A prospective observational study of acute traumatic coagulopathy in traumatic bleeding from the battlefield

Abstract

BACKGROUND Acute trauma coagulopathy (ATC) after military trauma has not been comprehensively studied. ATC is defined as a prolonged prothrombin time ratio (PTr) or reduced clot amplitude (A5) in viscoelastic testing. Compared to civilian trauma, military trauma has more injuries from explosions and gunshot wounds (GSWs), potentially leading to a different pathophysiology for traumatic coagulopathy. This study aimed to characterize military ATC on admission to a military hospital in Afghanistan and to explore any differences due to the mechanism of injury. METHODS Severely injured military casualties were enrolled in the study. Blood samples were taken on admission and after routine testing, waste plasma was prepared, frozen, and transported to the United Kingdom for in‐depth hemostatic analysis. RESULTS Seventy‐seven percent of casualties had ATC defined by a PTr greater than 1.2 and 19% when defined by rotational thromboelastometry (ROTEM) A5 less than 36 mm. Coagulation factor depletion correlated with degree of shock, particularly factor V (p < 0.01), factor X (p < 0.01), and fibrinogen levels (p < 0.01). Thrombin generation was well preserved. Fibrinolytic biomarkers were raised correlating with the degree of shock (p < 0.01), and 8% of casualties had hyperfibrinolysis on ROTEM analysis. Plasmin‐antiplasmin complexes (p < 0.01) and d‐dimer levels (p = 0.01) were higher and clot firmness lower (p = 0.02) in those injured by explosion compared to GSW's. CONCLUSIONS ATC was present and correlated with shock, similar to civilian trauma. Thrombin generation remained adequate. Fibrinogen and factor V levels were disproportionately low but still sufficient to allow clot formation. Fibrinolysis is a key feature, probably due to a tissue plasminogen activator surge at the time of injury. Blast injuries are associated with a greater activation of fibrinolysis than GSWs.

Exploratory Investigation of the Plasma Proteome Associated with the Endotheliopathy of Trauma

“…Coagulation factor V (FV) was the only coagulation factor with a statistically significant decrease in plasma abundance in EoT compared to non-EoT. EoT was associated with a hypocoaguable TEG profile, consistent with previous findings demonstrating an association between lower levels of circulating FV and acute coagulopathy following trauma [ 208 , 209 , 210 , 211 , 212 , 213 , 214 ]. A proportion of plasma FV undergoes endocytosis and is sequestered within platelet alpha granules [ 215 , 216 , 217 , 218 ], and this intra-platelet FV is integral for achieving hemostasis following traumatic hemorrhage [ 219 , 220 ].…”

Trauma-induced coagulopathy

“…Thrombin generation can be altered by dilution of coagulation factors following fluid therapy, rapid coagulation factor consumption immediately after injury, shock-related systemic acidosis and hypothermia 65,138,139 . Severely injured patients are prone to having reduced levels of factor V 5,140,141 , factor VII 141 , factor X 141 and fibrinogen early after injury 139,141 . However, the reports of decreases in the activity of coagulation factors following severe injury are inconsistent.…”

“…Importantly, a reduction in procoagulants is not necessarily accompanied by impaired thrombin generation 141,143 . Even though the levels of multiple procoagulants were reduced in patients with traumatic injury, circulating markers of thrombin generation (including prothrombin fragment 1.2 and thrombin-antithrombin complexes) were higher than in uninjured individuals or patients without evidence of TIC 141 . Elevation of these markers reflects formation of thrombi in sites where they are needed and may constitute a physiological response to injury, with increased thrombin generation in vivo leading to depletion of both procoagulant and anticoagulant factors.…”

“…The contributing role of tissue injury is also unclear and may be crucial in determining early fibrinolytic phenotypes. A study of military casualties showed that blast injuries (due to explosions) caused significantly more plasmin activation than gunshot wounds 141 . Interestingly, isolated shock or TBI are not associated with a pronounced TIC but, in combination with tissue injury, provoke a severe early TIC.…”

“…In the COMBAT 5 and PAMPer 6 randomized controlled trials, patients with transport times of >20 min were more likely to experience benefit from pre-hospital plasma administration than patients with transport times of ≤20 min 250 . Military settings pose their own challenges in terms of initial treatment and transport as well as different injury patterns, such as blast injuries, which result in diverse TIC phenotypes 141 .…”