández Castellet JC, Cruz N, Lavilla E, Pérez-Montaña A, Atucha JA, Moreno Beltrán ME, Moreno Macías JR, Salinas R, Del Rio-Garma J. Real-world effectiveness of caplacizumab vs the standard of care in immune thrombotic thrombocytopenic purpura. Blood Adv. 2022 Dec 27;6(24):6219-6227
54. Albanell-Fernández M, Monge-Escartín I, Carcelero-San Martín E, Riu Viladoms G, Ruiz-Boy S, Lozano M, Soy D, Moreno-Castaño AB, Diaz-Ricart M, Cid J. Real-world data of the use and experience of caplacizumab for the treatment of acquired thrombotic thrombocytopenic purpura: Case series. Transfus Apher Sci. 2023 Jun;62(3):103722.
55. Sarode R. Thrombotic thrombocytopenic purpura in caplacizumab era - An individualized approach. Transfus Apher Sci. 2023 Apr;62(2):103682.
56. Silvia Riva, Ilaria Mancini, Alberto Maino, Barbara Ferrari, Andrea Artoni, Pasquale Agosti and Flora Peyvandi. Long-term neuropsychological sequelae, emotional wellbeing and quality of life in patients with acquired thrombotic thrombocytopenic purpura. Heamatologica 2020 Jul;105(7):1957-1962.
57. Bowyer A, Brown P, Hopkins B, Scully M, Shepherd F, Lowe A, Mensah P, Maclean R, Kitchen S, van Veen JJ. Von Willebrand factor assays in patients with acquired immune thrombotic thrombocytopenia purpura treated with caplacizumab. Br J Haematol. 2022 May;197(3):349-358.
58. Mazepa MA, Masias C, Chaturvedi S. How targeted therapy disrupts the treatment paradigm for acquired TTP: the risks, benefits, and unknowns. Blood. 2019 Aug 1;134(5):415-420.
59. Völker LA, Kaufeld J, Miesbach W, Brähler S, Reinhardt M, Kühne L, Mühlfeld A, Schreiber A, Gaedeke J, Tölle M, Jabs WJ, Özcan F, Markau S, Girndt M, Bauer F, Westhoff TH, Felten H, Hausberg M, Brand M, Gerth J, Bieringer M, Bommer M, Zschiedrich S, Schneider J, Elitok S, Gawlik A, Gäckler A, Kribben A, Schwenger V, Schoenermarck U, Roeder M, Radermacher J, Bramstedt J, Morgner A, Herbst R, Harth A, Potthoff SA, von Auer C, Wendt R, Christ H, Brinkkoetter PT, Menne J. ADAMTS13 and VWF activities guide individualized caplacizumab treatment in patients with aTTP. Blood Adv. 2020 Jul 14;4(13):3093-3101.
60. Cuker A, Cataland SR, Coppo P, de la Rubia J, Friedman KD, George JN, Knoebl PN, Kremer Hovinga JA, Lämmle B, Matsumoto M, Pavenski K, Peyvandi F, Sakai K, Sarode R, Thomas MR, Tomiyama Y, Veyradier A, Westwood JP, Scully M. Redefining outcomes in immune TTP: an international working group consensus report. Blood. 2021 Apr 8;137(14):1855-1861.
61. Swisher KK, Terrell DR, Vesely SK, Kremer Hovinga JA, Lämmle B, George JN. Clinical outcomes after platelet transfusions in patients with thrombotic thrombocytopenic purpura. Transfusion. 2009 May;49(5):873-87.
62. 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 Jun;8(6):1201-8.
63. Kremer Hovinga JA, Coppo P, Lämmle B, Moake JL, Miyata T, Vanhoorelbeke K. Thrombotic thrombocytopenic purpura. Nat Rev Dis Primers. 2017 Apr 6;3:17020.
64. Scully M, McDonald V, Cavenagh J, Hunt BJ, Longair I, Cohen H, Machin SJ. A phase 2 study of the safety and efficacy of rituximab with plasma exchange in acute acquired thrombotic thrombocytopenic purpura. Blood. 2011 Aug 18;118(7):1746-53.
65. 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 Thromb Hemost 2019;25
66. Coppo P, Bubenheim M, Azoulay E, Galicier L, Malot S, Big´e N, et al. A regimen with caplacizumab, immunosuppression, and plasma exchange prevents unfavorable outcomes in immune-mediated TTP. Blood 2021;137:733–42.
67. Aksoy S, Harputluoglu H, Kilickap S, Dede DS, Dizdar O, Altundag K, Barista I. Rituximab-related viral infections in lymphoma patients. Leuk Lymphoma. 2007 Jul;48(7):1307-12.
68. Allison AC, Eugui EM. Mycophenolate mofetil and its mechanisms of action. Immunopharmacology. 2000 May;47(2-3):85-118.
69. Moake JL, Rudy CK, Troll JH, Schafer AI, Weinstein MJ, Colannino NM, Hong SL. Therapy of chronic relapsing thrombotic thrombocytopenic purpura with prednisone and azathioprine. Am J Hematol. 1985 Sep;20(1):73-9.
