Factor VIII Inhibitors in Mild and Moderate-severity Haemophilia A

C.R.M. Hay; C.A. Ludlam; B.T. Colvin; F.G.H. Hill; F.E. Preston; N. Wasseem; R. Bagnall; I.R. Peake; E. Berntorp; E.P. Mauser Bunschoten; K. Fijnvandraat; C.K. Kasper; G. White; E. Santagostino; the UK Haemophilia Centre Directors Organisation; on behalf of

doi:10.1055/s-0037-1615061

Thrombosis and Haemostasis, Inhaltsverzeichnis

Thromb Haemost 1998; 79(04): 762-766
DOI: 10.1055/s-0037-1615061

Rapid Communication

Schattauer GmbH

Factor VIII Inhibitors in Mild and Moderate-severity Haemophilia A

Authors

C.R.M. Hay

¹From the Departments of Haematology, Manchester Royal Infirmary, Manchester
C.A. Ludlam

²From the Departments of Haematology, Royal Infirmary of Edinburgh
B.T. Colvin

³From the Departments of Haematology, Royal London Hospital, Whitechapel, London
F.G.H. Hill

⁴From the Departments of Haematology, Birmingham Children’s Hospital, Ladywood, Birmingham
F.E. Preston

⁵From the Departments of Haematology, Royal Hallamshire Hospital, Sheffield, UMDS
N. Wasseem

⁶From the Departments of Haematology, Guys Hospital, London
R. Bagnall

⁶From the Departments of Haematology, Guys Hospital, London
I.R. Peake

⁷From the Departments of Haematology, Dept of Medicine and Pharmacology, University of Sheffield, United Kingdom

the UK Haemophilia Centre Directors Organisation

E. Berntorp

⁸From the Departments of Haematology, University Hospital, Malmö, Sweden
E.P. Mauser Bunschoten

⁹From the Departments of Haematology, Van Creveld Kliniek, Academisch Ziekenhuis, Utrecht, Netherlands
K. Fijnvandraat

¹⁰From the Departments of Haematology, Academic Medical Center, University of Amsterdam, Netherlands
C.K. Kasper

¹¹From the Departments of Haematology, Orthopaedic Hospital, Los Angeles, USA
G. White

¹²From the Departments of Haematology, University of North Carolina at Chapel Hill, N Carolina, USA
E. Santagostino

¹³From the Departments of Haematology, A Bianchi Bonomi Haemophilia Centre, Milan, Italy

Abstract

Summary

Twenty six patients with mild or moderate haemophilia A and inhibitors are described. The inhibitor was detected at a median age of 33 years, after a median of 5.5 bleeding episodes. This usually following intensive replacement therapy. The median presenting inhibitor titre was antihuman 11.6 BU/ml, antiporcine 1.45 BU/ml. Plasma basal factor VIII level declined from a median of 0.08 IU/ml to 0.01 IU/ml following the inhibitor development. This caused spontaneous bleeding in 22 and a bleeding pattern similar to acquired haemophilia in 17. Bleeding was often severe and caused two deaths.

The inhibitor disappeared spontaneously, or following immune tolerance induction, in 16 cases after a median of 9 months (range 0.5-46), with a return to the original baseline VIIIC level and bleeding pattern accompanied inhibitor loss. The inhibitor persisted in the remainder of the cases over a median period of 99 months (range 17-433 months) of follow-up. Inhibitors are an uncommon complication of mild haemophilia which frequently persist and may be associated with severe, life-threatening, haemorrhage.

Forty-one percent of treated haemophilic family members had a history of factor VIII inhibitors, suggesting a familial predisposition to develop inhibitors in these kindreds. Sixteen patients from 11 families were genotyped. Seven different missense mutations affecting the light chain were detected and two in the A2 domain. Five patients from three families had a mutation causing a substitution of Trp²²²⁹ by Cys in the C2 domain which appears to predispose to inhibitor formation since 7 of the 18 affected individuals have a history of inhibitor development.

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Referenzen

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