Combined oral contraceptives increase risk for VTE in women with severe thrombophilia

Use of combined oral contraceptives increased risk for venous thromboembolism among women with severe hereditary thrombophilia, according to the results of a meta-analysis.

This risk appeared modest among women with mild thrombophilia.

“Since their introduction in 1960, combined oral contraceptives, containing ethinylestradiol and a progestogen, are associated with an increased risk for VTE,” Elizabeth F.W. van Vlijmen, MD, PhD, professor in the division of hemostasis and thrombosis in University Medical Center Groningen in Groningen, Netherlands, and colleagues wrote. “Currently, WHO Medical Eligibility Criteria for contraceptive use state that combined oral contraceptive use in women with hereditary thrombophilias is associated with an unacceptable health risk.”

However, this risk was defined using cohort familial studies, which represented a higher-risk population.

Therefore, van Vlijmen and colleagues used the MEDLINE and EMBASE databases to analyze data from 12 case–control studies and three family cohort studies to assess additional risk for first VTE in women who have mild and severe hereditary thrombophilia and who used combined oral contraceptives.

Researchers defined mild thrombophilia as factor V Leiden and prothrombin G20210A mutation. They defined severe thrombophilia as antithrombin deficiency, protein C deficiency, protein S deficiency, double heterozygosity or homozygosity of factor V Leiden and prothrombin G20210A mutation.

Combined oral contraceptives use was associated with an increased risk for VTE among women with mild (RR = 5.89; 95% CI, 4.21-8.23) and severe (RR = 7.15; 95% CI, 2.93-17.45) thrombophilia.

A review of the family cohort studies showed that absolute VTE risk for 100 pill-years appeared far greater for women with severe thrombophilia (ORs = 4.3 to 4.6) than women with mild thrombophilia (ORs = 0.49 to 2).

Researchers also noted that risk for VTE per 100 pill-years of combined oral contraceptive use increased among individuals without thrombophilia, but researchers noted this population included family members who had family history of thrombophilia.

“Coinheritance of other thrombophilic defects could explain the more heightened risk in nonaffected women from families with severe thrombophilia; one of the family cohort studies indicated frequent coexistence of other thrombophilic defects,” the researchers wrote.

The incidence of VTE in combined oral contraceptives users without V Leiden or prothrombin G20210A mutation ranged from 0 (95% CI, 0-5.5) to 0.19 (95% CI, 0.07-0.41) in the family cohort studies.

Further, the incidence of VTE in per 100 pill-years was 0.19 (95% CI, 0.07-0.42) among women without double heterozygosity or homozygosity of FV Leiden or prothrombin G20210A mutation and ranged from 0.48 (95% CI, 0.01-1.4) to 0.7 (95% CI, 0-3.7) in women without antithrombin, protein C or protein S deficiency.

Researchers acknowledged that absolute risks were estimated using the family cohort studies and, thus, are more pronounced compared with the general population of combined oral contraceptive users.

“In women with known mild thrombophilia, detailed counseling on all contraceptive options is recommended to enable them to make an informed choice on the optimal contraceptive,” van Vlijmen and colleagues wrote. “It is recommended that combined oral contraceptive use should be avoided in asymptomatic women with known severe hereditary thrombophilia.” – by Nick Andrews

Disclos ure: The authors report no relevant financial disclosures.