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.

Early Diagnosis of Clinically Significant Hyperfibrinolysis Using Thrombelastography Velocity Curves

“…25 For LY30, patients with admission lysis values >3% were defined as having hyperfibrinolysis, a cutoff we previously identified was associated with a 2-fold increase in mortality and has since been validated as a critical threshold for defining hyperfibrinolysis and initiating antifibrinolytic therapy. 16,26 Because LY30 > 3% amounts to the 90 th percentile for fibrinolysis, the corresponding 90 th percentile values were chosen as hyperfibrinolysis cutoffs for velocity curves. Therefore, for velocity curves, hyperfibrinolysis was defined as MRL > 0.5 mm/min and TL > 60 mm reduction in clot amplitude.…”

“…To reduce the inherent survival bias included in the definition of MT, we also assessed patients by using the definition of substantial bleeding to account for early hemorrhagic deaths. [24][25][26][27][28] Substantial bleeding (SB) was defined as receiving the first unit of RBCs within 2 hours and more than 4 units of RBCs within the first 4 hours of arrival, or hemorrhagic death within 6 hours. Patients were considered as having a hemorrhagic death if they received at least 1 unit RBC and died within 6 hours of arrival.…”

The challenge in management of hemorrhagic shock in trauma

“…Fibrinolysis greater than 3% as measured by thromboelastometry is the critical value for initiation of antifibrinolytic therapy. 26 Tranexamic acid has been found to reduce the transfusion requirements and improve mortality in trauma patients. 16,27.…”

Point of Care and Factor Concentrate-Based Coagulation Algorithms

“…Trauma patients with hyperfibrinolysis documented by ROTEM have a significantly higher mortality compared to those without [23]. Hyperfibrinolysis > 3% is associated with massive transfusion [24]. Fibrinogen substitution as a substrate and prothrombin complex concentrate as an enzyme, guided by rotational thrombelastometry, can be safely used to enhance thrombin generation in patients with severe multiple trauma [25][26][27].…”