Contact factor mediated fibrinolysis is increased by the combined oral contraceptive pill

To study the fibrinolytic pathways and their relationship with the contact system in women using combined oral contraceptives (COCs).

Serial plasma samples were collected from 18 women before treatment with COCs containing 30 micrograms oestrogen during treatment cycles 3 and 6, and 2 weeks after stopping treatment. Fibrinolysis was measured before and after dextran sulphate mediated contact activation using fibrin plates.

Fibrinolysis increased significantly during cycles 3 and 6 (from 77% to 100% and 113%, respectively, P < 0.01) and showed a further increase after dextran sulphate activation (from 134% to 158% and 167%, respectively, P < 0.01). Tissue-plasminogen activator, urokinase-plasminogen activator and plasminogen activator inhibitor did not change significantly. There were significant elevations of Factor XII (from 0.92 u/ml to 1.43 u/ml, P < 0.01) and prekallikrein (0.94 u/ml to 1.10 u/ml, P < 0.05) in cycle 3, which both remained high at cycle 6 (P < 0.01) and decreased after stopping the COC. Alpha-2-macroglobulin and C1-esterase inhibitor showed no significant change, but alpha-1-antitrypsin increased from 0.85 u/ml to 1.11 u/ml by cycle 3 (P < 0.01), and returned to near normal levels after stopping the COC.

The increase in fibrinolysis may be due to increased levels of Factor XII and prekallikrein without a corresponding increase in their natural inhibitors (C1-esterase inhibitor and alpha-2-macroglobulin). A parallel increase in the intrinsic pathway of coagulation may be limited by elevated alpha-1-antitrypsin at the level of activated Factor XI. The increase in fibrinolysis caused by oral contraceptives may balance any potential thrombotic risk due to increased fibrinogen or vitamin K dependent coagulation factors.