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FVL is a very common inherited thrombophilia associated with a moderate increased lifetime risk for venous thromboembolism (VTE). Genetic testing for carrier status of can be controversial and is only indicated in a few circumstances where changes to clinical management would be affected. Genetic testing is not recommended the general population nor for the indication of early pregnancy loss. Treatment of VTE in FVL carriers should follow standard guidelines. January 2023 

What is FVL?

Factor V Leiden is an inherited clotting disorder, thrombophilia. It is characterized by a poor anticoagulation response to activated protein C (APC). Individuals with this type of APC resistance have a variant (called the Leiden variant) in the FV gene resulting in the production of a FV protein that is very slowly inactivated and so more thrombin is generated. For more on the coagulation pathway visit [Accessed Jan 2023]

How common is it?

Factor V Leiden is the most common inherited thrombophilia.

FVL carrier status (heterozygous, one copy of FVL) is observed in 20% of an unselected, symptomatic with VTE population. When there is also a strong family history of VTE, FVL is observed in 40% of individuals.

In the general (asymptomatic) population, frequency depends upon ethnicity.

  • European, Mediterranean, Middle Eastern ancestry = 3-7% of individuals are carriers of FVL
  • Asian, African, Indigenous Australian = extremely rare

Generalized to the Canadian population, over one million Canadians are carriers of the FVL variant.

It is rare for an individual to carry two copies of the FVL variant (homozygous). The prevalence is estimated to be about 1 in 5,000.

What are the associated risks?

General risk factors for a VTE are age, surgery, cancer, pregnancy, recent heart attack, prolonged immobilization (e.g. long air travel), and genetic factors.

Carrying the FVL variant is associated with an increased lifetime risk for VTE, but the absolute risk is very small and most individuals with FVL never experience a clot.

Those with one FVL variant (heterozygous) have a 3-5 fold increased lifetime risk of VTE. For perspective, a female of child-bearing age has about a 1 in 10,000 per year risk of VTE. A woman of child-bearing age with one FVL variant would have a ~3-5 in 10,000 per year risk of VTE.

FVL risk graph

   incidence of VTE
 in female of child-bearing age who are not taking oral contraceptives is approximately  1 in 10,000 per year

 Those with a first degree relative with a history of VTE the risk

 2 in 10,000 per year

 Those on combined oral contraceptive

4 in 10,000 per year

 Presence of one FVL variant (heterozygous)

3-5 in 10,000 per year
 Normal pregnancy is associated with a five- to tenfold increased risk of developing VTE

5-10 in 10,000 per year

  <1 in 1,000

 The presence of two FVL variants (homozygous)

 9-12 in 10,000 per year

 <1 in 1,000 per year

Risk is also associated with younger age of onset


Following a first unprovoked VTE, FVL carrier status is not associated with increased recurrence risk. Clinical circumstances of the event, adequacy of early treatment, and individual risk factors determine recurrence risk.

FVL carrier status is not associated with increased risk of mortality.

When should genetic testing NOT be considered?

Genetic testing for FVL carrier status can be controversial and general population screening is not recommended. There are predicted harms to carrier testing in asymptomatic individuals such as unnecessary exposure to thromboprophylaxis, or modifications to plans for birth control, surgery, travel and improperly labelling as an individual with a disease. 

FVL carrier testing is not recommended for women following early pregnancy loss.

When should genetic testing be considered?

FVL carrier testing may be considered in the following scenarios when the results of testing would affect clinical management:

  • Persons with a first, unprovoked VTE who are planning to stop anticoagulation
  • Females with a family history of VTE or a known inherited thrombophilia who are considering:
    • estrogen contraception or hormone replacement
    • prophylactic anticoagulation during pregnancy

How is VTE managed in FVL carriers?

VTE management depends on the clinical circumstances.

The first acute thrombosis should be treated according to standard guidelines. (see CHEST, Thrombosis Canada). There is no evidence to support improved health outcomes or changes to clinical management would be guided by FVL testing.

FVL carrier status alone is not an indication for long term anticoagulation therapy. The decision should be made based on an assessment of the risks for VTE recurrence and anticoagulant-related bleeding.

What should carriers of the FVL know?

Carriers should be informed about:

  • Circumstances that might increase the likelihood of VTE (obesity, age, surgery, reduced mobility due to injury or travel, use of oral contraceptives, HRT, or SERMs, and pregnancy)
  • The signs and symptoms of VTE that require immediate medical attention
  • The potential need for prophylactic anticoagulation in high-risk circumstances


Graham N, Rashiq H, Hunt BJ. Testing for thrombophilia: clinical update. Br J Gen Pract. 2014;64(619):e120-2. PMID: 24567617.

Hillis CM, Schimmer AD, Couban S, Crowther MA. The Canadian Choosing Wisely campaign: the Canadian Hematology Society's top five tests and treatments. Ann Hematol. 2015;94(4):541-5. PMID: 25637447.

Kearon C, Akl EA, Ornelas J, et al. Antithrombotic Therapy for VTE Disease: CHEST Guideline and Expert Panel Report. Chest. 2016;149(2):315-352. Erratum in: Chest. 2016;150(4):988. PMID: 26867832.

Kujovich JL. Factor V Leiden Thrombophilia. 1999 May 14 [Updated 2018 Jan 4]. In: Adam MP, Everman DB, Mirzaa GM, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2022. Available from:

MacCallum P, Bowles L, Keeling D. Diagnosis and management of heritable thrombophilias. BMJ. 2014 Jul 17;349:g4387. doi: 10.1136/bmj.g4387. PMID: 25035247

Solymoss S. Risk of venous thromboembolism with oral contraceptives. CMAJ. 2011;183(18):E1278-9. PMID: 22065358

Simone B, De Stefano V, Leoncini E, et al. Risk of venous thromboembolism associated with single and combined effects of Factor V Leiden, Prothrombin 20210A and Methylenetethraydrofolate reductase C677T: a meta-analysis involving over 11,000 cases and 21,000 controls. Eur J Epidemiol. 2013;28(8):621-47. PMID: 23900608

Thrombosis Canada. Thrombophilia: Factor V Leiden and Prothrombin Gene Mutation. Sept 2021. [Accessed Nov 2022]

Tseng E, Selby R. Testing for heritable thrombophilia in acute venous thromboembolism. CMAJ. 2017;189(26):E891. PMID: 28676580


Authors: S Morrison MS CGC, JC Carroll MD CCFP and JE Allanson MD FRCPC   


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