Unresponsive Thrombotic Thrombocytopenic Purpura (TTP): Challenges and Solutions

References

• Crawley JTB, Scully MA. Thrombotic thrombocytopenic purpura: basic pathophysiology and therapeutic strategies. Hematology Am Soc Hematol Educ Program. 2013;2013:292–299. doi:10.1182/asheducation-2013.1.292
   PubMed Web of Science ®Google Scholar
• Sadler JE. Pathophysiology of thrombotic thrombocytopenic purpura. Blood. 2017;130(10):1181–1188. doi:10.1182/blood-2017-04-636431
   PubMed Web of Science ®Google Scholar
• 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. doi:10.1056/NEJM199811263392202
   PubMed Web of Science ®Google Scholar
• Calabrò P, Gragnano F, Golia E, Grove EL. von Willebrand factor and venous thromboembolism: pathogenic link and therapeutic implications. Semin Thromb Hemost. 2018;44(3):249–260. doi:10.1055/s-0037-1605564
   PubMed Web of Science ®Google Scholar
• Gragnano F, Golia E, Natale F, et al. Von Willebrand factor and cardiovascular disease: from a biochemical marker to an attractive therapeutic target. Curr Vasc Pharmacol. 2017;15(5):404–415. doi:10.2174/1570161115666170201114835
   PubMed Web of Science ®Google Scholar
• Gragnano F, Sperlongano S, Golia E, et al. The role of von Willebrand factor in vascular inflammation: from pathogenesis to targeted therapy. Mediators Inflamm. 2017;2017:5620314. doi:10.1155/2017/5620314
   PubMed Web of Science ®Google Scholar
• Levi M, Scully M, Singer M. The role of ADAMTS-13 in the coagulopathy of sepsis. J Thromb Haemost. 2018;16(4):646–651. doi:10.1111/jth.13953
   PubMed Web of Science ®Google Scholar
• Kremer Hovinga JA, George JN, Longo DL. Hereditary thrombotic thrombocytopenic purpura. N Engl J Med. 2019;381(17):1653–1662. doi:10.1056/NEJMra1813013
   PubMed Web of Science ®Google Scholar
• Tsai HM, Lian EC. Antibodies to von Willebrand factor-cleaving protease in acute thrombotic thrombocytopenic purpura. N Engl J Med. 1998;339(22):1585–1594. doi:10.1056/NEJM199811263392203
   PubMed Web of Science ®Google Scholar
• Mariotte E, Azoulay E, Galicier L, 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(5):e237–245. doi:10.1016/S2352-3026(16)30018-7
   PubMed Web of Science ®Google Scholar
• 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(5):819–826. doi:10.1111/j.1365-2141.2008.07276.x
   PubMed Web of Science ®Google Scholar
• Miesbach W, Menne J, Bommer M, et al. Incidence of acquired thrombotic thrombocytopenic purpura in Germany: a hospital level study. Orphanet J Rare Dis. 2019;14(1):260. doi:10.1186/s13023-019-1240-0
   PubMed Web of Science ®Google Scholar
• Dane K, Chaturvedi S. Beyond plasma exchange: novel therapies for thrombotic thrombocytopenic purpura. Hematology Am Soc Hematol Educ Program. 2018;2018(1):539–547. doi:10.1182/asheducation-2018.1.539
   PubMed Web of Science ®Google Scholar
• Zheng XL, Vesely SK, Cataland SR, et al. ISTH guidelines for the diagnosis of thrombotic thrombocytopenic purpura. J Thromb Haemost. 2020;18(10):2486–2495. doi:10.1111/jth.15006
   PubMed Web of Science ®Google Scholar
• Coppo P, Bubenheim M, Azoulay E, et al. A regimen with caplacizumab, immunosuppression, and plasma exchange prevents unfavorable outcomes in immune-mediated TTP. Blood. 2021;137(6):733–742. doi:10.1182/blood.2020008021
   PubMedGoogle Scholar
• Mariotte E, Blet A, Galicier L, et al. Unresponsive thrombotic thrombocytopenic purpura in critically ill adults. Intensive Care Med. 2013;39(7):1272–1281. doi:10.1007/s00134-013-2873-4
   PubMed Web of Science ®Google Scholar
