Difference between revisions of "Acquired hemophilia A"

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Is there a regimen missing from this list?  Would you like to share a different dosage/schedule or an additional reference for a regimen?  Have you noticed an error?  Do you have an idea that will help the site grow to better meet your needs and the needs of many others?  You are [[How_to_contribute|invited to contribute to the site]].
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!colspan="4" align="center" style="color:white; font-size:125%; background-color:#31a354"|'''Section editors'''
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{{#lst:Editorial board transclusions|heme}}
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|style="background-color:#F0F0F0; width:15%"|[[File:Shruti.jpg|frameless|upright=0.3|center]]
 
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|style="width:35%"|<big>[[User:Shrutichaturvedi|Shruti Chaturvedi, MBBS, MSCI]]<br>Baltimore, MD</big><br>[https://www.linkedin.com/in/shruti-chaturvedi-bb83b126/ LinkedIn]
 
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|style="background-color:#F0F0F0; width:15%"|[[File:Tillman_Benjamin-2.jpg|frameless|upright=0.3|center]]
 
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|style="width:35%"|<big>[[User:Benjamintillman|Benjamin Tillman, MD]]<br>Nashville, TN</big>
 
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|<div style="background-color: #fee0d1; border: 1px solid #808000; padding: 5px; {{border-radius|16px}}" align="right"><font size="4"><b>{{#ask: [[-Has subobject::{{FULLPAGENAME}}]] |?Regimen |limit=10000|format=sum}} regimens on this page</b></font></div>
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|<div style="background-color: #fee0d1; border: 1px solid #808000; padding: 5px; {{border-radius|16px}}" align="right"><font size="4"><b>{{#ask: [[-Has subobject::{{FULLPAGENAME}}]] |?Regimen |limit=10000|format=sum}} [[Tutorial#Regimens|regimens]] on this page</b></font></div>
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<div style="background-color: #deebf6; border: 1px solid #808000; padding: 5px; {{border-radius|16px}}"><font size="4"><b>{{#ask: [[-Has subobject::{{FULLPAGENAME}}]] |?Variant |limit=10000|format=sum}} variants on this page</b></font></div>
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<div style="background-color: #deebf6; border: 1px solid #808000; padding: 5px; {{border-radius|16px}}"><font size="4"><b>{{#ask: [[-Has subobject::{{FULLPAGENAME}}]] |?Variant |limit=10000|format=sum}} [[Tutorial#Variants|variants]] on this page</b></font></div>
 
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This page is meant to cover regimens that are used in the context of acquired factor VIII inhibitors. See the '''[[inherited coagulopathy]]''' page for regimens relevant to inherited factor deficiency. In the future, we may add other acquired coagulopathy pages such as acquired vWD.<br>
 +
Incidence: 1.48/million/year<ref>Collins PW, Hirsch S, Baglin TP, Dolan G, Hanley J, Makris M, Keeling DM, Liesner R, Brown SA, Hay CR; UK Haemophilia Centre Doctors' Organisation. Acquired hemophilia A in the United Kingdom: a 2-year national surveillance study by the United Kingdom Haemophilia Centre Doctors' Organisation. Blood. 2007 Mar 1;109(5):1870-7. [https://doi.org/10.1182/blood-2006-06-029850 link to original article] [https://pubmed.ncbi.nlm.nih.gov/17047148/ PubMed]</ref>
 +
=Guidelines=
 +
'''Given the rapid change in evidence in many areas of hematology/oncology, readers are encouraged to consider any guideline published 5+ years ago to be for historical purposes, only.'''
 +
==International recommendations==
 +
*'''2009:''' Huth-Kühne et al. [https://doi.org/10.3324/haematol.2008.001743 International Recommendations On The Diagnosis And Treatment Of Patients With Acquired Hemophilia A] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc2663620/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/19336751/ PubMed]
  
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This page is meant to cover regimens that are used in the context of acquired factor inhibitors. See the '''[[inherited coagulopathy]]''' page for regimens relevant to inherited factor deficiency.
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=All lines of therapy=
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=Acquired factor VIII inhibitor, all lines of therapy=
 
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Incidence: 1.48/million/year<ref>Collins PW, Hirsch S, Baglin TP, Dolan G, Hanley J, Makris M, Keeling DM, Liesner R, Brown SA, Hay CR; UK Haemophilia Centre Doctors' Organisation. Acquired hemophilia A in the United Kingdom: a 2-year national surveillance study by the United Kingdom Haemophilia Centre Doctors' Organisation. Blood. 2007 Mar 1;109(5):1870-7. [http://www.bloodjournal.org/content/109/5/1870.long link to original article]  [https://www.ncbi.nlm.nih.gov/pubmed/17047148 PubMed]</ref>
 
  
 
==Cyclophosphamide & Prednisolone {{#subobject:2fd67|Regimen=1}}==
 
==Cyclophosphamide & Prednisolone {{#subobject:2fd67|Regimen=1}}==
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{| class="wikitable" style="float:right; margin-left: 5px;"
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<div class="toccolours" style="background-color:#eeeeee">
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|-
 
