E. Gonzalez Rodriguez1, J. Cardenas1, B. Cotton1, Y. Wang1, S. Ostrowski2, J. Stensballe2,3, P. Johansson1,2, J. Holcomb1, C. Wade1 1University Of Texas Health Science Center At Houston,Center For Translational Injury Research,Houston, TX, USA 2Copenhagen University Hospital,Section For Transfusion Medicine, Capital Region Blood Bank,Copenhagen, -, Denmark 3Copenhagen University Hospital,Department Of Anesthesia, Centre Of Head And Orthopedics,Copenhagen, , Denmark
Introduction: Traumatic endotheliopathy (EOT) is a syndrome that arises from breakdown of the glycocalyx. This results in shedding of syndecan-1 and endothelial activation, which triggers downstream effects that lead to coagulation disturbances, leakage, organ failure and poor outcomes. Because the hemostatic potential of patients with EOT is unclear, we aimed at characterizing it in this study. We hypothesized that the presence of EOT is associated with acute coagulation derangements as assessed by rapid thrombelastography (r-TEG) that are not found in syndrome-free patients.
Methods: To test our hypothesis, we conducted a prospective observational study in trauma patients with the highest level of activation. Demographic, clinical and laboratory data, injury severity (ISS) scores, and transfusion data were collected. Upon hospital arrival, blood samples were obtained to measure i) Syndecan-1 and soluble thrombomodulin (sTM) (from plasma), ii) hemostatic potential measured by r-TEG. Clinically meaningful r-TEG values are the activated clotting time (ACT), values over 128 seconds indicate factor deficiency or severe hemodilution; α-angle (abnormal < 56°) and maximal amplitude (MA) (hypocoagulable < 55; hypercoagulable > 72 mm), both altered in platelet dysfunction or hypofibrinogenemia. LY30 elevations (> 3.0%) reflect hyperfibrinolysis. Based on a previous study, patients were dichotomized into an EOT+ group (syndecan-1≥ 40 ng/ml) or EOT- group (< 40 ng/ml). Differences between groups were assessed with non-parametric tests.
Results:of the 527 that met inclusion criteria, 36% (n=189) had EOT+. Demographic data were comparable between groups. In general, patients with EOT+ had higher ISS (median EoT+ 24 vs.17 EoT-), but the frequency of TBI was similar in both groups. EOT+ patients had more endothelial activation/injury than syndrome-free patients indicated by higher sTM median levels (7.2 vs. 4.9 ng/ml; p<0.05). All r-TEG parameters, except LY30 were significantly different between groups. In contrast to EOT- patients, a higher proportion of EOT+ patients had prolonged ACT, and lower MA, α- angle values, and platelet counts (< 150 10 3 µl) than the EOT- group (Figure). These alterations reflected a hypocoagulable state in EOT+ patients. EOT+ patients required blood transfusions more frequently than EOT- patients (median 4-hour total blood units was 4 in EOT+ vs. 0 in EOT-; p<0.05).
Conclusion:EOT is a syndrome associated with a state of r-TEG hypocoagulability, and an increased need for early transfusion of blood products. This is likely driven by exposure and activation of the endothelium after glycocalyx breakdown triggered by sympathoadrenal activation after trauma.
