STUDIES IN INTRAVASCULAR COAGULATION. II. A COMPARISON OF THE EFFECT OF DICUMAROL AND HEPARIN ON CLOT FORMATION IN ISOLATED VENOUS SEGMENTS 1

Abstract

A method was developed for the study of clot formation in isolated venous segments in the dog. Coagulation occurred far more slowly in blood in contact with these endothelial-lined surfaces than in coated vessels currently employed in various in vitro technics. Studies of several phases of the coagulation sequence have demonstrated that a fibrin clot developed prior to the disappearance of demonstrable amts. of prothrombin or the elaboration of measurable quantities of clot accelerators. Since drug-induced hypoprothrombinemia is currently employed to inhibit intravascular coagulation in man, the effects of dicumarol and heparin on fibrin deposition was examined in 43 dogs. Severe dicumarol-induced hypoprothrombinemia and serum prothrombin conversion accelerator (SPCA) deficiency did not demonstrably retard fibrin deposition in an isolated vein segment unless sufficient dicumarol was administered to prolong greatly the in-vitro clotting time. In striking contrast, heparin, in therapeutic doses, significantly retarded clotting in similarly prepared segments. In animals in which both anticoagulants were given there was no evidence that the concomitant hypoprothrombinemia had potentiated the clot retarding effect of heparin. Although it has been previously established that dicumarol does retard intravascular coagulation, it is clear that, under the conditions of these expts. the anticoagulant effect of heparin is superior to that of dicumarol.