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|[[#top|back to top]]
 
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===Regimen {{#subobject:84e0fd|Variant=1}}===
 
===Regimen {{#subobject:84e0fd|Variant=1}}===
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{| class="wikitable" style="width: 100%; text-align:center;"  
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{| class="wikitable" style="width: 40%; text-align:center;"  
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!Study
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!style="width: 25%"|Study
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![[Levels_of_Evidence#Evidence|Evidence]]
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!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
|-
 
|-
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|[http://www.bloodjournal.org/content/109/5/1870.long Collins et al. 2007]
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|[https://doi.org/10.1182/blood-2006-06-029850 Collins et al. 2007]
 
|style="background-color:#ffffbe"|Review
 
|style="background-color:#ffffbe"|Review
 
|-
 
|-
 
|}
 
|}
 +
<div class="toccolours" style="background-color:#b3e2cd">
 
====Immunosuppressive therapy====
 
====Immunosuppressive therapy====
 
*[[Cyclophosphamide (Cytoxan)]] 1 to 2 mg/kg PO once per day
 
*[[Cyclophosphamide (Cytoxan)]] 1 to 2 mg/kg PO once per day
 
*[[Prednisolone (Millipred)]] 1 mg/kg PO once per day
 
*[[Prednisolone (Millipred)]] 1 mg/kg PO once per day
−
 
+
</div></div>
 
===References===
 
===References===
−
# Collins PW, Hirsch S, Baglin TP, Dolan G, Hanley J, Makris M, Keeling DM, Liesner R, Brown SA, Hay CR; UK Haemophilia Centre Doctors' Organisation. Acquired hemophilia A in the United Kingdom: a 2-year national surveillance study by the United Kingdom Haemophilia Centre Doctors' Organisation. Blood. 2007 Mar 1;109(5):1870-7. [http://www.bloodjournal.org/content/109/5/1870.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/17047148 PubMed]
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# '''Review:''' Collins PW, Hirsch S, Baglin TP, Dolan G, Hanley J, Makris M, Keeling DM, Liesner R, Brown SA, Hay CR; UK Haemophilia Centre Doctors' Organisation. Acquired hemophilia A in the United Kingdom: a 2-year national surveillance study by the United Kingdom Haemophilia Centre Doctors' Organisation. Blood. 2007 Mar 1;109(5):1870-7. [https://doi.org/10.1182/blood-2006-06-029850 link to original article] [https://pubmed.ncbi.nlm.nih.gov/17047148/ PubMed]
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==Cyclophosphamide & Prednisone {{#subobject:e5cfe6|Regimen=1}}==
 
==Cyclophosphamide & Prednisone {{#subobject:e5cfe6|Regimen=1}}==
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{| class="wikitable" style="float:right; margin-left: 5px;"
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===Regimen variant #1 {{#subobject:852fed|Variant=1}}===
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!style="width: 25%"|Study
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===Regimen #1 {{#subobject:852fed|Variant=1}}===
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!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
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{| class="wikitable" style="width: 100%; text-align:center;"  
 
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!Study
 
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![[Levels_of_Evidence#Evidence|Evidence]]
 
 
|-
 
|-
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|[http://annals.org/article.aspx?articleid=710728 Shaffer et al. 1997]
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|[https://doi.org/10.7326/0003-4819-127-3-199708010-00005 Shaffer et al. 1997]
 
|style="background-color:#ffffbe"|Case report
 
|style="background-color:#ffffbe"|Case report
 
|-
 
|-
 
|}
 
|}
 +
''Note: Per Shaffer et al. 1997, "the lower ends of these ranges became the standard therapy to minimize side effects"
 +
<div class="toccolours" style="background-color:#b3e2cd">
 
====Immunosuppressive therapy====
 
====Immunosuppressive therapy====
 
*[[Cyclophosphamide (Cytoxan)]] 100 to 200 mg PO once per day
 
*[[Cyclophosphamide (Cytoxan)]] 100 to 200 mg PO once per day
 
*[[Prednisone (Sterapred)]] 50 to 80 mg PO once per day
 
*[[Prednisone (Sterapred)]] 50 to 80 mg PO once per day
−
**Per Shaffer et al. 1997: "the lower ends of these ranges became the standard therapy to minimize side effects"
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'''Continued until therapeutic response''' "Cyclophosphamide and prednisone were continued at full doses until the factor VIII inhibitor titer decreased to zero; after this, the doses of prednisone and cyclophosphamide were slowly decreased."
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</div></div><br>
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'''Used until therapeutic response.''' "Cyclophosphamide and prednisone were continued at full doses until the factor VIII inhibitor titer decreased to zero; after this, the doses of prednisone and cyclophosphamide were slowly decreased."
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<div class="toccolours" style="background-color:#eeeeee">
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===Regimen variant #2 {{#subobject:852fed|Variant=1}}===
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===Regimen #2 {{#subobject:852fed|Variant=1}}===
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{| class="wikitable" style="width: 40%; text-align:center;"  
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{| class="wikitable" style="width: 100%; text-align:center;"  
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!style="width: 25%"|Study
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!Study
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!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
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![[Levels_of_Evidence#Evidence|Evidence]]
 
