The authors would like to thank Anita Yeager (Dept of Anesthesiology) for editorial assistance. The authors would also like to thank the Nursing and Respiratory Therapy staffs, (in particular, Jeff Majeski, RRT and Steve Bonnet, RRT) for their patience and assistance with this work.Role of the Sponsor: The funding organizations (NIH and Respironics) Tofacitinib JAK3 had no role in the design and conduct of the study; in the collection, analysis, and interpretation of the data; or in the preparation, review, or approval of the manuscript.
In patients with severe trauma, coagulopathy represents a frequent cause of death [1,2]. Prompt haemostatic intervention is necessary to prevent and correct life-threatening bleeding. Standard coagulation therapy consists of fresh frozen plasma (FFP), platelet concentrate and, in some countries, cryoprecipitate [3,4].

One approach proposed for preventing exsanguination has been to treat patients with a fixed ratio of FFP to red blood cells (RBC), but the optimal value of this ratio is still under debate [5-8]. It has been recently suggested that the time to intervention may also be an important determinant of patient outcomes [9,10].Our group has been exploring goal-directed coagulation management using fibrinogen concentrate and prothrombin complex concentrate (PCC), administered as early as possible according to thromboelastometric (TEM) measurements [11,12]. This approach supports timely and aggressive correction of coagulopathy.

It may also be considered as a strategy for reducing transfusion of allogeneic blood products: the need for FFP may be reduced by the administration of coagulation factors: fibrinogen, contained in fibrinogen concentrate, and factors II, VII, IX and X, contained in most PCCs. Furthermore, clinical and experimental data suggest that fibrinogen supplementation may also compensate for reduced platelet count [13,14]. Supplementation of fibrinogen may support primary haemostasis, because fibrinogen facilitates platelet aggregation by bridging platelet glycoprotein IIb/IIIa receptors [15]. In addition, the use of fibrinogen concentrate leads to increased firmness of the fibrin-based clot [16], whereas PCC administration may correct prolonged coagulation times through improved thrombin generation [17].We recently reported favourable outcomes in major trauma patients referred to our level 1 trauma centre and treated following TEM-guided haemostatic therapy with fibrinogen concentrate and PCC [12].

Observed mortality in this retrospective analysis was lower than that predicted by the Revised Injury Severity Classification Score (RISC) [18] and Trauma Injury Severity Score (TRISS) [19]. The treatment strategy eliminated time delays associated Cilengitide with standard coagulation testing and preparation of allogeneic blood products for transfusion: more than half of the patients received haemostatic therapy within an hour of admission to the emergency room (ER).