Impact of antithrombin III and enoxaparin dosage adjustment on prophylactic anti-Xa concentrations in trauma patients at high risk for venous thromboembolism: a randomized pilot trial

• Published in: Journal of thrombosis and thrombolysis Vol. 52; no. 4; pp. 1117 - 1128
• Main Authors: Droege, Molly Elizabeth, Droege, Christopher Allen, Philpott, Carolyn Dosen, Webb, Megan Leslie, Ernst, Neil Edward, Athota, Krishna, Wakefield, Devin, Dowd, Joseph Richard, Gomaa, Dina, Robinson, Bryce H. R., Hanseman, Dennis, Elterman, Joel, Mueller, Eric William
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.11.2021; Springer Nature B.V
• Subjects: Adult; Anticoagulants - therapeutic use; Antithrombin; Antithrombin III; Body mass index; Cardiology; Creatinine; Dosage; Drug dosages; Enoxaparin - classification; Enoxaparin - therapeutic use; Hematology; Humans; Laboratories; Medicine; Medicine & Public Health; Pilot Projects; Prospective Studies; Risk assessment; Thromboembolism; Thrombosis; Trauma; Venous Thromboembolism - drug therapy; Venous Thromboembolism - prevention & control; Enoxaparin; Deep vein thrombosis; Anti-Xa; Antithrombin; Prophylaxis
• ISSN: 0929-5305; 1573-742X
• DOI: 10.1007/s11239-021-02478-4

The impact of antithrombin III activity (AT-III) on prophylactic enoxaparin anti-factor Xa concentration (anti-Xa) is unknown in high-risk trauma patients. So too is the optimal anti-Xa-adjusted enoxaparin dosage. This prospective, randomized, pilot study sought to explore the association between AT-III and anti-Xa goal attainment and to preliminarily evaluate two enoxaparin dosage adjustment strategies in patients with subprophylactic anti-Xa. Adult trauma patients with Risk Assessment Profile (RAP) ≥ 5 prescribed enoxaparin 30 mg subcutaneously every 12 h were eligible. AT-III and anti-Xa were drawn 8 h after the third enoxaparin dose and compared between patients with anti-Xa ≥ 0.1 IU/mL (goal; control group) or anti-Xa < 0.1 IU/mL (subprophylactic; intervention group). The primary outcome was difference in baseline AT-III. Subsequently, intervention group patients underwent 1:1 randomization to either enoxaparin 40 mg every 12 h (up to 50 mg every 12 h if repeat anti-Xa < 0.1 IU/mL) (enox12) or enoxaparin 30 mg every 8 h (enox8) with repeat anti-Xa assessments. The proportion of patients achieving goal anti-Xa after dosage adjustment were compared. A total of 103 patients were included. Anti-Xa was subprophylactic in 50.5%. Baseline AT-III (median [IQR]) was 87% [80–98%] in control patients versus 82% [71–96%] in intervention patients ( p  = 0.092). Goal trough anti-Xa was achieved on first assessment in 38.1% enox12 versus 50% enox8 patients ( p  = 0.67), 84.6% versus 53.3% on second assessment ( p  = 0.11), and 100% vs. 54.5% on third trough assessment ( p  = 0.045). AT-III activity did not differ between high-risk trauma patients with goal and subprophylactic enoxaparin anti-Xa concentrations, although future investigation is warranted. Enoxaparin dose adjustment rather than frequency adjustment may be associated with a higher proportion of patients achieving goal anti-Xa over time.