 
|-
 
|-
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|[http://onlinelibrary.wiley.com/doi/10.1002/%28SICI%291096-8652%28199901%2960:1%3C70::AID-AJH12%3E3.0.CO;2-D/abstract Bayer et al. 1999]
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|[https://doi.org/10.1002/%28SICI)1096-8652%28199901)60:1%3C70::AID-AJH12%3E3.0.CO;2-D Bayer et al. 1999]
 
|style="background-color:#ffffbe"|Case report
 
|style="background-color:#ffffbe"|Case report
 
|-
 
|-
 
|}
 
|}
 +
<div class="toccolours" style="background-color:#b3e2cd">
 
====Immunosuppressive therapy====
 
====Immunosuppressive therapy====
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*[[Cyclophosphamide (Cytoxan)]] 100 PO once per day
+
*[[Cyclophosphamide (Cytoxan)]] 100 mg PO once per day
 
*[[Prednisone (Sterapred)]] 1 mg/kg PO once per day
 
*[[Prednisone (Sterapred)]] 1 mg/kg PO once per day
−
 
+
'''Continued until therapeutic response, then prednisone and cyclophosphamide were tapered slowly'''
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'''Used until therapeutic response.''' "Prednisone and cyclophosphamide were tapered slowly."
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</div></div><br>
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<div class="toccolours" style="background-color:#eeeeee">
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===Regimen #3 {{#subobject:404cf3|Variant=1}}===
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===Regimen variant #3 {{#subobject:404cf3|Variant=1}}===
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{| class="wikitable" style="width: 100%; text-align:center;"  
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{| class="wikitable" style="width: 40%; text-align:center;"  
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!Study
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!style="width: 25%"|Study
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![[Levels_of_Evidence#Evidence|Evidence]]
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!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
|-
 
|-
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|[https://www.ncbi.nlm.nih.gov/pubmed/8128430 Green et al. 1993]
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|[https://www.thieme-connect.de/products/ejournals/abstract/10.1055/s-0038-1649664 Green et al. 1993]
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|style="background-color:#91cf61"|Case series, >20 pts
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|style="background-color:#91cf61"|Randomized, fewer than 20 pts (E-esc)
 
|-
 
|-
 
|}
 
|}
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<div class="toccolours" style="background-color:#cbd5e8">
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====Preceding treatment====
 +
*[[#Prednisone_monotherapy|Prednisone]] x 21 d, with no response
 +
</div>
 +
<div class="toccolours" style="background-color:#b3e2cd">
 
====Immunosuppressive therapy====
 
====Immunosuppressive therapy====
−
*[[Prednisone (Sterapred)]] 1 mg/kg PO once per day
 
−
 
−
If no response to just prednisone after 21 days, change treatment to:
 
 
*[[Cyclophosphamide (Cytoxan)]] 2 mg/kg (route not specified) once per day
 
*[[Cyclophosphamide (Cytoxan)]] 2 mg/kg (route not specified) once per day
 
*[[Prednisone (Sterapred)]] 1 mg/kg PO once per day
 
*[[Prednisone (Sterapred)]] 1 mg/kg PO once per day
−
 
+
</div></div>
−
===References===
 
−
# For historic purposes only; case reports of varying doses & schedule: Herbst KD, Rapaport SI, Kenoyer DG, Stanton W, Feinstein DI. Syndrome of an acquired inhibitor of factor VIII responsive to cyclophosphamide and prednisone. Ann Intern Med. 1981 Nov;95(5):575-8. [http://annals.org/article.aspx?articleid=695187 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/6794408 PubMed]
 
−
# Green D, Rademaker AW, Briët E. A prospective, randomized trial of prednisone and cyclophosphamide in the treatment of patients with factor VIII autoantibodies. Thromb Haemost. 1993 Nov 15;70(5):753-7. [https://www.ncbi.nlm.nih.gov/pubmed/8128430 PubMed]
 
−
# Shaffer LG, Phillips MD. Successful treatment of acquired hemophilia with oral immunosuppressive therapy. Ann Intern Med. 1997 Aug 1;127(3):206-9. [http://annals.org/article.aspx?articleid=710728 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/9245226 PubMed]
 
−
# Bayer RL, Lichtman SM, Allen SL, Budman DR, Buchbinder A, Fetten J, Kolitz J, Loscalzo J. Acquired factor VIII inhibitors--successful treatment with an oral outpatient regimen. Am J Hematol. 1999 Jan;60(1):70-1. [http://onlinelibrary.wiley.com/doi/10.1002/%28SICI%291096-8652%28199901%2960:1%3C70::AID-AJH12%3E3.0.CO;2-D/abstract link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/9883809 PubMed]
 
−
# Collins PW, Hirsch S, Baglin TP, Dolan G, Hanley J, Makris M, Keeling DM, Liesner R, Brown SA, Hay CR; UK Haemophilia Centre Doctors' Organisation. Acquired hemophilia A in the United Kingdom: a 2-year national surveillance study by the United Kingdom Haemophilia Centre Doctors' Organisation. Blood. 2007 Mar 1;109(5):1870-7. [http://www.bloodjournal.org/content/109/5/1870.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/17047148 PubMed]
 
−
# Baudo F, Caimi T, de Cataldo F. Diagnosis and treatment of acquired haemophilia. Haemophilia. 2010 May;16(102):102-6.
 
