Optimal Dosing of Enoxaparin to Achieve Therapeutic Anticoagulation in Heart Transplant Recipients

Purpose The early post-heart transplantation (HT) period entails frequent biopsies, which poses a unique challenge to administration of therapeutic anticoagulation when indicated. Heightened sensitivity to enoxaparin has been described primarily in lung transplant recipients but has not been assessed in relation to anti-Xa levels specifically in HT recipients. Herein we report our institutional experience with a range of doses of enoxaparin relative to anti-Xa levels. Methods We examined HT recipients who received therapeutic anticoagulation with enoxaparin and included patients with steady state anti-Xa levels at appropriate post-dosing time intervals (i.e. 4 hours) and GFR > 30. Based on suspected heightened sensitivity to enoxaparin, we initiated doses below 1mg/kg every 12 hours (Q12). Spearman's rank correlation was used to relate non-parametric data. Results A total of 14 patients (2016-2019) were included. Average age at the time of enoxaparin exposure was 62 years, 71% were male. Four patients (29%) had a GFR 30-60 while 10 patients (71%) had a GFR > 60. Of 39 anti-Xa levels collected, levels correlated with dose of enoxaparin in mg/kg (rho=0.48, p=0.002, Figure) but not GFR (rho=0.04, p=0.80). Dosing of 1 mg/kg Q12 resulted in average anti-Xa levels above the therapeutic range (mean ± SEM: 1.13±0.23 IU/mL), whereas doses of 0.6mg/kg Q12 resulted in average levels of 0.75±0.07 IU/mL, the midpoint of the desired therapeutic anticoagulation range. Lower doses of enoxaparin (between 0.2-0.5 mg/kg Q12, including those used for prophylaxis) often resulted in anti-Xa levels approaching the therapeutic range (Figure). Conclusion In our small population of HT recipients requiring therapeutic anticoagulation, use of enoxaparin 0.6 mg/kg BID results in average anti-Xa levels at the midpoint of the therapeutic range (0.75 IU/mL) and represents a preferable dosing strategy to FDA-label dosing of 1mg/kg Q12.