Effect of pregnancy on the relationship between concentration and anticoagulant action of heparin*

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Abstract
The anticoagulant effect of heparin, as reflected by the slope of the relationship between heparin concentration and the logarithm of the activated partial thromboplastin time (APTT), was determined in citrated plasma of 7 women in the 3rd trimester of pregnancy and in 10 nonpregnant women of comparable age. Factors II, V and VII-XII, albumin, individual globulins, antithrombin III, fibrinogen, .alpha.-1-acid glycoprotein, .alpha.-1-antitrypsin, .alpha.-2-macroglobulin, prothrombin time and hematocrit were also determined. Baseline APTT (i.e., APTT without heparin) was 30.2 .+-. 3.0 s (mean .+-. SD) in the pregnant women and 29.6 .+-. 4.7 s in the controls (NS). The heparin slope value was 1.68 .+-. 0.46 ml/U in the pregnant women and 2.33 .+-. 0.49 ml/U in the controls, showing that the anticoagulant effect of heparin is decreased in pregnancy. The prothrombin time was also decreased in pregnancy (19.1 .+-. 0.8 vs. 23.1 .+-. 0.5 s; P < 0.01). Pregnancy was associated with a significant increase in the activity of factors VII, VIII, IX and X and in the concentrations of fibrinogen, .alpha.-1-globulin and .alpha.-1-antitrypsin. The plasma albumin concentration was decreased in the pregnant group. In both the pregnant and nonpregnant women (considered separately), the heparin slope value correlated negatively with factor XI activity (r = -0.85 and -0.71; P < 0.05). Baseline APTT, which consistently correlated with heparin slope value in previous reports on men and nonpregnant women, also showed such correlation in the nonpregnant group of the present study (r = 0.85; P < 0.05) but not in the group of pregnant women (r = -0.54; NS [not significant]). The relative heparin resistance in pregnancy in this investigation is consistent with clinical reports of increased heparin requirements during pregnancy.

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