Acquired thrombotic thrombocytopenic purpura

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*We have moved How I Treat articles to a dedicated page.
Last updated on 2024-12-02:7 regimens on this page
9 variants on this page
=Initial therapy=
==Caplacizumab monotherapy==
===Regimen===
Study 	Evidence
Kühne et al. 2024	Retrospective
====Supportive therapy====
*Caplacizumab (Cablivi)
===References===
#Retrospective: Kühne L, Knöbl P, Eller K, Thaler J, Sperr WR, Gleixner K, Osterholt T, Kaufeld J, Menne J, Buxhofer-Ausch V, Mühlfeld A, Seelow E, Schreiber A, Todorova P, Cukoski S, Jabs WJ, Özcan F, Gäckler A, Schönfelder K, Seibert FS, Westhoff T, Schwenger V, Eichenauer DA, Völker LA, Brinkkoetter PT. Management of immune thrombotic thrombocytopenic purpura without therapeutic plasma exchange. Blood. 2024 Oct 3;144(14):1486-1495. link to original article EuroPMC
==Caplacizumab & Plasma exchange==
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Peyvandi et al. 2016 (TITANTTP)	2010-10 to 2014-01 	Randomized Phase 2 (E-esc)	Plasma exchange	Reduced time to response (primary endpoint)
Scully et al. 2019 (HERCULES) 	2015-11 to 2017-04 	Phase 3 (E-esc) 	Plasma exchange	Shorter median time to platelet count normalization (primary endpoint)Lower composite outcome events (secondary endpoint)
Note: there is another trial named TITAN, in NSCLC.
====Supportive therapy====
*Caplacizumab (Cablivi) 10 mg IV once on day 1, then 10 mg SC once per day during plasma exchange and then for 30 additional days
* Plasma exchange with discontinuation of plasma exchange five days after normalization of platelet count. 
===References===
# TITAN: Peyvandi F, Scully M, Kremer Hovinga JA, Cataland S, Knöbl P, Wu H, Artoni A, Westwood JP, Mansouri Taleghani M, Jilma B, Callewaert F, Ulrichts H, Duby C, Tersago D; TITAN Investigators. Caplacizumab for acquired thrombotic thrombocytopenic purpura. N Engl J Med. 2016 Feb 11;374(6):511-522. link to original article EuroPMC NCT01151423
# HERCULES: Scully M, Cataland SR, Peyvandi F, Coppo P, Knöbl P, Kremer Hovinga JA, Metjian A, de la Rubia J, Pavenski K, Callewaert F, Biswas D, De Winter H, Zeldin RK; HERCULES Investigators. Caplacizumab treatment for acquired thrombotic thrombocytopenic purpura. N Engl J Med. 2019 Jan 24;380(4):335-346. Epub 2019 Jan 9. link to original article dosing details in abstract have been reviewed by our editors EuroPMC NCT02553317
==Plasma exchange==
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Rock et al. 1991	1982-1989 	Phase 3 (E-esc)	Plasma infusion	Seems to have longer OS
====Supportive therapy====
*Total plasma exchange as follows (minimum of 7 treatments in first 9 hospital days):
**Treatments 1 to 3: Exchange of 1.5 times the predicted plasma volume
**Treatment 4 onwards: Exchange of 1.0 times the predicted plasma volume
====Supportive therapy====
*Dipyridamole (Persantine) 400 mg (route not specified) once per day for at least two weeks
*Aspirin 325 mg PO once per day for at least two weeks
===References===
# Rock GA, Shumak KH, Buskard NA, Blanchette VS, Kelton JG, Nair RC, Spasoff RA; Canadian Apheresis Study Group. Comparison of plasma exchange with plasma infusion in the treatment of thrombotic thrombocytopenic purpura. N Engl J Med. 1991 Aug 8;325(6):393-7. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
# TITAN: Peyvandi F, Scully M, Kremer Hovinga JA, Cataland S, Knöbl P, Wu H, Artoni A, Westwood JP, Mansouri Taleghani M, Jilma B, Callewaert F, Ulrichts H, Duby C, Tersago D; TITAN Investigators. Caplacizumab for acquired thrombotic thrombocytopenic purpura. N Engl J Med. 2016 Feb 11;374(6):511-522. link to original article EuroPMC NCT01151423
# HERCULES: Scully M, Cataland SR, Peyvandi F, Coppo P, Knöbl P, Kremer Hovinga JA, Metjian A, de la Rubia J, Pavenski K, Callewaert F, Biswas D, De Winter H, Zeldin RK; HERCULES Investigators. Caplacizumab treatment for acquired thrombotic thrombocytopenic purpura. N Engl J Med. 2019 Jan 24;380(4):335-346. Epub 2019 Jan 9. link to original article EuroPMC NCT02553317
=Maintenance/Preemptive treatment=
==Rituximab monotherapy==
===Regimen===
Study 	Dates of enrollment	Evidence
Hie et al. 2014	2000-10 to 2012-01 	Registry
Note: this prospective registry trial left precise dosing details to physician discretion.
====Immunosuppressive therapy====
*Rituximab (Rituxan) 
===References===
# Retrospective: Hie M, Gay J, Galicier L, Provôt F, Presne C, Poullin P, Bonmarchand G, Wynckel A, Benhamou Y, Vanhille P, Servais A, Bordessoule D, Coindre JP, Hamidou M, Vernant JP, Veyradier A, Coppo P; French Thrombotic Microangiopathies Reference Centre. Preemptive rituximab infusions after remission efficiently prevent relapses in acquired thrombotic thrombocytopenic purpura. Blood. 2014 Jul 10;124(2):204-10. Epub 2014 May 28. link to original article EuroPMC
## Update: 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. Epub 2018 Sep 10. link to original article EuroPMC
=Relapsed or refractory=
These treatments are usually used in addition to therapeutic plasma exchange, not in its place. There are also many treatments reported at the case report or case series level.
