Animal models of trauma induced coagulopathy

Abstract

Animal models serve an essential role in the study of trauma-induced coagulopathy by allowing the control of experimental variables in a reproducible setting and serve as a platform for therapeutic testing. Large animal models offer advantages in terms of clinical realism, while small animal models are frequently used in mechanistic studies. In addition to traditional coagulation assays such as prothrombin time and activated thromboplastin time, more recent studies have used thromboelastography/thromboelastometry, platelet function testing, and measured the concentrations of circulating clotting factors. Models of isolated injury, such as hemorrhage, sepsis, and acidosis, have demonstrated an overall hypocoagulopathic state. In contrast, traumatic brain injury (TBI) with or without additional injuries induces an immediate activation of the coagulation system. Platelet and endothelial dysfunction has been documented in greater detail in TBI models relative to non-TBI models. Complex, multiple-insult models have shown hypocoagulopathic derangements that positively correlate with increases in injury severity. Aggressive crystalloid resuscitation, while aimed at reversing hypotension following trauma, creates hemodilution-induced coagulopathy. Artificial colloids can induce a hypocoagulopathic state, while plasma-based agents have shown promise in reversing both coagulation cascade derangements and platelet dysfunction. Animal models have enhanced our mechanistic understanding of TIC and served as a laboratory for testing promising therapies. However, future studies should more closely examine the temporal changes in coagulation immediately post-injury, collect pre-intervention coagulation data, and develop robust models of hyperfibrinolysis.