Thrombelastography-based dosing of enoxaparin for thromboprophylaxis in trauma and surgical patients

A randomized clinical trial

Christopher R. Connelly, Philbert Van, Kyle D. Hart, Scott G. Louis, Kelly A. Fair, Anfin S. Erickson, Elizabeth A. Rick, Erika C. Simeon, Eileen M. Bulger, Saman Arbabi, John B. Holcomb, Laura J. Moore, Martin Schreiber

    Research output: Contribution to journalArticle

    25 Citations (Scopus)

    Abstract

    Importance: Prophylactic enoxaparin is used to prevent venous thromboembolism (VTE) in surgical and trauma patients. However, VTE remains an important source of morbidity and mortality, potentially exacerbated by antithrombin III or anti-Factor Xa deficiencies and missed enoxaparin doses. Recent data suggest that a difference in reaction time (time to initial fibrin formation) greater than 1 minute between heparinase and standard thrombelastogram (TEG) is associated with a decreased risk of VTE. Objective: To evaluate the effectiveness of TEG-adjusted prophylactic enoxaparin dosing among trauma and surgical patients. Design, Setting, and Participants: This randomized clinical trial, conducted from October 2012 to May 2015, compared standard dosing (30mg twice daily) with TEG-adjusted enoxaparin dosing (35mg twice daily) for 185 surgical and trauma patients screened for VTE at 3 level I trauma centers in the United States. Main Outcomes and Measures: The incidence of VTE, bleeding complications, anti-Factor Xa deficiency, and antithrombin III deficiency. Results: Of the 185 trial participants, 89were randomized to the control group (median age, 44.0 years; 55.1% male) and 96 to the intervention group (median age, 48.5 years; 74.0% male). Patients in the intervention group received a higher median enoxaparin dose than control patients (35mg vs 30mg twice daily; P < .001). Anti-Factor Xa levels in intervention patientswere not higher than levels in control patients until day 6 (0.4 U/mL vs 0.21 U/mL; P < .001). Only 22 patients (11.9%) achieved a difference in reaction time greater than 1 minute, whichwas similar between the control and intervention groups (10.4% vs 13.5% ; P = .68). The time to enoxaparin initiationwas similar between the control and intervention groups (median [range] days, 1.0 [0.0-2.0] vs 1.0 [1.0-2.0]; P = .39), and the number of patients who missed at least 1 dosewas also similar (43 [48.3% ] vs 54 [56.3% ]; P = .30). Rates of VTE (6 [6.7% ] vs 6 [6.3% ]; P > .99)were similar, but the difference in bleeding complications (5 [5.6% ] vs 13 [13.5% ]; P = .08)was not statistically significant. Antithrombin III and anti-Factor Xa deficiencies and hypercoagulable TEG parameters, including elevated coagulation index (>3), maximum amplitude (>74 mm), and G value (>12.4 dynes/cm2), were prevalent in both groups. Identified risk factors for VTE included older age (61.0 years vs 46.0 years; P = .04), higher body mass index (calculated asweight in kilograms divided by height in meters squared; 30.6 vs 27.1; P = .03), increased Acute Physiology and Chronic Health Evaluation II score (8.5 vs 7.0; P = .03), and increased percentage of missed doses per patient (14.8% vs 2.5% ; P = .05). Conclusions and Relevance: The incidence of VTE was low and similar between groups; however, few patients achieved a difference in reaction time greater than 1 minute. Antithrombin III deficiencies and hypercoagulable TEG parameters were prevalent among patients with VTE. Low VTE incidence may be due to an early time to enoxaparin initiation and an overall healthier and less severely injured study population than previously reported.

    Original languageEnglish (US)
    JournalJAMA Surgery
    Volume151
    Issue number10
    DOIs
    StatePublished - Oct 1 2016

    Fingerprint

    Thrombelastography
    Enoxaparin
    Venous Thromboembolism
    Randomized Controlled Trials
    Wounds and Injuries
    Factor Xa
    Antithrombin III Deficiency
    Antithrombin III
    Incidence
    Heparin Lyase
    Hemorrhage
    APACHE
    Trauma Centers
    Fibrin
    Reaction Time
    Body Mass Index
    Age Groups
    Outcome Assessment (Health Care)
    Morbidity
    Control Groups

    ASJC Scopus subject areas

    • Surgery

    Cite this

    Thrombelastography-based dosing of enoxaparin for thromboprophylaxis in trauma and surgical patients : A randomized clinical trial. / Connelly, Christopher R.; Van, Philbert; Hart, Kyle D.; Louis, Scott G.; Fair, Kelly A.; Erickson, Anfin S.; Rick, Elizabeth A.; Simeon, Erika C.; Bulger, Eileen M.; Arbabi, Saman; Holcomb, John B.; Moore, Laura J.; Schreiber, Martin.

