Prothrombin complex concentrates in trauma and perioperative bleeding.

923 April 2015 P rothrombin complex concentrates (PCCs) are recommended in preference to other treatments such as therapeutic plasma for urgent reversal of vitamin K antagonists.1,2 PCCs contain either three or four coagulation factors (factors ii, iX, and X, with or without factor Vii) and, depending on formulation, low doses of coagulation inhibitors such as protein C, protein S, and heparin (table 1). There are considerable variations among countries in the availability and licensing status of PCCs. For example, four-factor PCCs have been used for many years in Europe, where their license is not restricted to vitamin K antagonist reversal—they have broad approval for “treatment and prophylaxis of bleeding in acquired deficiency of the prothrombin complex coagulation factors.” in the United States, however, the first four-factor PCC was only recently approved, specifically for urgent reversal of vitamin K antagonist therapy. The mechanism of action of PCCs is important for understanding their therapeutic applications. Vitamin K antagonists such as warfarin function by reducing levels of four coagulation factors: ii, Vii, iX, and X, with the aim of preventing thromboembolism. For patients with life-threatening bleeding, rapid replacement of these coagulation factors is required, and PCCs serve as a concentrated source of the required coagulation factors. Three-factor as well as four-factor PCCs have been explored for vitamin K antagonist reversal. however, due to the absence of factor Vii, it appears that three-factor PCCs are less suitable than four-factor PCCs for patients with an international normalized ratio (inr) greater than 3.7.3 in trauma and perioperative bleeding, patients present with a variety of coagulopathies. PCCs increase thrombin generation potential by ensuring adequate levels of the key coagulation factors—notably factor ii (prothrombin), whose conversion to thrombin is facilitated by activated factor X and activated factor V. treatment with PCCs may potentially be effective in facilitating hemostasis in trauma and perioperative bleeding. however, the potential role of PCCs in these settings must be considered in the context of other treatment options and the patient’s overall coagulation status. Fibrinogen is generally the first coagulation factor to decrease below critical levels during bleeding.4 The physiological response to trauma includes an increase in thrombin generation,5 whereas fibrinogen levels are typically reduced in trauma patients upon admission to hospital.6 in cardiovascular surgery, it has been shown that fibrin formation is impaired to a greater extent than thrombin generation after cardiopulmonary bypass.7 Coagulation management algorithms based on coagulation factor concentrates have been published in relation to cardiovascular surgery8,9 and trauma (fig. 1).10 Some authors advocate the use of PCC in accordance with implementing such algorithms although it should be noted that, after antifibrinolytic medication, fibrinogen supplementation is recommended as first-line hemostatic treatment.8,10,11 PCCs may subsequently be considered for patients with ongoing bleeding despite restoration of fibrinogen levels. Throughout the management of coagulopathic bleeding, therapy should be tailored to the patient’s coagulation status. Point-of-care assessment, for example using rotEm® (tem international Gmbh, Germany) or tEG® (haemonetics Corp., USA), can help determine which of the available hemostatic therapies (e.g., therapeutic plasma, platelets, coagulation factor concentrates, or cryoprecipitate) should be administered. A deficiency in thrombin generation is more likely to arise later during the course of surgery. The potential risk of thromboembolic complications necessitates a cautious approach when using PCCs in trauma and perioperative bleeding. in these settings— unlike vitamin K antagonist reversal—levels of coagulation