The effect of warfarin, heparin, and modern directly acting oral anticoagulants (dabigatran etexilate, rivaroxaban, apixaban) on the level of coagulation factors: V, VII, VIII, IX, XII, WF

Abstract

Heparin is common initial therapy administered to subjects with acute venous thromboembolism. Routine clinical practice in this case consists of immediate heparin therapy initiation and administration of warfarin sodium within 24 hours; administration of heparin is usually finished in 5 days. Patients with CF-LVAD (continuous flow left ventricular assist device) are also administered intravenous unfractionated heparin. Heparin mainly serves as anticoagulant via catalyzing antithrombin, which leads to factor II (thrombin), factor X inhibition, with smaller effect on IX, XI, XII. During the last 50 years warfarin has been the most common anticoagulant from vitamin K antagonists group which is used to treat patients with high risk of developing arterial and venous thrombosis. It has narrow therapeutic window due to unfavorable pharmacokinetics, thus requiring frequent monitoring, and it’s affected by interaction with concomitant medications and foods. Apart from this, effect of warfarin is not limited to the influence on hemostasis; it also has impact on all vitamin K-related proteins. Warfarin shows its anticoagulant effect through decreasing functional levels of vitamin K-related factors II, VII, IX and X. Synthesis of two physiologic anticoagulants — C and S proteins — is blocked at the same time. Warfarin competes with vitamin K, thus blocking vitamin K effects. Modern directly acting oral anticoagulants: direct thrombin inhibitor dabigatran and Xa factor inhibitors — rivaroxaban and apixaban, were developed as an alternative to warfarin. They also show non-hemostatic vascular effects via protease activated receptors (PARs).