Low factor VIII recovery in haemophilia A patients without inhibitor titre is not due to the presence of anti-factor VIII antibodies undetectable by the Bethesda assay.

Measurements of factor VIII (FVIII) recovery in previously untreated patients with haemophilia A were done as part of the clinical trial of safety and efficacy of the recombinant FVIII, Recombinate. In 22 of 72 assessable patients, positive inhibitor titres > or = 0.6 Bethesda units mL-1 were detected by the Bethesda assay in one or more plasma samples, and the remaining 50 patients were negative at all timepoints. Of the latter group, 16 individuals without inhibitors unexpectedly had both normal (111) and low (52) recoveries during the study. We investigated the possibility that other antibodies not detectable in the Bethesda assay were responsible for the low recovery, by using a highly sensitive immunopreciptation (IP) assay for detection of all antiFVIII antibodies. Eight of the 16 patients with low and normal recoveries did indeed have antibodies detected by the IP assay, and the remaining eight were negative. Four antibody-positive individuals had insignificantly low titres, and the other four had modest to high titres. In the latter group, antibodies were found with similar frequencies and titre in plasmas from patients with low or normal recovery. Low recovery in haemophilia A patients without inhibitor titres must therefore be attributed to factors other than antiFVIII.