70. 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.
71. Cataland SR, Jin M, Lin S, Kraut EH, George JN, Wu HM. Effect of prophylactic cyclosporine therapy on ADAMTS13 biomarkers in patients with idiopathic thrombotic thrombocytopenic purpura. Am J Hematol. 2008 Dec;83(12):911-5
72. Zappasodi P, Corso A, Castagnola C, Tajana M, Lunghi M, Bernasconi C. A successful combination of plasma exchange and intravenous cyclophosphamide in a patient with a refractory thrombotic thrombocytopenic purpura. Eur J Haematol. 1999 Oct;63(4):278-9
73. Ahmadpoor P, Aglae C, Garo F, Cariou S, Renaud S, Reboul P, Moranne O. Humanized anti CD-20 as an alternative in chronic management of relapsing thrombotic thrombocytopenic microangiopathy resistant to rituximab due to anti chimeric antibody. Int J Hematol. 2021 Mar;113(3):456-460.
74. Doyle AJ, Stubbs MJ, Lester W, Thomas W, Westwood JP, Thomas M, Percy C, Prasannan N, Scully M. The use of obinutuzumab and ofatumumab in the treatment of immune thrombotic thrombocytopenic purpura. Br J Haematol. 2022 Jul;198(2):391-396.
75. Shortt J, Oh DH, Opat SS. ADAMTS13 antibody depletion by bortezomib in thrombotic thrombocytopenic purpura. N Engl J Med. 2013 Jan 3;368(1):90-2
76. Van den Berg J, Kremer Hovinga JA, Pfleger C, Hegemann I, Stehle G, Holbro A, Studt JD. Daratumumab for immune thrombotic thrombocytopenic purpura. Blood Adv. 2022 Feb 8;6(3):993-997.
77. Tse B, Lim G, Sholzberg M, Pavenski K. Describing the point prevalence and characteristics of venous thromboembolism in patients with thrombotic thrombocytopenic purpura. J Thromb Haemost. 2020 Nov;18(11):2870-2877.
78. Dutt T, Shaw RJ, Stubbs M, Yong J, Bailiff B, Cranfield T, Crowley MP, Desborough M, Eyre TA, Gooding R, Grainger J, Hanley J, Haughton J, Hermans J, Hill Q, Humphrey L, Lowe G, Lyall H, Mohsin M, Nicolson PLR, Priddee N, Rampotas A, Rayment R, Rhodes S, Taylor A, Thomas W, Tomkins O, Van Veen JJ, Lane S, Toh CH, Scully M. Real-world experience with caplacizumab in the management of acute TTP. Blood. 2021 Apr 1;137(13):1731-1740.
79. Tuğrul Elverdi, Melis Dila Özer Çerme, Tahacan Aydın & Ahmet Emre Eşkazan. Do patients with immune-mediated thrombotic thrombocytopenic purpura receiving caplacizumab need antithrombotic therapy?, Expert Review of Clinical Pharmacology, 14:10, 1183-1188
80. Selvakumar S, Liu A, Chaturvedi S. Immune thrombotic thrombocytopenic purpura: Spotlight on long-term outcomes and survivorship. Front Med (Lausanne). 2023 Feb 28; 10:1137019.
81. Peyvandi F, Lavoretano S, Palla R, Feys HB, Vanhoorelbeke K, Battaglioli T, Valsecchi C, Canciani MT, Fabris F, Zver S, Réti M, Mikovic D, Karimi M, Giuffrida G, Laurenti L, Mannucci PM. ADAMTS13 and anti-ADAMTS13 antibodies as markers for recurrence of acquired thrombotic thrombocytopenic purpura during remission. Haematologica. 2008 Feb;93(2):232-9.
82. Cuker A. Adjuvant rituximab to prevent TTP relapse. Blood. 2016 Jun 16;127(24):2952-3
83. Westwood JP, Thomas M, Alwan F, McDonald V, Benjamin S, Lester WA, Lowe GC, Dutt T, Hill QA, Scully M. Rituximab prophylaxis to prevent thrombotic thrombocytopenic purpura relapse: outcome and evaluation of dosing regimens. Blood Adv. 2017 Jun 26;1(15):1159-1166.
84. Zheng, X.L.; Vesely, S.K.; Cataland, S.R.; Coppo, P.; Geldziler, B.; Iorio, A.; Matsumoto, M.; Mustafa, R.A.; Pai, M.; Rock, G.; et al. Good practice statements (GPS) for the clinical care of patients with thrombotic thrombocytopenic purpura. J. Thromb. Haemost. 2020 Oct;18(10):2503-12
85. Page EE, Kremer Hovinga JA, Terrell DR, Vesely SK, George JN. Rituximab reduces risk for relapse in patients with thrombotic thrombocytopenic purpura. Blood. 2016 Jun 16;127(24):3092-4.
