Summary
Antibodies to factor VIII (inhibitors) are usually produced at the beginning of treatment
with factor VIII and are rare in multitransfused patients. Such antibodies are deemed
to be patient-related, as supported by the description of a number of associated risk
factors. However, a second category of inhibitors has recently been identified, namely
antibodies occurring in multitransfused patients as a result of exposure to a particular
factor VIII concentrate. A first outbreak of product-related inhibitors was recently
described. The present paper describes the second well-documented occurrence of such
inhibitors.
Eight out of 140 multitransfused patients with severe haemophilia A developed an inhibitor
to factor VIII shortly after changing treatment to a double-virus inactivated plasma-derived
factor VIII concentrate. In addition to solvent-detergent treatment, this concentrate
was pasteurised at 63° C for 10 hours. Exposure to the pasteurised product before
inhibitor detection ranged from 9 to 45 days. Inhibitor titers varied between 2.2
and 60 Bethesda Units and recovery of transfused factor VIII ranged from 0.21 to 0.68
(expressed as IU/dl factor VIII rise per IU/kg administered). In contrast to usual
inhibitors in haemophilia A patients, these product-related inhibitors showed complex
inhibition kinetics. They were found specific for the factor VIII light chain. The
inhibitors gradually declined when exposure to the pasteurised product was stopped,
despite further treatment with other factor VIII concentrates. The present data stress
the importance of carefully monitored clinical studies, both in previously treated
and previously untreated patients, before introduction of a new or modified clotting
factor concentrate.
