Differentiating Pathologic from Physiologic Fibrinolysis: Not as Simple as Conventional Thrombelastography.

BACKGROUND: Conventional rapid-thrombelastography (rTEG) cannot differentiate fibrinolysis shutdown from hypofibrinolysis, as both of these patient populations have low fibrinolytic activity. Tissue plasminogen activator (tPA) TEG can identify depletion of fibrinolytic inhibitors, and its use in combination with rTEG has the potential to differentiate all three pathologic fibrinolytic phenotypes following trauma. We hypothesize tPA-TEG and rapid TEG (rTEG) in combination can further stratify fibrinolysis phenotypes post-injury to better stratify risk for mortality.

STUDY DESIGN: Adult trauma patients (n=981) with both rTEG and tPA-TEG performed <2 hours post-injury were included. rTEG LY30 was used to initially define fibrinolysis phenotypes (Hyperfibrinolysis >3%, Physiologic 0.9-3%, Shutdown <0.9%), with Youden Index then used to define pathologic extremes of tPA-TEG LY30 [tPA sensitive (depletion of fibrinolytic inhibitors) versus resistant] resulting in 9 groups that were assessed for risk of death.

RESULTS: The median NISS was 22, 21% were female, 45% had penetrating injury, and overall mortality was 13%. The tPA-TEG LY30 inflection point for increased mortality was>35.5% (tPA sensitive, OR mortality 9.2 P<0.001) and <0.3% (tPA resistance, OR mortality 6.3 p=0.04). Of the nine potential fibrinolytic phenotypes, five were associated with increased mortality. Overall, the 9 phenotypes provided a significantly better prediction of mortality than rTEG or tPA-TEG alone (AUROC=0.80 vs 0.63 and 0.75, respectively, p<0.0001). These could be condensed to three pathologic phenotypes (true hyperfibrinolysis, early fibrinolysis shutdown, and hypofibrinolysis).

CONCLUSIONS: The combination of rTEG and tPA-TEG increases the ability to predict mortality and suggests patient specific strategies for improved outcome.