86. Jestin M, Benhamou Y, Schelpe AS, Roose E, Provôt F, Galicier L, Hié M, Presne C, Poullin P, Wynckel A, Saheb S, Deligny C, Servais A, Girault S, Delmas Y, Kanouni T, Lautrette A, Chauveau D, Mousson C, Perez P, Halimi JM, Charvet-Rumpler A, Hamidou M, Cathébras P, Vanhoorelbeke K, Veyradier A, Coppo P; French Thrombotic Microangiopathies Reference Center. Preemptive rituximab prevents long-term relapses in immune-mediated thrombotic thrombocytopenic purpura. Blood. 2018 Nov 15;132(20):2143-2153.
87. Upreti H, Kasmani J, Dane K, Braunstein EM, Streiff MB, Shanbhag S, Moliterno AR, Sperati CJ, Gottesman RF, Brodsky RA, Kickler TS, Chaturvedi S. Reduced ADAMTS13 activity during TTP remission is associated with stroke in TTP survivors. Blood. 2019 Sep 26;134(13):1037-1045.
88. Roose E, Schelpe AS, Tellier E, Sinkovits G, Joly BS, Dekimpe C, Kaplanski G, Le Besnerais M, Mancini I, Falter T, Von Auer C, Feys HB, Reti M, Rossmann H, Vandenbulcke A, Pareyn I, Voorberg J, Greinacher A, Benhamou Y, Deckmyn H, Fijnheer R, Prohászka Z, Peyvandi F, Lämmle B, Coppo P, De Meyer SF, Veyradier A, Vanhoorelbeke K. Open ADAMTS13, induced by antibodies, is a biomarker for subclinical immune-mediated thrombotic thrombocytopenic purpura. Blood. 2020 Jul 16;136(3):353-361
89. Scully M, Knöbl P, Kentouche K, Rice L, Windyga J, Schneppenheim R, Kremer Hovinga JA, Kajiwara M, Fujimura Y, Maggiore C, Doralt J, Hibbard C, Martell L, Ewenstein B. Recombinant ADAMTS-13: first-in-human pharmacokinetics and safety in congenital thrombotic thrombocytopenic purpura. Blood. 2017 Nov 9;130(19):2055-2063.
2. Scully, M.; Yarranton, H.; Liesner, R.; Cavenagh, J.; Hunt, B.; Benjamin, S.; Bevan, D.; Mackie, I.; Machin, S. Regional UK TTP registry: Correlation with laboratory ADAMTS 13 analysis and clinical features. Br. J. Haematol. 2008, 142, 819–826.
3. Mariotte, E.; Azoulay, E.; Galicier, L.; Rondeau, E.; Zouiti, F.; Boisseau, P.; Poullin, P.; de Maistre, E.; Provôt, F.; Delmas, Y.; et al. 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, e237–e245.
4. Amorosi EL, Ultmann JE. Thrombotic thrombocytopenic Purpura: report of 16 cases and review of the literature. Medicine 1966;45:139–60.
5. George JN, Nester CM. Syndromes of thrombotic microangiopathy. N Engl J Med. 2014 Aug 14;371(7):654-66.
6. 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.
7. South K, Luken BM, Crawley JTB, et al. Conformational activation of ADAMTS13. Proc Natl Acad Sci USA. 2014;111(52):18578–18583.
8. Muia J, Zhu J, Gupta G, et al. Allosteric activation of ADAMTS13 by von Willebrand factor. Proc Natl Acad Sci USA. 2014;111 (52):18584–18589.
9. Deforche L, Roose E, Vandenbulcke A, et al. Linker regions and flexibility around the metalloprotease domain account for conformational activation of ADAMTS-13. J Thromb Haemost JTH.2015;13(11):2063–2075.
10. Crawley JTB, de Groot R, Xiang Y, et al. Unraveling the scissile bond: how ADAMTS13 recognizes and cleaves von Willebrand factor. Blood. 2011;118(12):3212–3221
11. Sadler JE What’s new in the diagnosis and pathophysiology of thrombotic thrombocytopenic purpura. Hematol Educ Program Am Soc Hematol Am Soc Hematol Educ Program. 2015;2015:631–636
12. 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.
13. Réti, M.; Farkas, P.; Csuka, D.; Rázsó, K.; Schlammadinger, Á.; Udvardy, M.L.; Madách, K.; Domján, G.; Bereczki, C.; Reusz, G.S.; et al. Complement activation in thrombotic thrombocytopenic purpura. J. Thromb. Haemost. 2012, 791-8
14. Turner, N.; Sartain, S.; Moake, J. Ultralarge von Willebrand factor-induced platelet clumping and activation of the alternative complement pathway in thrombotic thrombocytopenic purpura and the hemolytic-uremic syndromes. Hematol. Oncol. Clin. N.Am. 2015, 29, 509–524
15. Miyata, T.; Fan, X. A second hit for TMA. Blood 2012, 120, 1152–1154
16. Scheiflinger, F.; Knöbl, P.; Trattner, B.; Plaimauer, B.; Mohr, G.; Dockal, M.; Dorner, F.; Rieger, M. Nonneutralizing IgM and IgG antibodies to von Willebrand factor-cleaving protease (ADAMTS-13) in a patient with thrombotic thrombocytopenic purpura. Blood 2003, 102, 3241–3243.
