Thromboelastogram-guided enoxaparin dosing does not confer protection from deep venous thrombosis

A randomized controlled pilot trial

Scott G. Louis, Philbert Van, Gordon M. Riha, Jeffrey S. Barton, Nicholas R. Kunio, Samantha J. Underwood, Jerome A. Differding, Elizabeth Rick, Enrique Ginzburg, Martin Schreiber

    Research output: Contribution to journalArticle

    21 Citations (Scopus)

    Abstract

    Background: The incidence of deep venous thrombosis (DVT) remains high in general surgery and trauma patients despite widespread prophylaxis with enoxaparin. A recent study demonstrated decreased incidence of DVT if patients on enoxaparin had a change in R time (ΔR) of greater than 1 minute when heparinase-activated thromboelastography (TEG) was compared with normal TEG. We hypothesized that using ΔR-guided dosing would result in decreased DVT rates. Methods: A prospective, randomized controlled trial was performed at a Level 1 trauma center. Both trauma and general surgery patients were included. Upon enrollment, demographic data including age, sex, body mass index, and Acute Physiology and Chronic Health Evaluation II score were obtained. Enrolled patients were randomized to standard (30 mg twice a day) or TEG-guided dosing. Dose-adjusted patients underwent daily enoxaparin titration to achieve an ΔR of 1 minute to 2 minutes. Venous thromboembolism screening was performed per institutional protocol. Antithrombin III (AT-III) and anti-Xa levels were drawn at peak enoxaparin concentrations. Results: A total of 87 patients were enrolled. There was no difference in demographic data between the groups. No pulmonary emboli were identified. The control group had a DVT rate of 16%, while the experimental group had a rate of 14% (p = nonsignificant). The experimental group's median enoxaparin dosage, 50 mg twice a day, was significantly higher than that of the control (p <0.01). TEG ΔR was not different between the control and experimental groups. Beginning at Day 3, anti-Xa levels were higher in the experimental group (p <0.05). There was no difference in AT-III activity between the two groups; 67% of the patients demonstrated AT-III deficiency. Conclusion: TEG adjusted enoxaparin dosing led to significant increases in anti-Xa activity, which did not correlate with a decreased DVT rate. Failure to reduce the DVT rate and increase ΔR despite increased dosing and increased anti-Xa activity is consistent with the high rate of AT-III deficiency detected in this study cohort. These data suggest that the future of DVT prevention may not lie in the optimization of low molecular weight heparin therapy but rather in compounds that increase antithrombin directly or operate independently of the AT-III pathway. LEVEL OF EVIDENCE: Therapeutic study, level III.

    Original languageEnglish (US)
    Pages (from-to)937-943
    Number of pages7
    JournalJournal of Trauma and Acute Care Surgery
    Volume76
    Issue number4
    DOIs
    StatePublished - 2014

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    Enoxaparin
    Thrombelastography
    Venous Thrombosis
    Randomized Controlled Trials
    Antithrombin III
    Antithrombin III Deficiency
    Demography
    Heparin Lyase
    Control Groups
    APACHE
    Antithrombins
    Trauma Centers
    Low Molecular Weight Heparin
    Incidence
    Venous Thromboembolism
    Wounds and Injuries
    Embolism
    Body Mass Index
    Cohort Studies
    Lung

    Keywords

    • deep venous thrombosis
    • enoxaparin
    • Thromboelastography

    ASJC Scopus subject areas

    • Critical Care and Intensive Care Medicine
    • Surgery

    Cite this

    Thromboelastogram-guided enoxaparin dosing does not confer protection from deep venous thrombosis : A randomized controlled pilot trial. / Louis, Scott G.; Van, Philbert; Riha, Gordon M.; Barton, Jeffrey S.; Kunio, Nicholas R.; Underwood, Samantha J.; Differding, Jerome A.; Rick, Elizabeth; Ginzburg, Enrique; Schreiber, Martin.

    In: Journal of Trauma and Acute Care Surgery, Vol. 76, No. 4, 2014, p. 937-943.

    Research output: Contribution to journalArticle

    Louis, Scott G. ; Van, Philbert ; Riha, Gordon M. ; Barton, Jeffrey S. ; Kunio, Nicholas R. ; Underwood, Samantha J. ; Differding, Jerome A. ; Rick, Elizabeth ; Ginzburg, Enrique ; Schreiber, Martin. / Thromboelastogram-guided enoxaparin dosing does not confer protection from deep venous thrombosis : A randomized controlled pilot trial. In: Journal of Trauma and Acute Care Surgery. 2014 ; Vol. 76, No. 4. pp. 937-943.
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    abstract = "Background: The incidence of deep venous thrombosis (DVT) remains high in general surgery and trauma patients despite widespread prophylaxis with enoxaparin. A recent study demonstrated decreased incidence of DVT if patients on enoxaparin had a change in R time (ΔR) of greater than 1 minute when heparinase-activated thromboelastography (TEG) was compared with normal TEG. We hypothesized that using ΔR-guided dosing would result in decreased DVT rates. Methods: A prospective, randomized controlled trial was performed at a Level 1 trauma center. Both trauma and general surgery patients were included. Upon enrollment, demographic data including age, sex, body mass index, and Acute Physiology and Chronic Health Evaluation II score were obtained. Enrolled patients were randomized to standard (30 mg twice a day) or TEG-guided dosing. Dose-adjusted patients underwent daily enoxaparin titration to achieve an ΔR of 1 minute to 2 minutes. Venous thromboembolism screening was performed per institutional protocol. Antithrombin III (AT-III) and anti-Xa levels were drawn at peak enoxaparin concentrations. Results: A total of 87 patients were enrolled. There was no difference in demographic data between the groups. No pulmonary emboli were identified. The control group had a DVT rate of 16{\%}, while the experimental group had a rate of 14{\%} (p = nonsignificant). The experimental group's median enoxaparin dosage, 50 mg twice a day, was significantly higher than that of the control (p <0.01). TEG ΔR was not different between the control and experimental groups. Beginning at Day 3, anti-Xa levels were higher in the experimental group (p <0.05). There was no difference in AT-III activity between the two groups; 67{\%} of the patients demonstrated AT-III deficiency. Conclusion: TEG adjusted enoxaparin dosing led to significant increases in anti-Xa activity, which did not correlate with a decreased DVT rate. Failure to reduce the DVT rate and increase ΔR despite increased dosing and increased anti-Xa activity is consistent with the high rate of AT-III deficiency detected in this study cohort. These data suggest that the future of DVT prevention may not lie in the optimization of low molecular weight heparin therapy but rather in compounds that increase antithrombin directly or operate independently of the AT-III pathway. LEVEL OF EVIDENCE: Therapeutic study, level III.",
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    T2 - A randomized controlled pilot trial

