Moderate Anticoagulation by Salicylate Prevents Thrombosis Without Bleeding Complications. An Experimental Study in Rats

Biochem Pharmacol. 1988 Dec 15;37(24):4743-5. doi: 10.1016/0006-2952(88)90346-2.

Abstract

It has previously been shown that salicylate (S) acts as a vitamin K (vit K)-antagonist inducing a decrease in plasma levels of vit K-dependent clotting factors and inhibiting the vit K-dependent carboxylation reaction in the liver. In this study we evaluated whether this biochemical effect had a possible functional role. Indeed, we tested in rats the antithrombotic potency of S (175 mg/kg/i.p. twice a day for 3 days) on experimentally induced venous thrombosis. Its possible haemorrhagic effect was evaluated by measuring the bleeding time. Low-dose warfarin (W) (0.2, 0.1, 0.1 mg/kg/i.v. for 3 days) was utilized as control drug. To check for a possible potentiation between S and W, we tested the effects of their combination (S + W). Thrombotest was used to monitor the anticoagulant effect of each treatment. The incidence of thrombus formation, after venous stasis, was not significantly affected by any of the treatments used, but a significant reduction in thrombus weight was observed after either S or W treatment. Both drugs partially prolonged the Thrombotest without affecting either the bleeding time or the peri-operative mortality (mainly due to internal bleeding). When the combination S + W was used, no significant benefit was observed on the prevention of thrombus incidence or weight, although a marked Thrombotest prolongation was recorded. On the other hand this combination resulted in a pronounced bleeding tendency, as expressed in a significant prolongation of bleeding time and increased total mortality. Thus S, at doses inducing moderate anticoagulation may prevent venous thrombosis without relevant bleeding complications.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anticoagulants*
  • Drug Interactions
  • Male
  • Rats
  • Salicylates / administration & dosage
  • Salicylates / pharmacology*
  • Salicylic Acid
  • Thrombophlebitis / prevention & control*
  • Warfarin / administration & dosage
  • Warfarin / pharmacology

Substances

  • Anticoagulants
  • Salicylates
  • Warfarin
  • Salicylic Acid