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 dependent on the concentrations of Factor VII. PCCs rapidly restore deficient coagulation factor concentrations to achieve hemostasis, but as with all procoagulants, the effect is balanced against thromboembolic risk. The latter is dependent on both the dose of PCCs and individual patient prothrombotic predisposition. PCCs are Food and Drug Administration approved for the reversal of vitamin K antagonists in the setting of coagulopathy or bleeding and therefore can be administered in these patients when urgent surgery is required. There is, however, a 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 laboratory and clinical variables, including point-of-care coagulation testing, in order to balance hemostatic benefits while minimizing 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.

Comparison of 4-Factor Prothrombin Complex Concentrate With Frozen Plasma for Management of Hemorrhage During and After Cardiac Surgery

“…Although specific compositions vary depending on the manufacturer, 4-factor PCCs contain vitamin K–dependent coagulation factors (factors II, VII, IX, and X), the anticoagulant proteins C and S (some also contain antithrombin), and small amounts of heparin. 12 The advantages of PCCs relative to FP are that they are pathogen reduced, do not require ABO blood group matching or thawing (allowing for near-patient storage and timely administration), are manufactured from pooled plasma (decreasing the risk of transfusion-related acute lung injury), require substantially lower volumes to achieve dose equivalence with FP (decreasing the risk of transfusion-associated circulatory overload), and may lead to greater thrombin generation (improving hemostatic effectiveness). 12 , 13 , 14 , 15 On the other hand, because PCCs do not contain the full, balanced complement of procoagulants and anticoagulants that are present in FP, they may be less effective in restoring hemostasis, may carry a higher thrombosis risk (possibly owing to an imbalance in factor II to antithrombin ratio), or both.…”

Adjuncts to Blood Component Therapies for the Treatment of Bleeding in the Intensive Care Unit

“…Other four component PCCs available in most countries include both Beriplex P/N and Octaplex (Octapharma, Vienna, Austria), and others is listed in table 1. (5, 46–48) Multiple international guidelines recommend the use of four component PCCs rather than plasma or fresh frozen plasma as a primary treatment for the emergent reversal of warfarin. (5) Advantages of PCCs for acute warfarin reversal include ease of storage, rapid INR correction, small infusion volume (~20 ml per 500IU), and viral inactivation and/or nanofiltration.…”

“…(5, 46–48) Multiple international guidelines recommend the use of four component PCCs rather than plasma or fresh frozen plasma as a primary treatment for the emergent reversal of warfarin. (5) Advantages of PCCs for acute warfarin reversal include ease of storage, rapid INR correction, small infusion volume (~20 ml per 500IU), and viral inactivation and/or nanofiltration. (5) One report from the United Kingdom National Health Service suggested that PCCs for emergency warfarin reversal were more cost-effective than plasma.…”

“…(5) Advantages of PCCs for acute warfarin reversal include ease of storage, rapid INR correction, small infusion volume (~20 ml per 500IU), and viral inactivation and/or nanofiltration. (5) One report from the United Kingdom National Health Service suggested that PCCs for emergency warfarin reversal were more cost-effective than plasma. (49)…”

“…Although allogeneic blood transfusions are classically used as the primary management strategy in bleeding patients, the role of adjuncts to blood component therapies is increasingly being utilized. (3–5) Specifically, factor concentrates represent important therapeutic options to manage bleeding and will be reviewed. The increasing use of algorithm-based management protocols in bleeding patients is also an important part of adjunctive hemostasis strategies.…”