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

Citation
Gm. Harris et al., Decreased plasma tissue factor pathway inhibitor in women taking combined oral contraceptives, AM J HEMAT, 60(3), 1999, pp. 175-180
Citations number
29
Categorie Soggetti
Hematology,"Cardiovascular & Hematology Research
Journal title
AMERICAN JOURNAL OF HEMATOLOGY
ISSN journal
03618609 → ACNP
Volume
60
Issue
3
Year of publication
1999
Pages
175 - 180
Database
ISI
SICI code
0361-8609(199903)60:3<175:DPTFPI>2.0.ZU;2-G
Abstract
Use of combined oral contraceptives (OC) is associated with a significant r isk of thrombosis. The mechanisms of this effect are not clearly defined. T issue factor pathway inhibitor (TFPI) is a circulating anti-coagulant that inhibits the earliest steps in activation of the extrinsic coagulation path way, It plays a central role in control of coagulation but its contribution to the thrombotic risk associated with OC has not been assessed, Plasma TF PI antigen and activity, factor VIIa, prothrombin fragments 1&2, von Willeb rand antigen, fibrinogen, and low density lipoprotein cholesterol were meas ured by standard assays in women taking OC (aged 16 to 45 years, n = 40) an d age-matched women not taking OC (controls, n = 40). Plasma TFPI antigen d id 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% confi dence 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. Plas ma factor VIIa activity and prothrombin fragments 1&2 were also significant ly increased in women using OC (both P < 0.001), indicating activation of t he extrinsic coagulation pathway, These results demonstrate that normal cyc lic variations in estrogen and/or progesterone do not significantly alter p lasma TFPI levels. However, estrogens and/or progestogens in OC result in a ctivation of the extrinsic coagulation pathway and significantly reduce pla sma TFPI, its major circulating inhibitor. Reduced plasma TFPI levels may u nderlie the thrombotic effects of OC. Am. J. Hematol. 60:175-180, 1999. (C) 1999 Wiley-Liss, Inc.