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

Moore, Hunter B. MD; Moore, Ernest E. MD; Gonzalez, Eduardo MD; Chapman, Michael P. MD; Chin, Theresa L. MD; Silliman, Christopher C. MD, PhD; Banerjee, Anirban PhD; Sauaia, Angela MD, PhD

Journal of Trauma and Acute Care Surgery: December 2014 - Volume 77 - Issue 6 - p 811–817
doi: 10.1097/TA.0000000000000341
WTA 2014 Plenary Papers
Editor's Choice

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.

From the Departments of Surgery (H.B.M., E.E.M., E.G., M.P.C., T.L.C., A.B., A.S.) and Pediatrics (C.C.S.), University of Colorado Denver; Department of Surgery (E.E.M.), Denver Health Medical Center; and Bonfils Blood Center (C.C.S.), Denver, Colorado.

Submitted: January 15, 2014, Revised: April 9, 2014, Accepted: April 28, 2014, Published online: July 21, 2014.

This study was presented at the 44th Annual Meeting of the Western Trauma Association, March 3, 2014, in Steamboat Springs, Colorado, and at the Annual Meeting of the American College of Surgeons’ Committee on Trauma (ACS COT), March 20, 2014, in Philadelphia, Pennsylvania. The first author (H.B.M.) received the Best Clinical Research Manuscript award in ACS COT’s 2014 Resident Trauma Papers Competition.

The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Supplemental digital content is available for this article. Direct URL citations appear in the printed text, and links to the digital files are provided in the HTML text of this article on the journal’s Web site (www.jtrauma.com).

Address for reprints: Ernest E. Moore, MD, Department of Surgery, Denver Health Medical Center, 655 Broadway, Ste 365, Denver, CO 80203; email: ernest.moore@dhha.org.

© 2014 Lippincott Williams & Wilkins, Inc.