    AU - Louis, Scott G.

    AU - Van, Philbert

    AU - Riha, Gordon M.

    AU - Barton, Jeffrey S.

    AU - Kunio, Nicholas R.

    AU - Underwood, Samantha J.

    AU - Differding, Jerome A.

    AU - Rick, Elizabeth

    AU - Ginzburg, Enrique

    AU - Schreiber, Martin

    PY - 2014

    Y1 - 2014

    N2 - Background: The incidence of deep venous thrombosis (DVT) remains high in general surgery and trauma patients despite widespread prophylaxis with enoxaparin. A recent study demonstrated decreased incidence of DVT if patients on enoxaparin had a change in R time (ΔR) of greater than 1 minute when heparinase-activated thromboelastography (TEG) was compared with normal TEG. We hypothesized that using ΔR-guided dosing would result in decreased DVT rates. Methods: A prospective, randomized controlled trial was performed at a Level 1 trauma center. Both trauma and general surgery patients were included. Upon enrollment, demographic data including age, sex, body mass index, and Acute Physiology and Chronic Health Evaluation II score were obtained. Enrolled patients were randomized to standard (30 mg twice a day) or TEG-guided dosing. Dose-adjusted patients underwent daily enoxaparin titration to achieve an ΔR of 1 minute to 2 minutes. Venous thromboembolism screening was performed per institutional protocol. Antithrombin III (AT-III) and anti-Xa levels were drawn at peak enoxaparin concentrations. Results: A total of 87 patients were enrolled. There was no difference in demographic data between the groups. No pulmonary emboli were identified. The control group had a DVT rate of 16%, while the experimental group had a rate of 14% (p = nonsignificant). The experimental group's median enoxaparin dosage, 50 mg twice a day, was significantly higher than that of the control (p <0.01). TEG ΔR was not different between the control and experimental groups. Beginning at Day 3, anti-Xa levels were higher in the experimental group (p <0.05). There was no difference in AT-III activity between the two groups; 67% of the patients demonstrated AT-III deficiency. Conclusion: TEG adjusted enoxaparin dosing led to significant increases in anti-Xa activity, which did not correlate with a decreased DVT rate. Failure to reduce the DVT rate and increase ΔR despite increased dosing and increased anti-Xa activity is consistent with the high rate of AT-III deficiency detected in this study cohort. These data suggest that the future of DVT prevention may not lie in the optimization of low molecular weight heparin therapy but rather in compounds that increase antithrombin directly or operate independently of the AT-III pathway. LEVEL OF EVIDENCE: Therapeutic study, level III.

    AB - Background: The incidence of deep venous thrombosis (DVT) remains high in general surgery and trauma patients despite widespread prophylaxis with enoxaparin. A recent study demonstrated decreased incidence of DVT if patients on enoxaparin had a change in R time (ΔR) of greater than 1 minute when heparinase-activated thromboelastography (TEG) was compared with normal TEG. We hypothesized that using ΔR-guided dosing would result in decreased DVT rates. Methods: A prospective, randomized controlled trial was performed at a Level 1 trauma center. Both trauma and general surgery patients were included. Upon enrollment, demographic data including age, sex, body mass index, and Acute Physiology and Chronic Health Evaluation II score were obtained. Enrolled patients were randomized to standard (30 mg twice a day) or TEG-guided dosing. Dose-adjusted patients underwent daily enoxaparin titration to achieve an ΔR of 1 minute to 2 minutes. Venous thromboembolism screening was performed per institutional protocol. Antithrombin III (AT-III) and anti-Xa levels were drawn at peak enoxaparin concentrations. Results: A total of 87 patients were enrolled. There was no difference in demographic data between the groups. No pulmonary emboli were identified. The control group had a DVT rate of 16%, while the experimental group had a rate of 14% (p = nonsignificant). The experimental group's median enoxaparin dosage, 50 mg twice a day, was significantly higher than that of the control (p <0.01). TEG ΔR was not different between the control and experimental groups. Beginning at Day 3, anti-Xa levels were higher in the experimental group (p <0.05). There was no difference in AT-III activity between the two groups; 67% of the patients demonstrated AT-III deficiency. Conclusion: TEG adjusted enoxaparin dosing led to significant increases in anti-Xa activity, which did not correlate with a decreased DVT rate. Failure to reduce the DVT rate and increase ΔR despite increased dosing and increased anti-Xa activity is consistent with the high rate of AT-III deficiency detected in this study cohort. These data suggest that the future of DVT prevention may not lie in the optimization of low molecular weight heparin therapy but rather in compounds that increase antithrombin directly or operate independently of the AT-III pathway. LEVEL OF EVIDENCE: Therapeutic study, level III.

    KW - deep venous thrombosis

    KW - enoxaparin

    KW - Thromboelastography

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