Effects of pregnancy and lactation on warfarin-induced changes in blood coagulation-related parameters in rats

Effects of pregnancy and lactation on warfarin-induced changes in blood coagulation-related parameters were examined in rats. Warfarin (0.5 mg/kg/day) was given orally to pregnant and non-pregnant rats for 3 days from gestation day (GD) 17 to 19 or to lactating and non-pregnant rats for 3 days from post partum day (PPD) 10 to 12. Blood samples were collected from the rats on the day following the last administration (GD 20 or PPD 13) to measure prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen (FIB), thrombotest (TBT), factor VII and X activities and anti-thrombin III concentration (ATIII). Administration of warfarin to non-pregnant rats resulted in significant prolongation of APTT and TBT and significant decreases in factor VII and X activities. On the other hand, similar but not significant changes were observed in pregnant rats and similar significant but less prominent changes were observed in lactating rats. The reduction of the anticoagulant effects of warfarin may partially be related to high plasma 17beta-estradiol concentration in pregnant rats and to high plasma prolactin concentration in lactating rats, respectively.