    In: JAMA Surgery, Vol. 151, No. 10, 01.10.2016.

    Research output: Contribution to journalArticle

    Connelly, CR, Van, P, Hart, KD, Louis, SG, Fair, KA, Erickson, AS, Rick, EA, Simeon, EC, Bulger, EM, Arbabi, S, Holcomb, JB, Moore, LJ & Schreiber, M 2016, 'Thrombelastography-based dosing of enoxaparin for thromboprophylaxis in trauma and surgical patients: A randomized clinical trial', JAMA Surgery, vol. 151, no. 10. https://doi.org/10.1001/jamasurg.2016.2069
    Connelly, Christopher R. ; Van, Philbert ; Hart, Kyle D. ; Louis, Scott G. ; Fair, Kelly A. ; Erickson, Anfin S. ; Rick, Elizabeth A. ; Simeon, Erika C. ; Bulger, Eileen M. ; Arbabi, Saman ; Holcomb, John B. ; Moore, Laura J. ; Schreiber, Martin. / Thrombelastography-based dosing of enoxaparin for thromboprophylaxis in trauma and surgical patients : A randomized clinical trial. In: JAMA Surgery. 2016 ; Vol. 151, No. 10.
    @article{51acb48623ef4f19a95e840ec391d4f6,
    title = "Thrombelastography-based dosing of enoxaparin for thromboprophylaxis in trauma and surgical patients: A randomized clinical trial",
    abstract = "Importance: Prophylactic enoxaparin is used to prevent venous thromboembolism (VTE) in surgical and trauma patients. However, VTE remains an important source of morbidity and mortality, potentially exacerbated by antithrombin III or anti-Factor Xa deficiencies and missed enoxaparin doses. Recent data suggest that a difference in reaction time (time to initial fibrin formation) greater than 1 minute between heparinase and standard thrombelastogram (TEG) is associated with a decreased risk of VTE. Objective: To evaluate the effectiveness of TEG-adjusted prophylactic enoxaparin dosing among trauma and surgical patients. Design, Setting, and Participants: This randomized clinical trial, conducted from October 2012 to May 2015, compared standard dosing (30mg twice daily) with TEG-adjusted enoxaparin dosing (35mg twice daily) for 185 surgical and trauma patients screened for VTE at 3 level I trauma centers in the United States. Main Outcomes and Measures: The incidence of VTE, bleeding complications, anti-Factor Xa deficiency, and antithrombin III deficiency. Results: Of the 185 trial participants, 89were randomized to the control group (median age, 44.0 years; 55.1{\%} male) and 96 to the intervention group (median age, 48.5 years; 74.0{\%} male). Patients in the intervention group received a higher median enoxaparin dose than control patients (35mg vs 30mg twice daily; P < .001). Anti-Factor Xa levels in intervention patientswere not higher than levels in control patients until day 6 (0.4 U/mL vs 0.21 U/mL; P < .001). Only 22 patients (11.9{\%}) achieved a difference in reaction time greater than 1 minute, whichwas similar between the control and intervention groups (10.4{\%} vs 13.5{\%} ; P = .68). The time to enoxaparin initiationwas similar between the control and intervention groups (median [range] days, 1.0 [0.0-2.0] vs 1.0 [1.0-2.0]; P = .39), and the number of patients who missed at least 1 dosewas also similar (43 [48.3{\%} ] vs 54 [56.3{\%} ]; P = .30). Rates of VTE (6 [6.7{\%} ] vs 6 [6.3{\%} ]; P > .99)were similar, but the difference in bleeding complications (5 [5.6{\%} ] vs 13 [13.5{\%} ]; P = .08)was not statistically significant. Antithrombin III and anti-Factor Xa deficiencies and hypercoagulable TEG parameters, including elevated coagulation index (>3), maximum amplitude (>74 mm), and G value (>12.4 dynes/cm2), were prevalent in both groups. Identified risk factors for VTE included older age (61.0 years vs 46.0 years; P = .04), higher body mass index (calculated asweight in kilograms divided by height in meters squared; 30.6 vs 27.1; P = .03), increased Acute Physiology and Chronic Health Evaluation II score (8.5 vs 7.0; P = .03), and increased percentage of missed doses per patient (14.8{\%} vs 2.5{\%} ; P = .05). Conclusions and Relevance: The incidence of VTE was low and similar between groups; however, few patients achieved a difference in reaction time greater than 1 minute. Antithrombin III deficiencies and hypercoagulable TEG parameters were prevalent among patients with VTE. Low VTE incidence may be due to an early time to enoxaparin initiation and an overall healthier and less severely injured study population than previously reported.",
    author = "Connelly, {Christopher R.} and Philbert Van and Hart, {Kyle D.} and Louis, {Scott G.} and Fair, {Kelly A.} and Erickson, {Anfin S.} and Rick, {Elizabeth A.} and Simeon, {Erika C.} and Bulger, {Eileen M.} and Saman Arbabi and Holcomb, {John B.} and Moore, {Laura J.} and Martin Schreiber",
    year = "2016",
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    day = "1",
    doi = "10.1001/jamasurg.2016.2069",
    language = "English (US)",
    volume = "151",
    journal = "JAMA Surgery",
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    TY - JOUR

