International Journal of Hematology

DOI: 10.1007/s12185-019-02633-x Pages: 641-649

Effects of low-dose combined oral contraceptives and protein S K196E mutation on anticoagulation factors: a prospective observational study

1. National Cerebral and Cardiovascular Center, Department of Perinatology and Gynecology

2. Chayamachi Ladies Clinic

3. National Cerebral and Cardiovascular Center, Laboratory of Clinical Chemistry

4. National Cerebral and Cardiovascular Center, Department of Molecular Pathogenesis

5. National Cerebral and Cardiovascular Center, Department of Statistics and Data Analysis, Center for Cerebral and Cardiovascular Disease Information

6. National Cerebral and Cardiovascular Center, Department of Cardiovascular Medicine

7. National Cerebral and Cardiovascular Center, Department of Preventive Cardiology

8. National Cerebral and Cardiovascular Center, Department of Cerebrovascular Medicine

Correspondence to:
Takekazu Miyoshi
Tel: +81-6-6833-5012
Email: gomiyoshi0327@yahoo.co.jp

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Abstract

The association between low-dose combined oral contraceptives (COCs) and anticoagulation factors in Japanese women has been rarely studied. A total of 394 Japanese women with a new beginning cycle of COC use were enrolled, of whom 335 women visited the clinic within 4 weeks after starting the first cycle of COC. Visits occurred in the active phase (272 women) and the placebo phase (63 women). Free protein S (PS) antigen and activity levels and antithrombin activity levels decreased significantly in both the active and placebo phase groups. Protein C (PC) activity levels increased significantly in both groups. Larger reductions in free PS antigen and activity levels occurred with COC comprising either 30 µg ethinylestradiol/desogestrel or 20 µg ethinylestradiol/drospirenone than that comprising 35 µg ethinylestradiol/norethisterone. In four women with the Japanese-specific PS K196E mutation, mean PS activity was 65% before COC use and 57% during COC use, indicating further decrease with COC use. In conclusion, decreased antigen and activity levels of PS and antithrombin and increased activity levels of PC were observed even during the first cycle of low-dose COC use. The effects on PS and PC activities were also observed in the hormone-free interval.

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