• Allford SL, Hunt BJ, Rose P, Machin SJ; Haemostasis and Thrombosis Task Force, British Committee for Standards in Haematology. Guidelines on the diagnosis and management of the thrombotic microangiopathic haemolytic anaemias. Br J Haematol. 2003;120(4):556–573. doi:10.1046/j.1365-2141.2003.04049.x
   PubMed Web of Science ®Google Scholar
• Scully M, Cataland S, Coppo P, et al. Consensus on the standardization of terminology in thrombotic thrombocytopenic purpura and related thrombotic microangiopathies. J Thromb Haemost. 2017;15(2):312–322. doi:10.1111/jth.13571
   PubMed Web of Science ®Google Scholar
• Cuker A, Cataland SR, Coppo P, et al. Redefining outcomes in immune TTP: an International Working Group Consensus Report. Blood. 2021;137:1855–1861. doi:10.1182/blood.2020009150
   PubMed Web of Science ®Google Scholar
• George JN. The remarkable diversity of thrombotic thrombocytopenic purpura: a perspective. Blood Adv. 2018;2(12):1510–1516. doi:10.1182/bloodadvances.2018018432
   PubMed Web of Science ®Google Scholar
• Bayer G, von Tokarski F, Thoreau B, et al. Etiology and outcomes of thrombotic microangiopathies. Clin J Am Soc Nephrol. 2019;14(4):557–566. doi:10.2215/CJN.11470918
   PubMed Web of Science ®Google Scholar
• Zheng XL, Vesely SK, Cataland SR, et al. Good practice statements (GPS) for the clinical care of patients with thrombotic thrombocytopenic purpura. J Thromb Haemost. 2020;18(10):2503–2512. doi:10.1111/jth.15009
   PubMed Web of Science ®Google Scholar
• Azoulay E, Bauer PR, Mariotte E, et al. Expert statement on the ICU management of patients with thrombotic thrombocytopenic purpura. Intensive Care Med. 2019;45(11):1518–1539. doi:10.1007/s00134-019-05736-5
   PubMed Web of Science ®Google Scholar
• Padmanabhan A, Connelly-Smith L, Aqui N, et al. Guidelines on the use of therapeutic apheresis in clinical practice - evidence-based approach from the writing committee of the American Society for Apheresis: the eighth special issue. J Clin Apher. 2019;34(3):171–354. doi:10.1002/jca.21705
   PubMed Web of Science ®Google Scholar
• Piedrafita A, Ribes D, Cointault O, Chauveau D, Faguer S, Huart A. Plasma exchange and thrombotic microangiopathies: from pathophysiology to clinical practice. Transfus Apher Sci. 2020;59(6):102990. doi:10.1016/j.transci.2020.102990
   PubMed Web of Science ®Google Scholar
• Rock GA, Shumak KH, Buskard NA, et al. Comparison of plasma exchange with plasma infusion in the treatment of thrombotic thrombocytopenic purpura. Canadian Apheresis Study Group. N Engl J Med. 1991;325(6):393–397. doi:10.1056/NEJM199108083250604
   PubMed Web of Science ®Google Scholar
• Neyrinck MM, Vrielink H; Joint Task Force for Education and Certification. Calculations in apheresis. J Clin Apher. 2015;30(1):38–42. doi:10.1002/jca.21347
   PubMed Web of Science ®Google Scholar
• Zheng XL, Vesely SK, Cataland SR, et al. ISTH guidelines for treatment of thrombotic thrombocytopenic purpura. J Thromb Haemost. 2020;18(10):2496–2502. doi:10.1111/jth.15010
   PubMed Web of Science ®Google Scholar
• 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(6):398–403. doi:10.1056/NEJM199108083250605
   PubMed Web of Science ®Google Scholar
• 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(9):659–665. doi:10.1016/j.ejim.2015.07.021
   PubMed Web of Science ®Google Scholar
• Scully M. Rituximab in the treatment of TTP. Hematology. 2012;17(Suppl 1):S22–24. doi:10.1179/102453312X13336169155178
   PubMed Web of Science ®Google Scholar
