Fibrinolysis greater than 3% is the critical value for initiation of antifibrinolytic therapy

Abstract

Background: The acute coagulopathy of trauma is present in up to one third of patients by the time of admission, and the recent CRASH-2 and MATTERs trials have focused worldwide attention on hyperfibrinolysis as a component of acute coagulopathy of trauma. Thromboelastography (TEG) is a powerful tool for analyzing fibrinolyis, but a clinically relevant threshold for defining hyperfibrinolysis has yet to be determined. Recent data suggest that the accepted normal upper bound of 7.5% for 30-minute fibrinolysis (LY30) by TEG is inappropriate in severe trauma, as the risk of death rises at much lower levels of clot lysis. We wished to determine the validity of this hypothesis and establish a threshold value to treat fibrinolysis, based on prediction of massive transfusion requirement and risk of mortality.

Methods: Patients with uncontrolled hemorrhage, meeting the massive transfusion protocol (MTP) criteria at admission (n = 73), represent the most severely injured trauma population at our center (median Injury Severity Score [ISS], 30; interquartile range, 20-38). Citrated kaolin TEG was performed at admission blood samples from this population, stratified by LY30, and evaluated for transfusion requirement and 28-day mortality. The same analysis was conducted on available field blood samples from all non-MTP trauma patients (n = 216) in the same period. These represent the general trauma population.

Results: Within the MTP-activating population, the cohort of patients with LY30 of 3% or greater was shown to be at much higher risk for requiring a massive transfusion (90.9% vs. 30.5%, p = 0.0008) and dying of hemorrhage (45.5% vs. 4.8%, p = 0.0014) than those with LY30 less than 3%. Similar trends were seen in the general trauma population.

Conclusion: LY30 of 3% or greater defines clinically relevant hyperfibrinolysis and strongly predicts the requirement for massive transfusion and an increased risk of mortality in trauma patients presenting with uncontrolled hemorrhage. This threshold value for LY30 represents a critical indication for the treatment of fibrinolysis.

Level of evidence: Prognostic study, level III.

Figure 1

Massive transfusion risk versus LY30. The risk of requiring a massive transfusion (≥10 U of PRBCs by the 6-hour postinjury time point) rises sharply above the LY30 threshold value of 3% (p = 0.0008). There is no statistically significant difference in the massive transfusion risk between the subcohorts (0% compared with >0% to <3%, p = 0.7, and ≥3% to <7.5% compared with ≥7.5%, p = 1.0).

Figure 2

All-cause 28-day mortality versus LY30. The risk of death rises sharply above the LY30 threshold value of 3% (p = 0.0034). There is no statistically significant difference in the mortality risk between the subcohorts (0% compared with >0% to <3%, p = 1.0, and ≥3% to <7.5% compared with ≥7.5%, p = 0.33).

Figure 3

Hemorrhagic mortality versus LY30. Similar to all-cause mortality, the risk of death clearly attributable to bleeding is markedly higher above the LY30 threshold value of 3% (p = 0.0014). There is no statistically significant difference in the mortality risk between the subcohorts (0% compared with >0% to <3%, p = 0.57, and ≥3% to <7.5% compared with ≥7.5%, p = 1.0).

Figure 4

Outcomes versus LY30 in the GT population. A, Plot of massive transfusion risk versus LY30 shows trend of increasing risk with increasing LY30. B, Plot of all-cause 28-day mortality versus LY30 demonstrates trend of increasing mortality with increasing LY30. Both of these outcomes display the same pattern of a sharp increase in risk at the threshold of LY30 of 3% or greater as in the MTP-activating population; however, the effect is much more marked at the 7.5% threshold, reflecting the lower pretest probability of massive transfusion or death in the highly heterogeneous GT population.