17. Rieger, M.; Mannucci, P.M.; Kremer Hovinga, J.A.; Herzog, A.; Gerstenbauer, G.; Konetschny, C.; Zimmermann, K.; Scharrer,I.; Peyvandi, F.; Galbusera, M.; et al. ADAMTS13 autoantibodies in patients with thrombotic microangiopathies and other immunomediated diseases. Blood 2005, 106, 1262–1267
18. Thomas, M.R.; de Groot, R.; Scully, M.A.; Crawley, J.T. Pathogenicity of Anti-ADAMTS13 Autoantibodies in Acquired Thrombotic Thrombocytopenic Purpura. EBioMedicine 2015, 2, 942–952
19. Zheng, X.L.; Wu, H.M.; Shang, D.; Falls, E.; Skipwith, C.G.; Cataland, S.R.; Bennett, C.L.; Kwaan, H.C. Multiple domains of ADAMTS13 are targeted by autoantibodies against ADAMTS13 in patients with acquired idiopathic thrombotic thrombocytopenic purpura. Haematologica 2010, 95, 1555–1562.
20. Yamaguchi, Y.; Moriki, T.; Igari, A.; Nakagawa, T.; Wada, H.; Matsumoto, M.; Fujimura, Y.; Murata, M. Epitope analysis ofautoantibodies to ADAMTS13 in patients with acquired thrombotic thrombocytopenic purpura. Thromb. Res. 2011, 128, 169–173.
21. Verbij FC, Fijnheer R, Voorberg J, et al. Acquired TTP: ADAMTS13 meets the immune system. Blood Rev. 2014;28(6):227–234
22. Ferrari, S.; Scheiflinger, F.; Rieger, M.; Mudde, G.; Wolf, M.; Coppo, P.; Girma, J.P.; Azoulay, E.; Brun-Buisson, C.; Fakhouri, F.; 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.
23. Ferrari, S.; Mudde, G.C.; Rieger, M.; Veyradier, A.; Kremer Hovinga, J.A.; Scheiflinger, F. IgG subclass distribution of antiADAMTS13 antibodies in patients with acquired thrombotic thrombocytopenic purpura. J. Thromb. Haemost. 2009, 7, 1703–1710.
24. Bettoni, G.; Palla, R.; Valsecchi, C.; Consonni, D.; Lotta, L.A.; Trisolini, S.M.; Mancini, I.; Musallam, K.M.; Rosendaal, F.R.; Peyvandi, F. ADAMTS-13 activity and autoantibodies classes and subclasses as prognostic predictors in acquired thrombotic thrombocytopenic purpura. J. Thromb. Haemost. 2012, 10, 1556–1565.
25. Kosugi, N.; Tsurutani, Y.; Isonishi, A.; Hori, Y.; Matsumoto, M.; Fujimura, Y. Influenza A infection triggers thrombotic thrombocytopenic purpura by producing the anti-ADAMTS13 IgG inhibitor. Intern. Med. 2010, 49, 689–693.
26. Franchini, M. Thrombotic thrombocytopenic purpura: Proposal of a new pathogenic mechanism involving Helicobacter pylori infection. Med. Hypotheses 2005, 65, 1128–1131.
27. Talebi, T.; Fernandez-Castro, G.; Montero, A.J.; Stefanovic, A.; Lian, E. A case of severe thrombotic thrombocytopenic purpura with concomitant Legionella pneumonia: Review of pathogenesis and treatment. Am. J. Ther. 2011, 18, e180–e185.
28. Yagita, M.; Uemura, M.; Nakamura, T.; Kunitomi, A.; Matsumoto, M.; Fujimura, Y. Development of ADAMTS13 inhibitor in apatient with hepatitis C virus-related liver cirrhosis causes thrombotic thrombocytopenic purpura. J. Hepatol. 2005, 42, 420–421.
29. Gunther, K.; Garizio, D.; Nesara, P. ADAMTS13 activity and the presence of acquired inhibitors in human immunodeficiency virus-related thrombotic thrombocytopenic purpura. Transfusion 2007, 47, 1710–1716.
30. Lotta, L.A.; Valsecchi, C.; Pontiggia, S.; Mancini, I.; Cannavò, A.; Artoni, A.; Mikovic, D.; Meloni, G.; Peyvandi, F. Measurement and prevalence of circulating ADAMTS13-specific immune complexes in autoimmune thrombotic thrombocytopenic purpura. J. Thromb. Haemost. 2014, 12, 329–336.
31. Ferrari, S.; Palavra, K.; Gruber, B.; Kremer Hovinga, J.A.; Knöbl, P.; Caron, C.; Cromwell, C.; Aledort, L.; Plaimauer, B.;Turecek, P.L.; et al. Persistence of circulating ADAMTS13-specific immune complexes in patients with acquired thrombotic thrombocytopenic purpura. Haematologica 2014, 99, 779–787.
