Pharmacokinetics of heparin VII: Effect of pregnancy on the relationship between concentration and anticoagulant action of heparin in rats.

The effect of pregnancy on the anticoagulant action of heparin was determined by comparing the slope of the relationship between the natural logarithm of the activated partial thromboplastin time (APTT) and heparin concentration (the heparin slope) in the plasma of pregnant and nonpregnant female inbred Lewis rats. Also determined were the prothrombin time, hematocrit, and the activities of coagulation factors II, VII, VIII, X, XI, and XII. The heparin slope was significantly decreased in pregnant rats at the 20th day of gestation but not in rats at the 10th day of gestation, indicative of a decreased anticoagulant action of heparin in late pregnancy. The hematocrit and prothrombin time were decreased, and the baseline APTT (i.e., the APTT without added heparin) as well as the activities of factors II, VII, and X were increased in pregnant rats at the 20th day of gestation. Both pregnant and nonpregnant animals showed a significant negative correlation between prothrombin time and factor II activity and a significant positive correlation between the activities of factors II and X. The effects of pregnancy in rats on heparin slope, prothrombin time, hematocrit, and factors VII, VIII, X, and XII are qualitatively the same as those in pregnant women in the third trimester. The increases in factor II activity and baseline APTT found in the rats were not observed in humans. Pregnant rats, like pregnant women, are relatively resistant to the anticoagulant action of heparin.