Rituximab in der Behandlung der erworbenen Hämophilie A bei einem Patienten mit Polymyalgia rheumatica

L. Braunert; M. Bruegel; C. Pfrepper; J. Thiery; D. Niederwieser

doi:10.1055/s-0037-1619069

Hämostaseologie, Table of Contents

Hamostaseologie 2010; 30(S 01): S40-S43
DOI: 10.1055/s-0037-1619069

Case report

Schattauer GmbH

Rituximab in der Behandlung der erworbenen Hämophilie A bei einem Patienten mit Polymyalgia rheumatica

Rituximab in the treatment of acquired haemophilia A in a patient with polymyalgia rheumatica

Authors

L. Braunert

¹Department of Internal Medicine, Division of Hematology/Oncology/Hemostasis, University of Leipzig
M. Bruegel

²Institute of Laboratory Medicine, Clinical Chemistry and Molecular Diagnostics, University of Leipzig
C. Pfrepper

¹Department of Internal Medicine, Division of Hematology/Oncology/Hemostasis, University of Leipzig
J. Thiery

²Institute of Laboratory Medicine, Clinical Chemistry and Molecular Diagnostics, University of Leipzig
D. Niederwieser

¹Department of Internal Medicine, Division of Hematology/Oncology/Hemostasis, University of Leipzig

Abstract

Summary

Acquired hemophilia A is a rare but potentially life-threatening bleeding disorder. It is caused by the development of autoantibodies directed against coagulation factor VIII in adults or elderly patients, who do not have a personal or family history of bleeding. Case: A man (age: 76 years) on prednisone and leflunomide for polymyalgia rheumatica developed spontaneous severe haematomas. The patient was diagnosed with acquired factor VIII deficiency (FVIII activity 1.2%, FVIII inhibitor 31.7 BU). Due to the active bleeding diathesis, treatment was administered with activated prothrombin complex concentrates (FEIBA®, Baxter). Immunosuppressive treatment with a combination of oral prednisone (1 mg/kg daily) and cyclophosphamide (1,5 mg/kg daily) was administered to reduce the FVIII inhibitor. However, after two weeks of treatment, FVIII was only 3% and no clinical improvement was observed. Treatment with the anti CD20 monoclonal antibody rituximab intravenously at 375 mg/m² once weekly for four consecutive weeks was started. The patient showed rapid clinical improvement following rituximab treatment. He achieved a complete remission defined as return to normal FVIII activity and undetectable FVIII inhibitor titer. After a follow-up of six months no relapse occurred. Conclusion: Rituximab appears an effective and well-tolerated treatment for patients with acquired haemophilia.

Zusammenfassung:

Die erworbene Hämophilie A ist eine seltene mit einer lebensbedrohlichen Blutungsneigung einhergehende Gerinnungsstörung. Sie wird verursacht durch Autoantikörper gegen den Gerinnungsfaktor VIII und tritt bei bisher gerinnungsunauffälligen erwachsenen Patienten auf. Kasuistik: Ein 76-jähriger Patient mit Polymyalgia rheumatica entwickelt plötzlich eine spontane Blutungsneigung. In der Gerinnungsdiagnostik fällt eine verminderte Faktor-VIII-Aktivität (1,2%) auf, bei Nachweis eines Faktor-VIII-Inhibitors (31,7 BU) im Bethesda-Assay. Damit wird die Diagnose einer erworbenen Hämophilie A gestellt. Zur Therapie der akuten Blutungssituation erfolgt die Gabe von aktiviertem Prothrombinkomplexkonzentrat (FEIBA®, Baxter). Die immunsuppressive Behandlung wird mit Prednisolon (pro Tag 1 mg/kg) und Cyclophosphamid (pro Tag 1,5 mg/kg) begonnen. Bei fehlendem Ansprechen wird nach zwei Wochen eine Behandlung mit dem CD20-Antikörper Rituximab eingeleitet (375 mg/m² i. v. wöchentlich für 4 Wochen). Der Patient zeigte rasche klinische Besserung der Blutungsneigung und erreicht eine komplette Remission mit normaler Faktor-VIII-Aktivität bei fehlendem Nachweis eines Hemmkörpers. Sechs Monate nach Ende der Therapie befindet sich der Patient in anhaltender kompletter Remission. Schlussfolgerung: Rituximab ermöglicht eine effektive und gut verträgliche Behandlung der auf Steroide und Cyclophosphamid resistenten erworbenen Hemmkörperhämophilie.

