Summary
The role of factor VIIa in haemostasis has been studied using a canine model of factor
VIII deficiency. Highly purified human factor VIIa was administered to dogs at a dosage
of 0.5 μg/kg. At selected times pre- and post-infusion, haemostasis was evaluated
by the cuticle bleeding time. Plasma was collected for the assay of various parameters,
including fibrinopeptide A (FPA) as a marker for thrombin generation in vivo. Factor
VIIa infusion resulted in a 6-fold increase of factor VII clotting activity with z
t1/2 of 2 h. FPA levels which were 1.4 ng/ml before infusion, did not increase significantly
in haemophilic dogs. In normal dogs, however, FPA levels rose to a mean value of 190
ng/ml 30 min post-infusion. It appeared that thrombin generation by factor VIIa infusion
had occurred mainly via the intrinsic, factor VIIIdependent pathway. In factor VIII-deficient
dogs, factor VIIa infusion did not correct cuticle bleeding, but an inconsistent haemostatic
effect was observed 15–30 min post-infusion. Similar results were obtained in haemophilic
dogs with circulating antibodies against factor VIII. The haemostatic effectivity
could not be improved by increasing the factor VIIa dosage up to 40-fold. Although
these data suggest that the extrinsic, factor VIIdependent factor X activation provides
only a minor pathway of thrombin generation in vivo, it is possible that the suboptimal
haemostatic effect noted may be promoted in bleeding situations where tissue factor
availability is less limited. As such, factor VIIa may prove useful in the treatment
of haemophilia A patients with acquired inhibitors to factor VIII.
