Acquired hemophilia A

Section editors
	Shruti Chaturvedi, MBBS, MSCI Baltimore, MD LinkedIn		Benjamin Tillman, MD Nashville, TN

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 inhibitors. See the inherited coagulopathy page for regimens relevant to inherited factor deficiency.

Guidelines

• 2009: International Recommendations On The Diagnosis And Treatment Of Patients With Acquired Hemophilia A

Acquired hemophilia A, all lines of therapy

Incidence: 1.48/million/year

Cyclophosphamide & Prednisolone

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Regimen

Study	Evidence
Collins et al. 2007	Review

Immunosuppressive therapy

• Cyclophosphamide (Cytoxan) 1 to 2 mg/kg PO once per day
• Prednisolone (Millipred) 1 mg/kg PO once per day

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

Cyclophosphamide & Prednisone

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Variant #1

Study	Evidence
Shaffer et al. 1997	Case report

Immunosuppressive therapy

• Cyclophosphamide (Cytoxan) 100 to 200 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"

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."

Variant #2

Study	Evidence
Bayer et al. 1999	Case report

Immunosuppressive therapy

• Cyclophosphamide (Cytoxan) 100 PO once per day
• Prednisone (Sterapred) 1 mg/kg PO once per day

Used until therapeutic response. "Prednisone and cyclophosphamide were tapered slowly."

Variant #3

Study	Evidence
Green et al. 1993	Randomized, <20 pts (E)

Preceding treatment

• Prednisone x 21 d, with no response

Immunosuppressive therapy

• Cyclophosphamide (Cytoxan) 2 mg/kg (route not specified) once per day
• Prednisone (Sterapred) 1 mg/kg PO once per day

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. 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 verified protocol PubMed
4. 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 verified protocol 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

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Regimen

Study	Evidence
Collins et al. 2007	Review

Immunosuppressive therapy

• Prednisolone (Millipred) 1 mg/kg PO once per day

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

Prednisone monotherapy

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Regimen

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

Immunosuppressive therapy

• Prednisone (Sterapred) 1 mg/kg PO once per day

Varying duration

Subsequent treatment

• Green et al. 1993, if no response after 21 days: Cyclophosphamide versus Cyclophosphamide & Prednisone

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

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Variant #1, low-dose

Study	Evidence
Yao et al. 2014	Case report

Immunosuppressive therapy

• Rituximab (Rituxan) 100 mg/m² IV once per day on days 1, 8, 15, 22

28-day course

Variant #2, standard-dose

Study	Evidence
Field et al. 2006	Case series

Immunosuppressive therapy

• Rituximab (Rituxan) 375 mg/m² IV once per day on days 1, 8, 15, 22

28-day course

References

1. 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 protocol 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. 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