The effect of
ancrod-induced defibrinogenation on
thrombosis and bleeding time was determined in anesthetized rats. Functional plasma
fibrinogen levels were reduced 42, 71, 94 and 93% by
ancrod doses of 5, 10, 20 and 30 U/kg, respectively, while a 2.5 U/kg dose was without significant effect.
Ancrod inhibited vena cava
thrombosis induced by partial stasis of blood flow combined with mild
vascular injury.
Thrombus weight was decreased 85 and 93% by the 10 and 20 U/kg doses, but was unaffected at lower doses. In contrast,
ancrod doses of up to 30 U/kg did not significantly decrease carotid artery thrombi formed in response to oxidative transmural vessel injury.
Ancrod caused a dose-dependent increase in bleeding time measured by puncturing small mesenteric arteries with a
hypodermic needle. The bleeding time increase was approximately 38% in response to the 2.5 and 5 U/kg doses, and 182% in response to the 10 U/kg dose. These studies demonstrate that
ancrod-induced reductions in plasma
fibrinogen more effectively inhibit venous compared to arterial
thrombosis, although these activities require doses that also increase bleeding time in small arteries.