Semin Thromb Hemost 2002; 28(3): 285-290
DOI: 10.1055/s-2002-32664
Copyright © 2002 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA. Tel.: +1(212) 584-4662

Inhibitor Development in Previously Untreated Patients with Hemophilia A: A Prospective Long-Term Follow-Up Comparing Plasma-Derived and Recombinant Products

Wolfhart Kreuz1 , Carmen Escuriola Ettingshausen1 , Alex Zyschka1 , Johannes Oldenburg2 , Inmaculada Martinez Saguer1 , Silke Ehrenforth1 , Thomas Klingebiel1
  • 1The Centre of Pediatrics III, Department of Hematology and Oncology, Comprehensive Care Centre of Thrombosis and Haemostasis, Johann-Wolfgang-Goethe-University Hospital, Frankfurt am Main and the Institute of Human Genetics (J. Oldenburg) University, Würzburg, Germany
  • 2German Red Cross Blood Bank, Frankfurt Am Main, Germany
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Publikationsverlauf

Publikationsdatum:
04. Juli 2002 (online)

ABSTRACT

In order to assess inhibitor development in previously untreated patients (PUPs) with severe (factor VIII [FVIII]<1%) and moderate (FVIII 1 to 5%) hemophilia A, a prospective study was initiated in 1976. During the 23-year study period, 72 hemophiliacs were frequently exposed prophylactically or on demand to plasma-derived (pd) (n = 51) or recombinant FVIII (rFVIII) (n = 21) concentrates (median 270 exposure days [ED]). Inhibitor testing was performed before the first exposure and at regular intervals thereafter. Of the 72 hemophilia A patients, 22 (32%) developed an inhibitor after 15 ED in median (range 4 to 195); 17 (77%) were high responders (>5 Bethesda Units [BU]), and the remaining 5 patients (23%) were low responders (>0.6 to 5 BU). The severely affected patients (n = 46) showed a significantly higher frequency of inhibitor formation (43%) than did the moderate ones (8%). Comparing the severely affected patients receiving pd products exclusively (n = 35) with those treated with recombinant concentrate (n = 11), 37% of the pd group developed a high-titer inhibitor (>5 BU, median 290 ED in noninhibitor patients) and 36% of the recombinant group (median 49 ED in the noninhibitor patients). However, the exposure status of the recombinant noninhibitor patients is rather low and therefore remains a high risk of developing further inhibitors in the future. The mutation type profile revealed no difference between the pd- and the recombinant-treated patients.

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