Date of Award


Document Type


Degree Name

Master of Science (M.S.)


Graduate School

First Advisor

Katherine Knapp

First Committee Member

Warren J. Schneider

Second Committee Member

James W. Blankenship

Third Committee Member

Alice S. Hunter

Fourth Committee Member

Kathryn A. Taubert


Continuing the study of the relationships between fibrin investment of the tumor, vascularity, and tumor growth, we decided to investigate the relationship of warfarin sodium anticoagulation with tumor growth and vascularization. It was reasoned that if the previously observed altered tumor growth was due the heparin’s anticoagulant effect rather than a direct effect upon the tumor, another anticoagulant with a different mechanism of action would have the same tumor growth reducing capabilities. Warfarin sodium produces reduced fibrin polymer formation by a mechanism entirely different from that of heparin. Heparins’ immediate anticoagulant activity results from a blockade of thrombin’s activity results from a blockade of thrombin’s activity on fibrinogen, prevention of prothrombin conversion to thrombin, and a reduction in platelet adhesiveness. Warfarin’s delayed activity, however, is through an inhibition of vitamin K activity leading to reduced synthesis of several clotting factors. With the decision to use warfarin sodium, experiments were designed to test the hypothesis that a reduction of prevention of fibrin formation and thus tumor encasement with this polymer would alter tumor growth. It was also hypothesized that, accompanying the altered tumor growth, several macroscopic factors including tumor vascularization, extent of tumor attachment, vasodilation of host blood vessels in the locale of the implanted tumor, and local edema fluid would be altered. Experiments were conducted to determine the relationship between the dose of warfarin sodium administered and the degree of alteration of tumor growth and the related factors. An inverse dose-response relationship between dose of warfarin and tumor growth and the related parameters was hypothesized.





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