Comparison of postpartum anti-Xa levels following enoxaparin administration to prevent venous thromboembolism using 2 weight-based protocols: a randomized controlled trial

Abstract

Background: During the postpartum period, enoxaparin is given to high-risk women to prevent venous thromboembolism, a leading cause of maternal mortality. Enoxaparin activity is measured by peak plasma anti-Xa levels. The prophylactic range of anti-Xa is 0.2 to 0.6 IU/mL. Values above and below this range represent subprophylactic and supraprophylactic levels, respectively. Weight-based enoxaparin administration was superior to fixed-dose enoxaparin administration in achieving an anti-Xa prophylactic range. However, it is unknown which weight-based enoxaparin administration is superior (once daily weight categories vs 1 mg/kg body weight).

Objective: This study aimed to compare the efficacy in reaching prophylactic anti-Xa levels and adverse effects profile of the 2 weight-based enoxaparin dosing protocols.

Study design: A randomized open-label controlled trial was conducted. Women after delivery, who were intended to receive enoxaparin, were randomized to receive either enoxaparin treatment according to 1 mg/kg (up to 100 mg) or weight categories (≤90 kg, 40 mg; 91-130 kg, 60 mg; 131-170 kg, 80 mg; >170 kg, 100 mg). Plasma anti-Xa levels were obtained 4 hours after the second enoxaparin administration (day 2 of enoxaparin treatment). If the woman was still hospitalized, anti-Xa levels were also obtained on day 4. The primary endpoint was the proportion of women with anti-Xa levels within the prophylactic range at day 2. In addition, data regarding anti-Xa levels in different weight groups and rates of venous thromboembolism and adverse effects were evaluated.

Results: Of note, 60 and 64 women received enoxaparin according to 1 mg/kg and weight categories, respectively; moreover, 55 (92%) and 27 (42%) women reached the prophylactic range of anti-Xa at day 2, respectively (P<.0001). The mean anti-Xa levels on day 2 were 0.34±0.09 and 0.19±0.06 IU/mL, respectively (P<.0001). The anti-Xa levels were higher in the 1 mg/kg group than in the weight categories group in the subanalysis of different weight categories (51-70, 71-90, and 91-130 kg). There was no difference in anti-Xa levels on day 4 compared with day 2 in both cohorts (n=25). There was no case of supraprophylactic anti-Xa levels, venous thromboembolism events, or serious hemorrhage.

Conclusion: Postpartum enoxaparin administration at 1 mg/kg was superior to weight categories in reaching anti-Xa prophylactic levels without leading to serious adverse effects. Given the high efficacy and safety profile, enoxaparin at 1 mg/kg once daily should be considered the preferred protocol for postpartum venous thromboembolism prophylaxis.

Trial registration: ClinicalTrials.gov NCT02856295.

Keywords: enoxaparin; postpartum; prophylaxis; venous thromboembolism; weight.