• Salles G, Barrett M, Foà R, et al. Rituximab in B-cell hematologic malignancies: a review of 20 years of clinical experience. Adv Ther. 2017;34(10):2232–2273. doi:10.1007/s12325-017-0612-x
   PubMed Web of Science ®Google Scholar
• Taylor RP, Lindorfer MA. Drug insight: the mechanism of action of rituximab in autoimmune disease–the immune complex decoy hypothesis. Nat Clin Pract Rheumatol. 2007;3(2):86–95. doi:10.1038/ncprheum0424
   PubMedGoogle Scholar
• Hua Q, Zhu Y, Liu H. Severe and fatal adverse events risk associated with rituximab addition to B-cell non-Hodgkin’s lymphoma (B-NHL) chemotherapy: a meta-analysis. J Chemother. 2015;27(6):365–370. doi:10.1179/1973947815Y.0000000025
   PubMed Web of Science ®Google Scholar
• 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. doi:10.1182/blood-2014-10-559211
   PubMed Web of Science ®Google Scholar
• George JN. Corticosteroids and rituximab as adjunctive treatments for thrombotic thrombocytopenic purpura. Am J Hematol. 2012;87(Suppl 1):S88–91. doi:10.1002/ajh.23126
   PubMed Web of Science ®Google Scholar
• Froissart A, Buffet M, Veyradier A, et al. Efficacy and safety of first-line rituximab in severe, acquired thrombotic thrombocytopenic purpura with a suboptimal response to plasma exchange. Experience of the French Thrombotic Microangiopathies Reference Center. Crit Care Med. 2012;40(1):104–111. doi:10.1097/CCM.0b013e31822e9d66
   PubMed Web of Science ®Google Scholar
• Puisset F, White-Koning M, Kamar N, et al. Population pharmacokinetics of rituximab with or without plasmapheresis in kidney patients with antibody-mediated disease. Br J Clin Pharmacol. 2013;76(5):734–740. doi:10.1111/bcp.12098
   PubMed Web of Science ®Google Scholar
• Tun NM, Villani GM. Efficacy of rituximab in acute refractory or chronic relapsing non-familial idiopathic thrombotic thrombocytopenic purpura: a systematic review with pooled data analysis. J Thromb Thrombolysis. 2012;34(3):347–359. doi:10.1007/s11239-012-0723-9
   PubMed Web of Science ®Google Scholar
• 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(7):1746–1753. doi:10.1182/blood-2011-03-341131
   PubMed Web of Science ®Google Scholar
• Westwood J-P, 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(3):481–490. doi:10.1111/jth.12114
   PubMed Web of Science ®Google Scholar
• Benhamou Y, Paintaud G, Azoulay E, et al. 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. doi:10.1002/ajh.24559
   PubMed Web of Science ®Google Scholar
• Reddy MS, Hofmann S, Shen YM, et al. Comparison of low fixed dose versus standard-dose rituximab to treat thrombotic thrombocytopenic purpura in the acute phase and preemptively during remission. Transfus Apher Sci. 2020;59(6):102885. doi:10.1016/j.transci.2020.102885
   PubMed Web of Science ®Google Scholar
• Joly BS, Coppo P, Veyradier A. An update on pathogenesis and diagnosis of thrombotic thrombocytopenic purpura. Expert Rev Hematol. 2019;12(6):383–395. doi:10.1080/17474086.2019.1611423
   PubMed Web of Science ®Google Scholar
• 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(2):233–238. doi:10.1160/TH07-12-0753
   PubMed Web of Science ®Google Scholar
• Hie M, Gay J, Galicier L, et al. Preemptive rituximab infusions after remission efficiently prevent relapses in acquired thrombotic thrombocytopenic purpura. Blood. 2014;124(2):204–210. doi:10.1182/blood-2014-01-550244
   PubMed Web of Science ®Google Scholar
• Delrue M, Baylatry MT, Joly A-C, et al. Efficacy of subcutaneous preemptive rituximab in immune-mediated thrombotic thrombocytopenic purpura: experience from the first 12 cases. Am J Hematol. 2021;96(1):E26–E29. doi:10.1002/ajh.26022
