The hyperfibrinolytic phenotype is the most lethal and resource intense presentation of fibrinolysis in massive transfusion patients

John R. Taylor, Erin E. Fox, John B. Holcomb, Sandro Rizoli, Kenji Inaba, Martin Schreiber, Karen Brasel, Thomas M. Scalea, Charles E. Wade, Eileen Bulger, Bryan A. Cotton

    Research output: Contribution to journalArticle

    10 Citations (Scopus)

    Abstract

    BACKGROUND Among bleeding patients, we hypothesized that the hyperfibrinolytic (HF) phenotype would be associated with the highest mortality, whereas shutdown (SD) patients would have the greatest complication burden. METHODS Severely injured patients predicted to receive a massive transfusion at 12 Level I trauma centers were randomized to one of two transfusion ratios as described in the Pragmatic, Randomized, Optimal Platelet and Plasma Ratio trial. Fibrinolysis phenotypes were determined based on admission clot lysis at 30 minutes (LY30): SD ≤0.8%, physiologic (PHYS) 0.9-2.9%, and HF ≥3%. Univariate and multivariate analysis was performed. Logistic regression was used to adjust for age, gender, arrival physiology, shock, injury severity, center effect, and treatment arm. RESULTS Among the 680 patients randomized, 547(80%) had admission thrombelastography (TEG) values available to determine fibrinolytic phenotypes. Compared to SD and PHYS, HF patients had higher Injury Severity Score (25 vs. 25 vs. 34), greater base deficit (-8 vs. -6 vs. -12) and were more uniformly hypocoagulable on admission by PT, PTT, and TEG values; all p <0.001. HF patients also received more red blood cells, plasma, and platelets (at 3, 6, and 24 hours); had fewer ICU-, ventilator-, and hospital-free days; and had higher 24-hour and 30-day mortality. There were no differences in complications between the three phenotypes. Multivariate logistic regression demonstrated that HF on admission was associated with a threefold higher mortality (OR 3.06, 95% CI 1.57-5.95, p = 0.001). CONCLUSIONS Previous data have shown that both the SD and HF phenotypes are associated with increased mortality and complications in the general trauma population. However, in a large cohort of bleeding patients, HF was confirmed to be a much more lethal and resource-intense phenotype. These data suggest that further research into the understanding of SD and HF is warranted to improve outcomes in this patient population. LEVEL OF EVIDENCE Prognostic, level II.

    Original languageEnglish (US)
    Pages (from-to)25-30
    Number of pages6
    JournalJournal of Trauma and Acute Care Surgery
    Volume84
    Issue number1
    DOIs
    StatePublished - Jan 1 2018

    Fingerprint

    Fibrinolysis
    Phenotype
    Thrombelastography
    Mortality
    Blood Platelets
    Logistic Models
    Hemorrhage
    Injury Severity Score
    Trauma Centers
    Wounds and Injuries
    Mechanical Ventilators
    Population
    Shock
    Multivariate Analysis
    Erythrocytes
    Research

    Keywords

    • complications
    • fibrinolysis
    • Hemorrhage
    • hyperfibrinolysis

    ASJC Scopus subject areas

    • Surgery
    • Critical Care and Intensive Care Medicine

    Cite this

    The hyperfibrinolytic phenotype is the most lethal and resource intense presentation of fibrinolysis in massive transfusion patients. / Taylor, John R.; Fox, Erin E.; Holcomb, John B.; Rizoli, Sandro; Inaba, Kenji; Schreiber, Martin; Brasel, Karen; Scalea, Thomas M.; Wade, Charles E.; Bulger, Eileen; Cotton, Bryan A.

    In: Journal of Trauma and Acute Care Surgery, Vol. 84, No. 1, 01.01.2018, p. 25-30.

    Research output: Contribution to journalArticle

    Taylor, John R. ; Fox, Erin E. ; Holcomb, John B. ; Rizoli, Sandro ; Inaba, Kenji ; Schreiber, Martin ; Brasel, Karen ; Scalea, Thomas M. ; Wade, Charles E. ; Bulger, Eileen ; Cotton, Bryan A. / The hyperfibrinolytic phenotype is the most lethal and resource intense presentation of fibrinolysis in massive transfusion patients. In: Journal of Trauma and Acute Care Surgery. 2018 ; Vol. 84, No. 1. pp. 25-30.
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    abstract = "BACKGROUND Among bleeding patients, we hypothesized that the hyperfibrinolytic (HF) phenotype would be associated with the highest mortality, whereas shutdown (SD) patients would have the greatest complication burden. METHODS Severely injured patients predicted to receive a massive transfusion at 12 Level I trauma centers were randomized to one of two transfusion ratios as described in the Pragmatic, Randomized, Optimal Platelet and Plasma Ratio trial. Fibrinolysis phenotypes were determined based on admission clot lysis at 30 minutes (LY30): SD ≤0.8{\%}, physiologic (PHYS) 0.9-2.9{\%}, and HF ≥3{\%}. Univariate and multivariate analysis was performed. Logistic regression was used to adjust for age, gender, arrival physiology, shock, injury severity, center effect, and treatment arm. RESULTS Among the 680 patients randomized, 547(80{\%}) had admission thrombelastography (TEG) values available to determine fibrinolytic phenotypes. Compared to SD and PHYS, HF patients had higher Injury Severity Score (25 vs. 25 vs. 34), greater base deficit (-8 vs. -6 vs. -12) and were more uniformly hypocoagulable on admission by PT, PTT, and TEG values; all p <0.001. HF patients also received more red blood cells, plasma, and platelets (at 3, 6, and 24 hours); had fewer ICU-, ventilator-, and hospital-free days; and had higher 24-hour and 30-day mortality. There were no differences in complications between the three phenotypes. Multivariate logistic regression demonstrated that HF on admission was associated with a threefold higher mortality (OR 3.06, 95{\%} CI 1.57-5.95, p = 0.001). CONCLUSIONS Previous data have shown that both the SD and HF phenotypes are associated with increased mortality and complications in the general trauma population. However, in a large cohort of bleeding patients, HF was confirmed to be a much more lethal and resource-intense phenotype. These data suggest that further research into the understanding of SD and HF is warranted to improve outcomes in this patient population. LEVEL OF EVIDENCE Prognostic, level II.",
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    AU - Taylor, John R.

