Effect of oral contraceptives on vitamin K-dependent clotting activtiy

Vitamin K-dependent clotting factor activity was studied in young, healthy women being treated with various oral contraceptive drugs. In one series of studies, the anticoagulant response to a dose of bishydroxycoumarin was diminished following treatment with an estrogen-progestin mixture; the metabolism of the anticoagulant was unaffected. Thus the amount of coumarin-type drug required to produce a desired anticoagulant effect in women taking oral contraceptives may be increased. In other studies, a marked shortening of the prothrombin time was observed in the plasmas of a majority of the women treated with oral contraceptives for two months or longer. This effect was demonstrated only after storage of the patients' plasmas in plastic tubes for 16 hours or more at 4 to 6° C. Following storage, the vitamin K-dependent clotting activity of pooled treated plasma was 4.8 times that of pooled control plasma. This effect persisted for at least seven days following discontinuance of therapy but disappeared after one month. Assays of specific factors demonstrated an increase in the activity of factor X in stored plasmas from treated subjects. Oral contraceptives may affect the plasma of treated subjects so that there is in vitro activation of one or more of the inactive precursors of the vitamin K-dependent clotting factors.