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Time course and outcomes associated with transient versus persistent fibrinolytic phenotypes after injury

A nested, prospective, multicenter cohort study

Roberts, Derek J., MD, PhD; Kalkwarf, Kyle J., MD; Moore, Hunter B., MD; Cohen, Mitchell J., MD; Fox, Erin E., PhD; Wade, Charles E., PhD; Cotton, Bryan A., MD

Journal of Trauma and Acute Care Surgery: February 2019 - Volume 86 - Issue 2 - p 206–213
doi: 10.1097/TA.0000000000002099
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BACKGROUND Temporal changes in fibrinolytic activity after injury and their impact on outcomes remain poorly defined. We conducted a prospective, multicenter cohort study to determine the incidence of fibrinolytic phenotypes after injury and the trajectories and associated outcomes of these phenotypes over time.

METHODS We included adults that arrived within 6 hours of injury to three American Level I trauma centers. Clot lysis at 30 minutes (LY-30) was measured at presentation and at 3 hours, 6 hours, 12 hours, 24 hours, 48 hours, 72 hours, 96 hours, and 120 hours. LY-30 was used to categorize patients into the following fibrinolytic phenotypes: fibrinolysis shutdown (SD, LY-30 ≤0.8%), physiologic fibrinolysis (PHYS, LY-30 >0.8% to <3%), or hyperfibrinolysis (HF, LY-30 ≥3%). We used multivariable logistic regression to estimate adjusted odds ratios for mortality.

RESULTS We included 795 adults (median age, 38 years; median Injury Severity Scale score, 21). In total, 44% presented with SD, 36% with PHYS, and 21% with HF. Mortality was highest among those who presented with HF (20%) followed by SD (10%) and PHYS (7%) (p = 0.001). While mortality within the first 24 hours was highest with admission HF (14% vs. 5% SD vs. 4% PHYS; p = 0.001), both admission HF (7%) and SD (6%) had higher mortality after 24 hours compared with PHYS (3%) (p = 0.04). All patients who presented with HF switched into another phenotype or died within 24 hours. The majority of patients that presented in SD remained in that phenotype, including 71% at 24 hours and 72% at 120 hours. Persistent SD at 24 hours was independently associated with increased mortality after 24 hours (odds ratio, 3.20; 95% confidence interval, 1.51–6.67).

CONCLUSION Approximately 70% of major trauma patients who present with SD remain in this phenotype up to 120 hours postinjury. In contrast, patients presenting with HF transition into another phenotype or die within 24 hours. While early mortality is highest with the HF phenotype, persistent SD at 24 hours is associated with elevated late mortality.

LEVEL OF EVIDENCE Prognostic and epidemiological study, level II.

From the Division of Vascular and Endovascular Surgery (D.J.R.), Department of Surgery, University of Ottawa, Ottawa, Ontario, Canada; Department of Surgery (K.J.K., E.E.F., C.E.W., B.A.C.), Center for Translational Injury Research (D.J.R., K.J.K., E.E.F., C.E.W., B.A.C.), The University of Texas Health Science Center, Houston, Texas; Department of Surgery (H.B.M., M.J.C.), University of Colorado Denver, Aurora; and Denver Health Medical Center (M.J.C.), Denver, Colorado.

Submitted: September 1, 2017, Revised: October 4, 2018, Accepted: October 10, 2018, Published online: October 29, 2018.

Address for reprints: Derek J. Roberts, MD, PhD, Division of Vascular and Endovascular Surgery, Department of Surgery, University of Ottawa, The Ottawa Hospital, Civic Campus, Rm A280, 1053 Carling Ave, Ottawa, Ontario, Canada K1Y 4E9; email:

This work was completed at the Center for Translational Injury Research, The University of Texas Health Science Center, Houston, Texas.

This work was presented at the 76th Annual Meeting of The American Association for the Surgery of Trauma and the Clinical Congress of Acute Care Surgery in Baltimore, Maryland, on September 15, 2017 (oral podium presentation).

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© 2019 Lippincott Williams & Wilkins, Inc.