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  • Title: Contact factor mediated fibrinolysis is increased by the combined oral contraceptive pill.
    Author: Campbell SJ, Mackie IJ, Robinson GE, Machin SJ.
    Journal: Br J Obstet Gynaecol; 1993 Jan; 100(1):79-84. PubMed ID: 8427844.
    Abstract:
    OBJECTIVE: To study the fibrinolytic pathways and their relationship with the contact system in women using combined oral contraceptives (COCs). DESIGN: 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. RESULTS: 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. CONCLUSIONS: 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.
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