    T1 - Thrombelastography-based dosing of enoxaparin for thromboprophylaxis in trauma and surgical patients

    T2 - A randomized clinical trial

    AU - Connelly, Christopher R.

    AU - Van, Philbert

    AU - Hart, Kyle D.

    AU - Louis, Scott G.

    AU - Fair, Kelly A.

    AU - Erickson, Anfin S.

    AU - Rick, Elizabeth A.

    AU - Simeon, Erika C.

    AU - Bulger, Eileen M.

    AU - Arbabi, Saman

    AU - Holcomb, John B.

    AU - Moore, Laura J.

    AU - Schreiber, Martin

    PY - 2016/10/1

    Y1 - 2016/10/1

    N2 - Importance: Prophylactic enoxaparin is used to prevent venous thromboembolism (VTE) in surgical and trauma patients. However, VTE remains an important source of morbidity and mortality, potentially exacerbated by antithrombin III or anti-Factor Xa deficiencies and missed enoxaparin doses. Recent data suggest that a difference in reaction time (time to initial fibrin formation) greater than 1 minute between heparinase and standard thrombelastogram (TEG) is associated with a decreased risk of VTE. Objective: To evaluate the effectiveness of TEG-adjusted prophylactic enoxaparin dosing among trauma and surgical patients. Design, Setting, and Participants: This randomized clinical trial, conducted from October 2012 to May 2015, compared standard dosing (30mg twice daily) with TEG-adjusted enoxaparin dosing (35mg twice daily) for 185 surgical and trauma patients screened for VTE at 3 level I trauma centers in the United States. Main Outcomes and Measures: The incidence of VTE, bleeding complications, anti-Factor Xa deficiency, and antithrombin III deficiency. Results: Of the 185 trial participants, 89were randomized to the control group (median age, 44.0 years; 55.1% male) and 96 to the intervention group (median age, 48.5 years; 74.0% male). Patients in the intervention group received a higher median enoxaparin dose than control patients (35mg vs 30mg twice daily; P < .001). Anti-Factor Xa levels in intervention patientswere not higher than levels in control patients until day 6 (0.4 U/mL vs 0.21 U/mL; P < .001). Only 22 patients (11.9%) achieved a difference in reaction time greater than 1 minute, whichwas similar between the control and intervention groups (10.4% vs 13.5% ; P = .68). The time to enoxaparin initiationwas similar between the control and intervention groups (median [range] days, 1.0 [0.0-2.0] vs 1.0 [1.0-2.0]; P = .39), and the number of patients who missed at least 1 dosewas also similar (43 [48.3% ] vs 54 [56.3% ]; P = .30). Rates of VTE (6 [6.7% ] vs 6 [6.3% ]; P > .99)were similar, but the difference in bleeding complications (5 [5.6% ] vs 13 [13.5% ]; P = .08)was not statistically significant. Antithrombin III and anti-Factor Xa deficiencies and hypercoagulable TEG parameters, including elevated coagulation index (>3), maximum amplitude (>74 mm), and G value (>12.4 dynes/cm2), were prevalent in both groups. Identified risk factors for VTE included older age (61.0 years vs 46.0 years; P = .04), higher body mass index (calculated asweight in kilograms divided by height in meters squared; 30.6 vs 27.1; P = .03), increased Acute Physiology and Chronic Health Evaluation II score (8.5 vs 7.0; P = .03), and increased percentage of missed doses per patient (14.8% vs 2.5% ; P = .05). Conclusions and Relevance: The incidence of VTE was low and similar between groups; however, few patients achieved a difference in reaction time greater than 1 minute. Antithrombin III deficiencies and hypercoagulable TEG parameters were prevalent among patients with VTE. Low VTE incidence may be due to an early time to enoxaparin initiation and an overall healthier and less severely injured study population than previously reported.

