A clinically relevant and bias-controlled murine model to study acute traumatic coagulopathy

Abstract

Acute traumatic coagulopathy (ATC) is an acute and endogenous mechanism triggered by the association of trauma and hemorrhage. Several animal models have been developed, but some major biases have not yet been identified. Our aim was to develop a robust and clinically relevant murine model to study this condition. Anesthetized adult Sprague Dawley rats were randomized into 4 groups: C, control; T, trauma; H, hemorrhage; TH, trauma and hemorrhage (n = 7 each). Trauma consisted of laparotomy associated with four-limb and splenic fractures. Clinical variables, ionograms, arterial and hemostasis blood tests were compared at 0 and 90 min. ATC and un-compensated shock were observed in group TH. In this group, the rise in prothrombin time and activated partial thromboplastin was 29 and 40%, respectively. Shock markers, compensation mechanisms and coagulation pathways were all consistent with human pathophysiology. The absence of confounding factors, such as trauma-related bleeding or dilution due to trans-capillary refill was verified. This ethic, cost effective and bias-controlled model reproduced the specific and endogenous mechanism of ATC and will allow to identify potential targets for therapeutics in case of trauma-related hemorrhage.

Figure 1

Experimental protocol. Group C, without trauma without hemorrhage; T, trauma without hemorrhage; H, hemorrhage without trauma; TH, hemorrhage with trauma (n = 7 in each group).

Figure 2

Hemodynamic variables. C, Control; T, Trauma; H, Hemorrhage; TH, Trauma and hemorrhage, n = 7 per group. Values represent mean ± SEM. *p < 0.05 compared with group C; ^†p < 0.05 for repeated measure ANOVA, meaning a statistically significant effect of time in concerned group.

Figure 3

General coagulation assays. Box and whisker plot of general coagulation assays at 90 min in each experimental group. C, Control; T, Trauma; H, Hemorrhage; TH, Trauma and hemorrhage, n = 7 per group. Whiskers represent the 5th and 95th percentiles. *p < 0.05 versus C T and H. Ratios were calculated for each animal as follows: (value at 90 min)/(value at 0 min).

Figure 4

Shock variables. Mean values at 0 min and 90 min in each experimental group. C, Control; T, Trauma; H, Hemorrhage; TH, Trauma and hemorrhage, n = 7 per group. ^†p < 0.05 compared with 0 min in the same group, *p < 0.05 versus C T and H. Data are presented as mean ± SEM.

Figure 5

Coagulation factors. Histograms of specific coagulation factors at 0 min and 90 min in each experimental group. C, Control; T, Trauma; H, Hemorrhage; TH, Trauma and hemorrhage, n = 7 per group. ^†p < 0.05 compared with 0 min in the same group, *p < 0.05 versus C T and H. **p < 0.05 versus C and T. Data are presented as mean ± SEM.