Difference between revisions of "Acquired thrombotic thrombocytopenic purpura"
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{| class="wikitable" style="text-align:center; width:100%;" | {| class="wikitable" style="text-align:center; width:100%;" | ||
− | !colspan="4 | + | ! colspan="4" style="color:white; font-size:125%; background-color:#31a354" align="center" |'''Section editors''' |
|- | |- | ||
− | |style="background-color:#F0F0F0; width:15%"|[[File:Shruti.jpg|frameless|upright=0.3|center]] | + | | style="background-color:#F0F0F0; width:15%" |[[File:Shruti.jpg|frameless|upright=0.3|center]] |
− | |style="width:35%"|<big>[[User:Shrutichaturvedi|Shruti Chaturvedi, MBBS, MSCI]]<br>Baltimore, MD</big><br>[https://www.linkedin.com/in/shruti-chaturvedi-bb83b126/ LinkedIn] | + | | style="width:35%" |<big>[[User:Shrutichaturvedi|Shruti Chaturvedi, MBBS, MSCI]]<br>Baltimore, MD</big><br>[https://www.linkedin.com/in/shruti-chaturvedi-bb83b126/ LinkedIn] |
− | |style="background-color:#F0F0F0; width:15%"|[[File:Tillman_Benjamin-2.jpg|frameless|upright=0.3|center]] | + | | style="background-color:#F0F0F0; width:15%" |[[File:Tillman_Benjamin-2.jpg|frameless|upright=0.3|center]] |
− | |style="width:35%"|<big>[[User:Benjamintillman|Benjamin Tillman, MD]]<br>Nashville, TN</big> | + | | style="width:35%" |<big>[[User:Benjamintillman|Benjamin Tillman, MD]]<br>Nashville, TN</big> |
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|} | |} | ||
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===Regimen {{#subobject:0e1e05|Variant=1}}=== | ===Regimen {{#subobject:0e1e05|Variant=1}}=== | ||
{| class="wikitable" style="width: 100%; text-align:center;" | {| class="wikitable" style="width: 100%; text-align:center;" | ||
− | !style="width: 25%"|Study | + | ! style="width: 25%" |Study |
− | !style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]] | + | ! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]] |
− | !style="width: 25%"|Comparator | + | ! style="width: 25%" |Comparator |
− | !style="width: 25%"|[[Levels_of_Evidence#Efficacy|Efficacy]] | + | ! style="width: 25%" |[[Levels_of_Evidence#Efficacy|Efficacy]] |
|- | |- | ||
|[https://www.nejm.org/doi/full/10.1056/NEJM199108083250604 Rock et al. 1991] | |[https://www.nejm.org/doi/full/10.1056/NEJM199108083250604 Rock et al. 1991] | ||
− | |style="background-color:#1a9851"|Phase III (E) | + | | style="background-color:#1a9851" |Phase III (E) |
|Plasma infusion | |Plasma infusion | ||
− | |style="background-color:#91cf60"|Seems to have superior OS | + | | style="background-color:#91cf60" |Seems to have superior OS |
|- | |- | ||
|} | |} | ||
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===References=== | ===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. [https://www.nejm.org/doi/full/10.1056/NEJM199108083250604 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/2062330 PubMed] | # 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. [https://www.nejm.org/doi/full/10.1056/NEJM199108083250604 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/2062330 PubMed] | ||
+ | |||
+ | == Caplacizumab == | ||
+ | |||
+ | === Regimen === | ||
+ | {| class="wikitable" | ||
+ | !Study | ||
+ | !Evidence | ||
+ | !Comparator | ||
+ | !Efficacy | ||
+ | |- | ||
+ | |[https://www.nejm.org/doi/10.1056/NEJMoa1806311 Scully et al. HERCULES 2019] | ||
+ | |Phase III | ||
+ | |placebo | ||
+ | |Shorter median time to platelet count normalization. | ||
+ | Lower composite outcome events (death, relapse). | ||
+ | |} | ||
+ | |||
+ | ==== Supportive therapy ==== | ||
+ | * Plasma exchange with discontinuation of plasma exchange five days after normalization of platelet count. | ||
+ | |||
+ | === References === | ||
+ | # Scully M, Cataland SR, Peyvandi F, Coppo P, Knobl P, Kermer Hovinga JA, Metjian A, de la Rubia J, Pavenksi K, Callewart F, Biswas D, De Winter H, et al, for teh HERCULES Investigators. Caplacizumab treatment for acquired thrombotic thrombocytopenic purpura. N Engl J Med 2019; 380:335-346. [https://www.nejm.org/doi/10.1056/NEJMoa1806311 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/30625070 PubMed] | ||
=Maintenance/Preemptive treatment= | =Maintenance/Preemptive treatment= | ||
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===Regimen {{#subobject:8bca2c|Variant=1}}=== | ===Regimen {{#subobject:8bca2c|Variant=1}}=== | ||
{| class="wikitable" style="width: 100%; text-align:center;" | {| class="wikitable" style="width: 100%; text-align:center;" | ||
− | !style="width: 50%"|Study | + | ! style="width: 50%" |Study |
− | !style="width: 50%"|[[Levels_of_Evidence#Evidence|Evidence]] | + | ! style="width: 50%" |[[Levels_of_Evidence#Evidence|Evidence]] |
