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

Woolley, Tom; Gwyther, Robert; Parmar, Kiran; Kirkman, Emrys; Watts, Sarah; Midwinter, Mark; Lucca, J Dalle; Hunt, Beverley J.

doi:10.1111/trf.15658

Cited by 9 publications

(12 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…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 ].…”

Section: Discussionsupporting

confidence: 87%

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

Krocker

Lee

Henriksen

et al. 2022

IJMS

View full text Add to dashboard Cite

Background: The endotheliopathy of trauma (EoT) is associated with increased mortality following injury. Herein, we describe the plasma proteome related to EoT in order to provide insight into the role of the endothelium within the systemic response to trauma. Methods: 99 subjects requiring the highest level of trauma activation were included in the study. Enzyme-linked immunosorbent assays of endothelial and catecholamine biomarkers were performed on admission plasma samples, as well as untargeted proteome quantification utilizing high-performance liquid chromatography and tandem mass spectrometry. Results: Plasma endothelial and catecholamine biomarker abundance was elevated in EoT. Patients with EoT (n = 62) had an increased incidence of death within 24 h at 21% compared to 3% for non-EoT (n = 37). Proteomic analysis revealed that 52 out of 290 proteins were differentially expressed between the EoT and non-EoT groups. These proteins are involved in endothelial activation, coagulation, inflammation, and oxidative stress, and include known damage-associated molecular patterns (DAMPs) and intracellular proteins specific to several organs. Conclusions: We report a proteomic profile of EoT suggestive of a surge of DAMPs and inflammation driving nonspecific activation of the endothelial, coagulation, and complement systems with subsequent end-organ damage and poor clinical outcome. These findings support the utility of EoT as an index of cellular injury and delineate protein candidates for therapeutic intervention.

show abstract

Section: Discussionsupporting

confidence: 87%

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

Krocker

Lee

Henriksen

et al. 2022

IJMS

View full text Add to dashboard Cite

show abstract

“…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.…”

Section: Inappropriate Thrombin Generationmentioning

confidence: 99%

“…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.…”

Section: Inappropriate Thrombin Generationmentioning

confidence: 99%

“…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.…”

Section: Mechanismsmentioning

confidence: 99%

“…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 .…”

Section: Box 1 | Critical Appraisal Of Tic Studiesmentioning

confidence: 99%

See 2 more Smart Citations

Trauma-induced coagulopathy

Moore

Kornblith

et al. 2021

Nat Rev Dis Primers

408

464

View full text Add to dashboard Cite

Injury is the fourth leading cause of mortality worldwide, accounting for 9% of deaths globally (4.9 million people) in 2016 (ref. 1 ). Moreover, the burden is highest in individuals <50 years of age, among whom injury as a cause of death is second only to infectious diseases. Early preventable deaths after injury in civilian 2 and military 3 settings are primarily attributable to uncontrolled haemorrhage 2-8 , whereas later preventable deaths are typically due to hypercoagulability 9 . Consequently, there is intense interest worldwide in the pathogenesis of trauma-induced coagulopathy (TIC) to attenuate its adverse effects on the outcomes of seriously injured patients.Impaired coagulation following sudden death from injury has been observed for centuries 10 and, in the 1960s, the first clinical laboratory documentation of the temporal changes in coagulation following severe injury were documented 11 . However, early endogenous drivers of coagulopathy were not specifically investigated until 1982, when a case series of patients with major abdominal vascular injuries highlighted TIC as a common direct cause of early post-injury mortality: 89% of the deaths were bleeding-related, yet half occurred after mechanical control of bleeding sites -in other words, they were due to coagulopathy 12 . The remaining ongoing quagmire is the inability to distinguish between patients with exsanguinating injuries whose TIC is the result of metabolic failure (that is, who are bleeding because they are dying) from patients whose TIC is the cause of the ongoing blood loss (that is, who are dying because they are bleeding) 13 . Furthermore, not all patients with abnormalities in laboratory coagulation tests are bleeding 14 .Despite the long-term fascination with changes in coagulation resulting from shock and tissue injury 15 , there is no standard definition of TIC, which refers to abnormal coagulation capacity attributable to trauma. The term TIC was established during the Trans-Agency Consortium for Trauma Induced Coagulopathy Workshop conducted by the National Institutes of Health in April 2010 to describe the variety of phenomena that characterize this condition. TIC can manifest as a spectrum of phenotypes from hypocoagulation to hypercoagulation (fig. 1), as a function of several interactive factors, including (but not limited to) tissue injury, presence of shock and, in particular, time from injury (fig. 2).

show abstract