−
 
 
−
==Emicizumab monotherapy {{#subobject:f198c0|Regimen=1}}==
 
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{| class="wikitable" style="float:right; margin-left: 5px;"
 
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|-
 
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|[[#top|back to top]]
 
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|}
 
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===Regimen {{#subobject:cbc686|Variant=1}}===
 
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{| class="wikitable" style="width: 100%; text-align:center;"
 
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!Study
 
−
![[Levels_of_Evidence#Evidence|Evidence]]
 
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!Comparator
 
−
![[Levels_of_Evidence#Efficacy|Efficacy]]
 
−
|-
 
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|[http://www.nejm.org/doi/full/10.1056/NEJMoa1703068 Oldenburg et al. 2017]
 
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|style="background-color:#1a9851"|Phase III
 
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|No prophylaxis
 
−
|style="background-color:#1a9850"|Lower bleeding rate
 
−
|-
 
−
|}
 
−
To be completed
 
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====Therapy====
 
−
*[[Emicizumab-kxwh (Hemlibra)]]
 
 
===References===
 
===References===
−
# Oldenburg J, Mahlangu JN, Kim B, Schmitt C, Callaghan MU, Young G, Santagostino E, Kruse-Jarres R, Negrier C, Kessler C, Valente N, Asikanius E, Levy GG, Windyga J, Shima M. Emicizumab prophylaxis in hemophilia A with inhibitors. N Engl J Med. 2017 Aug 31;377(9):809-818. Epub 2017 Jul 10. [http://www.nejm.org/doi/full/10.1056/NEJMoa1703068 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/28691557 PubMed]
+
# '''Case series:''' Herbst KD, Rapaport SI, Kenoyer DG, Stanton W, Feinstein DI. Syndrome of an acquired inhibitor of factor VIII responsive to cyclophosphamide and prednisone. Ann Intern Med. 1981 Nov;95(5):575-8. [https://doi.org/10.7326/0003-4819-95-5-575 link to original article] [https://pubmed.ncbi.nlm.nih.gov/6794408/ PubMed]
−
 
+
# Green D, Rademaker AW, Briët E. A prospective, randomized trial of prednisone and cyclophosphamide in the treatment of patients with factor VIII autoantibodies. Thromb Haemost. 1993 Nov 15;70(5):753-7. [https://doi.org/10.1055/s-0038-1649664 link to original article] [https://pubmed.ncbi.nlm.nih.gov/8128430/ PubMed]
 +
# '''Case report:''' Shaffer LG, Phillips MD. Successful treatment of acquired hemophilia with oral immunosuppressive therapy. Ann Intern Med. 1997 Aug 1;127(3):206-9. [https://doi.org/10.7326/0003-4819-127-3-199708010-00005 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/9245226/ PubMed]
 +
# '''Case report:''' Bayer RL, Lichtman SM, Allen SL, Budman DR, Buchbinder A, Fetten J, Kolitz J, Loscalzo J. Acquired factor VIII inhibitors--successful treatment with an oral outpatient regimen. Am J Hematol. 1999 Jan;60(1):70-1. [https://doi.org/10.1002/%28SICI)1096-8652%28199901)60:1%3C70::AID-AJH12%3E3.0.CO;2-D link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/9883809/ PubMed]
 +
# '''Case series:''' Collins PW, Hirsch S, Baglin TP, Dolan G, Hanley J, Makris M, Keeling DM, Liesner R, Brown SA, Hay CR; UK Haemophilia Centre Doctors' Organisation. Acquired hemophilia A in the United Kingdom: a 2-year national surveillance study by the United Kingdom Haemophilia Centre Doctors' Organisation. Blood. 2007 Mar 1;109(5):1870-7. [https://doi.org/10.1182/blood-2006-06-029850 link to original article] [https://pubmed.ncbi.nlm.nih.gov/17047148/ PubMed]
 
==Prednisolone monotherapy {{#subobject:78729f|Regimen=1}}==
 
==Prednisolone monotherapy {{#subobject:78729f|Regimen=1}}==
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{| class="wikitable" style="float:right; margin-left: 5px;"
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<div class="toccolours" style="background-color:#eeeeee">
−
|-
 
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|[[#top|back to top]]
 
