Hyperfibrinolysis, physiologic fibrinolysis, and fibrinolysis shutdown: the spectrum of postinjury fibrinolysis and relevance to antifibrinolytic therapy - PubMed (original) (raw)

Hyperfibrinolysis, physiologic fibrinolysis, and fibrinolysis shutdown: the spectrum of postinjury fibrinolysis and relevance to antifibrinolytic therapy

Hunter B Moore et al. J Trauma Acute Care Surg. 2014 Dec.

Abstract

Background: Fibrinolysis is a physiologic process maintaining patency of the microvasculature. Maladaptive overactivation of this essential function (hyperfibrinolysis) is proposed as a pathologic mechanism of trauma-induced coagulopathy. Conversely, the shutdown of fibrinolysis has also been observed as a pathologic phenomenon. We hypothesize that there is a level of fibrinolysis between these two extremes that have a survival benefit for the severely injured patients.

Methods: Thrombelastography and clinical data were prospectively collected on trauma patients admitted to our Level I trauma center from 2010 to 2013. Patients with an Injury Severity Score (ISS) of 15 or greater were evaluated. The percentage of fibrinolysis at 30 minutes by thrombelastography was used to stratify three groups as follows: hyperfibrinolysis (≥3%), physiologic (0.081-2.9%), and shutdown (0-0.08%). The threshold for hyperfibrinolysis was based on existing literature. The remaining groups were established on a cutoff of 0.8%, determined by the highest point of specificity and sensitivity for mortality on a receiver operating characteristic curve.

Results: One hundred eighty patients were included in the study. The median age was 42 years (interquartile range [IQR], 28-55 years), 70% were male, and 21% had penetrating injuries. The median ISS was 29 (IQR, 22-36), and the median base deficit was 9 mEq/L (IQR, 6-13 mEq/L). Distribution of fibrinolysis was as follows: shutdown, 64% (115 of 180); physiologic, 18% (32 of 180); and hyperfibrinolysis, 18% (33 of 180). Mortality rates were lower for the physiologic group (3%) compared with the hyperfibrinolysis (44%) and shutdown (17%) groups (p = 0.001).

Conclusion: We have identified a U-shaped distribution of death related to the fibrinolysis system in response to major trauma, with a nadir in mortality, with level of fibrinolysis after 30 minutes between 0.81% and 2.9%. Exogenous inhibition of the fibrinolysis system in severely injured patients requires careful selection, as it may have an adverse affect on survival.

Level of evidence: Prognostic study, level III.

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Figures

Figure 1

Figure 1

Blood product transfusions between phenotypes. The y axis represents the number of specific blood products transfused within 6 hours of injury. The figure includes only patients who received a transfusion. Overall RBC and plasma transfusion units were higher in the hyperfibrinolysis phenotype and remained statistically significant after pairwise adjustment between both the physiologic and shutdown groups. *p < 0.05 after pairwise adjustment. Cryo, croprecipitate.

Figure 2

Figure 2

U-shaped distribution of mortality related to fibrinolysis phenotype. The y axis represents the percentage of mortality per phenotype. There is a U-shaped distribution of mortality, with a nadir in mortality identified in the physiologic group (Ly30 between 0.9% and 2.8%). Percentage of Ly30 higher and lower than this range had statistical increases in mortality. Hyper, hyperfibrinolysis; Ly30, percentage of fibrinolysis 30 minutes after reaching maximum amplitude measured by thombelastography; Physiologic, physiologic fibrinolysis; Shutdown, fibrinolysis shutdown.

Figure 3

Figure 3

Distribution of mortality according to fibrinolytic phenotype. The y axis represents the percentage of total mortality per phenotype. The hyperfibrinolytic phenotype had a high frequency of mortality associated with hemorrhage. The shutdown phenotype has a high frequency of organ failureYrelated death. TBI did not reach statistical difference between phenotypes but was more common in the shutdown cohort. *p < 0.05. Hyper, hyperfibrinolysis; Shutdown, fibrinolysis shutdown; TBI, traumatic brain injury.

Figure 4

Figure 4

Survival curve of different phenotypes of fibrinolysis. Curve demonstrates the time from injury to survival patterns between the fibrinolysis phenotypes. The y axis represents the percentage of survival, and the x axis represents hours from injury. Survival, hours after injury.

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