32. Mancini, I.; Ferrari, B.; Valsecchi, C.; Pontiggia, S.; Fornili, M.; Biganzoli, E.; Peyvandi, F.; Investigators, I.G.o.T. ADAMTS13- specific circulating immune complexes as potential predictors of relapse in patients with acquired thrombotic thrombocytopenic purpura. Eur. J. Intern. Med. 2017, 39, 79–83
33. Westwood, J.P.; Langley, K.; Heelas, E.; Machin, S.J.; Scully, M. Complement and cytokine response in acute Thrombotic Thrombocytopenic Purpura. Br. J. Haematol. 2014, 164, 858–866
34. Jang, M.J.; Chong, S.Y.; Kim, I.H.; Kim, J.H.; Jung, C.W.; Kim, J.Y.; Park, J.C.; Lee, S.M.; Kim, Y.K.; Lee, J.E.; et al. Clinical features of severe acquired ADAMTS13 deficiency in thrombotic thrombocytopenic purpura: The Korean TTP registry experience. Int. J.Hematol. 2011, 93, 163–169.
35. Benhamou, Y.; Boelle, P.Y.; Baudin, B.; Ederhy, S.; Gras, J.; Galicier, L.; Azoulay, E.; Provôt, F.; Maury, E.; Pène, F.; et al. Cardiac troponin-I on diagnosis predicts early death and refractoriness in acquired thrombotic thrombocytopenic purpura. Experience of the French Thrombotic Microangiopathies Reference Center. J. Thromb. Haemost. 2015, 13, 293–302
36. Vesely, S.K.; George, J.N.; Lämmle, B.; Studt, J.D.; Alberio, L.; El-Harake, M.A.; Raskob, G.E. 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, 60–68.
37. Bell WR, Braine HG, Ness PM, Kickler TS. Improved survival in thrombotic thrombocytopenic purpura-hemolytic uremic syndrome. Clinical experience in 108 patients. N Engl J Med 1991;325:398–403.
38. Mackie I, Mancini I, Muia J, Kremer Hovinga J, Nair S, Machin S, Baker R. International Council for Standardization in Haematology (ICSH) recommendations for laboratory measurement of ADAMTS13. Int J Lab Hematol. 2020 Dec;42(6):685-696.
39. Coppo P, Schwarzinger M, Buffet M, Wynckel A, Clabault K, Presne C, et al. Predictive features of severe acquired ADAMTS13 deficiency in idiopathic thrombotic microangiopathies: the French TMA reference center experience. PLoS One 2010;5:e10208
40. Bendapudi P.K., Hurwitz S., Fry A., Marques M.B., Waldo S.W., Li A. Derivation and external validation of the PLASMIC score for rapid assessment of adults with thrombotic microangiopathies: a cohort study. Lancet Haematol. 2017;4:157–164.
41. Li A, Khalighi PR, Wu Q, Garcia DA. External validation of the PLASMIC score: a clinical prediction tool for thrombotic thrombocytopenic purpura diagnosis and treatment. J Thromb Haemost 2018;16:164–9
42. Paydary K, Banwell E, Tong J, Chen Y, Cuker A. Diagnostic accuracy of the PLASMIC score in patients with suspected thrombotic thrombocytopenic purpura: A systematic review and meta-analysis. Transfusion. 2020 Sep;60(9):2047-2057.
43. Zheng XL, Vesely SK, Cataland SR, Coppo P, Geldziler B, Iorio A, Matsumoto M, Mustafa RA, Pai M, Rock G, Russell L, Tarawneh R, Valdes J, Peyvandi F. ISTH guidelines for treatment of thrombotic thrombocytopenic purpura. J Thromb Haemost. 2020 Oct;18(10):2496-2502. doi: 10.1111/jth.15010. Epub 2020 Sep 11.
44. Rock, G.A.; Shumak, K.H.; Buskard, N.A.; Blanchette, V.S.; Kelton, J.G.; Nair, R.C.; Spasoff, R.A. Comparison of plasma exchange with plasma infusion in the treatment of thrombotic thrombocytopenic purpura. Canadian Apheresis Study Group. N. Engl. J.Med. 1991, 325, 393–397
45. Coppo P, Bussel A, Charrier S, Adrie C, Galicier L, Boulanger E, et al. High-dose plasma infusion versus plasma exchange as early treatment of thrombotic thrombocytopenic purpura/hemolytic-uremic syndrome. Medicine (Baltimore) 2003;82:27–38
46. Scully M, Hunt BJ, Benjamin S, Liesner R, Rose P, Peyvandi F, Cheung B, Machin SJ; British Committee for Standards in Haematology. Guidelines on the diagnosis and management of thrombotic thrombocytopenic purpura and other thrombotic microangiopathies. Br J Haematol. 2012 Aug;158(3):323-35.