−
|}
 
 
===Regimen {{#subobject:6e2d2d|Variant=1}}===
 
===Regimen {{#subobject:6e2d2d|Variant=1}}===
−
{| class="wikitable" style="width: 100%; text-align:center;"  
+
{| class="wikitable" style="width: 40%; text-align:center;"  
−
!Study
+
!style="width: 25%"|Study
−
![[Levels_of_Evidence#Evidence|Evidence]]
+
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
|-
 
|-
−
|[http://www.bloodjournal.org/content/109/5/1870.long Collins et al. 2007]
+
|[https://doi.org/10.1182/blood-2006-06-029850 Collins et al. 2007]
 
|style="background-color:#ffffbe"|Review
 
|style="background-color:#ffffbe"|Review
 
|-
 
|-
 
|}
 
|}
 +
<div class="toccolours" style="background-color:#b3e2cd">
 
====Immunosuppressive therapy====
 
====Immunosuppressive therapy====
 
*[[Prednisolone (Millipred)]] 1 mg/kg PO once per day
 
*[[Prednisolone (Millipred)]] 1 mg/kg PO once per day
−
 
+
</div></div>
 
===References===
 
===References===
−
# Collins PW, Hirsch S, Baglin TP, Dolan G, Hanley J, Makris M, Keeling DM, Liesner R, Brown SA, Hay CR; UK Haemophilia Centre Doctors' Organisation. Acquired hemophilia A in the United Kingdom: a 2-year national surveillance study by the United Kingdom Haemophilia Centre Doctors' Organisation. Blood. 2007 Mar 1;109(5):1870-7. [http://www.bloodjournal.org/content/109/5/1870.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/17047148 PubMed]
+
# '''Review:''' Collins PW, Hirsch S, Baglin TP, Dolan G, Hanley J, Makris M, Keeling DM, Liesner R, Brown SA, Hay CR; UK Haemophilia Centre Doctors' Organisation. Acquired hemophilia A in the United Kingdom: a 2-year national surveillance study by the United Kingdom Haemophilia Centre Doctors' Organisation. Blood. 2007 Mar 1;109(5):1870-7. [https://doi.org/10.1182/blood-2006-06-029850 link to original article] [https://pubmed.ncbi.nlm.nih.gov/17047148/ PubMed]
−
 
 
 
==Prednisone monotherapy {{#subobject:dcf925|Regimen=1}}==
 
==Prednisone monotherapy {{#subobject:dcf925|Regimen=1}}==
−
{| class="wikitable" style="float:right; margin-left: 5px;"
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<div class="toccolours" style="background-color:#eeeeee">
−
|-
 
−
|[[#top|back to top]]
 
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|}
 
 
===Regimen {{#subobject:c5ce2e|Variant=1}}===
 
===Regimen {{#subobject:c5ce2e|Variant=1}}===
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{| class="wikitable" style="width: 100%; text-align:center;"  
+
{| class="wikitable" style="width: 40%; text-align:center;"  
−
!Study
+
!style="width: 25%"|Study
−
![[Levels_of_Evidence#Evidence|Evidence]]
+
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
|-
 
|-
−
|[https://www.ncbi.nlm.nih.gov/pubmed/6792737 Green et al. 1981]
+
|[https://pubmed.ncbi.nlm.nih.gov/6792737 Green et al. 1981]
 
|style="background-color:#ffffbe"|Case report, review
 
|style="background-color:#ffffbe"|Case report, review
 +
|-
 +
|[https://www.thieme-connect.de/products/ejournals/abstract/10.1055/s-0038-1649664 Green et al. 1993]
 +
| style="background-color:#91cf61" |Non-randomized part of RCT
 
|-
 
|-
 
|}
 
|}
 +
<div class="toccolours" style="background-color:#b3e2cd">
 
====Immunosuppressive therapy====
 
====Immunosuppressive therapy====
 
*[[Prednisone (Sterapred)]] 1 mg/kg PO once per day
 
*[[Prednisone (Sterapred)]] 1 mg/kg PO once per day
−
 
+
'''Continued for varying durations (see individual papers)'''
 +
</div>
 +
<div class="toccolours" style="background-color:#cbd5e7">
 +
====Subsequent treatment====
 +
*Green et al. 1993, if no response after 21 days: [[#Cyclophosphamide_monotherapy_888|Cyclophosphamide]] versus [[#Cyclophosphamide_.26_Prednisone|Cyclophosphamide & Prednisone]]
 +
</div></div>
 
