A 4-factor prothrombin complex concentrate (4F-PCC), containing therapeutic doses of vitamin K-dependent coagulation factors, was recently licensed in the United States for reversal of vitamin K antagonist therapy. However, given the emergence of several oral anticoagulants for which there are no specific reversal agents, and the existence of many other complex bleeding disorders, it is likely that clinicians will seek to use 4F-PCCs for any number of off-label indications. Thus, the goal of this review is to explore practical issues regarding 4F-PCC, with an emphasis on issues relevant to blood bankers and pathologists. Specifically, our aims are to (1) examine the role of 4F-PCC in vitamin K antagonist reversal, (2) review its potential use in the treatment of hemorrhage due to novel oral anticoagulants, and (3) explore potential uses in liver disease, trauma-associated bleeding, and rare coagulopathies. Safety and other practical considerations of 4F-PCCs will also be discussed.

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