Dosing and Monitoring of Low‐Molecular‐Weight Heparin in High‐Risk Pregnancy: Single‐Center Experience

Abstract

Study Objective. To evaluate dosing requirements and monitoring patterns of low‐molecular‐weight heparin (LMWH) when usedinhigh‐risk pregnancy. Design. Retrospective, observational, cohort study. Setting. University‐affiliated medical center. Patients. Forty‐nine women treated with LMWH between 2001 and 2005 for either prophylaxis or treatment of venous thromboembolism during pregnancy and monitored with antifactor Xa activity. Measurements and Main Results. Data were obtained on 53 pregnancies in the 49 women. The primary outcome was change in dosing requirements of LMWH throughout pregnancy as determined by the corresponding antifactor Xa activity peak levels. Mean starting doses of twice‐daily enoxaparin and doses most proximate to delivery were 39.2 mg (range 30–60 mg) and 55.0 mg (range 30–100 mg, p=0.06), respectively, for the prophylaxis group and 83.0 mg (range 30–180 mg) and 85.7 mg (range 30–160 mg, p=0.41), respectively, for the therapeutic group. Weight‐based mean starting doses and doses most proximate to delivery were 0.46 and 0.62 mg/kg (p=0.03), respectively, for the prophylaxis group and 0.90 and 0.87 mg/kg (p=0.29), respectively, for the therapeutic group. Dose changes were required in 9 (69%) of 13 pregnancies and 21 (55%) of 38 pregnancies (data from two of the 40 pregnancies were excluded—one in a patient receiving dalteparin, and one in a patient with mitral valve replacement who had higher antifactor Xa goals) in the prophylaxis and therapeutic groups, respectively, to achieve target antifactor Xa activity. The weight‐based prophylactic dose was consistently 0.6 mg/kg in all three trimesters, achieving a mean ± SD target antifactor Xa activity of 0.39 ± 0.18 units/ml, whereas the therapeutic dose was 0.9 mg/kg to maintain antifactor Xa activity of 0.71 ± 0.22 units/ml. Conclusion. Dose changes for LMWH throughout pregnancy as guided by antifactor Xa activity were common. A significant increase in the LMWH dose requirements in the prophylactic group suggests that more frequent monitoring of antifactor Xa activity may be appropriate in pregnant patients to maintain target anticoagulant levels.