Definition and drivers of acute traumatic coagulopathy: clinical and experimental investigations

Abstract

Summary. Background: Acute traumatic coagulopathy (ATC) is an impairment of hemostasis that occurs early after injury and is associated with a 4-fold higher mortality, increased transfusion requirements and organ failure. Objectives: The purpose of the present study was to develop a clinically relevant definition of ATC and understand the etiology of this endogenous coagulopathy. Patients/methods: We conducted a retrospective cohort study of trauma patients admitted to five international trauma centers and corroborated our findings in a novel rat model of ATC. Coagulation status on emergency department arrival was correlated with trauma and shock severity, mortality and transfusion requirements. 3646 complete records were available for analysis. Results: Patients arriving with a prothrombin time ratio (PTr) > 1.2 had significantly higher mortality and transfusion requirements than patients with a normal PTr (mortality: 22.7% vs. 7.0%; P < 0.001. Packed red blood cells: 3.5 vs. 1.2 units; P < 0.001. Fresh frozen plasma: 2.1 vs. 0.8 units; P < 0.001). The severity of ATC correlated strongly with the combined degree of injury and shock. The rat model controlled for exogenously induced coagulopathy and mirrored the clinical findings. Significant coagulopathy developed only in animals subjected to both trauma and hemorrhagic shock (PTr: 1.30. APTTr: 1.36; both P < 0.001 compared with sham controls). Conclusions: ATC develops endogenously in response to a combination of tissue damage and shock. It is associated with increased mortality and transfusion requirements in a dose-dependent manner. When defined by standard clotting times, a PTr > 1.2 should be adopted as a clinically relevant definition of ATC.

Diverse coagulopathies in a rabbit model with different abdominal injuries

“…Fung et al [15] also evaluated nontraumatic hemorrhage without impairing coagulation in an ovine model. Some reports have shown that hemorrhagic shock may play an integral role in the progression of early coagulopathy, [16,17] but our results revealed that hypoperfusion, lower temperature and acidosis may exacerbate the development of coagulopathy. Coagulation dysfunction was not initiated by the isolated hemorrhagic shock.…”

The pathogenesis of traumatic coagulopathy

“…Hypoperfusion plays a critical role in the pathogenesis of ATC as demonstrated in numerous clinical studies [3,6,[42][43][44][45][46][47][48][49][50][51], animal models [6,50] and in vitro experiments [22,51]. These data indicate that as shock severity increases, the PT and INR rise [4,5,7,52] and coagulation factor levels fall [6,48]. The most compelling of these studies, that included 3646 patients, demonstrated that ATC (INR > 1.2) occurred only when significant hypoperfusion (base deficit > 6 mmol.l…”

“…This is mainly due to the recognition that many patients who are bleeding when they come to the emergency department have an established coagulopathy before the dilutional effects of fluid resuscitation. Traumatic coagulopathy has been demonstrated in patients who received little or no intravenous fluid therapy, negating the long-held belief that iatrogenic haemodilution is the main causative factor in traumatic coagulopathy [3][4][5][6]. This has led to the use of new terminology: acute traumatic coagulopathy (ATC); acute coagulopathy of trauma shock or traumainduced coagulopathy.…”

Mechanisms of trauma-induced coagulopathy

“…A multicenter retrospective study of over 3646 trauma patients confirmed that the severity of TIC is strongly associated with combined severe injury and shock. 32 A synergistic effect of materials released from tissue injury with inflammation and anticoagulant factors induced by endothelial injury and tissue hypoxia likely mediate this relationship to produce TIC.…”