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Deep venous thromboses (DVT) continue to cause significant morbidity in critically ill patients. Standard prophylaxis for high risk patients includes twice-daily dosing with 30 mg enoxaparin. Despite prophylaxis, DVT rates still exceed 10% to 15%. Anti-Xa levels are used to measure the activity of enoxaparin and 12-hour trough levels ≤0.1 IU/mL have been associated with higher rates of DVT in orthopedic patients. We hypothesized that low Anti-Xa levels would be found in critically ill trauma and surgical patients and that low levels would be associated with higher rates of DVT.All patients on the surgical intensive care unit (ICU) service were prospectively followed. In the absence of contraindications, patients were given prophylactic enoxaparin and anti-Xa levels were drawn after the third dose. Trough levels ≤0.1 IU/mL were considered low. Screening duplex exams were obtained within 48 hours of admission and then weekly. Patients were excluded if they did not receive a duplex, if they had a prior DVT, or if they lacked correctly timed anti-Xa levels. DVT rates and demographic data were compared between patients with low and normal anti-Xa levels.Data were complete for 54 patients. Eighty-five percent suffered trauma (Injury Severity Score of 25 ± 12) and 74% were male. Overall, 27 patients (50%) had low anti-Xa levels. Patients with low anti-Xa levels had significantly more DVTs than those with normal levels (37% vs. 11%, p = 0.026), despite similar age, body mass index, Injury Severity Score, creatinine clearance, high risk injuries, and ICU/ventilator days.Standard dosing of enoxaparin leads to low anti-Xa levels in half of surgical ICU patients. Low levels are associated with a significant increase in the risk of DVT. These data support future studies using adjusted-dose enoxaparin.