47. Kathrin Eller, Paul Knoebel, Sevcan A. Bakkaloglu, Jan J. Menne, Paul T. Brinkkoetter, Leonie Grandt, Ursula Thiem, Paul Coppo, Marie Scully and Maria C. Haller. European renal best practice endorsement of guidelines for diagnosis and therapy of thrombotic thrombocytopenic purpura published by the International Society on thrombosis and Haemostasis. Nephrol Dial Transplant (2022) 37: 1229–1234
48. Balduini, C.L.; Gugliotta, L.; Luppi, M.; Laurenti, L.; Klersy, C.; Pieresca, C.; Quintini, G.; Iuliano, F.; Re, R.; Spedini, P.; et al. High versus standard dose methylprednisolone in the acute phase of idiopathic thrombotic thrombocytopenic purpura: A randomized study. Ann. Hematol. 2010, 89, 591–596
49. Callewaert F, Roodt J, Ulrichts H, Stohr T, van Rensburg WJ, Lamprecht S, 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; 120:3603–10.
50. Peyvandi F, Scully M, Kremer Hovinga JA, Cataland S, Knobl ¨ P, Wu H, et al. Caplacizumab for acquired thrombotic thrombocytopenic Purpura. N Engl J Med 2016; 374:511–22.
51. Scully M, Cataland SR, Peyvandi F, Coppo P, Knobl ¨ P, Kremer Hovinga JA, et al. Caplacizumab treatment for acquired thrombotic thrombocytopenic Purpura. N Engl J Med 2019; 380:335–46
52. Flora Peyvandi, Spero Cataland, Marie Scully, Paul Coppo, Paul Knoebl, Johanna A. Kremer Hovinga, Ara Metjian, Javier de la Rubia, Katerina Pavenski, Jessica Minkue Mi Edou, Hilde De Winter, Filip Callewaert; Caplacizumab prevents refractoriness and mortality in acquired thrombotic thrombocytopenic purpura: integrated analysis. Blood Adv 2021; 5 (8): 2137–2141.
53. Izquierdo CP, Mingot-Castellano ME, Fuentes AEK, García-Arroba Peinado J, Cid J, Jimenez MM, Valcarcel D, Gómez-Seguí I, de la Rubia J, Martin P, Goterris R, Hernández L, Tallón I, Varea S, Fernández M, García-Muñoz N, Vara M, Zarzoso MF, García-Candel F, Paciello ML, García-García I, Zalba S, Campuzano V, Gala JM, Estévez JV, Jiménez GM, López Lorenzo JL, Arias EG, Freiría C, Solé M, Ávila Idrovo LF, Hernández Castellet JC, Cruz N, Lavilla E, Pérez-Montaña A, Atucha JA, Moreno Beltrán ME, Moreno Macías JR, Salinas R, Del Rio-Garma J. Real-world effectiveness of caplacizumab vs the standard of care in immune thrombotic thrombocytopenic purpura. Blood Adv. 2022 Dec 27;6(24):6219-6227
54. Albanell-Fernández M, Monge-Escartín I, Carcelero-San Martín E, Riu Viladoms G, Ruiz-Boy S, Lozano M, Soy D, Moreno-Castaño AB, Diaz-Ricart M, Cid J. Real-world data of the use and experience of caplacizumab for the treatment of acquired thrombotic thrombocytopenic purpura: Case series. Transfus Apher Sci. 2023 Jun;62(3):103722.
55. Sarode R. Thrombotic thrombocytopenic purpura in caplacizumab era - An individualized approach. Transfus Apher Sci. 2023 Apr;62(2):103682.
56. Silvia Riva, Ilaria Mancini, Alberto Maino, Barbara Ferrari, Andrea Artoni, Pasquale Agosti and Flora Peyvandi. Long-term neuropsychological sequelae, emotional wellbeing and quality of life in patients with acquired thrombotic thrombocytopenic purpura. Heamatologica 2020 Jul;105(7):1957-1962.
57. Bowyer A, Brown P, Hopkins B, Scully M, Shepherd F, Lowe A, Mensah P, Maclean R, Kitchen S, van Veen JJ. Von Willebrand factor assays in patients with acquired immune thrombotic thrombocytopenia purpura treated with caplacizumab. Br J Haematol. 2022 May;197(3):349-358.
58. Mazepa MA, Masias C, Chaturvedi S. How targeted therapy disrupts the treatment paradigm for acquired TTP: the risks, benefits, and unknowns. Blood. 2019 Aug 1;134(5):415-420.
59. Völker LA, Kaufeld J, Miesbach W, Brähler S, Reinhardt M, Kühne L, Mühlfeld A, Schreiber A, Gaedeke J, Tölle M, Jabs WJ, Özcan F, Markau S, Girndt M, Bauer F, Westhoff TH, Felten H, Hausberg M, Brand M, Gerth J, Bieringer M, Bommer M, Zschiedrich S, Schneider J, Elitok S, Gawlik A, Gäckler A, Kribben A, Schwenger V, Schoenermarck U, Roeder M, Radermacher J, Bramstedt J, Morgner A, Herbst R, Harth A, Potthoff SA, von Auer C, Wendt R, Christ H, Brinkkoetter PT, Menne J. ADAMTS13 and VWF activities guide individualized caplacizumab treatment in patients with aTTP. Blood Adv. 2020 Jul 14;4(13):3093-3101.
