Disseminated intravascular coagulation or acute coagulopathy of trauma shock early after trauma? An observational study

Abstract

Introduction: It is debated whether early trauma-induced coagulopathy (TIC) in severely injured patients reflects disseminated intravascular coagulation (DIC) with a fibrinolytic phenotype, acute coagulopathy of trauma shock (ACoTS) or yet other entities. This study investigated the prevalence of overt DIC and ACoTS in trauma patients and characterized these conditions based on their biomarker profiles.

Methods: An observational study was carried out at a single Level I Trauma Center. Eighty adult trauma patients (≥18 years) who met criteria for full trauma team activation and had an arterial cannula inserted were included. Blood was sampled a median of 68 minutes (IQR 48 to 88) post-injury. Data on demography, biochemistry, injury severity score (ISS) and mortality were recorded. Plasma/serum was analyzed for biomarkers reflecting tissue/endothelial cell/glycocalyx damage (histone-complexed DNA fragments, Annexin V, thrombomodulin, syndecan-1), coagulation activation/inhibition (prothrombinfragment 1+2, thrombin/antithrombin-complexes, antithrombin, protein C, activated protein C, endothelial protein C receptor, protein S, tissue factor pathway inhibitor, vWF), factor consumption (fibrinogen, FXIII), fibrinolysis (D-dimer, tissue-type plasminogen activator, plasminogen activator inhibitor-1) and inflammation (interleukin (IL)-6, terminal complement complex (sC5b-9)). Comparison of patients stratified according to the presence or absence of overt DIC (International Society of Thrombosis and Hemostasis (ISTH) criteria) or ACoTS (activated partial thromboplastin time (APTT) and/or international normalized ratio (INR) above normal reference).

Results: No patients had overt DIC whereas 15% had ACoTS. ACoTS patients had higher ISS, transfusion requirements and mortality (all P < 0.01) and a biomarker profile suggestive of enhanced tissue, endothelial cell and glycocalyx damage and consumption coagulopathy with low protein C, antithrombin, fibrinogen and FXIII levels, hyperfibrinolysis and inflammation (all P < 0.05). Importantly, in non-ACoTS patients, apart from APTT/INR, higher ISS correlated with biomarkers of enhanced tissue, endothelial cell and glycocalyx damage, protein C activation, coagulation factor consumption, hyperfibrinolysis and inflammation, that is, resembling that observed in patients with ACoTS.

Conclusions: ACoTS and non-ACoTS may represent a continuum of coagulopathy reflecting a progressive early evolutionarily adapted hemostatic response to the trauma hit and both are parts of TIC whereas DIC does not appear to be part of this early response.

Figure 1

Correlations between fibrinogen or FXIII and different biomarkers in ACoTS or non-ACoTS patients. Correlations between fibrinogen (A-D) or FXIII (E-H) and biomarkers of tissue damage (hcDNA), thrombin generation (PF1.2, TAT) and fibrinolysis (D-dimer) on admission in 80 trauma patients stratified according to presence (ACoTS) or absence (no ACoTS) of ACoTS defined as APTT or INR above normal reference (n = 12). Rho and P-values are shown for correlations between fibrinogen or FXIII and the mentioned variables in patients with ACoTS (black circles, filled lines) or without ACoTS (white circles, dashed lines): A) log₁₀ hcDNA (%) vs. fibrinogen (g/l), B) log₁₀ PF1.2 (nmol/l) vs. fibrinogen (g/l), C) Log₁₀ TAT (ng/ml) vs. fibrinogen (g/l), D) Log₁₀ D-dimer (ng/ml) vs. fibrinogen (g/l), E) log₁₀ hcDNA (%) vs. FXIII (microg/ml), F) log₁₀ PF1.2 (nmol/l) vs. FXIII (microg/ml), G) Log₁₀ TAT (ng/ml) vs. FXIII (microg/ml), H) Log₁₀ D-dimer (ng/ml) vs. FXIII (microg/ml).

Figure 2

Association between assessment time-point, trauma hit and type of coagulopathy in trauma patients. Association between assessment time-point (blood sampling), trauma hit (tissue injury, shock) and trauma-induced coagulopathy (TIC), acute coagulopathy of trauma shock (ACoTS), non-ACoTS, disseminated intravascular coagulation (DIC) and non-DIC. We infer that TIC represents an early (minutes) progressive endogenous response to the trauma hit (tissue injury, shock) ranging from and covering both non-ACoTS and ACoTS (defined as moderately increased plasma based coagulation tests), with a biomarker profile indicative of endothelial and glycocalyx damage, factor consumption, hyperfibrinolysis and inflammation. The immediate hemostatic response to trauma is probably evolutionarily adapted to improve the chance of survival by, for example, inducing local hemostasis while preserving perfusion and oxygen delivery [16] with ACoTS representing an exaggerated non-adapted response in patients that without immediate life support would have succumbed. Progression to overt DIC does not appear to be part of the early response to trauma but may occur later (hours or days) post-injury, probably driven by a combination of the tissue injury exerted by the initial trauma hit, systemic endothelial dysfunction/damage, exhaustion of the natural anticoagulant pathways and/or excessive inflammation. Whether early TIC progresses to DIC may be determined by a combination of exogenous factors (the early trauma hit and later hits) [30] and endogenous factors (genetically determined response to the hits).