    AB - Importance: Prophylactic enoxaparin is used to prevent venous thromboembolism (VTE) in surgical and trauma patients. However, VTE remains an important source of morbidity and mortality, potentially exacerbated by antithrombin III or anti-Factor Xa deficiencies and missed enoxaparin doses. Recent data suggest that a difference in reaction time (time to initial fibrin formation) greater than 1 minute between heparinase and standard thrombelastogram (TEG) is associated with a decreased risk of VTE. Objective: To evaluate the effectiveness of TEG-adjusted prophylactic enoxaparin dosing among trauma and surgical patients. Design, Setting, and Participants: This randomized clinical trial, conducted from October 2012 to May 2015, compared standard dosing (30mg twice daily) with TEG-adjusted enoxaparin dosing (35mg twice daily) for 185 surgical and trauma patients screened for VTE at 3 level I trauma centers in the United States. Main Outcomes and Measures: The incidence of VTE, bleeding complications, anti-Factor Xa deficiency, and antithrombin III deficiency. Results: Of the 185 trial participants, 89were randomized to the control group (median age, 44.0 years; 55.1% male) and 96 to the intervention group (median age, 48.5 years; 74.0% male). Patients in the intervention group received a higher median enoxaparin dose than control patients (35mg vs 30mg twice daily; P < .001). Anti-Factor Xa levels in intervention patientswere not higher than levels in control patients until day 6 (0.4 U/mL vs 0.21 U/mL; P < .001). Only 22 patients (11.9%) achieved a difference in reaction time greater than 1 minute, whichwas similar between the control and intervention groups (10.4% vs 13.5% ; P = .68). The time to enoxaparin initiationwas similar between the control and intervention groups (median [range] days, 1.0 [0.0-2.0] vs 1.0 [1.0-2.0]; P = .39), and the number of patients who missed at least 1 dosewas also similar (43 [48.3% ] vs 54 [56.3% ]; P = .30). Rates of VTE (6 [6.7% ] vs 6 [6.3% ]; P > .99)were similar, but the difference in bleeding complications (5 [5.6% ] vs 13 [13.5% ]; P = .08)was not statistically significant. Antithrombin III and anti-Factor Xa deficiencies and hypercoagulable TEG parameters, including elevated coagulation index (>3), maximum amplitude (>74 mm), and G value (>12.4 dynes/cm2), were prevalent in both groups. Identified risk factors for VTE included older age (61.0 years vs 46.0 years; P = .04), higher body mass index (calculated asweight in kilograms divided by height in meters squared; 30.6 vs 27.1; P = .03), increased Acute Physiology and Chronic Health Evaluation II score (8.5 vs 7.0; P = .03), and increased percentage of missed doses per patient (14.8% vs 2.5% ; P = .05). Conclusions and Relevance: The incidence of VTE was low and similar between groups; however, few patients achieved a difference in reaction time greater than 1 minute. Antithrombin III deficiencies and hypercoagulable TEG parameters were prevalent among patients with VTE. Low VTE incidence may be due to an early time to enoxaparin initiation and an overall healthier and less severely injured study population than previously reported.

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