===References===
 
===References===
−
# Green D, Lechner K. A survey of 215 non-hemophilic patients with inhibitors to Factor VIII. Thromb Haemost. 1981 Jun 30;45(3):200-3. [https://www.ncbi.nlm.nih.gov/pubmed/6792737 PubMed]
+
# '''Case series:''' Green D, Lechner K. A survey of 215 non-hemophilic patients with inhibitors to Factor VIII. Thromb Haemost. 1981 Jun 30;45(3):200-3. [https://pubmed.ncbi.nlm.nih.gov/6792737/ PubMed]
−
# Spero JA, Lewis JH, Hasiba U. Corticosteroid therapy for acquired F VIII:C inhibitors. Br J Haematol. 1981 Aug;48(4):635-42. [https://www.ncbi.nlm.nih.gov/pubmed/6791677 PubMed] content property of [http://hemonc.org HemOnc.org]
+
# '''Case series:''' Spero JA, Lewis JH, Hasiba U. Corticosteroid therapy for acquired F VIII:C inhibitors. Br J Haematol. 1981 Aug;48(4):635-42. [https://doi.org/10.1111/j.1365-2141.1981.00635.x link to original article] [https://pubmed.ncbi.nlm.nih.gov/6791677/ PubMed] content property of [https://hemonc.org HemOnc.org]
−
# Green D, Rademaker AW, Briët E. A prospective, randomized trial of prednisone and cyclophosphamide in the treatment of patients with factor VIII autoantibodies. Thromb Haemost. 1993 Nov 15;70(5):753-7. [https://www.ncbi.nlm.nih.gov/pubmed/8128430 PubMed]
+
# Green D, Rademaker AW, Briët E. A prospective, randomized trial of prednisone and cyclophosphamide in the treatment of patients with factor VIII autoantibodies. Thromb Haemost. 1993 Nov 15;70(5):753-7. [https://www.thieme-connect.de/products/ejournals/abstract/10.1055/s-0038-1649664 link to original article] [https://pubmed.ncbi.nlm.nih.gov/8128430/ PubMed]
−
# Delgado J, Jimenez-Yuste V, Hernandez-Navarro F, Villar A. Acquired haemophilia: review and meta-analysis focused on therapy and prognostic factors. Br J Haematol. 2003 Apr;121(1):21-35. [http://onlinelibrary.wiley.com/doi/10.1046/j.1365-2141.2003.04162.x/abstract link to original article]
+
# '''Review:''' Delgado J, Jimenez-Yuste V, Hernandez-Navarro F, Villar A. Acquired haemophilia: review and meta-analysis focused on therapy and prognostic factors. Br J Haematol. 2003 Apr;121(1):21-35. [https://doi.org/10.1046/j.1365-2141.2003.04162.x link to original article]
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==Rituximab monotherapy {{#subobject:6d79c2|Regimen=1}}==
 
==Rituximab monotherapy {{#subobject:6d79c2|Regimen=1}}==
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{| class="wikitable" style="float:right; margin-left: 5px;"
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<div class="toccolours" style="background-color:#eeeeee">
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===Regimen variant #1, low-dose {{#subobject:3f2f14|Variant=1}}===
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{| class="wikitable" style="width: 40%; text-align:center;"  
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!style="width: 25%"|Study
 +
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
|-
 
|-
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|[[#top|back to top]]
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|[https://doi.org/10.1179/1607845414y.0000000152 Yao et al. 2014]
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|}
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|style="background-color:#ffffbe"|Case report
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===Regimen #1 {{#subobject:3f9925|Variant=1}}===
 
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{| class="wikitable" style="width: 100%; text-align:center;"
 
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!Study
 
−
![[Levels_of_Evidence#Evidence|Evidence]]
 
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|-
 
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|[http://th.schattauer.de/en/contents/archive/issue/1975/manuscript/21293.html Leissinger et al. 2014]
 
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|style="background-color:#91cf61"|Phase II
 
 
|-
 
|-
 
|}
 
|}
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<div class="toccolours" style="background-color:#b3e2cd">
 
====Immunosuppressive therapy====
 
====Immunosuppressive therapy====
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*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once per day on days 1, 8, 15, 22
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*[[Rituximab (Rituxan)]] 100 mg/m<sup>2</sup> IV once per day on days 1, 8, 15, 22
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'''28-day course'''
 
'''28-day course'''
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</div></div><br>
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===Regimen #2 {{#subobject:3f2f14|Variant=1}}===
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<div class="toccolours" style="background-color:#eeeeee">
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{| class="wikitable" style="width: 100%; text-align:center;"  
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===Regimen variant #2, standard-dose {{#subobject:3f9925|Variant=1}}===
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!Study
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{| class="wikitable" style="width: 40%; text-align:center;"  
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![[Levels_of_Evidence#Evidence|Evidence]]
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!style="width: 25%"|Study
 +
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
|-
 
|-
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|[http://www.maneyonline.com/doi/full/10.1179/1607845414Y.0000000152 Yao et al. 2014]
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|[https://doi.org/10.1111/j.1365-2516.2006.01342.x Field et al. 2006]
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|style="background-color:#ffffbe"|Case report
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|style="background-color:#ffffbe"|Case series
 
|-
 
|-
 
|}
 
|}
 +
<div class="toccolours" style="background-color:#b3e2cd">
 
====Immunosuppressive therapy====
 
====Immunosuppressive therapy====
−
*[[Rituximab (Rituxan)]] 100 mg/m<sup>2</sup> IV once per day on days 1, 8, 15, 22
+
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once per day on days 1, 8, 15, 22
−
 
 
 
'''28-day course'''
 