60. Cuker A, Cataland SR, Coppo P, de la Rubia J, Friedman KD, George JN, Knoebl PN, Kremer Hovinga JA, Lämmle B, Matsumoto M, Pavenski K, Peyvandi F, Sakai K, Sarode R, Thomas MR, Tomiyama Y, Veyradier A, Westwood JP, Scully M. Redefining outcomes in immune TTP: an international working group consensus report. Blood. 2021 Apr 8;137(14):1855-1861.
61. Swisher KK, Terrell DR, Vesely SK, Kremer Hovinga JA, Lämmle B, George JN. Clinical outcomes after platelet transfusions in patients with thrombotic thrombocytopenic purpura. Transfusion. 2009 May;49(5):873-87.
62. 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 Jun;8(6):1201-8.
63. Kremer Hovinga JA, Coppo P, Lämmle B, Moake JL, Miyata T, Vanhoorelbeke K. Thrombotic thrombocytopenic purpura. Nat Rev Dis Primers. 2017 Apr 6;3:17020.
64. Scully M, McDonald V, Cavenagh J, Hunt BJ, Longair I, Cohen H, Machin SJ. A phase 2 study of the safety and efficacy of rituximab with plasma exchange in acute acquired thrombotic thrombocytopenic purpura. Blood. 2011 Aug 18;118(7):1746-53.
65. 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 Thromb Hemost 2019;25
66. Coppo P, Bubenheim M, Azoulay E, Galicier L, Malot S, Big´e N, et al. A regimen with caplacizumab, immunosuppression, and plasma exchange prevents unfavorable outcomes in immune-mediated TTP. Blood 2021;137:733–42.
67. Aksoy S, Harputluoglu H, Kilickap S, Dede DS, Dizdar O, Altundag K, Barista I. Rituximab-related viral infections in lymphoma patients. Leuk Lymphoma. 2007 Jul;48(7):1307-12.
68. Allison AC, Eugui EM. Mycophenolate mofetil and its mechanisms of action. Immunopharmacology. 2000 May;47(2-3):85-118.
69. Moake JL, Rudy CK, Troll JH, Schafer AI, Weinstein MJ, Colannino NM, Hong SL. Therapy of chronic relapsing thrombotic thrombocytopenic purpura with prednisone and azathioprine. Am J Hematol. 1985 Sep;20(1):73-9.
70. 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.
71. Cataland SR, Jin M, Lin S, Kraut EH, George JN, Wu HM. Effect of prophylactic cyclosporine therapy on ADAMTS13 biomarkers in patients with idiopathic thrombotic thrombocytopenic purpura. Am J Hematol. 2008 Dec;83(12):911-5
72. Zappasodi P, Corso A, Castagnola C, Tajana M, Lunghi M, Bernasconi C. A successful combination of plasma exchange and intravenous cyclophosphamide in a patient with a refractory thrombotic thrombocytopenic purpura. Eur J Haematol. 1999 Oct;63(4):278-9
73. Ahmadpoor P, Aglae C, Garo F, Cariou S, Renaud S, Reboul P, Moranne O. Humanized anti CD-20 as an alternative in chronic management of relapsing thrombotic thrombocytopenic microangiopathy resistant to rituximab due to anti chimeric antibody. Int J Hematol. 2021 Mar;113(3):456-460.
74. Doyle AJ, Stubbs MJ, Lester W, Thomas W, Westwood JP, Thomas M, Percy C, Prasannan N, Scully M. The use of obinutuzumab and ofatumumab in the treatment of immune thrombotic thrombocytopenic purpura. Br J Haematol. 2022 Jul;198(2):391-396.
75. Shortt J, Oh DH, Opat SS. ADAMTS13 antibody depletion by bortezomib in thrombotic thrombocytopenic purpura. N Engl J Med. 2013 Jan 3;368(1):90-2
76. Van den Berg J, Kremer Hovinga JA, Pfleger C, Hegemann I, Stehle G, Holbro A, Studt JD. Daratumumab for immune thrombotic thrombocytopenic purpura. Blood Adv. 2022 Feb 8;6(3):993-997.
77. Tse B, Lim G, Sholzberg M, Pavenski K. Describing the point prevalence and characteristics of venous thromboembolism in patients with thrombotic thrombocytopenic purpura. J Thromb Haemost. 2020 Nov;18(11):2870-2877.
78. Dutt T, Shaw RJ, Stubbs M, Yong J, Bailiff B, Cranfield T, Crowley MP, Desborough M, Eyre TA, Gooding R, Grainger J, Hanley J, Haughton J, Hermans J, Hill Q, Humphrey L, Lowe G, Lyall H, Mohsin M, Nicolson PLR, Priddee N, Rampotas A, Rayment R, Rhodes S, Taylor A, Thomas W, Tomkins O, Van Veen JJ, Lane S, Toh CH, Scully M. Real-world experience with caplacizumab in the management of acute TTP. Blood. 2021 Apr 1;137(13):1731-1740.
