FACTOR-VII-DEFICIENT SUBSTRATE PLASMAS DEPLETED OF PROTEIN-C RAISE THE SENSITIVITY OF THE FACTOR-VII BIOASSAY TO ACTIVATED FACTOR-VII - AN INTERNATIONAL STUDY

Plasma from healthy individuals, pregnant women and patients on warfar in were distributed to 3 laboratories supporting major cardiovascular surveys (Northwick Park, Muenster and Houston) for assay of factor VII Coagulant activity (VII(c)) with their own bio-assays. The mean VII(c ) in 147 samples agreed to within 1% of standard in Northwick Park and Houston, but was 14% of standard lower in Muenster owing to its more potent standard. In samples with an increased VII(c) the Northwick Par k assay gave a higher result than the other assays owing to its increa sed responsiveness to activated factor VII (VII(a)). Thus when VII(a) concentrations were determined directly with a clotting assay which ut ilises a soluble recombinant tissue factor, the increase in VII(c) wit h increase in VII(a) was considerably greater with the Northwick Park assay than the Muenster assay. This feature of the Northwick Park assa y was traced to the virtual absence of protein C in its substrate plas ma. Factor V(a) appears rate-limiting for the coagulant expression Of VII(a) in test plasma. If the thrombotic response to release of tissue factor is determined by the circulating concentration of VII(a), then the Northwick Park factor VII bio-assay may be preferable to other bi o-assays currently employed to estimate risk of acute coronary events.