Thrombosis AustraliaThrombosis Australia is a central information and resource hub for the community proudly brought to you by the Perth Blood Institute Our Thrombosis Australia Advisory Panel consists of seven eminent Australian healthcare professionals. Thrombosis Australia Advisory Panel If you are a healthcare professional you can access the Thrombosis Australia Professionals site here: Thrombosis Australia Professionals About us About Thrombosis Tools & Resources Your stories News and information What's on Get involved For professionals Factor V Leiden The F5 gene delivers instructions for making the coagulation protein factor V, which is made mainly by cells in the liver. Factor V Leiden (FVL) is a genetic mutation of F5, which increases the possibility of blood clots, mainly in the legs and lungs. People with FVL generally do not develop abnormal blood clots, however if they do, these irregular clots can lead to long-lasting serious health issues or become life-threatening. The coagulation cascade is regulated by many different proteins. Activated protein C (APC) is one that usually inactivates coagulation factor V and therefore slows down the clotting process, preventing blood clots from growing too big. People with FVL thrombophilia, factor V cannot be deactivated or disabled in a normal way by APC. This results in the clotting process staying active for a longer than a typical period of time, elevating the risk of developing abnormal blood clots. Risk factors Affects both males and females. Women have an elevated risk to develop blood clots during pregnancy or if taking hormone oestrogen. Family history – inheriting the genetic mutation from one or both parents. Inheriting one gene marginally elevates the risk of developing blood clots (5%); inheriting two copies of the defective gene significantly raises the risk. More common in white or people of European descent. Immobility – extended times of sitting (for example a long flight). Oestrogens – oral contraceptives, hormone replacement therapy. Surgeries or injuries. Non-O blood type – more common with blood types A, B or AB. Symptoms Factor V Leiden itself does not cause symptoms it is the mutation of the F5 gene which increases the risk for developing clots. Therefore, the first sign may be the development of a clot. Symptoms vary and are dependent on where the clot is located in the body. Clot in the deep vein – deep vein thrombosis (DVT) Pain Swelling Redness Warmth Clot which has travelled to the lungs – pulmonary embolism (PE) Sudden shortness of breath Chest pain when breathing in Cough which produces blood-streaked sputum Rapid heartbeat Inherited thrombophilia There are various factors which can lead to inherited thrombophilia – FVL, prothrombin G2021A mutation, deficiencies in natural anticoagulants (antithrombin, proteins C and S), hyperhomocysteinemia and elevations in clotting factors VIII and XI. The most common type is FVL with prothrombin-related thrombophilia the second. Factor V Leiden is the most common genetic risk factor for VTE. The FVL gene mutation is found in 20-25% of patients with VTE and 50% of people with inherited or familial thrombophilia. Factor V Leiden is the most prevalent inherited type of thrombophilia with 3-8% of people of European descent to carry one defective gene and approximately 1 in 5,000 who have two copies of the mutation. Compared to the general population where roughly 1 in 1,000 people each year will develop an abnormal blood clot; those with one copy of the FVL mutation the probability raises to 3-8 per 1,000, and the risk significantly increases to 80 in 1,000 in those with two copies of the defective gene. The most common FVL thrombophilia mutation, and has the lower risk is referred to as ‘heterozygous’, which means two different versions of the factor V gene are inherited (one from each parent). The more serious version of thrombophilia FVL is called ‘homozygous’ where the same form of the gene is inherited, one from your mother and one from your father. The Odds Ratio for VTE for heterozygous factor V Leiden is 4.2 compared to 11.5 for homozygous FVL gene mutation. COVID-19 and FVL A retrospective study published in January 2023, investigated the association between factor V Leiden and COVID-19. The occurrence of FVL mutation detected in COVID-19 patients with a history of thrombotic events was higher than in those without a record of thrombosis. Therefore, FVL can be viewed as a significant risk factor towards an elevated progression of the COVID-19 infection in regard to morbidity and mortality. It is recommended that FVL should be explored in COVID-19 patients and used as a prognostic factor for suitable treatments. References F5 gene: MedlinePlus Genetics Factor V Leiden thrombophilia: MedlinePlus Genetics Factor V Leiden - Symptoms and causes - Mayo Clinic Heterozygous vs. Homozygous: Definitions and Differences (verywellhealth.com) Inherited Thrombophilia - PubMed (nih.gov) Hereditary thrombophilia - PubMed (nih.gov) Kiraz, A. et al. (2023). Contribution of genotypes in prothrombin and factor V Leiden to COVID-19 and disease severity in patients at high risk for hereditary thrombophilia. Journal of Medical Virology, 92.2:e28457-n/a. Kujovich, J.L. (2011). Factor V Leiden thrombophilia. Genetics in Medicine, 13.1:1-16. Nicholson, M., Chan, N., Bhagirath, V., & Ginsberg, J. (2020). Prevention of venous thromboembolism in 2020 and beyond. J Clin Med. 9(8): 2467. doi:10.3390/jcm9082467.