Injectable hemostatic adjuncts in trauma: Fibrinogen and the FIinTIC study.

Abstract

F adequate hemostasis, sufficient amounts of thrombin and coagulable substrate are fundamental prerequisites. In addition to platelets, on whose surfaces most of the thrombin is generated, fibrinogen can be considered as the substrate of the coagulation process. If sufficient thrombin is formed, it converts fibrinogen into stable fibrin, which determines the firmness of the developing clot in the presence of activated coagulation factor XIII (Fig. 1). Under physiologic conditions, fibrinogen availability is regulated through dynamic changes in synthesis and breakdown to preserve coagulation function. As a consequence of blood loss, consumption of coagulation factors, dilutional coagulopathy, hypothermia and acidosis, as well as profibrinolytic activation, fibrinogen may reach critical levels earlier than any other procoagulant factor and also platelets even before packed red blood cell concentrate administration becomes necessary. Floccard et al. have described even significant drops in fibrinogen levels to occur already during the ultra early prehospital phase of care when comparing blood samples obtained from bleeding trauma patients at the scene and at the time point of arrival to the trauma bay (fibrinogen median, 2.6 g/L; interquartile range [IQR], 2.3Y3.1; 95% confidence interval [CI], 2.4Y2.9 vs. 2.1 g/L; IQR, 1.4Y2.5; 95% CI, 1.7Y2.3) (changes, j0.6 g/L; IQR, j1.1 to j0.3; 95%CI,j0.9 toj0.3;pG 0.001). In this study, fibrinogen levels decreased substantially as a function of injury severity reflected by Injury Severity Scores (ISSs). Recently, Kimura et al. have reported similar results when searching retrospectively for predictors of hypofibrinogenemia in 290 blunt traumapatients upon admission to aLevel 1 trauma center during a 3-year period. Their multivariate regression analysis identified patient’s age (odds ratio [OR], 0.97; p G 0.001), Triage Revised Trauma Score (T-RTS including Glasgow Coma Scale [GCS] score, respiratory rate, and systolic blood pressure; OR, 0.81; p = 0.003), and prehospital volume therapy (OR, 2.54; p = 0.01) as independent predictors for early hypofibrinogenemia. In contrast todisseminated intravascular coagulopathy, there is no generalized intravascular microcoagulation with increased consumption in trauma-induced coagulopathy. Instead, there is hemorrhage-related loss of coagulation factors and platelets with subsequent dilution of procoagulant factors due to (uncritical) volume resuscitation with direct effect on fibrinogen polymerization. Dilution of fibrinogen by crystalloid fluids and additional reduced fibrin interlinkage by synthetic colloids has been discussed. Recently, experimental data confirmed significant fibrinogen breakdown by acidosis following hypoperfusion with no effect on fibrinogen synthesis, while hypothermia decreased fibrinogen synthesis with no effect on fibrinogen degradation. Furthermore, synthesis and degradation seem to be regulated through different mechanisms, and a potential deficit in fibrinogen availability during hypothermia has been suggested.