Pharmacokinetics and pharmacodynamics of subcutaneous heparin during the early third trimester of pregnancy

OBJECTIVE: Our purpose was to study the pharmacokinetics and pharmacodynamics of heparin administered subcutaneously during the early third trimester of pregnancy. STUDY DESIGN: We gave subcutaneous heparin (143 units/kg) to six pregnant women (mean gestational age 27.1 ± 1.2 weeks) and to six women who were not pregnant, who served as controls. We serially measured plasma heparin concentrations and activated partial thromboplastin times over 10 hours and compared the time courses of these two measures in the two groups. We calculated the mean peak plasma heparin concentration, time to peak plasma heparin concentration, peak activated partial thromboplastin time, and time to peak activated partial thromboplastin time and compared these variables in the two groups. RESULTS: Plasma heparin concentrations changed significantly over time in both pregnant and nonpregnant subjects. However, the peak plasma heparin concentration in pregnant subjects was significantly lower than in controls (0.11 ± 0.017 units/ml vs 0.23 ± 0.036 units/ml) and the time to peak plasma heparin concentration was significantly shorter in the pregnant patients compared with the nonpregnant controls (113 ± 20 minutes vs 222 ± 20 minutes). The peak activated partial thromboplastin time (30.3 ± 1.7 seconds) was significantly lower and time to peak activated partial thromboplastin time (137 ± 31 minutes) significantly shorter in the pregnant women compared with nonpregnant controls (50 ± 4.0 seconds; 230 ± 26 minutes). CONCLUSIONS: Subcutaneous administration of heparin to pregnant patient results in lower plasma heparin concentrations and clinically insignificant prolongation of the activated partial thromboplastin time compared with equivalent doses administered to nonpregnant women. These findings have important implications for the dosing and monitoring of subcutaneous heparin in pregnant women.