HHE Sponsored supplement: Managing perioperative bleed - Page 25

concentrate or placebo. Plasma fibrinogen concentrations remained higher in the fibrinogen concentrate group up to 12h after admission. Mortality and thromboembolic complications were similar between groups. 31 potentially counteract low platelet counts, by increasing overall clot firmness. 29 Velik-Salcher et al investigated the effect of fibrinogen concentrate transfusion on blood loss in a thrombocytopenic swine model (target platelet count < 30,000/µl). Transfusion of fibrinogen concentrate (250mg/kg body weight) resulted in lower blood loss and improved survival rate compared with transfusion of 2U of PC. 29 In situations where platelet count is low or platelet function is compromised and PCs are not available, high fibrinogen supplementation might be considered as a treatment option. 30 Thrombin generation is initially not deficient in major trauma Compromised thrombin generation does not appear an initial problem in the early stages of TIC. 32,33 Therefore thrombin-generating coagulation factors such as prothrombin complex concentrate (PCC) are not advocated as first-line therapy in trauma. 34 Importantly, prolonged standard coagulation tests such as international normalised ratio (INR), prothrombin time (PT), activated partial thromboplastin time, ROTEM clotting time or TEG r- and k-time do not sufficiently reflect impaired thrombin production. For example, Dunbar and Chandler reported 15 trauma patients with prolonged PT and INR suggestive of TIC. Even though PT was >18 sec and INR was >1.5, thrombin generation was three-fold higher compared with controls (p=0.01). 32 Fibrinogen supplementation Nascimento et al randomised 50 hypotensive adult trauma patients to either 6g fibrinogen In severe bleeding trauma patients, fibrinogen is the first coagulation factor that reaches critical low levels 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 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 25 HHE 2018 | hospitalhealthcare.com