Acute Fibrinolysis Shutdown after Injury Occurs Frequently and Increases Mortality: A Multicenter Evaluation of 2,540 Severely Injured Patients

Abstract

Background: Fibrinolysis is a physiologic process that maintains microvascular patency by breaking down excessive fibrin clot. Hyperfibrinolysis is associated with a doubling of mortality. Fibrinolysis shutdown, an acute impairment of fibrinolysis, has been recognized as a risk factor for increased mortality. The purpose of this study was to assess the incidence and outcomes of fibrinolysis phenotypes in 2 urban trauma centers.

Study design: Injured patients included in the analysis were admitted between 2010 and 2013, were 18 years of age or older, and had an Injury Severity Score (ISS) > 15. Admission fibrinolysis phenotypes were determined by the clot lysis at 30 minutes (LY30): shutdown ≤ 0.8%, physiologic 0.9% to 2.9%, and hyperfibrinolysis ≥ 3%. Logistic regression was used to adjust for age, arrival blood pressure, ISS, mechanism, and facility.

Results: There were 2,540 patients who met inclusion criteria. Median age was 39 years (interquartile range [IQR] 26 to 55 years) and median ISS was 25 (IQR 20 to 33), with a mortality rate of 21%. Fibrinolysis shutdown was the most common phenotype (46%) followed by physiologic (36%) and hyperfibrinolysis (18%). Hyperfibrinolysis was associated with the highest death rate (34%), followed by shutdown (22%), and physiologic (14%, p < 0.001). The risk of mortality remained increased for hyperfibrinolysis (odds ratio [OR] 3.3, 95% CI 2.4 to 4.6, p < 0.0001) and shutdown (OR 1.6, 95% CI 1.3 to 2.1, p = 0.0003) compared with physiologic when adjusting for age, ISS, mechanism, head injury, and blood pressure (area under the receiver operating characteristics curve 0.82, 95% CI 0.80 to 0.84).

Conclusions: Fibrinolysis shutdown is the most common phenotype on admission and is associated with increased mortality. These data provide additional evidence of distinct phenotypes of coagulation impairment and that individualized hemostatic therapy may be required.

Figure 1

Incidence and mortality of severely injured trauma patients stratified by fibrinolysis phenotype.

Figure 2

Survival time differences between fibrinolysis phenotypes. (A) Overall in-hospital survival; (B) a focused segment of the first 72 hours of survival after injury. Patients are stratified by fibrinolysis phenotype and vertical bars represent 95% confidence intervals. Hyper, hyperfibrinolysis; Phy, physiologic; SD, shutdown; Fib, fibrinolysis.

Figure 3

Differences in causes of mortality between phenotypes.