September 13, 2016
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VTE history in female relatives increases absolute thrombotic risk

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A family history of thrombosis in women may increase the risk for venous thromboembolism in women taking oral contraceptives, according to the results of a cohort study.

The risk appeared particularly heightened in women with hormonally related VTE, results also showed.

Women whose families have a history of thrombosis have an increased risk for VTE. These risks are heightened by the use of oral contraceptives and are greater after pregnancy.

“It is unknown whether this family-conferred risk is hormone or sex specific: Is a young woman at higher hormone-related risk if her mother or sister had combined oral contraceptive- or pregnancy-related VTE than if her father or brother had thrombosis?” Elizabeth van Vlijmen, MD, PhD, professor of hematology and internal medicine at University Medical Center Groningen in the Netherlands, and colleagues wrote. “This would be relevant for counselling purposes.”

van Vlijmen and colleagues retrospectively followed 1,005 female relatives of probands with VTE included in a family-based cohort study. In total, 604 relatives came from a family with a female proband and 401 came from a family with a male proband.

Among female probands, 394 had hormonally related VTE and 206 had VTE that was not hormonally related.

With a follow-up of 24.195 person-years, the researchers observed 84 instances of VTE, 82% of which were related to combined oral contraceptive use or pregnancy postpartum. Women on study had a crude absolute VTE incidence rate of 0.35 (95% CI, 0.28-0.43) per 100 person-years.
The risk for VTE did not significantly differ based on proband sex (female vs. male incidence rate, 0.32 vs. 0.39).

However, several factors significantly increased VTE risk, including young age (< 45 years at the time of first VTE) in a female proband (P = .045), thrombophilia (P < .0001), oral contraceptive use (P = .008) and pregnancy (P < .0001).

The researchers conducted a heterogeneity analysis, which showed significantly higher risks for pregnancy-related VTE in relatives of female probands (HR = 11.6; 95% CI, 6.3-21.3) compared with male probands (HR = 6.6; 95% CI, 2.8-15.2).

The VTE risk also increased in relatives of female probands who used oral contraceptives (HR = 3.6; 95% CI, 1.8-7.1).

Further, relatives of female probands with hormonally related VTE had a significantly higher absolute risk for VTE than relatives of those without hormonally related VTE (incidence rate, 0.43 vs. 0.13; HR = 3.28; 95% CI, 1.5-7.9).

The researchers noted that the higher risks associated with pregnancy and, to a lesser extent, oral contraceptive use occurred mainly in relatives of patients with hormonally related VTE.

Study limitations include the potential overestimation of absolute VTE risk and the lack of objective techniques to validate all VTE events. Further, the researchers could not adjust their findings for certain possible mitigating factors, such as BMI, surgery and trauma.

“Although further research is needed, our findings suggest that a family history originating from a female patient, that is, a mother or a sister, especially when the patient experienced a combined oral contraceptive- or pregnancy-related VTE may further increase VTE risk in her female relatives,” van Vlijmen and colleagues wrote. “This information could be important in the counseling of women on contraceptive options.” – by Cameron Kelsall

Disclosures: van Vlijmen reports no relevant financial disclosures. Please see the full study for a list of all other researchers’ relevant financial disclosures.