Caspase-11 Contributes to Trauma-Induced Coagulopathy in a Murine Polytrauma Model

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Introduction: Trauma-induced coagulopathy (TIC) results in significant morbidity and mortality. Caspase-4/11 is associated with disseminated intravascular coagulation in sepsis, but its role in polytrauma is unknown. We sought to investigate the effects of caspase-11 in a murine polytrauma model. Methods: C57BL/6 (WT) and caspase-11-/- mice were subjected to polytrauma consisting of a blind cardiac puncture with removal of 25% total blood volume, liver crush, and bilateral pseudofracture induced by hindlimb crush and injection of crushed bone solution from an age/weight-matched syngeneic donor. After 24h, liver and blood were collected from experimental and control groups (n = 4). Additionally, Caspase-11 expression was measured by Western blot (WB) of whole liver lysate. Prothrombin time (PT) and activated partial thromboplastin time (aPTT) were measured. Platelet aggregation in whole blood was investigated using impedance aggregometry with thrombin as the aggregating agent. Results: Polytrauma induces expression of caspase-11 as shown by WB, suggesting its involvement in TIC. After polytrauma, WT mice aPTT levels (18.1vs42.7sec p < 0.0001) significantly increased. Caspase-11-/- mice had a markedly lower aPTT at baseline vs WT (p < 0.01). After trauma, aPTT did not change in caspase-11-/- mice (10.7vs8.7sec) remaining lower than baseline control WT levels. After injury, PT values slightly increased in WT (13.3vs14.4sec), and caspase-11-/- mice (11.6 vs 12.8 sec) but did not reach the level of control WT mice. Conclusion: Caspase-11 contributes to TIC by alteration of the coagulation profile. Caspase-11 does not seem to significantly affect platelet aggregation. Our data suggest that inhibition of caspase-11 may be a future therapeutic option for TIC.

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