OC 47.3 - Tissue Plasminogen Activator (tPA)-Challenge Thrombelastography (TEG) is a Quantitative Measure of Fibrinolytic Inhibitors with Mortality Risk Implications

Background: Fibrinolysis phenotypes impact postinjury outcomes, but determining them with conventional TEG has been elusive. Based on experimental work, we developed a tPA-challenge TEG, and showed it to be superior to rapid TEG in identifying patients requiring massive transfusions, which correlates with depletion of fibrinolysis inhibitors. Recently, we showed that 12hrs postinjury tPA-TEG is a robust predictor of venous thromboembolism(VTE), which correlates with elevated fibrinolysis inhibitors.

Aims: Define fibrinolysis phenotypes representing abnormal hyper/hypofibrinolysis combining conventional rapid TEG(rTEG) and tPA(75ng/ml)-TEG based on their lethality potential.

Methods: Trauma patients(n =1179) meeting the highest level of activation were prospectively enrolled from 2014 to 2020, under a waiver of consent. Citrated blood samples were analyzed using the TEG-5000 Hemostasis Analyzer. TEG percent clot lysis 30min after maximum amplitude(LY30, %) quantified fibrinolysis by rTEG, and by adding 75ng/mL exogenous tPA, tPA-TEG. Thresholds were defined by the Youden Index.

Results: By stratifying each of the three rTEG-defined fibrinolysis phenotypes into tPA sensitivity/normal/resistance, we created a 3x3 matrix with 9 groups. We observed the typical U-shaped curve of increased mortality within each rTEG phenotype stratified by the tPA-TEG(Figure 1-A). However, when tPA-TEG was sub-stratified by the rTEG phenotypes, the U-shaped mortality distribution was observed only in the tPA-sensitive group(Figure 1-B). We identified four major phenotypes(Figure 2): 1)True Hyperfibrinolysis(53% mortality/9% incidence): combination of tPA-sensitive and rTEG-hyperfibrinolysis, i.e., patients with active fibrinolysis and depletion of inhibitors; 2)Early shutdown(26% mortality/12% incidence): tPA-sensitive with either rTEG physiologic or shutdown; i.e., patients depleted of fibrinolytic inhibitors but with low systemic fibrinolysis, 3)Hypofibrinolysis(10% mortality/25% incidence): tPA-normal and r-TEG shutdown or tPA-resistant; i.e., patients without fibrinolytic response; and 4)Non-pathologic: all other combinations(4% mortality/53% incidence).

Conclusion(s): Combining a tPA TEG with conventional rTEG elucidates unique phenotypes that reflect mortality risk and provides an improved platform to investigate the pathogenesis of trauma-induced coagulopathy.