Keywords

Acquired haemophilia - rituximab - polymyalgia rheumatica

Schlüsselwörter

Erworbene Hämophilie - Rituximab - Polymyalgia rheumatica

Full Text

References

Literatur
1 Abshire T, Kenet G. Recombinant factor VIIa: review of efficacy, dosing regimens and safety in patients with congenital and acquired factor VIII or IX inhibitors. J Thromb Haemost 2004; 02: 899-909.
2 Aggarwal A, Grewal R, Green RJ. et al. Rituximab for autoimmune haemophilia: a proposed treatment algorithm. Haemophilia 2005; 11: 13-19.
3 Baxter Corp. FEIBA VH Anti-inhibitor coagulant complex Vapor Heated Summary of Product Characteristics. 2005
4 Borg JY, Levesque H. for the SACHA study group. Epidemiology and one-year outcomes in patients with acquired haemophilia in France. J Thromb Haemost. 2007 05. (Suppl 1): O-M-062.
5 Collins PW, Hirsch S, Baglin TP. et al. Acquired hemophilia A in the United Kingdom Haemophilia Centre Doctors Organisation. Blood 2007; 109: 1870-1877.
6 Croom KF, McCormack PL. Recombinant factor VIIa (eptacog α): a review of ist use in congenital hemophilia with inhibitors, acquired hemophilia, and other congenital bleeding disorders. BioDrugs 2008; 22: 121-136.
7 Delgado J, Jimenenz-Yuste V, Hernandez-Navarro F. et al. Acquired haemophilia: review and metaanalysis focused on therapy and prognostic factors. Br J Haematol 2003; 121: 21-35.
8 Dimichele D, Negrier C. A retrospective postlicensure survey of FEIBA efficacy and safety. Haemophilia 2006; 12: 352-362.
9 Franchini M. Recombinant factor VIIa: a review on its clinical use. Int J Hematol 2006; 83: 126-138.
10 Franchini M. Rituximab in the treatment of adult acquired hemophilia A: a systemic review. Crit Rev Oncol Hematol 2007; 63: 47-52.
11 Green D, Lechner K. A survey of 215 non-hemophilic patients with inhibitors to factor VIII. Thromb Haemost 1981; 45: 200-203.
12 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: 753-757.
13 Huth-Kühne A, Baudo F, Collins P. et al. International recommendations on the diagnosis and treatment of patients with acquired hemophilia A. Haematologica 2009; 94: 566-1182.
14 Kain S, Copeland TS, Leahy MF. Treatment of refractory autoimmune (acquired) haemophilia with anti-CD 20 (rituximab). Br J Haematol 2002; 119: 578.
15 Kessler CM. New perspectives in hemophilia treatment. Hematology Am Soc Hematol Educ Program. 2005: 429-435.
16 Knöbl P, Spannagl M. (Hrsg). Erworbene Hemmkörper-Hämophilie. Stuttgart: Ligatur; 2009
17 Leissinger CA, Becton DL, Ewing NP. et al. Prophylactic treatment with activated prothrombin complex concentrate (FEIBA) reduces the frequency of bleeding episodes in paediatric patients with haemophilia A and inhibitors. Haemophilia 2007; 13: 249-255.
18 Lottenberg R, Kentro TB, Kitchens CS. Acquired hemophilia. A natural history study of 16 patients with factor VIII inhibitors receiving little or no therapy. Arch Intern Med 1987; 147: 1077-1081.
19 Ma AD, Carrizosa D. Acquired factor VIII inhibitors: pathophysiology and treatment. Haematology Am Soc Hematol educ Program. 2006: 432-437.
20 Maillard H, Launay D, Hachulla E. et al. Rituximab in postpartum-related acquired hemophilia. Am J Med 2006; 119: 86-88.
21 Novo Nordisc Health Care AG. NovoSeven Summary of Product Characteristics. 2006
22 Roberts HR, Monroe DM, White GC. The use of recombinat factor VIIa in the treatment of bleeding disorders. Blood 2004; 104: 3858-3864.
23 Sallah S. Treatment of acquired haemophilia with factor eight inhibitor bypassing activity. Haemophilia 2004; 10: 169-173.
24 Sperr WR, Lechner K, Pabinger I. Rituximab fort he treatment of acquired antibodies to factor VIII. Haematologica 2007; 92: 66-71.
25 Sumner MJ, Geldziler BD, Pedersen M. et al. Treatment of acquired hemophilia with recombinant activated FVII:a critical appraisal. Haemophilia 2007; 13: 451-461.
26 Wiestner A, Cho HJ, Asch AS. et al. Rituximab in the treament of aquired FVIII inhibitors. Blood 2002; 100: 3426-3428.