When and how to test for Factor V Leiden mutation – pro

The two situations that bring about testing for Factor V Leiden are when an individual presents with a clotting complication, such as Deep Venous Thrombosis(DVT), or when a family history brings him or her for a consultation. American College of Medical Genetics offered a guideline in 2007. There is a 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. Most laboratories screen ‘at risk’ patients with either a snake venom (e.g. dilute Russell’s viper venom time) based test or an aPTT based test. In both methods, the time it takes for blood to clot is shortened in the presence of the factor V Leiden mutation. This is done by running two tests simultaneously, one test is run in the presence of activated protein C (APC) and the other, in the absence. A ratio is determined based on the two tests and the results signify to the laboratory whether APC is working or not. These are quick, three minute, automated tests that most hospital laboratories can easily perform.

On the other hand,  when family history brings a patient to a workup, only the specific mutation analysis test should be performed. The mutation (a 1691G→A substitution) removes a cleavage site of the restriction endonuclease MnlI, so PCR, treatment with MnlI, and then DNA electrophoresis will give a diagnosis.

For patients who are suspected to have the Factor V Leiden mutation, the recommended tests is the direct mutation analysis. If positive, only testing for prothrombin 20210A is recommended.

Wayne W. Grody et al, American College of Medical Genetics Consensus Statement on Factor V Leiden Mutation Testing Genetics in Medicine (2001) 3, 139–148

Herskovits AZ, Lemire SJ, Longtine J, Dorfman DM (November 2008). “Comparison of Russell viper venom-based and activated partial thromboplastin time-based screening assays for resistance to activated protein C”. American Journal of Clinical Pathology 130 (5): 796–804.

Segers K, Dahlbäck B, Nicolaes GA (September 2007). “Coagulation factor V and thrombophilia: background and mechanisms”. Thrombosis and Haemostasis 98 (3): 530–42.


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