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Thromb Haemost 1995; 74(06): 1402-1406
DOI: 10.1055/s-0038-1649954
Rapid Communications
Schattauer GmbH Stuttgart

Haemophilia A: Mutation Type Determines Risk of Inhibitor Formation

R Schwaab
1   The Institut für Experimentelle Hämatologie und Transfusionsmedizin, Bonn, Germany
,
H-H Brackmann
1   The Institut für Experimentelle Hämatologie und Transfusionsmedizin, Bonn, Germany
,
C Meyer
1   The Institut für Experimentelle Hämatologie und Transfusionsmedizin, Bonn, Germany
,
J Seehafer
2   The Institut für Hormon- und Fortpflanzungsforschung, Hamburg, Germany
,
M Kirchgesser
1   The Institut für Experimentelle Hämatologie und Transfusionsmedizin, Bonn, Germany
,
A Haack
1   The Institut für Experimentelle Hämatologie und Transfusionsmedizin, Bonn, Germany
,
K Olek
2   The Institut für Hormon- und Fortpflanzungsforschung, Hamburg, Germany
,
E G D Tuddenham
3   The Haemostasis Research Group, M. R. C. Clinical Sciences Centre, Royal Postgraduate Medical School, Hammersmith Hospital, London, UK
,
J Oldenburg
1   The Institut für Experimentelle Hämatologie und Transfusionsmedizin, Bonn, Germany
› Author Affiliations
Further Information

Publication History

Received: 13 April 1995

Accepted after resubmission 30 August 1995

Publication Date:
10 July 2018 (online)

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Summary

The formation of factor VIII antibodies is a major problem for replacement therapy of haemophilia A patients. Antibodies occur in 5-30% of patients with severe haemophilia A. The reason for antibody formation is still unknown. In this study we correlate for the first time different factor VIII gene mutations, stop- and missense mutations, large and small deletions and intrachromosomal intron 22 recombinations to antibody formation. A total of 364 patients with known inhibitor status of our institute, of the database, and of 3 studies representing intron-22-inversion data are included. The results show that the risk for developing factor VIII antibodies is strongly related to stop mutations, large deletions and intrachromosomal recombinations. A probable explanation could be the complete lack of endogenous circulating factor VIII protein in these cases. Other factors that might be important for the pathogenesis of inhibitor formation, e. g. the antenatal period, as well as possible therapeutic effects, are discussed.

 

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