Contraception in Patients with Family History of Factor V Leiden

Key Considerations for Contraceptive Choice

Progestin-only contraceptives, such as Nexplanon, do not increase venous thromboembolism (VTE) risk in the same manner as combined oral contraceptives containing estrogen, according to the American College of Medical Genetics 1, 2
The 30-fold increased VTE risk applies to combined oral contraceptives in factor V Leiden heterozygotes, not progestin-only methods, as stated by the American College of Medical Genetics 1, 2
Combined oral contraceptives alone increase thrombosis risk 4-fold, which escalates to 30-fold in factor V Leiden heterozygotes, primarily driven by the estrogen component, as reported by the American College of Medical Genetics 2

The American College of Medical Genetics recommends factor V Leiden testing for women with a family history of thromboembolism, APC resistance, or documented factor V Leiden mutation who are contemplating hormonal contraception 1, 2
Women with a family history of thromboembolism should be counseled about their risks and options and considered for testing, depending on the overall clinical situation, as suggested by the American College of Medical Genetics 1, 2
Nexplanon can be prescribed safely without testing, as it does not carry the estrogen-related thrombotic risk, according to the American College of Medical Genetics 1, 2
If testing shows factor V Leiden positive, Nexplanon remains an appropriate choice, as progestin-only methods are not contraindicated in thrombophilia, as stated by the American College of Medical Genetics 1, 2
If the patient has a personal history of VTE, this would be a contraindication to all hormonal contraception, including Nexplanon, and testing becomes mandatory, as reported by the American College of Medical Genetics 1, 2

In pregnancy contexts, heterozygous factor V Leiden carriers with family history of VTE have low absolute antepartum risk, but this does not directly translate to contraceptive decision-making, as noted in Blood advances 3
The American College of Medical Genetics explicitly states that routine screening of all asymptomatic women is not recommended due to cost-effectiveness concerns and potential psychosocial harms, such as insurance discrimination and job-related issues 1

The American College of Medical Genetics recommends testing for factor V Leiden in relatives of individuals known to have factor V Leiden or those with a family history of thromboembolism, APC resistance, or documented factor V Leiden mutation 4, 5, 6, 7
Testing may be considered for women contemplating or using oral contraceptives with a personal history of thromboembolism or other medical risk factors, according to the American College of Medical Genetics 4, 5, 6, 7
The American College of Medical Genetics specifies that testing is recommended for relatives of individuals with venous thrombosis under age 50 7

Heterozygous factor V Leiden carriers have a venous thrombosis rate of only 0.19-0.56% per year, which is a modest absolute risk 8

Random screening of the general population for factor V Leiden is explicitly not recommended by the American College of Medical Genetics 7, 9
The American Heart Association notes that there may be unanticipated risks and psychosocial effects from screening for thrombophilias, including job-related issues or denial of healthcare coverage 8, 10

Heterozygous carriers of the factor V Leiden mutation who have a first‑degree relative with venous thromboembolism exhibit a low absolute antepartum VTE risk of 0.5 % (95 % CI 0.06 %–1.21 %)【11】.