title: Prothrombin Complex Concentrates for Bleeding in the Perioperative Setting.
abstract: Prothrombin complex concentrates (PCCs) contain vitamin K-dependent clotting factors (II, VII, IX, and X) and are marketed as 3 or 4 factor-PCC formulations depending on the concentrations of factor VII. PCCs rapidly restore deficient coagulation factor concentrations to achieve hemostasis, but like with all procoagulants, the effect is balanced against thromboembolic risk. The latter is dependent on both the dose of PCCs and the individual patient prothrombotic predisposition. PCCs are approved by the US Food and Drug Administration for the reversal of vitamin K antagonists in the setting of coagulopathy or bleeding and, therefore, can be administered when urgent surgery is required in patients taking warfarin. However, there is growing experience with the off-label use of PCCs to treat patients with surgical coagulopathic bleeding. Despite their increasing use, there are limited prospective data related to the safety, efficacy, and dosing of PCCs for this indication. PCC administration in the perioperative setting may be tailored to the individual patient based on the laboratory and clinical variables, including point-of-care coagulation testing, to balance hemostatic benefits while minimizing the prothrombotic risk. Importantly, in patients with perioperative bleeding, other considerations should include treating additional sources of coagulopathy such as hypofibrinogenemia, thrombocytopenia, and platelet disorders or surgical sources of bleeding. Thromboembolic risk from excessive PCC dosing may be present well into the postoperative period after hemostasis is achieved owing to the relatively long half-life of prothrombin (factor II, 60-72 hours). The integration of PCCs into comprehensive perioperative coagulation treatment algorithms for refractory bleeding is increasingly reported, but further studies are needed to better evaluate the safe and effective administration of these factor concentrates.
authors.affiliation: From the Divisions of Cardiothoracic Anesthesiology and Critical Care Medicine, Duke University Medical Center, Durham, North Carolina.
authors.forename: Kamrouz
authors.initials: K
authors.lastname: Ghadimi
authors.forename: Jerrold H
authors.initials: JH
authors.lastname: Levy
authors.forename: Ian J
authors.initials: IJ
authors.lastname: Welsby
mesh_terms: D000465:Algorithms; D000818:Animals; D000925:Anticoagulants / Q000009:adverse effects; D001777:Blood Coagulation / Q000187:drug effects*; D001779:Blood Coagulation Factors / Q000009:adverse effects / Q000627:therapeutic use*; D016063:Blood Loss, Surgical / Q000517:prevention & control*; D002626:Chemistry, Pharmaceutical; D002985:Clinical Protocols; D006490:Hemostatics / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D056687:Off-Label Use; D019990:Perioperative Care / Q000009:adverse effects / Q000379:methods*; D019106:Postoperative Hemorrhage / Q000097:blood / Q000209:etiology / Q000517:prevention & control*; D017410:Practice Guidelines as Topic; D018570:Risk Assessment; D012307:Risk Factors; D013923:Thromboembolism / Q000097:blood / Q000139:chemically induced; D016896:Treatment Outcome
chemical_list: D000925:Anticoagulants; D001779:Blood Coagulation Factors; D006490:Hemostatics; C025667:prothrombin complex concentrates