Primary Fibrinolysis Lowers Trauma Survival

Major Finding: Mortality was 64% in patients with primary fibrinolysis vs. 29% in those with transient fibrinolysis and 18% with no fibrinolysis.

Data Source: A retrospective analysis of point-of-care testing for primary fibrinolysis in 61 consecutive trauma patients.

Disclosures: Dr. Kashuk and Dr. Hoyt disclosed no conflicts.

CHICAGO — Primary fibrinolysis occurs early after severe injury, and is associated with massive transfusion requirements, the presence of coagulopathy, and hemorrhage-related death.

Primary fibrinolysis also is associated with poor clot strength as measured by rapid thrombelastography “G” value, which has emerged as a rapid point-of-care test for such assessments, said Dr. Jeffry L. Kashuk, lead author of a retrospective analysis of primary fibrinolysis.

Dr. Kashuk reported on 61 consecutive trauma patients treated at Denver Health Medical Center who required transfusion within 6 hours of admission. Penetrating injuries were present in 51% of the patients, and 52% required massive transfusion of more than 10 units. Rapid thrombelastography (r-TEG) was performed by adding tissue factor to uncitrated whole blood.

Primary fibrinolysis (PF) was identified in 11 patients, 34% of whom required massive transfusion. PF was defined by an estimated percent lysis (EPL) greater than 15%, and coagulopathy as clot strength equal to a G value of less than 5.3 dynes/cm

PF occurred early, at a median of 58 minutes postinjury vs. a median of 104 minutes for transient fibrinolysis, said Dr. Kashuk, chief of the acute care surgery section and associate director of the Shock Trauma Center at Penn State University, Hershey.

PF was significantly associated with hypothermia in the emergency department, increased red blood cells, depressed fibrinogen at 1 hour, prolonged partial thromboplastin time in ED and, at 6 hours postinjury, increased international normalized ratio (INR) and lower hemoglobin.

All r-TEG findings were significantly associated with PF and included activated clotting time, clot formation time, alpha angle, maximum amplitude, EPL, and G value—all at a P value less than .0001.

A total of 64% of patients with PF died, compared with 29% with transient fibrinolysis and 18% with no fibrinolysis (P = .027), Dr. Kashuk said.

For every 1U drop in G-value postinjury, the risk of PF increased by more than 30% and death by more than 10%.

In logistic regression analysis, the best clinical variable to predict PF was presenting temperature in the ED, whereas INR and hemoglobin in the ED were the best laboratory predictors. Among r-TEG values, G-value—or clot strength at 1 hour—had a highly significant correlation with PF (P = .02), he said.

“These data warrant renewed emphasis on the precise timing and early diagnosis of fibrinolysis in the injured patient. Such investigations could allow for timely administration of antifibrinolytic agents in this cohort,” he said.

The study is important because it takes comprehensive point-of-care testing using r-TEG to a “new level” and describes the importance and risks of primary fibrinolysis, said invited discussant Dr. David B. Hoyt, executive director of the American College of Surgeons. The findings also suggest there is a specific group of patients with a primary fibrinolytic state that occurs upon presentation and is associated with the sickest patients postinjury.

“This observation is particularly important as it could be the potential target for intervention at a time when our traditional thinking suggests that inhibition of fibrinolysis might potentially be dangerous and actually enhance coagulopathy,” he said. “This is very important work.”

Dr. Hoyt questioned what is thought to be the cause of the primary fibrinolytic state and how practical the r-TEG test is in most trauma centers. Dr. Kashuk said the researchers think fibrinolysis is a normal physiologic response to thrombosis that might be critical for survival under shock and low-flow states. When fibrinolysis is observed early on, it is most likely related to factors associated with shock and endothelial injury rather than to physiologic exhaustion. When consumptive coagulopathy is observed, it follows PF, suggesting that the lytic process is driving the consumption of clotting factors rather than the reverse, he said. Furthermore, because this is happening quite early, there is a window of opportunity for therapy before the consumptive state occurs.

He added that the r-TEG test (Haemonetics Inc.) seems to be the only one rapidly available to both identify and quantify fibrinolysis and that point-of-care testing has the added potential of being able to guide therapy.

Hemorrhagic shock accounts for 50% of deaths worldwide from trauma via exsanguination or postinjury coagulopathy. The mechanistic link between PF and acute coagulopathy of trauma remains to be clearly elucidated, even though the association between PF and shock has been recognized for more than 100 years.