Decreased plasma tissue factor pathway inhibitor in women taking combined oral contraceptives

• Published in: American journal of hematology Vol. 60; no. 3; pp. 175 - 180
• Main Authors: Harris, Geoffrey M., Stendt, Caroline L., Vollenhoven, Beverley J., Gan, T. Eng, Tipping, Peter G.
• Format: Journal Article
• Language: English
• Published: New York John Wiley & Sons, Inc 01.03.1999; Wiley-Liss
• Subjects: Adolescent; Adult; Biological and medical sciences; Blood Coagulation - drug effects; Cholesterol, LDL - blood; coagulation; Contraceptives, Oral, Combined - adverse effects; Down-Regulation; Drug toxicity and drugs side effects treatment; factor VIIa; Factor VIIa - metabolism; Female; Fibrinogen - metabolism; Fibrinolytic Agents - blood; Humans; lipoprotein; Lipoproteins - blood; Medical sciences; Middle Aged; oral contraceptive; Peptide Fragments - metabolism; Pharmacology. Drug treatments; Protein Precursors - metabolism; prothrombin; Prothrombin - metabolism; thrombosis; Thrombosis - blood; Thrombosis - etiology; tissue factor pathway inhibitor; Toxicity: cardiovascular system; von Willebrand Factor - metabolism; Blood coagulation; Kunitz inhibitor; Steroid hormone; Toxicity; Oral administration; Cardiovascular disease; Activation; Thrombosis; Vascular disease; Estroprogestagen; Extrinsic pathway; Risk factor; Contraceptive; Tissue factor pathway inhibitor; Women; Hemic System; Risk Factors; Thrombosis > women; Biology; Contraception; Family Planning; Research Methodology; Embolism; Diseases; Oceania; Blood Coagulation Effects > women; Developed Countries; Oral Contraceptives, Combined; Clinical Research; Hematological Effects; Vascular Diseases; Contraceptive Methods; Research Report; Physiology; Oral Contraceptives; Australia; Thromboembolism
• ISSN: 0361-8609; 1096-8652
• DOI: 10.1002/(SICI)1096-8652(199903)60:3<175::AID-AJH1>3.0.CO;2-X

Use of combined oral contraceptives (OC) is associated with a significant risk of thrombosis. The mechanisms of this effect are not clearly defined. Tissue factor pathway inhibitor (TFPI) is a circulating anti‐coagulant that inhibits the earliest steps in activation of the extrinsic coagulation pathway. It plays a central role in control of coagulation but its contribution to the thrombotic risk associated with OC has not been assessed. Plasma TFPI antigen and activity, factor VIIa, prothrombin fragments 1&2, von Willebrand antigen, fibrinogen, and low density lipoprotein cholesterol were measured by standard assays in women taking OC (aged 16 to 45 years, n = 40) and age‐matched women not taking OC (controls, n = 40). Plasma TFPI antigen did not vary significantly across the menstrual cycle in controls. Women on OC had a 25% reduction in plasma TFPI antigen (median 51.0 ng/ml; 95% confidence intervals [CI] 37.5 to 85.5; control 68.0 ng/ml, CI 61.0 to 95.0; P < 0.001) and a 29% reduction in TFPI activity (78.5 U/ml, CI 57.5 to 107.5; control 111.0 U/ml, CI 79.5 to 171.0; P < 0.001) compared to controls. Plasma factor VIIa activity and prothrombin fragments 1&2 were also significantly increased in women using OC (both P < 0.001), indicating activation of the extrinsic coagulation pathway. These results demonstrate that normal cyclic variations in estrogen and/or progesterone do not significantly alter plasma TFPI levels. However, estrogens and/or progestogens in OC result in activation of the extrinsic coagulation pathway and significantly reduce plasma TFPI, its major circulating inhibitor. Reduced plasma TFPI levels may underlie the thrombotic effects of OC. Am. J. Hematol. 60:175–180, 1999. © 1999 Wiley‐Liss, Inc.