==Methylprednisolone monotherapy==
===Regimen variant #1, "High-dose"===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Balduini et al. 2009	2000-2006 	Phase 3 (E-esc)	Methylprednisolone; standard-dose	Might have higher CR rate
====Immunosuppressive therapy====
*Methylprednisolone (Solumedrol) 10 mg/kg/day IV on days 1 to 3, then 2.5 mg/kg/day IV on days 4 to 23
23-day course
===Regimen variant #2, "Standard-dose"===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Balduini et al. 2009	2000-2006 	Phase 3 (C)	Methylprednisolone; high-dose	Might have lower CR rate
====Immunosuppressive therapy====
*Methylprednisolone (Solumedrol) 1 mg/kg/day IV on days 1 to 3, then 2.5 mg/kg/day IV on days 4 to 23
23-day course
===References===
# Balduini CL, Gugliotta L, Luppi M, Laurenti L, Klersy C, Pieresca C, Quintini G, Iuliano F, Re R, Spedini P, Vianelli N, Zaccaria A, Pogliani EM, Musso R, Bobbio Pallavicini E, Quarta G, Galieni P, Fragasso A, Casella G, Noris P, Ascari E; Italian TTP Study Group. High versus standard dose methylprednisolone in the acute phase of idiopathic thrombotic thrombocytopenic purpura: a randomized study. Ann Hematol. 2010 Jun;89(6):591-6. Epub 2009 Dec 23. link to original article dosing details in abstract have been reviewed by our editors EuroPMC
==Rituximab monotherapy==
===Regimen variant #1===
Study 	Dates of enrollment 	Evidence
de la Rubia et al. 2010	2003-10 to 2008-05 	Retrospective
Clark et al. 2015 	2008-11-20 to 2012-12-28	Phase 2
====Immunosuppressive therapy====
*Rituximab (Rituxan) 375 mg/m2 IV once on day 1
====Supportive therapy====
*Prednisone (Sterapred) 50 mg PO once on day 1, given prior to rituximab
*Diphenhydramine (Benadryl) 50 mg PO once on day 1, given prior to rituximab
*Acetaminophen (Tylenol) 325 mg PO once on day 1, given prior to rituximab
7-day cycle for 4 cycles (4-week course)
===Regimen variant #2===
Study 	Dates of enrollment	Evidence
Froissart et al. 2012	2005-10 to 2008-05 	Non-randomized
====Immunosuppressive therapy====
*Rituximab (Rituxan) (dose not specified) IV for 4 doses (timing not specified)
15-day course
===References===
# Retrospective: de la Rubia J, Moscardó F, Gómez MJ, Guardia R, Rodríguez P, Sebrango A, Zamora C, Debén G, Goterris R, López R, Peña F, Pujol M, Vidaller A, Del Río-Garma J, Sanz MA; Grupo Español de Aféresis. Efficacy and safety of rituximab in adult patients with idiopathic relapsing or refractory thrombotic thrombocytopenic purpura: results of a Spanish multicenter study. Transfus Apher Sci. 2010 Dec;43(3):299-303. Epub 2010 Oct 12. link to original article dosing details in abstract have been reviewed by our editors EuroPMC
# Froissart A, Buffet M, Veyradier A, Poullin P, Provôt F, Malot S, Schwarzinger M, Galicier L, Vanhille P, Vernant JP, Bordessoule D, Guidet B, Azoulay E, Mariotte E, Rondeau E, Mira JP, Wynckel A, Clabault K, Choukroun G, Presne C, Pourrat J, Hamidou M, Coppo P; 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: experience of the French Thrombotic Microangiopathies Reference Center. Crit Care Med. 2012 Jan;40(1):104-11. link to original article EuroPMC
# Review: Lim W, Vesely SK, George JN. The role of rituximab in the management of patients with acquired thrombotic thrombocytopenic purpura. Blood. 2015 Mar 5;125(10):1526-31. Epub 2015 Jan 8. Review. link to original article link to PMC article EuroPMC
# Clark WF, Rock G, Barth D, Arnold DM, Webert KE, Yenson PR, Kelton JG, Li L, Foley SR; members of the Canadian Apheresis Group. A phase-II sequential case-series study of all patients presenting to four plasma exchange centres with presumed relapsed/refractory thrombotic thrombocytopenic purpura treated with rituximab. Br J Haematol. 2015 Jul;170(2):208-17. Epub 2015 Apr 8. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
==Vincristine monotherapy==
===Regimen===
Study 	Dates of enrollment	Evidence
Ferrara et al. 1999	Not reported 	Pilot, fewer than 20 patients
====Chemotherapy====
*Vincristine (Oncovin) 1.4 mg/m2 IV once on day 1, then 1 mg IV once per day on days 4 & 7
14-day cycle for 2 cycles
===References===
# Ferrara F, Copia C, Annunziata M, Spasiano A, Di Grazia C, Palmieri S, Prossomariti L, Mele G. Vincristine as salvage treatment for refractory thrombotic thrombocytopenic purpura. Ann Hematol. 1999 Nov;78(11):521-3. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
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