Haematologica, Vol 94, Issue 8, 1181-1182 doi:10.3324/haematol.2009.011841
Copyright © 2009 by Ferrata Storti Foundation
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Disorders of Hemostasis

Cautions and caveats to the treatment of acquired hemophilia A

Angela Huth-Kühne* on behalf of the International Expert Panel on Acquired Hemophilia (IPAcHe)

* International Expert Panel on Acquired Hemophilia (IPAcHe): Angela Huth-Kühne, Francesco Baudo, Peter Collins, Jørgen Ingerslev, Craig M. Kessler, Hervé Lévesque, Maria Eva Mingot Castellano, Midori Shima and Jean St-Louis

Correspondence: Angela Huth-Kühne, SRH Kurpfalzkrankenhaus and Haemophilia Centre Heidelberg gGmbH, Bonhoefferstrasse 5, 69123 Heidelberg, Germany. E-mail:angela.huth-kuehne{at}kkh.srh.de

Key words: treatment, acquired hemophilia A.

We thank Pier Mannnucci and Flora Peyvandi for their recent editorial1 in which they drew attention to and largely concurred with our international recommendations for the diagnosis and treatment of patients with acquired hemophilia A,2 both published in the April issue of Haematologica. We would, however, like to re-emphasize three important issues relevant to treating patients with autoantibodies to FVIII.

Congenital hemophilia complicated by alloantibodies presents a serious therapeutic challenge in the treatment of bleeding episodes, and several recent studies indeed support the use of rFVIIa in a single large dose (270 mcg/kg) rather than repeated smaller doses in treating hemarthroses in these patients.3,4 Due to safety concerns, we strongly caution against the use of single high-dose rFVIIa in the typically much older and multi-morbid patient population with considerable thromboembolic risk factors who present with bleeding related to acquired hemophilia.5,6 Younger acquired hemophilia patients who bleed post-partum may represent a different patient profile. However, we emphasize that so far there has been no experience with single-dose rFVIIa in acquired hemophilia. It is also important to recognize that joint bleeding in acquired hemophilia is unusual, and because most bleeds are soft, they may not respond well to higher single doses of rFVIIa.

The high risk of life-threatening bleeding in acquired hemophilia patients justifies an aggressive therapeutic approach to inhibitor eradication, with the aim of minimizing the time during which the patient may experience fatal bleeding. While we concur that complications related to immunosuppressive therapy are common,7–9 we emphasize that a rapid eradication of autoantibodies and a short duration of treatment are of primary importance. The literature does not support any preference for treatment with corticosteroids alone compared to combination therapy with cyclophosphamide,8–11 therefore we do not recommend one regimen over the other unless contraindications are present, the patient has been pre-treated with corticosteroids for other conditions or is of child-bearing age.

Due to the variable phenotypic presentation associated with this disorder, patients with acquired hemophilia typically present with either spontaneous or traumatic bleeding or an isolated prolonged pre-operative aPTT without bleeding symptoms. Initial presentation is frequently to a physician unfamiliar and/or inexperienced with the disorder. We agree with Drs Mannucci and Peyvandi that the single most important recommendation to the non-specialist physician confronted with a possible case of acquired hemophilia is to suspect this disorder and seek professional advice from a hemophilia center with expertise in managing inhibitors as soon as possible. Furthermore, guidance for initial emergency treatment if the patient is unstable and cannot be transferred immediately may be beneficial. In order to achieve this goal, a general awareness and understanding of this rare but often fatal disorder within the general medical community is necessary to ensure rapid diagnosis, appropriate treatment and avoid mistreatment such as even minor invasive procedures.

Finally, in the absence of high-level clinical evidence or the means with which to generate data in this rare and diverse patient population, we encourage all physicians who treat patients with acquired hemophilia to actively contribute to existing registries that document and monitor patient management and outcomes.


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References
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 References
 
  1. Mannucci PM, Peyvandi F. Autoimmune hemophilia at rescue. Haematologica 2009;94:459-61.[Free Full Text]
  2. Huth-Kuhne A, Baudo F, Collins P, Ingerslev J, Kessler CM, Levesque H, et al. International recommendations on the diagnosis and treatment of patients with acquired hemophilia A. Haematologica 2009;94:566-75.[Abstract/Free Full Text]
  3. Kavakli K, Makris M, Zulfikar B, Erhardtsen E, Abrams ZS, Kenet G. Home treatment of haemarthroses using a single dose regimen of recombinant activated factor VII in patients with haemophilia and inhibitors. A multi-centre, randomised, double-blind, cross-over trial. Thromb Haemost 2006;95:600-5.[Web of Science][Medline]
  4. Santagostino E, Mancuso ME, Rocino A, Mancuso G, Scaraggi F, Mannucci PM. A prospective randomized trial of high and standard dosages of recombinant factor VIIa for treatment of hemarthroses in hemophiliacs with inhibitors. J Thromb Haemost 2006;4:367-71.[CrossRef][Web of Science][Medline]
  5. Hay CR, Brown S, Collins PW, Keeling DM, Liesner R. The diagnosis and management of factor VIII and IX inhibitors: a guideline from the United Kingdom Haemophilia Centre Doctors Organisation. Br J Haematol 2006;133:591-605.[CrossRef][Web of Science][Medline]
  6. Guillet B, Pinganaud C, Proulle V, Dreyfus M, Lambert T. Myocardial infarction occurring in a case of acquired haemophilia during the treatment course with recombinant activated factor VII. Thromb Haemost 2002;88:698-9.[Web of Science][Medline]
  7. 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;121:21-35.[CrossRef][Web of Science][Medline]
  8. Borg JY, Levesque H, for the SACHA study group. Epidemiology and one-year outcomes in patients with acquired hemophilia in France. J Thromb Haemost 2007;5 Suppl_1: O-M-062.
  9. Collins PW, Hirsch S, Baglin TP, Dolan G, Hanley J, Makris M, et al. Acquired hemophilia A in the United Kingdom: a 2-year national surveillance study by the United Kingdom Haemophilia Centre Doctors' Organisation. Blood 2007;109:1870-7.[Abstract/Free Full Text]
  10. Green D, Rademaker AW, Briet E. A prospective, randomized trial of prednisone and cyclophosphamide in the treatment of patients with factor VIII autoantibodies. Thromb Haemost 1993;70:753-7.[Web of Science][Medline]
  11. Sperr WR, Lechner K, Pabinger I. Rituximab for the treatment of acquired antibodies to factor VIII. Haematologica 2007;92:66-71.[Abstract/Free Full Text]




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