Management of Genetic Thrombophilia

Genetic Testing and Risk Assessment

The American College of Medical Genetics recommends testing for Factor V Leiden and prothrombin G20210A mutations in individuals with a first episode of venous thrombosis under age 50, venous thrombosis in unusual sites, recurrent venous thrombosis, or a strong family history of thrombotic disease 1, 2
Testing may also be considered in individuals with venous thrombosis over age 50, except when active malignancy is present, and in women with recurrent pregnancy loss or severe pregnancy complications 2
The lifetime risk for venous thromboembolism (VTE) in Factor V Leiden heterozygotes is approximately 10% and for homozygotes is over 80% 3

The American Heart Association recommends a target INR of 2.5 (range 2.0-3.0) for all treatment durations, and balancing bleeding risk against thrombosis risk when considering indefinite anticoagulation 3, 4
Major bleeding risk with chronic warfarin therapy may reach 8% per year, and risk factors for bleeding include age ≥65, variable INRs, history of GI bleeding, hypertension, cerebrovascular disease, heart disease, anemia, malignancy, and renal insufficiency 3

Women with thrombophilia and personal history of VTE should avoid hormonal contraceptives, and consider alternative contraceptive methods and thromboprophylaxis during the postpartum period 1, 2, 3, 5
For long-distance travelers with genetic thrombophilia, frequent ambulation, calf muscle exercise, or sitting in an aisle seat, and consider properly fitted below-knee graduated compression stockings (15-30 mmHg at ankle) 6

Patients testing positive for Factor V Leiden should be considered for testing of other thrombophilias, particularly prothrombin G20210A, and genetic counseling should be offered to explain relative risk implications and risk to other relatives 1

Combined oral contraceptives produce a 30-fold increase in thrombotic risk when the Factor V Leiden mutation is also present, compared to a 4-fold increase with COCs alone 7, 8
The absolute risk remains relatively low in young women, with an estimated 15 deaths per million woman-years in Factor V Leiden carriers using COCs, compared to 4 deaths per million woman-years with COCs alone 8
Factor V Leiden is considered a "known thrombogenic mutation" and is listed as an absolute contraindication to COC use in current contraceptive guidelines, according to the American Academy of Dermatology 9

The American College of Medical Genetics recommends against routine screening for Factor V Leiden in asymptomatic women contemplating or using oral contraceptives 7, 8
The American College of Medical Genetics recommends Factor V Leiden testing for women with a history of venous thromboembolism during pregnancy or oral contraceptive use 10
Women with a personal history of venous thromboembolism should avoid COCs regardless of Factor V Leiden status, as recommended by the American Academy of Pediatrics 11
The risk of pregnancy complications, including venous thromboembolism, should be weighed against contraceptive risks in women with Factor V Leiden mutation 8

The American College of Medical Genetics recommends consideration of testing in women with a family history of thromboembolism, activated protein C resistance, or documented Factor V Leiden mutation 8, 10