Four-factor prothrombin complex concentrate for urgent reversal of vitamin K antagonists in patients with major bleeding.

V itamin K antagonists (VKAs), such as warfarin, are widely used for prevention and treatment of arterial and venous thrombosis. Although oral or intravenous vitamin K and fresh frozen plasma are often used to reverse the antico-agulant effects of warfarin in patients who are bleeding, this approach has important limitations. Restoration of hemosta-sis with vitamin K relies on the hepatic synthesis of vitamin K–dependent procoagulant proteins, factors II (prothrombin), VII, IX, and X, a process that takes >6 hours. Fresh frozen plasma provides an immediate source of functional vitamin K–dependent clotting proteins, but large volumes are often required to normalize the international normalized ratio (INR). This can be problematic because it takes time to match blood type and thaw and infuse fresh frozen plasma, and the large volumes can lead to fluid overload, particularly in patients with compromised cardiac or renal function. Prothrombin complex concentrate (PCC) provides an alternative to fresh frozen plasma for reversal of VKA-induced coagulopathy (Table). Originally developed as a source of factor IX for treatment of patients with hemophilia B, 3-factor PCC contains factors II, IX, and X but little or no factor VII. In contrast to 3-factor PCC, 4-factor PCC also contains significant amounts of factor VII. Both 3-and 4-factor PCC contain protein C and protein S, and some may also contain small amounts of heparin, which is added to prevent activation of the clotting proteins. PCC contains the vitamin K-dependent clotting proteins in a lyophilized form and can be stored at room temperature for several years. No thawing or blood-type matching is required, and after reconstitution with a small volume of sterile water (20–40 mL), PCC can be rapidly administered without risk of fluid overload. Additional advantages of PCC over fresh frozen plasma include a negligible risk of viral transmission and transfusion-related acute lung injury. 1 Potential disadvantages of PCC are increased cost compared with fresh frozen plasma and a small risk of thromboembolic complications. 2 Both plasma and PCC require coadministration of vitamin K for sustained warfarin reversal because the half-life of factor VII, a key vitamin K–dependent clotting factor, is only 6 to 8 hours, whereas warfarin has a half-life of several days. Current guidelines recommend 4-factor PCC for situations where rapid reversal of VKA-induced coagulopathy is needed, such as in patients who require urgent surgery or in those with a life-threatening bleed. If 4-factor PCC is unavailable, 3-factor PCC can be …