|- | |- | ||
|[http://www.bloodjournal.org/content/124/2/204.long Hie et al. 2014] | |[http://www.bloodjournal.org/content/124/2/204.long Hie et al. 2014] | ||
− | |style="background-color:#91cf61"|Registry | + | | style="background-color:#91cf61" |Registry |
|- | |- | ||
|} | |} | ||
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===Variant #1, "High-dose" {{#subobject:0ea120|Variant=1}}=== | ===Variant #1, "High-dose" {{#subobject:0ea120|Variant=1}}=== | ||
{| class="wikitable" style="width: 100%; text-align:center;" | {| class="wikitable" style="width: 100%; text-align:center;" | ||
− | !style="width: 25%"|Study | + | ! style="width: 25%" |Study |
− | !style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]] | + | ! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]] |
− | !style="width: 25%"|Comparator | + | ! style="width: 25%" |Comparator |
− | !style="width: 25%"|[[Levels_of_Evidence#Efficacy|Efficacy]] | + | ! style="width: 25%" |[[Levels_of_Evidence#Efficacy|Efficacy]] |
|- | |- | ||
|[http://link.springer.com/article/10.1007%2Fs00277-009-0877-5 Balduini et al. 2009] | |[http://link.springer.com/article/10.1007%2Fs00277-009-0877-5 Balduini et al. 2009] | ||
− | |style="background-color:#1a9851"|Phase III (E) | + | | style="background-color:#1a9851" |Phase III (E) |
|Standard-dose methylprednisolone | |Standard-dose methylprednisolone | ||
− | |style="background-color:#d9ef8b"|Might have superior CR rate | + | | style="background-color:#d9ef8b" |Might have superior CR rate |
|- | |- | ||
|} | |} | ||
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===Variant #2, "Standard-dose" {{#subobject:84ebef|Variant=1}}=== | ===Variant #2, "Standard-dose" {{#subobject:84ebef|Variant=1}}=== | ||
{| class="wikitable" style="width: 100%; text-align:center;" | {| class="wikitable" style="width: 100%; text-align:center;" | ||
− | !style="width: 25%"|Study | + | ! style="width: 25%" |Study |
− | !style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]] | + | ! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]] |
− | !style="width: 25%"|Comparator | + | ! style="width: 25%" |Comparator |
− | !style="width: 25%"|[[Levels_of_Evidence#Efficacy|Efficacy]] | + | ! style="width: 25%" |[[Levels_of_Evidence#Efficacy|Efficacy]] |
|- | |- | ||
|[http://link.springer.com/article/10.1007%2Fs00277-009-0877-5 Balduini et al. 2009] | |[http://link.springer.com/article/10.1007%2Fs00277-009-0877-5 Balduini et al. 2009] | ||
− | |style="background-color:#1a9851"|Phase III (C) | + | | style="background-color:#1a9851" |Phase III (C) |
|High-dose methylprednisolone | |High-dose methylprednisolone | ||
− | |style="background-color:#fee08b"|Might have inferior CR rate | + | | style="background-color:#fee08b" |Might have inferior CR rate |
|- | |- | ||
|} | |} | ||
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===Variant #1 {{#subobject:8bca2c|Variant=1}}=== | ===Variant #1 {{#subobject:8bca2c|Variant=1}}=== | ||
{| class="wikitable" style="width: 100%; text-align:center;" | {| class="wikitable" style="width: 100%; text-align:center;" | ||
− | !style="width: 50%"|Study | + | ! style="width: 50%" |Study |
− | !style="width: 50%"|[[Levels_of_Evidence#Evidence|Evidence]] | + | ! style="width: 50%" |[[Levels_of_Evidence#Evidence|Evidence]] |
|- | |- | ||
|[http://www.trasci.com/article/S1473-0502(10)00162-X/fulltext de la Rubia et al. 2010] | |[http://www.trasci.com/article/S1473-0502(10)00162-X/fulltext de la Rubia et al. 2010] | ||
− | |style="background-color:#91cf61"|Non-randomized | + | | style="background-color:#91cf61" |Non-randomized |
|- | |- | ||
|[https://onlinelibrary.wiley.com/doi/10.1111/bjh.13408/full Clark et al. 2015] | |[https://onlinelibrary.wiley.com/doi/10.1111/bjh.13408/full Clark et al. 2015] | ||
− | |style="background-color:#91cf61"|Phase II | + | | style="background-color:#91cf61" |Phase II |
|- | |- | ||
|} | |} | ||
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===Variant #2 {{#subobject:a31c78|Variant=1}}=== | ===Variant #2 {{#subobject:a31c78|Variant=1}}=== | ||
{| class="wikitable" style="width: 100%; text-align:center;" | {| class="wikitable" style="width: 100%; text-align:center;" | ||
− | !style="width: 50%"|Study | + | ! style="width: 50%" |Study |
− | !style="width: 50%"|[[Levels_of_Evidence#Evidence|Evidence]] | + | ! style="width: 50%" |[[Levels_of_Evidence#Evidence|Evidence]] |
|- | |- | ||
|[https://www.ncbi.nlm.nih.gov/pubmed/21926591 Froissart et al. 2012] | |[https://www.ncbi.nlm.nih.gov/pubmed/21926591 Froissart et al. 2012] | ||
− | |style="background-color:#91cf61"|Non-randomized | + | | style="background-color:#91cf61" |Non-randomized |
|- | |- | ||
