THE EFFECT OF PROPHYLACTIC HEPARIN TREATMENT ON ENHANCED THROMBIN GENERATION IN PREGNANCY

Objective: To assess the activation status of blood coagulation in thrombosis-prone pregnant women receiving a reduced dosage of heparin. Methods: Forty-three women were given subcutaneous heparin treatment during pregnancy; the dosage was monitored so that the heparin (anti-Xa) level was within the stipulated range of 0.08-0.15 anti-Xa units 3 hours after injection. Several coagulation variables were investigated and some routine analyses were performed. The results were compared with those of a control group of 26 healthy pregnant women. Results: Compared with the control values, hemoglobin (P < .01), fibrinogen (P < .05), and total protein S (P < .01) were increased already before heparin treatment was started and continued to be increased significantly throughout pregnancy. During heparin treatment, protein C levels (P < .01) and the factors measured by prothrombin time (P < .001) were increased compared with the controls. Antithrombin decreased, though not as much as when patients are given therapeutic dosages. The fibrinolytic inhibitors behaved as in normal pregnancy. Three variables measuring thrombin formation or coagulation activation (ie, thrombin-antithrombin complexes, D-dimers, and soluble fibrin) were increased in a high proportion before heparin treatment was started; they normalized somewhat during treatment. Conclusions: In early pregnancy, women with previous thrombotic episodes have high plasma levels of coagulation variables and of markers of coagulation activation compared with controls. Such changes may be used to predict the need for treatment and, in the future, to control treatment.