    AU - Fox, Erin E.

    AU - Holcomb, John B.

    AU - Rizoli, Sandro

    AU - Inaba, Kenji

    AU - Schreiber, Martin

    AU - Brasel, Karen

    AU - Scalea, Thomas M.

    AU - Wade, Charles E.

    AU - Bulger, Eileen

    AU - Cotton, Bryan A.

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    N2 - BACKGROUND Among bleeding patients, we hypothesized that the hyperfibrinolytic (HF) phenotype would be associated with the highest mortality, whereas shutdown (SD) patients would have the greatest complication burden. METHODS Severely injured patients predicted to receive a massive transfusion at 12 Level I trauma centers were randomized to one of two transfusion ratios as described in the Pragmatic, Randomized, Optimal Platelet and Plasma Ratio trial. Fibrinolysis phenotypes were determined based on admission clot lysis at 30 minutes (LY30): SD ≤0.8%, physiologic (PHYS) 0.9-2.9%, and HF ≥3%. Univariate and multivariate analysis was performed. Logistic regression was used to adjust for age, gender, arrival physiology, shock, injury severity, center effect, and treatment arm. RESULTS Among the 680 patients randomized, 547(80%) had admission thrombelastography (TEG) values available to determine fibrinolytic phenotypes. Compared to SD and PHYS, HF patients had higher Injury Severity Score (25 vs. 25 vs. 34), greater base deficit (-8 vs. -6 vs. -12) and were more uniformly hypocoagulable on admission by PT, PTT, and TEG values; all p <0.001. HF patients also received more red blood cells, plasma, and platelets (at 3, 6, and 24 hours); had fewer ICU-, ventilator-, and hospital-free days; and had higher 24-hour and 30-day mortality. There were no differences in complications between the three phenotypes. Multivariate logistic regression demonstrated that HF on admission was associated with a threefold higher mortality (OR 3.06, 95% CI 1.57-5.95, p = 0.001). CONCLUSIONS Previous data have shown that both the SD and HF phenotypes are associated with increased mortality and complications in the general trauma population. However, in a large cohort of bleeding patients, HF was confirmed to be a much more lethal and resource-intense phenotype. These data suggest that further research into the understanding of SD and HF is warranted to improve outcomes in this patient population. LEVEL OF EVIDENCE Prognostic, level II.

    AB - BACKGROUND Among bleeding patients, we hypothesized that the hyperfibrinolytic (HF) phenotype would be associated with the highest mortality, whereas shutdown (SD) patients would have the greatest complication burden. METHODS Severely injured patients predicted to receive a massive transfusion at 12 Level I trauma centers were randomized to one of two transfusion ratios as described in the Pragmatic, Randomized, Optimal Platelet and Plasma Ratio trial. Fibrinolysis phenotypes were determined based on admission clot lysis at 30 minutes (LY30): SD ≤0.8%, physiologic (PHYS) 0.9-2.9%, and HF ≥3%. Univariate and multivariate analysis was performed. Logistic regression was used to adjust for age, gender, arrival physiology, shock, injury severity, center effect, and treatment arm. RESULTS Among the 680 patients randomized, 547(80%) had admission thrombelastography (TEG) values available to determine fibrinolytic phenotypes. Compared to SD and PHYS, HF patients had higher Injury Severity Score (25 vs. 25 vs. 34), greater base deficit (-8 vs. -6 vs. -12) and were more uniformly hypocoagulable on admission by PT, PTT, and TEG values; all p <0.001. HF patients also received more red blood cells, plasma, and platelets (at 3, 6, and 24 hours); had fewer ICU-, ventilator-, and hospital-free days; and had higher 24-hour and 30-day mortality. There were no differences in complications between the three phenotypes. Multivariate logistic regression demonstrated that HF on admission was associated with a threefold higher mortality (OR 3.06, 95% CI 1.57-5.95, p = 0.001). CONCLUSIONS Previous data have shown that both the SD and HF phenotypes are associated with increased mortality and complications in the general trauma population. However, in a large cohort of bleeding patients, HF was confirmed to be a much more lethal and resource-intense phenotype. These data suggest that further research into the understanding of SD and HF is warranted to improve outcomes in this patient population. LEVEL OF EVIDENCE Prognostic, level II.

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    KW - Hemorrhage

    KW - hyperfibrinolysis

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