ANTI-THROMBOTIC EFFECTS OF WARFARIN AND HEPARIN FOLLOWING INFUSIONS OF TISSUE THROMBOPLASTIN IN RABBITS - CLINICAL IMPLICATIONS

Google Scholar
  • 1 January 1979
    • journal article
    • research article
    • Vol. 94  (3) , 481-489
Abstract
An animal model for the production of stasis thrombi was used. Rabbits treated with warfarin (1.5 mg/kg per day) showed a maximal increase in prothrombin time and decreases in factor VII, factor X and prothrombin within 48 h with no additional changes occurring after 10 days of drug administration. Xa [activated factor X] inhibitory activity was unchanged after 48 h of warfarin treatment but was significantly increased by the 10th day. When thrombosis was induced by infusions of 60 .mu.g of tissue thromboplastin, the warfarin regimen produced an antithrombotic effect by the 6th h, which increased to significance by day 2 and was further significantly increased by day 10. The 3 stages correspond to the initial depletion of the vitamin K-dependent clotting factors, the maximal depletion of these proteins and the maximal increase in Xa inhibitory activity, respectively. The antithrombotic potential of warfarin is separated into 2 components: an early effect related to the decrease in factor VII and a delayed augmentation of Xa inhibitory activity. I.v. heparin alone (5 U[units]/kg) did not protect against infusions of 60 .mu.g of tissue thromboplastin but did provide an antithrombotic effect against 45 .mu.g of the same infusate. Higher doses of heparin did protect against infusion of 60 .mu.g of tissue thromboplastin. After 48 h of warfarin treatment, 5 U/kg heparin increased protection against 60 .mu.g of tissue thromboplastin to a degree equivalent to that provided after 10 days of warfarin therapy alone.