The antiplatelet activity of ancrod on administration to rabbits.
Ancrod, a thrombin-like enzyme purified from the venom of Calloselasma rhodostoma, was administered to rabbits intravenously, and blood samples were obtained at 1, 3, 6, 10, and 24 hours after infusion. Ancrod caused a rapid and sustained defibrinogenation within the first 6 hours, with production of fibrinogen degradation products (FDPs) peaking at 1 hour and declining to background level at 6 hours. No significant changes in platelet count, white cell count, or hematocrit was observed. Citrated PRP prepared 1, 3, and 6 hours after ancrod infusion showed diminished aggregation, adenosine triphosphate (ATP) release, and thromboxane B2 formation on the addition of collagen. Although platelet suspension prepared from defibrinogenated platelet-rich plasma (PRP) at 3 hours showed no significant change in aggregation and ATP-releasing activity, the latent period of platelet aggregation was prolonged. When the remaining platelet-poor plasma obtained from defibrinogenated PRP at 3 hours was used to suspend the normal washed platelets prepared from PRP before ancrod infusion, the platelets showed a similar defect in aggregation and release action. Addition of fibrinogen (200 micrograms/ml to 2 mg/ml) to the above preparation partially restored aggregation but not capacity for secretion and thromboxane formation. When normal washed platelets were suspended with the defibrinogenated plasma, prepared by mixing ancrod with normal plasma in vitro and removing the formed fibrin, the platelet suspension showed impaired platelet aggregability, and the aggregability could be restored to the normal level by the addition of exogenous fibrinogen to this preparation.(ABSTRACT TRUNCATED AT 250 WORDS)
Chang
M C
MC
Pharmacological Institute, College of Medicine, National Taiwan University.
Huang
T F
TF
D000721:Ancrod / Q000494:pharmacology*; D000818:Animals; D011464:Epoprostenol / Q000096:biosynthesis; D005260:Female; D005338:Fibrin Fibrinogen Degradation Products / Q000032:analysis; D005340:Fibrinogen / Q000032:analysis / Q000494:pharmacology; D008297:Male; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D011817:Rabbits
D005338:Fibrin Fibrinogen Degradation Products; D010975:Platelet Aggregation Inhibitors; D005340:Fibrinogen; D011464:Epoprostenol; D000721:Ancrod