   PubMed Web of Science ®Google Scholar
• Vendramin C, Thomas M, Westwood J-P, McGuckin S, Scully M. Rituximab-induced acute and delayed serum sickness in thrombotic thrombocytopenic purpura: the role of anti-rituximab antibodies. Br J Haematol. 2019;184(5):858–861. doi:10.1111/bjh.15177
   PubMed Web of Science ®Google Scholar
• Robertz J, Andres M, Mansouri Taleghani B, Koneth I, Binet I, Kremer Hovinga JA. Obinutuzumab in two patients suffering from immune-mediated thrombotic thrombocytopenic purpura intolerant to rituximab. Am J Hematol. 2019;94(10):E259–E261. doi:10.1002/ajh.25583
   PubMed Web of Science ®Google Scholar
• Al-Samkari H, Grace RF, Connors JM. Ofatumumab for acute treatment and prophylaxis of a patient with multiple relapses of acquired thrombotic thrombocytopenic purpura. J Thromb Thrombolysis. 2018;46(1):81–83. doi:10.1007/s11239-018-1647-9
   PubMed Web of Science ®Google Scholar
• Scully M, Cataland SR, Peyvandi F, et al. Caplacizumab treatment for acquired thrombotic thrombocytopenic purpura. N Engl J Med. 2019;380(4):335–346. doi:10.1056/NEJMoa1806311
   PubMed Web of Science ®Google Scholar
• Peyvandi F, Scully M, Kremer Hovinga JA, et al. Caplacizumab for acquired thrombotic thrombocytopenic purpura. N Engl J Med. 2016;374(6):511–522. doi:10.1056/NEJMoa1505533
   PubMed Web of Science ®Google Scholar
• Völker LA, Kaufeld J, Miesbach W, et al. Real-world data confirm the effectiveness of caplacizumab in acquired thrombotic thrombocytopenic purpura. Blood Adv. 2020;4(13):3085–3092. doi:10.1182/bloodadvances.2020001973
   PubMed Web of Science ®Google Scholar
• Picod A, Veyradier A, Coppo P. Should all patients with immune-mediated thrombotic thrombocytopenic purpura receive caplacizumab? J Thromb Haemost. 2021;19(1):58–67. doi:10.1111/jth.15194
   PubMed Web of Science ®Google Scholar
• Goshua G, Sinha P, Hendrickson JE, Tormey C, Bendapudi PK, Lee AI. Cost effectiveness of caplacizumab in acquired thrombotic thrombocytopenic purpura. Blood. 2021;137(7):969–976. doi:10.1182/blood.2020006052
   PubMed Web of Science ®Google Scholar
• 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(2):349–357. doi:10.1111/j.1537-2995.2007.01530.x
   PubMed Web of Science ®Google Scholar
• 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(2):183–191. doi:10.1111/ejh.12706
   PubMed Web of Science ®Google Scholar
• Balduini CL, Gugliotta L, Luppi M, et al. High versus standard dose methylprednisolone in the acute phase of idiopathic thrombotic thrombocytopenic purpura: a randomized study. Ann Hematol. 2010;89(6):591–596. doi:10.1007/s00277-009-0877-5
   PubMed Web of Science ®Google Scholar
• Bobbio-Pallavicini E, Porta C, Centurioni R, et al. Vincristine sulfate for the treatment of thrombotic thrombocytopenic purpura refractory to plasma-exchange. The Italian Cooperative Group for TTP. Eur J Haematol. 1994;52(4):222–226. doi:10.1111/j.1600-0609.1994.tb00649.x
   PubMed Web of Science ®Google Scholar
• O’Connor NT, O’Shea MJ, Hill LF. Vincristine for thrombotic thrombocytopenic purpura. Lancet. 1992;340(8817):490. doi:10.1016/0140-6736(92)91815-p
   PubMed Web of Science ®Google Scholar
• Beloncle F, Buffet M, Coindre J-P, et al. Splenectomy and/or cyclophosphamide as salvage therapies in thrombotic thrombocytopenic purpura: the French TMA Reference Center experience. Transfusion. 2012;52(11):2436–2444. doi:10.1111/j.1537-2995.2012.03578.x
   PubMed Web of Science ®Google Scholar
