Effect of vitamin K antagonists on coagulation factors and illustration of transient hypercoagulability

The graph illustrates the pharmacologic basis for providing overlap with heparin during initial warfarin anticoagulation in patients with DVT and other thromboses.

• Factor VII and protein C (PC) have similar short half-lives of approximately 6 hours (up to 9 hours for PC) and are the first vitamin K-dependent clotting factors to decline following warfarin initiation.
• FVII deficiency causes the PT to be prolonged but is not sufficient to produce an antithrombotic effect, which requires deficiency of FX or prothrombin (factor II).
• Full antithrombotic effect occurs when deficiency of FX or prothrombin occurs (factor level <25%). FX half-life is approximately 40 hours and prothrombin approximately 60 hours.
• Thus, there is a transient procoagulant effect before the antithrombotic effect occurs.

The curves represent average values among 4 patients with DVT treated with warfarin 30 mg on day 1, followed by 20 mg on day 2, followed by 10 mg daily. Factor half-lives are approximate.