Diagnostic Criteria

Suggestive Findings

Factor V Leiden thrombophilia should be suspected in individuals with the following clinical, laboratory, and family history findings:

• Clinical findings. A history of one or recurrent venous thromboembolism (VTE) manifesting as deep vein thrombosis (DVT) or pulmonary embolism (PE), especially at a young age and in the absence of strong risk factors for VTE

• Laboratory findings. Low activated protein C (APC) resistance on APC resistance qualitative and quantitative assays

Source: GeneReviews — "Factor V Leiden Thrombophilia"

Differential Diagnosis

The differential diagnosis of venous thromboembolism (VTE) includes several other inherited thrombophilic disorders, including those caused by other variants in F5, and acquired thrombophilic disorders (outside of the scope of this GeneReview). Prothrombin thrombophilia is characterized by VTE manifesting most commonly in adults as deep vein thrombosis (DVT) in the legs or pulmonary embolism. The clinical expression of prothrombin thrombophilia is variable; many individuals heterozygous or homozygous for the 20210GA F2 variant never develop thrombosis, and while most heterozygotes who develop thrombotic complications remain asymptomatic until adulthood, some have recurrent thromboembolism before age 30 years.

Source: GeneReviews — "Factor V Leiden Thrombophilia"

Management Guidelines

Evaluations Following Initial Diagnosis

To assess the risk for venous thromboembolism (VTE) in an individual found to have a factor V Leiden variant, the following are recommended:

• DNA analysis for prothrombin thrombophilia (F2 variant c.*97GA, commonly known as 20210GA)

• Multiple phospholipid-dependent coagulation assays for a lupus inhibitor

• Serologic assays for anticardiolipin antibodies and anti-beta-2-glycoprotein 1 antibodies

For high-risk individuals (i.e., those with a history of recurrent VTE, especially at a young age, or those with strong family history of VTE at a young age), evaluation should also include assays of:

• Protein C activity

• Antithrombin activity

• Protein S activity or free protein S antigen

Note: Measurement of the following is NOT recommended:

• Plasma concentration of homocysteine, as no data support a change in duration of anticoagulation or the use of vitamin supplementation in individuals with hyperhomocysteinemia and a history of VTE

• MTHFR variants, as no clinical rationale for this testing exists

• Factor VIII and other clotting factor levels

Treatment of Manifestations

Treatment of VTE in Adults

The management of individuals with factor V Leiden thrombophilia depends on the clinical circumstances. The first acute thrombosis should be treated according to current guidelines . For initial treatment of VTE, current guidelines suggest a direct oral anticoagulant (dabigatran, edoxaban, rivaroxaban, or apixaban) over warfarin because of a lower bleeding risk and gr...

Source: GeneReviews — "Factor V Leiden Thrombophilia"

Surveillance Guidelines

Individuals receiving long-term anticoagulation require periodic reevaluation of their clinical course to confirm that the benefits of anticoagulation continue to outweigh the risk of bleeding. Factor V Leiden heterozygotes who do not require long-term anticoagulation may benefit from evaluation prior to exposure to circumstantial risk factors such as surgery or pregnancy.

Source: GeneReviews — "Factor V Leiden Thrombophilia"