• Zheng X, Pallera AM, Goodnough LT, Sadler JE, Blinder MA. Remission of chronic thrombotic thrombocytopenic purpura after treatment with cyclophosphamide and rituximab. Ann Intern Med. 2003;138(2):105–108. doi:10.7326/0003-4819-138-2-200301210-00011
   PubMed Web of Science ®Google Scholar
• Robak P, Robak T. Bortezomib for the treatment of hematologic malignancies: 15 years later. Drugs R D. 2019;19(2):73–92. doi:10.1007/s40268-019-0269-9
   PubMed Web of Science ®Google Scholar
• Eskazan AE. Bortezomib therapy in patients with relapsed/refractory acquired thrombotic thrombocytopenic purpura. Ann Hematol. 2016;95(11):1751–1756. doi:10.1007/s00277-016-2804-x
   PubMed Web of Science ®Google Scholar
• Patriquin CJ, Thomas MR, Dutt T, et al. Bortezomib in the treatment of refractory thrombotic thrombocytopenic purpura. Br J Haematol. 2016;173(5):779–785. doi:10.1111/bjh.13993
   PubMed Web of Science ®Google Scholar
• 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. doi:10.1182/bloodadvances.2017009308
   PubMed Web of Science ®Google Scholar
• Moake JL, Rudy CK, Troll JH, et al. Therapy of chronic relapsing thrombotic thrombocytopenic purpura with prednisone and azathioprine. Am J Hematol. 1985;20(1):73–79. doi:10.1002/ajh.2830200110
   PubMed Web of Science ®Google Scholar
• Ding J, Baer MR, Hess JR, Zimrin AB. Intravenous immunoglobulin as salvage therapy for refractory thrombotic thrombocytopenic purpura. Am J Hematol. 2018;93(3):E77–E79. doi:10.1002/ajh.25007
   PubMed Web of Science ®Google Scholar
• Chapin J, Weksler B, Magro C, Laurence J. Eculizumab in the treatment of refractory idiopathic thrombotic thrombocytopenic purpura. Br J Haematol. 2012;157(6):772–774. doi:10.1111/j.1365-2141.2012.09084.x
   PubMed Web of Science ®Google Scholar
• Vigna E, Petrungaro A, Perri A, et al. Efficacy of eculizumab in severe ADAMTS13-deficient thrombotic thrombocytopenic purpura (TTP) refractory to standard therapies. Transfus Apher Sci. 2018;57(2):247–249. doi:10.1016/j.transci.2018.03.005
   PubMed Web of Science ®Google Scholar
• Samuni Y, Goldstein S, Dean OM, Berk M. The chemistry and biological activities of N-acetylcysteine. Biochim Biophys Acta. 2013;1830(8):4117–4129. doi:10.1016/j.bbagen.2013.04.016
   PubMed Web of Science ®Google Scholar
• Turner N, Nolasco L, Moake J. Generation and breakdown of soluble ultralarge von Willebrand factor multimers. Semin Thromb Hemost. 2012;38(1):38–46. doi:10.1055/s-0031-1300950
   PubMed Web of Science ®Google Scholar
• 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(2):593–603. doi:10.1172/JCI41062
   PubMed Web of Science ®Google Scholar
• Anfossi G, Russo I, Massucco P, Mattiello L, Cavalot F, Trovati M. N-acetyl-L-cysteine exerts direct anti-aggregating effect on human platelets. Eur J Clin Invest. 2001;31(5):452–461. doi:10.1046/j.1365-2362.2001.00815.x
   PubMed Web of Science ®Google Scholar
• 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(4):678–683. doi:10.1007/s11239-015-1259-6
   PubMed Web of Science ®Google Scholar
• Kappers-Klunne MC, Wijermans P, Fijnheer R, et al. Splenectomy for the treatment of thrombotic thrombocytopenic purpura. Br J Haematol. 2005;130(5):768–776. doi:10.1111/j.1365-2141.2005.05681.x
   PubMed Web of Science ®Google Scholar
• 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(5):349–355.
   PubMed Web of Science ®Google Scholar
• 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. doi:10.1182/blood-2017-06-788026
   PubMed Web of Science ®Google Scholar
• 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(5):936–944. doi:10.1111/j.1538-7836.2011.04224.x
   PubMed Web of Science ®Google Scholar