Clinical and mechanistic drivers of acute traumatic coagulopathy

Abstract

Background Acute Traumatic Coagulopathy (ATC) occurs after severe injury and shock and is associated with increased bleeding, morbidity and mortality. The effects of ATC and hemostatic resuscitation on outcome are not well-explored. The PRospective Observational Multicenter Major Trauma Transfusion (PROMMTT) study provided a unique opportunity to characterize coagulation and the effects of resuscitation on ATC after severe trauma. Methods Blood samples were collected upon arrival on a subset of PROMMTT patients. Plasma clotting factor levels were prospectively assayed for coagulation factors. These data were analyzed with comprehensive PROMMTT clinical data. Results There were 1198 patients with laboratory results of whom 41.6% were coagulopathic. Using International Normalized Ratio (INR)≥1.3, 41.6% (448) of patients were coagulopathic while 20.5% (214) were coagulopathic using partial thromboplastin time (PTT)≥35. Coagulopathy was primarily associated with a combination of an ISS>15 and a BD<−6 (P<.05). Regression modeling for INR-based coagulopathy shows that pre-hospital crystalloid (odds ratio (OR)=1.05), Injury Severity Score (ISS, OR=1.03), Glasgow Coma Scale (OR=0.93), heart rate (OR=1.08), systolic blood pressure (OR=0.96), base deficit (BD, OR=0.92) and temperature (OR=0.84) were significant predictors of coagulopathy (all P<.03). A subset of 165 patients had blood samples collected and coagulation factor analysis performed. Elevated ISS and BD were associated with elevation of aPC and depletion of factors (all P<.05). Reductions in factors I, II, V, VIII and an increase in aPC drive ATC (all p<.04). Similar results were found for PTT-defined coagulopathy. Conclusions ATC is associated with depletion of factors I, II, V, VII, VIII, IX and X and is driven by the activation of the protein C system. These data provide additional mechanistic understanding of the drivers of coagulation abnormalities after injury. Further understanding of the drivers of ATC and the effects of resuscitation can guide factor guided resuscitation and correction of coagulopathy after injury.

Acute traumatic coagulopathy and trauma-induced coagulopathy: an overview

“…ATC that is caused by trauma-induced tissue injury and/or traumatic shock (generalized tissue hypoperfusion) presents as systemic activation of coagulation responses associated with increased fibrinolysis [19,26,27]. The clinical features of ATC can be summarized as follows [11,18,[28][29][30]:…”

“…Pathophysiologic mechanism of increased fibrinolysis in ATC ATC presents as systemic activation of coagulation associated with increased fibrinolysis [19,26,27], and the increased fibrin(ogen)olysis is the most characteristic feature.…”

Clotting Factor XIII and desmopressin improve hemostasis in uncontrolled bleeding

“…More recently, early fibrinolysis, platelet dysfunction, clotting factor inactivation and depletion, were described in acute traumatic coagulopathy [18][19][20] . To approach those multiple conditions, pharmacological agents have been incorporated in the management of coagulopathy 6,7 .…”

“…Consequently, more time is allowed before undesirable pressure is applied to an initially vulnerable clot 28 . Moreover, permissive hypotension contributes to vasoconstriction and reduces dilutional effect on coagulopathy 4,19 .…”

A Prospective, Randomized Trial of Intravenous Hydroxocobalamin Versus Whole Blood Transfusion Compared to No Treatment for Class III Hemorrhagic Shock Resuscitation in a Prehospital Swine Model

“…Large-volume crystalloid resuscitation can dilute coagulation factors and worsen survival. 6,46,47 Current Committee on Tactical Combat Casualty Care guidelines recommend 500 mL of Hextend (Biotime Inc.), a synthetic colloid, because of the smaller weight and volume. 48 However, studies have not confirmed efficacy in shock and have documented risk including coagulopathies.…”