HPE CSL Managing Perioperative Bleeding handbook - Page 25

Trauma Augmentation of thrombin generation To increase thrombin generation, PCCs and activated recombinant factor VII (rFVIIa) have been studied in trauma- related bleeding. 6,8,35–37 Two randomised controlled studies failed to show a survival benefit in trauma patients receiving rFVIIa. 35,36 PCC preparations can be formulated with either three factors (FII, FIX, FX) or four factors (FII, FVII, FIX, FX). 38 Beyond emergency reversal of vitamin K antagonists, data on PCC use in trauma are limited and prospective trials have not yet been performed. 39–44 The European guidelines on management of major bleeding and coagulopathy following trauma recommend administration of PCC primarily for the emergency reversal of vitamin K-dependent oral anticoagulation and for treatment of Xa inhibitors. 18 In bleeding trauma patients with thrombo- elastometric signs of delayed initiation of the coagulation process, PCC can be considered. 18 Josef et al compared PCC administration in coagulopathic (INR >1.5) trauma patients with pelvic and lower extremity fractures with patients who were treated with FFP. Patients who received PCC had faster correction of INR and shorter time to surgical intervention compared with patients who received FFP. PCC therapy was also associated “In severe bleeding trauma patients, fibrinogen is the first coagulation factor that reaches critical low levels” with lower overall blood product requirements (p=0.02) and lower transfusion costs (p=0.0001). 37 Trauma patients on vitamin K antagonists and direct oral anticoagulants In another study, the same group reported 45 trauma patients, 85% on warfarin, who received 51 doses of PCC. PCC application resulted in a rapid correction in INR and reduction in blood product transfusion. 39 Majeed et al reported 84 bleeding patients under rivaroxaban or apixaban who received PCC at a median dose of 2000U for the reversal. Intracranial haemorrhage was the most common bleeding event, followed by gastrointestinal bleeding. PCCs were assessed as effective in 69.1% of patients. 45 Currently, there are no studies published on the effectiveness of PCC in trauma patients on direct oral anticoagulants (DOACs). 46 However, our experiences with major trauma patients on DOACs revealed that high doses of PCC (50U/kg body weight) are necessary to control bleeding. Risk of thromboembolic events Joseph et al reported an incidence of thromboembolic events in the range of 6% after PCC administration in a heterogeneous group of trauma patients. 47 Our group has shown that PCC administration resulted in a substantial and prolonged increase in endogenous thrombin generation compared with patients who received no coagulation therapy or fibrinogen concentrate only. 48 PCCs are potent pro-coagulants and, as such, the possibility of associated thromboembolic complications should be c onsidered carefully. 49 Robust safety data related to PCC use in TIC are still lacking. Studies on the use of coagulation factor concentrates in trauma Data showing that fibrinogen supplementation improves survival in trauma patients are still limited. In a retrospective study the administration of fibrinogen concentrate along with PCC (4 factor concentrate) resulted in favourable survival rates compared with those predicted by both the trauma injury severity score and the revised injury severity classification score. 6 Innerhofer et al compared FFP transfusion versus coagulation factor concentrate (fibrinogen hospitalpharmacyeurope.com 25