79. Tuğrul Elverdi, Melis Dila Özer Çerme, Tahacan Aydın & Ahmet Emre Eşkazan. Do patients with immune-mediated thrombotic thrombocytopenic purpura receiving caplacizumab need antithrombotic therapy?, Expert Review of Clinical Pharmacology, 14:10, 1183-1188
80. Selvakumar S, Liu A, Chaturvedi S. Immune thrombotic thrombocytopenic purpura: Spotlight on long-term outcomes and survivorship. Front Med (Lausanne). 2023 Feb 28; 10:1137019.
81. Peyvandi F, Lavoretano S, Palla R, Feys HB, Vanhoorelbeke K, Battaglioli T, Valsecchi C, Canciani MT, Fabris F, Zver S, Réti M, Mikovic D, Karimi M, Giuffrida G, Laurenti L, Mannucci PM. ADAMTS13 and anti-ADAMTS13 antibodies as markers for recurrence of acquired thrombotic thrombocytopenic purpura during remission. Haematologica. 2008 Feb;93(2):232-9.
82. Cuker A. Adjuvant rituximab to prevent TTP relapse. Blood. 2016 Jun 16;127(24):2952-3
83. Westwood JP, Thomas M, Alwan F, McDonald V, Benjamin S, Lester WA, Lowe GC, Dutt T, Hill QA, Scully M. Rituximab prophylaxis to prevent thrombotic thrombocytopenic purpura relapse: outcome and evaluation of dosing regimens. Blood Adv. 2017 Jun 26;1(15):1159-1166.
84. Zheng, X.L.; Vesely, S.K.; Cataland, S.R.; Coppo, P.; Geldziler, B.; Iorio, A.; Matsumoto, M.; Mustafa, R.A.; Pai, M.; Rock, G.; et al. Good practice statements (GPS) for the clinical care of patients with thrombotic thrombocytopenic purpura. J. Thromb. Haemost. 2020 Oct;18(10):2503-12
85. Page EE, Kremer Hovinga JA, Terrell DR, Vesely SK, George JN. Rituximab reduces risk for relapse in patients with thrombotic thrombocytopenic purpura. Blood. 2016 Jun 16;127(24):3092-4.
86. Jestin M, Benhamou Y, Schelpe AS, Roose E, Provôt F, Galicier L, Hié M, Presne C, Poullin P, Wynckel A, Saheb S, Deligny C, Servais A, Girault S, Delmas Y, Kanouni T, Lautrette A, Chauveau D, Mousson C, Perez P, Halimi JM, Charvet-Rumpler A, Hamidou M, Cathébras P, Vanhoorelbeke K, Veyradier A, Coppo P; French Thrombotic Microangiopathies Reference Center. Preemptive rituximab prevents long-term relapses in immune-mediated thrombotic thrombocytopenic purpura. Blood. 2018 Nov 15;132(20):2143-2153.
87. Upreti H, Kasmani J, Dane K, Braunstein EM, Streiff MB, Shanbhag S, Moliterno AR, Sperati CJ, Gottesman RF, Brodsky RA, Kickler TS, Chaturvedi S. Reduced ADAMTS13 activity during TTP remission is associated with stroke in TTP survivors. Blood. 2019 Sep 26;134(13):1037-1045.
88. Roose E, Schelpe AS, Tellier E, Sinkovits G, Joly BS, Dekimpe C, Kaplanski G, Le Besnerais M, Mancini I, Falter T, Von Auer C, Feys HB, Reti M, Rossmann H, Vandenbulcke A, Pareyn I, Voorberg J, Greinacher A, Benhamou Y, Deckmyn H, Fijnheer R, Prohászka Z, Peyvandi F, Lämmle B, Coppo P, De Meyer SF, Veyradier A, Vanhoorelbeke K. Open ADAMTS13, induced by antibodies, is a biomarker for subclinical immune-mediated thrombotic thrombocytopenic purpura. Blood. 2020 Jul 16;136(3):353-361
89. Scully M, Knöbl P, Kentouche K, Rice L, Windyga J, Schneppenheim R, Kremer Hovinga JA, Kajiwara M, Fujimura Y, Maggiore C, Doralt J, Hibbard C, Martell L, Ewenstein B. Recombinant ADAMTS-13: first-in-human pharmacokinetics and safety in congenital thrombotic thrombocytopenic purpura. Blood. 2017 Nov 9;130(19):2055-2063.
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Trisolini, S. M., Laganà, A. and Capria, S. (2024) “IMMUNE THROMBOTIC THROMBOCYTOPENIC PURPURA: PATHOPHYSIOLOGY, DIAGNOSIS AND OPEN ISSUES”, Mediterranean Journal of Hematology and Infectious Diseases, 16(1), p. e2024060. doi: 10.4084/MJHID.2024.060.
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Review Articles
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