Summary
This study examined dose-response relationships between activated recombinant factorVII
(rFVIIa) and (1) in vivo haemostasis and (2) in vitro measures of coagulation and platelet function. Anesthetized swine were used. Ear
bleeding time (BT) was measured and blood was sampled following increasing doses of
rFVIIa (0, 90, 180, 360 and 720 μg/kg; n = 6) or saline (n = 6). BT was not altered
by rFVIIa. Prothrombin time (PT) using standard or pig-specific methods was decreased
by rFVIIa. Activated clotting time (ACT) was decreased by rFVIIa. Thromboelastography
using collagen (COLL) or pig thromboplastin (p-ThP) as agonist demonstrated shorter
reaction times, shortened time to reach maximum velocity of clot formation, and increased
α -angle in the presence of rFVIIa. rFVIIa dosing increased maximum velocity of clot
formation when p-ThP was used to initiate the reaction but not when COLL was used.
rFVIIa at the highest concentration increased maximum amplitude when COLL was used
to initiate the reaction. Platelet aggregation was not altered by rFVIIa. Following
completion of the dose escalation phase, a severe liver injury was produced. rFVIIa
altered neither blood loss nor survival time following injury but improved mean arterial
pressure. A small increase in systemic thrombin-antithrombin III complex occurred
after administration of rFVIIa at doses of 180 μg/kg and above. However, there was
no histological evidence of intravascular coagulation after rFVIIa administration.
In summary, rFVIIa activity was detectable in vitro but did not change haemostasis
in normal swine.
Keywords
Pharmacological haemostasis - liver injury - trauma - thromboelastography
