Warfarin is the most commonly used agent for long-term anticoagulation in the setting of venous thromboses and pulmonary thromboembolism.  Warfarin inhibits the vitamin K dependent g-carboxylation of the glutamic acid residues of clotting factors II, VII, IX and X, causing production of dysfunctional coagulation proteins.

The therapeutic effect of warfarin is monitored by measuring the prothrombin time (PT).  The international normalized ratio (INR) is a standardized PT.  The target INR for therapeutic warfarin anticoagulation is 2-3.   Bleeding is a common complication of warfarin therapy and the risk is increased with INRs above 3.0.  Treatment of life-threatening bleeding requires rapid reversal using fresh frozen plasma.  Vitamin K can help to reverse warfarin action, but the effects take time.

(Choice B)  Protamine is used for heparin reversal.  It acts by binding and chemically inactivating heparin.

(Choice C)  Aminocaproic acid is an antifibrinolytic agent that inhibits plasminogen activators and, to a lesser degree, antiplasmin activity.  Aminocaproic acid helps achieve hemostasis when fibrinolysis is the cause of bleeding.

(Choice E)  Whereas fresh frozen plasma contains all of the coagulation factors, cryoprecipitate contains only cold-soluble proteins (Factor VIII, fibrinogen, von Willebrand factor, and vitronectin).

(Choice F)  Desmopressin is a synthetic analogue of anti-diuretic hormone (ADH) used in the treatment of diabetes insipidus.  At high doses, desmopressin increases factor VIII activity in patients with hemophilia A and von Willebrand disease.  High-dose desmopressin can help control bleeding associated with these disorders.

Educational Objective:
Both vitamin K and fresh frozen plasma are used for reversing warfarin-induced anticoagulation.  Fresh frozen plasma rapidly reverses warfarin's effects whereas vitamin K requires time for clotting factor re-synthesis.