'''28-day course'''
−
 
+
</div></div>
 
===References===
 
===References===
−
# '''Review:''' Franchini M. Rituximab in the treatment of adult acquired hemophilia A: a systematic review. Crit Rev Oncol Hematol. 2007 Jul;63(1):47-52. [http://www.croh-online.com/article/S1040-8428%2806%2900225-3/abstract link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/17236786/ PubMed]
+
# '''Case series:''' Field JJ, Fenske TS, Blinder MA. Rituximab for the treatment of patients with very high-titre acquired factor VIII inhibitors refractory to conventional chemotherapy. Haemophilia. 2007 Jan;13(1):46-50. [https://doi.org/10.1111/j.1365-2516.2006.01342.x link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/17212724/ PubMed]
−
# Kempton CL, Allen G, Hord J, Kruse-Jarres R, Pruthi RK, Walsh C, Young G, Soucie JM. Eradication of factor VIII inhibitors in patients with mild and moderate hemophilia A. Am J Hematol. 2012 Sep;87(9):933-6. [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3645919/ link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/22733686 PubMed]
+
# '''Review:''' Franchini M. Rituximab in the treatment of adult acquired hemophilia A: a systematic review. Crit Rev Oncol Hematol. 2007 Jul;63(1):47-52. [https://doi.org/10.1016/j.critrevonc.2006.11.004 link to original article] [https://pubmed.ncbi.nlm.nih.gov/17236786/ PubMed]
−
# Leissinger C, Josephson CD, Granger S, Konkle BA, Kruse-Jarres R, Ragni MV, Journeycake JM, Valentino L, Key NS, Gill JC, McCrae KR, Neufeld EJ, Manno C, Raffini L, Saxena K, Torres M, Marder V, Bennett CM, Assmann SF. Rituximab for treatment of inhibitors in haemophilia A. A Phase II study. Thromb Haemost. 2014 Sep 2;112(3):445-58. [http://th.schattauer.de/en/contents/archive/issue/1975/manuscript/21293.html link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/24919980 PubMed]
+
# '''Case report:''' Yao Q, Zhu X, Liu Y, Zhang F, Yuan T, Xu J, Wang X. Low-dose rituximab in the treatment of acquired haemophilia. Hematology. 2014 Dec;19(8):483-6. [https://doi.org/10.1179/1607845414y.0000000152 link to original article] [https://pubmed.ncbi.nlm.nih.gov/24611711/ PubMed]
−
# Yao Q, Zhu X, Liu Y, Zhang F, Yuan T, Xu J, Wang X. Low-dose rituximab in the treatment of acquired haemophilia. Hematology. 2014 Dec;19(8):483-6. [http://www.maneyonline.com/doi/full/10.1179/1607845414Y.0000000152 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/24611711 PubMed]
 
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=References=
 
=References=
 
<references/>
 
<references/>
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[[Category:Acquired hemophilia A regimens]]
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[[Category:Acquired coagulopathy regimens]]
 
 
[[Category:Disease-specific pages]]
 
[[Category:Disease-specific pages]]
 
[[Category:Autoimmune hematologic conditions]]
 
[[Category:Autoimmune hematologic conditions]]
 
[[Category:Bleeding disorders]]
 
[[Category:Bleeding disorders]]

Latest revision as of 20:09, 27 June 2024

Back to Top

Section editor
Tillman Benjamin-2.jpg
 Benjamin Tillman, MD
Vanderbilt University
Nashville, TN, USA
LinkedIn
5 regimens on this page
7 variants on this page


This page is meant to cover regimens that are used in the context of acquired factor VIII inhibitors. See the inherited coagulopathy page for regimens relevant to inherited factor deficiency. In the future, we may add other acquired coagulopathy pages such as acquired vWD.
Incidence: 1.48/million/year[1]

Guidelines

Given the rapid change in evidence in many areas of hematology/oncology, readers are encouraged to consider any guideline published 5+ years ago to be for historical purposes, only.

International recommendations

All lines of therapy

Cyclophosphamide & Prednisolone

Regimen

Study Evidence
Collins et al. 2007 Review

Immunosuppressive therapy

References

  1. Review: Collins PW, Hirsch S, Baglin TP, Dolan G, Hanley J, Makris M, Keeling DM, Liesner R, Brown SA, Hay CR; UK Haemophilia Centre Doctors' Organisation. Acquired hemophilia A in the United Kingdom: a 2-year national surveillance study by the United Kingdom Haemophilia Centre Doctors' Organisation. Blood. 2007 Mar 1;109(5):1870-7. link to original article PubMed

Cyclophosphamide & Prednisone

Regimen variant #1

Study Evidence
Shaffer et al. 1997 Case report

Note: Per Shaffer et al. 1997, "the lower ends of these ranges became the standard therapy to minimize side effects"

Immunosuppressive therapy

Continued until therapeutic response "Cyclophosphamide and prednisone were continued at full doses until the factor VIII inhibitor titer decreased to zero; after this, the doses of prednisone and cyclophosphamide were slowly decreased."


