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

Measurements of factor VIII (FVIII) recovery in previously untreated patien ts with haemophilia A were done as part of the clinical trial of safety and efficacy of the recombinant FVIII, Recombinate(TM). In 22 of 72 assessable patients, positive inhibitor titres greater than or equal to 0.6 Bethesda units mL(-1) were detected by the Bethesda assay in one or more plasma samp les, and the remaining 50 patients were negative at all timepoints. Of the latter group, 16 individuals without inhibitors unexpectedly had both norma l (111) and low (52) recoveries during the study. We investigated the possi bility that other antibodies not detectable in the Bethesda assay were resp onsible for the low recovery, by using a highly sensitive immunopreciptatio n (IP) assay for detection of all antiFVIII antibodies. Eight of the 16 pat ients with low and normal recoveries did indeed have antibodies detected by the IP assay, and the remaining eight were negative. Four antibody-positiv e Individuals had insignificantly low titres, and the other four had modest to high titres. In the latter group, antibodies were found with similar fr equencies and titre in plasmas from patients with low or normal recovery. L ow recovery in haemophilia A patients without inhibitor titres must therefo re be attributed to factors other than antiFVIII.