|} | |} | ||
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===Regimen {{#subobject:8892fc|Variant=1}}=== | ===Regimen {{#subobject:8892fc|Variant=1}}=== | ||
{| class="wikitable" style="width: 100%; text-align:center;" | {| class="wikitable" style="width: 100%; text-align:center;" | ||
− | !style="width: 50%"|Study | + | ! style="width: 50%" |Study |
− | !style="width: 50%"|[[Levels_of_Evidence#Evidence|Evidence]] | + | ! style="width: 50%" |[[Levels_of_Evidence#Evidence|Evidence]] |
|- | |- | ||
|[https://www.ncbi.nlm.nih.gov/pubmed/10602896 Ferrara et al. 1999] | |[https://www.ncbi.nlm.nih.gov/pubmed/10602896 Ferrara et al. 1999] | ||
− | |style="background-color:#ffffbe"|Pilot, <20 patients | + | | style="background-color:#ffffbe" |Pilot, <20 patients |
|- | |- | ||
|} | |} |
Revision as of 18:57, 6 February 2019
Section editors | |||
---|---|---|---|
Shruti Chaturvedi, MBBS, MSCI Baltimore, MD |
Benjamin Tillman, MD Nashville, TN |
5 regimens on this page
7 variants on this page
|
Initial therapy
Plasma exchange
back to top |
Regimen
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Rock et al. 1991 | Phase III (E) | Plasma infusion | Seems to have superior 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
- Treatments 4 onwards: Exchange of 1.0 times the predicted plasma volume
Supportive medications
- 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 contains verified protocol PubMed
Caplacizumab
Regimen
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Scully et al. HERCULES 2019 | Phase III | placebo | Shorter median time to platelet count normalization.
Lower composite outcome events (death, relapse). |
Supportive therapy
- Plasma exchange with discontinuation of plasma exchange five days after normalization of platelet count.
References
- Scully M, Cataland SR, Peyvandi F, Coppo P, Knobl P, Kermer Hovinga JA, Metjian A, de la Rubia J, Pavenksi K, Callewart F, Biswas D, De Winter H, et al, for teh HERCULES Investigators. Caplacizumab treatment for acquired thrombotic thrombocytopenic purpura. N Engl J Med 2019; 380:335-346. link to original article PubMed
Maintenance/Preemptive treatment
Rituximab monotherapy
back to top |
Regimen
Study | Evidence |
---|---|
Hie et al. 2014 | Registry |
Note: this prospective registry trial left precise dosing details to physician discretion.
Immunosuppressive therapy
References
- 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 PubMed
- 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 PubMed
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; the reader is guided to the 2015 Blood article, "How I treat refractory thrombotic thrombocytopenic purpura" for further details.
Methylprednisolone monotherapy
back to top |
Variant #1, "High-dose"
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Balduini et al. 2009 | Phase III (E) | Standard-dose methylprednisolone | Might have superior CR rate |
Immunosuppressive therapy
- Methylprednisolone (Solumedrol) as follows:
- Days 1 to 3: 10 mg/kg/day IV
- Days 4 to 23: 2.5 mg/kg/day IV
Variant #2, "Standard-dose"
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Balduini et al. 2009 | Phase III (C) | High-dose methylprednisolone | Might have inferior CR rate |
Immunosuppressive therapy
- Methylprednisolone (Solumedrol) as follows:
- Days 1 to 3: 1 mg/kg/day IV
- Days 4 to 23: 2.5 mg/kg/day IV
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 contains protocol PubMed
Rituximab monotherapy
back to top |
Variant #1
Study | Evidence |
---|---|
de la Rubia et al. 2010 | Non-randomized |
Clark et al. 2015 | Phase II |
Full text of de la Rubia et al. 2010 is not available for review.
Immunosuppressive therapy
- Rituximab (Rituxan) 375 mg/m2 IV once per week
Supportive medications
- Prednisone (Sterapred) 50 mg PO once prior to Rituximab (Rituxan)
- Diphenhydramine (Benadryl) 50 mg PO once prior to Rituximab (Rituxan)
- Acetaminophen (Tylenol) 325 mg PO once prior to Rituximab (Rituxan)
4-week course
Variant #2
Study | Evidence |
---|---|
Froissart et al. 2012 | Non-randomized |
Immunosuppressive therapy
- Rituximab (Rituxan) (dose not specified) IV
Four doses in 15 days
References
- 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 contains protocol PubMed
- 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. PubMed
- 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 PubMed
- 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 contains verified protocol PubMed
Vincristine monotherapy
back to top |
Regimen
Study | Evidence |
---|---|
Ferrara et al. 1999 | Pilot, <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
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. contains protocol PubMed