HPE CSL Managing Perioperative Bleeding handbook - Page 22

Trauma Coagulation factor concentrates in trauma Many trauma patients exsanguinate due to uncontrolled haemorrhage and coagulopathy and prompt surgical control of the source of bleeding and rapid haemostatic therapy are crucial Herbert Schöchl MD AUVA Trauma Centre Salzburg, Austria; Ludwig Boltzmann Institute for Experimental Clinical and Traumatology, AUVA Research Centre, Vienna, Austria Trauma is the leading cause of death in the first four decades of life. 1 Many of these patients exsanguinate due to uncontrolled haemorrhage and trauma- induced coagulopathy (TIC). 2 TIC occurs early after severe injury and is associated with a substantial increase in blood loss, higher transfusion requirements and an approximately four-fold higher mortality compared with non-coagulopathic patients. 3,4 Prompt surgical control of the bleeding source and rapid haemostatic therapy is crucial in order to optimise outcome. Data suggest that early transfusion of high ratios of plasma and platelet concentrate (PC), predominantly in a fixed 1:1:1 ratio with red blood cells (RBCs), is associated with improved outcome in patients with severe trauma- related bleeding. 5,6 Some European trauma units have established a more targeted approach to treat coagulopathic trauma victims. The concept of a goal-directed and individualised haemostatic therapy is largely based on visco-elastic test results and consists of purified coagulation factor concentrates (CFCs). 6–9 22 A confounder of poor outcome A variety of studies revealed that TIC is an important confounder of poor outcome. TIC occurs early after severe injury and is associated with a substantial increase in bleeding rate, transfusion requirements and a four-fold higher hospitalpharmacyeurope.com mortality. 3,10 Exsanguination is potentially avoidable by rapid surgical bleeding control. Additionally it is crucial to achieve optimal haemostatic conditions in order to avoid further blood loss. Therefore, early haemostatic therapy might also minimise allogeneic blood transfusion requirements, potentially avoiding massive transfusion and thereby improving outcomes. The first coagulation factor reaching critical low levels In the course of severe bleeding, coagulation factors do not decrease simultaneously. In major trauma, fibrinogen reaches critical low levels earlier than any other coagulation proteins and has been identified as the primary coagulation factor deficiency in severe bleeding. 11 Hypofibrinogenemia upon admission to the emergency room (ER) is an independent predictor of poor outcome and is strongly related to the severity of shock. 12–14 Fibrinogen plays a central role in both primary and secondary haemostasis; it is not only the precursor of fibrin but is also fundamental in aggregating and linking platelets. 15 Activated platelets express surface glycoprotein IIb/IIIa receptors that have a high affinity to fibrinogen. 15 Floccard et al 16 collected blood samples of trauma patients at the scene of accident and found a median fibrinogen concentration of 1.2g/l in patients with an Injury Severity Score (ISS) >40. A further significant drop of fibrinogen was observed before ER admission. In a prospective observational study including 1122 trauma patients, Hagemo et al showed that fibrinogen <2.3g/l resulted in a substantial increase in 28-day mortality. 12 Schlimp et al analysed data from 675 trauma patients upon ER admission and observed that fibrinogen strongly correlated with shock severity. Patients admitted to the ER with a base deficit >6mmol/l showed fibrinogen levels <2.0g/l in 81% and fibrinogen concentrations of <1.5g/l in 63% of the cases. 17 McQuilten et al reported an adjusted odds ratio of 3.28 (95% CI 1.17–6.28, p<0.01) for mortality when fibrinogen was <1g/l upon ER admission compared with patients with fibrinogen levels between 2 and 4g/l. 13 Fibrinogen supplementation Based on these findings, current European guidelines on management of major bleeding in trauma recommend supplementation of fibrinogen when plasma concentrations are in the range of 1.5 to 2.0g/l, 18 although there is currently little evidence to directly support this recommendation. 19 Fibrinogen supplementation may be achieved through transfusion of large volumes of fresh frozen plasma (FFP), cryoprecipitate or fibrinogen concentrate. The fibrinogen content of FFP is relatively low (~2.5g/l). 20,21 If FFP is transfused in a 1:1 ratio with RBCs, it is almost impossible to keep fibrinogen concentration above a threshold of >1.5g/l, particularly in massively transfused patients. 20 Rourke et al reported that FFP and PC were not sufficient to maintain fibrinogen concentration above the recommended level of 1.5g/l; albeit with RBCs and FFP transfused in 1:2 ratios. In particular, patients who received >10 RBC had low (<1.5g/l) fibrinogen concentrations. Only