Jessica C Cardenas1, Yao-Wei Wang2, Jay V Karri2, Seenya Vincent2, Andrew P Cap3, Bryan A Cotton4, Charles E Wade4. 1. The Center for Translational Injury Research, Department of Surgery, UTHealth McGovern Medical School, Houston, TX, United States of America; Red Duke Trauma Institute, Memorial Hermann Hospital, Houston, TX, United States of America. Electronic address: Jessica.C.Cardenas@uth.tmc.edu. 2. Red Duke Trauma Institute, Memorial Hermann Hospital, Houston, TX, United States of America. 3. The Center for Translational Injury Research, Department of Surgery, UTHealth McGovern Medical School, Houston, TX, United States of America; U.S. Army Institute of Surgical Research, Fort Sam Houston, San Antonio, TX, United States of America. 4. The Center for Translational Injury Research, Department of Surgery, UTHealth McGovern Medical School, Houston, TX, United States of America; Red Duke Trauma Institute, Memorial Hermann Hospital, Houston, TX, United States of America.
Abstract
BACKGROUND: The high incidence of venous thromboembolism (VTE) following trauma persists in spite of aggressive thromboprophylaxis strategies. Approximately half of VTE patients do not achieve the recommended anti-FXa response to enoxaparin anticoagulation (0.1-0.4 IU/mL), however, research to explain or correct this phenomenon is lacking. We hypothesized that antithrombin III (AT) deficiency is associated with poor enoxaparin responsiveness in trauma patients that develop VTE which can be reversed through supplementation with AT. METHODS AND FINDINGS: A retrospective cohort study was performed on plasma collected from trauma patients who did and did not develop pulmonary embolism (PE) as well as healthy volunteers. AT levels, thrombin generation, and anti-FXa levels were measured in the collected plasma at baseline and in response to supplementation with AT concentrate at 120-200% or plasma (30% volume). A total of 54 PE patients and 46 non-PE patients were enrolled in this study for analysis. Compared to healthy volunteers, trauma patients had lower levels of AT, elevated thrombin generation, and lower anti-FXa levels in response to enoxaparin. Moreover, thrombin generation was higher and responses to enoxaparin were lower in patients who developed PE compared to those who did not develop PE. We found that supplementation with AT, but not plasma, increased AT levels and improved enoxaparin-mediated inhibition of thrombin generation. CONCLUSIONS: Supplementation with AT may provide a novel adjunct therapy to increase the effectiveness of enoxaparin thromboprophylaxis and reduce the incidence of VTE in the trauma population.
BACKGROUND: The high incidence of venous thromboembolism (VTE) following trauma persists in spite of aggressive thromboprophylaxis strategies. Approximately half of VTEpatients do not achieve the recommended anti-FXa response to enoxaparin anticoagulation (0.1-0.4 IU/mL), however, research to explain or correct this phenomenon is lacking. We hypothesized that antithrombinIII (AT) deficiency is associated with poor enoxaparin responsiveness in traumapatients that develop VTE which can be reversed through supplementation with AT. METHODS AND FINDINGS: A retrospective cohort study was performed on plasma collected from traumapatients who did and did not develop pulmonary embolism (PE) as well as healthy volunteers. AT levels, thrombin generation, and anti-FXa levels were measured in the collected plasma at baseline and in response to supplementation with AT concentrate at 120-200% or plasma (30% volume). A total of 54 PEpatients and 46 non-PEpatients were enrolled in this study for analysis. Compared to healthy volunteers, traumapatients had lower levels of AT, elevated thrombin generation, and lower anti-FXa levels in response to enoxaparin. Moreover, thrombin generation was higher and responses to enoxaparin were lower in patients who developed PE compared to those who did not develop PE. We found that supplementation with AT, but not plasma, increased AT levels and improved enoxaparin-mediated inhibition of thrombin generation. CONCLUSIONS: Supplementation with AT may provide a novel adjunct therapy to increase the effectiveness of enoxaparin thromboprophylaxis and reduce the incidence of VTE in the trauma population.
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