Thromboembolism and oral contraceptive medication.

That oral contraceptive medication may induce a hypercoagulable blood state has been investigated using conventional blood coagulation assay methods. However such studies have been uninformative for the individual patient. In thrombotic states the action of the plasma fibrinolytic enzyme system on the thrombus releases fibrin proteolysis products. These products complex with fibrinogen forming fibrinogen proteolysis product complexes of molecular weight between 400000 and 1 million. In blood hypercoagulability fibrinogen-fibrin monomer complexes of 650000 molecular weight are formed. Activation of the plasma fibrinolytic enzyme system produces fibrinogenolysis with fibrinogen derivatives of 257000 molecular weight or less. These fibrinogen-fibrin complexes may be identified in patient plasma by gel elution chromatography. Mixed patterns are diagnostic of actual thrombosis or active fibrin deposition. A computer program for the analysis of the fibrinogen elution pattern has been developed. An abnormal pattern is common in late pregnancy and during the 1st month postpartum. A patient on oral contraceptive medication having gross hypercoagulability with thrombosis was shown to have an abnormal chromatographic pattern which reverted to normal when medication was discontinued. Other patients either asymptomatic or with unconfirmed thromboembolic disease also showed abnormal fibrinogen chromatographic patterns which reverted to normal within 2-4 weeks after stopping use of oral contraceptives. A fibrinogen abnormality in a control group was 5% but in treated groups 15-27%. The fibrinogen chromatographic elution pattern provides a direct measure by which thrombogenic activity of oral contraceptives may be evaluated.