American College of Medical Genetics Consensus Statement on Factor V Leiden Mutation Testing

Abstract

SUMMARY OF ISSUES AND RECOMMENDATIONSIssue 1: Which methodology should be used: Factor V Leiden DNA testing or functional activated protein C (APC) resistance testing? Recommendation 1When appropriate clinical care requires testing for the factor V Leiden allele, either direct DNA-based genotyping or a factor V Leiden-specific functional assay is recommended. Patients who test positive by a functional assay should then be further studied with the DNA test for confirmation and to distinguish heterozygotes from homozygotes. Patients on heparin therapy or with known lupus anticoagulant should proceed directly to molecular testing if the modified functional assay is not used. When relatives of individuals known to have factor V Leiden are tested, the DNA method is recommended.Issue 2: Who should be tested? Recommendation 2Opinions and practices regarding factor V Leiden testing vary. Some physicians advocate testing of all patients with venous thrombosis except when active malignancy is present. Others exclude testing in patients over age 60 in the absence of a family history of thrombosis or a previous thrombotic event.There is growing consensus that testing should be performed in at least the following circumstances (these are the same general recommendations for testing for any thrombophilia): Age <50, any venous thrombosis. Venous thrombosis in unusual sites (such as hepatic, mesenteric, and cerebral veins). Recurrent venous thrombosis. Venous thrombosis and a strong family history of thrombotic disease. Venous thrombosis in pregnant women or women taking oral contraceptives. Relatives of individuals with venous thrombosis under age 50. Myocardial infarction in female smokers under age 50.Testing may also be considered in the following situations:Venous thrombosis, age >50, except when active malignancy is present. Relatives of individuals known to have factor V Leiden. Knowledge that they have factor V Leiden may influence management of pregnancy and may be a factor in decision-making regarding oral contraceptive use. Women with recurrent pregnancy loss or unexplained severe preeclampsia, placental abruption, intrauterine fetal growth retardation, or stillbirth. Knowledge of factor V Leiden carrier status may influence management of future pregnancies.Random screening of the general population for factor V Leiden is not recommended.Routine testing is not recommended for patients with a personal or family history of arterial thrombotic disorders (e.g., acute coronary syndromes or stroke) except for the special situation of myocardial infarction in young female smokers. Testing may be worthwhile for young patients (<50 years of age) who develop acute arterial thrombosis in the absence of other risk factors for atherosclerotic arterial occlusive disease. Neither prenatal testing nor routine newborn screening is recommended.Issue 3: Should testing be offered to individuals with environmental risk factors? Recommendation 3Factor V Leiden testing is recommended in women with venous thromboembolism during pregnancy or...

ACMG Practice Guideline: lack of evidence for MTHFR polymorphism testing

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Are genetic tests exceptional? Lessons from a qualitative study on thrombophilia

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“…2 In our study, the proportion of subjects receiving any antihypertensive drug at base line was 30 percent in the intervention group and 31 percent in the control group. The proportion of subjects receiving cholesterol-lowering drugs at base line was also similar in the two groups.…”

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