Regimen variant #2

Study Evidence
Bayer et al. 1999 Case report

Immunosuppressive therapy

Continued until therapeutic response, then prednisone and cyclophosphamide were tapered slowly


Regimen variant #3

Study Evidence
Green et al. 1993 Randomized, fewer than 20 pts (E-esc)

Preceding treatment

Immunosuppressive therapy

References

  1. Case series: Herbst KD, Rapaport SI, Kenoyer DG, Stanton W, Feinstein DI. Syndrome of an acquired inhibitor of factor VIII responsive to cyclophosphamide and prednisone. Ann Intern Med. 1981 Nov;95(5):575-8. link to original article PubMed
  2. Green D, Rademaker AW, Briët E. A prospective, randomized trial of prednisone and cyclophosphamide in the treatment of patients with factor VIII autoantibodies. Thromb Haemost. 1993 Nov 15;70(5):753-7. link to original article PubMed
  3. Case report: Shaffer LG, Phillips MD. Successful treatment of acquired hemophilia with oral immunosuppressive therapy. Ann Intern Med. 1997 Aug 1;127(3):206-9. link to original article contains dosing details in manuscript PubMed
  4. Case report: Bayer RL, Lichtman SM, Allen SL, Budman DR, Buchbinder A, Fetten J, Kolitz J, Loscalzo J. Acquired factor VIII inhibitors--successful treatment with an oral outpatient regimen. Am J Hematol. 1999 Jan;60(1):70-1. link to original article contains dosing details in manuscript PubMed
  5. Case series: Collins PW, Hirsch S, Baglin TP, Dolan G, Hanley J, Makris M, Keeling DM, Liesner R, Brown SA, Hay CR; UK Haemophilia Centre Doctors' Organisation. Acquired hemophilia A in the United Kingdom: a 2-year national surveillance study by the United Kingdom Haemophilia Centre Doctors' Organisation. Blood. 2007 Mar 1;109(5):1870-7. link to original article PubMed

Prednisolone monotherapy

Regimen

Study Evidence
Collins et al. 2007 Review

Immunosuppressive therapy

References

  1. Review: Collins PW, Hirsch S, Baglin TP, Dolan G, Hanley J, Makris M, Keeling DM, Liesner R, Brown SA, Hay CR; UK Haemophilia Centre Doctors' Organisation. Acquired hemophilia A in the United Kingdom: a 2-year national surveillance study by the United Kingdom Haemophilia Centre Doctors' Organisation. Blood. 2007 Mar 1;109(5):1870-7. link to original article PubMed

Prednisone monotherapy

Regimen

Study Evidence
Green et al. 1981 Case report, review
Green et al. 1993 Non-randomized part of RCT

Immunosuppressive therapy

Continued for varying durations (see individual papers)

Subsequent treatment

References

  1. Case series: Green D, Lechner K. A survey of 215 non-hemophilic patients with inhibitors to Factor VIII. Thromb Haemost. 1981 Jun 30;45(3):200-3. PubMed
  2. Case series: Spero JA, Lewis JH, Hasiba U. Corticosteroid therapy for acquired F VIII:C inhibitors. Br J Haematol. 1981 Aug;48(4):635-42. link to original article PubMed content property of HemOnc.org
  3. Green D, Rademaker AW, Briët E. A prospective, randomized trial of prednisone and cyclophosphamide in the treatment of patients with factor VIII autoantibodies. Thromb Haemost. 1993 Nov 15;70(5):753-7. link to original article PubMed
  4. Review: Delgado J, Jimenez-Yuste V, Hernandez-Navarro F, Villar A. Acquired haemophilia: review and meta-analysis focused on therapy and prognostic factors. Br J Haematol. 2003 Apr;121(1):21-35. link to original article

Rituximab monotherapy

Regimen variant #1, low-dose

Study Evidence
Yao et al. 2014 Case report

Immunosuppressive therapy

28-day course


Regimen variant #2, standard-dose

Study Evidence
Field et al. 2006 Case series

Immunosuppressive therapy

28-day course

References

  1. Case series: Field JJ, Fenske TS, Blinder MA. Rituximab for the treatment of patients with very high-titre acquired factor VIII inhibitors refractory to conventional chemotherapy. Haemophilia. 2007 Jan;13(1):46-50. link to original article contains dosing details in abstract PubMed
  2. Review: Franchini M. Rituximab in the treatment of adult acquired hemophilia A: a systematic review. Crit Rev Oncol Hematol. 2007 Jul;63(1):47-52. link to original article PubMed
  3. Case report: Yao Q, Zhu X, Liu Y, Zhang F, Yuan T, Xu J, Wang X. Low-dose rituximab in the treatment of acquired haemophilia. Hematology. 2014 Dec;19(8):483-6. link to original article PubMed

References

  1. ↑ Collins PW, Hirsch S, Baglin TP, Dolan G, Hanley J, Makris M, Keeling DM, Liesner R, Brown SA, Hay CR; UK Haemophilia Centre Doctors' Organisation. Acquired hemophilia A in the United Kingdom: a 2-year national surveillance study by the United Kingdom Haemophilia Centre Doctors' Organisation. Blood. 2007 Mar 1;109(5):1870-7. link to original article PubMed
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