For most medical conditions requiring anticoagulation, the target international normalized ratio (INR) is 2.0 to 3.0. Two notable exceptions to this general rule are patients with mechanical heart valves and antiphospholipid antibody syndrome, who require more intense anticoagulation, with a goal INR of 2.5 to 3.5. A prolonged INR without clinically evident bleeding necessitates cessation of warfarin administration, observation, and serial INR measurements.

Patients on warfarin who experience clinically significant bleeding are eligible for reversal of their anticoagulation with three approaches: (1) stop warfarin therapy, (2) administer vitamin K, and (3) administer fresh frozen plasma (FFP) or prothrombin complex concentrates (PCCs).³

Vitamin K is often included in first-line therapy for the reversal of anticoagulation. However, normalization of INR values with only vitamin K is often slow because of the time needed for hepatic synthesis of vitamin K dependent coagulation factors. While the increase in factor VII following intravenous vitamin K administration causes the INR to fall within 4 hours, the more important increase in factor II requires 24 hours to affect the INR. This correction of coagulation factor levels takes even longer with administration of oral vitamin K.

Because of this delay to optimal reversal, it is recommended to combine vitamin K therapy with fresh frozen plasma or prothrombin complex concentrates.

Fresh frozen plasma contains all vitamin K–dependent factors and is often used in conjunction with vitamin K and prothrombin complex concentrates. However, one significant side effect remains the volume-associated sequelae from fluid overload suffered as a result of infusion. Additionally, FFP is the most commonly blamed blood product in transfusion-related acute lung injury (TRALI), and the risks and benefits of transfusion must be carefully weighed in each patient. ²

Prothrombin complex concentrates (PCCs) provide an extremely rapid and effective method to replace deficient clotting factors and correct INR. PCCs are pooled plasma products that contain factors I, IX, and X with variable amounts of factor VII and proteins C and S. When compared with Vitamin K administration, PCC injection obtained maximum correction of INR after 30 minutes compared to 24 hours after IV vitamin K administration.¹