What Is Factor V Leiden (FVL)?
Factor V Leiden is a gene mutation of one of the clotting factors in the blood, which leads to an increased risk of blood clotting and thrombotic events. According to NCBI, Factor V Leiden thrombophilia is characterized by ”a poor anticoagulant response to activated protein C (APC) and an increased risk for venous thromboembolism (VTE).” The Factor V Leiden mutation should not be confused with factor V deficiency.
As the most common VTE, deep vein thrombosis (DVT) often affects the leg veins. Individuals with Factor V Leiden have a low relative risk of experiencing thrombosis in unusual locations. After the treatment of the first VTE, the Leiden variant has a lower absolute risk of recurrent thrombosis.
According to a systematic review by NCBI, the Leiden variant is the most common cause of the activated protein C resistance (APC resistance) phenotype. Discrepancies in heterozygotes and homozygotes have been described in the context of protein C resistance. Activated protein C (APC) is a naturally occurring anticoagulant that plays a critical role in maintaining the balance of procoagulant and anticoagulant mechanisms in the human body.
Individuals born with a copy of the mutation are at a higher risk of developing vein clots (deep vein thrombosis, DVT) and pulmonary embolism (PE) due to protein C resistance (PCR), but are not more prone to heart attacks, strokes, or arterial blood clots than the general population. Combined with antiphospholipid antibodies, another thrombotic defect, factor V Leiden can significantly increase an individual's risk of thrombosis.
Inheriting a copy of the factor V Leiden mutation increases the risk of developing abnormal blood clots and experiencing symptoms of DVT and pulmonary embolism (PE). While most individuals born with the Leiden mutation never develop abnormal blood clots, some are at a high risk of long-term health problems, like venous thrombosis, adverse pregnancy outcomes, recurrent miscarriages, and life-threatening blood clots.
Who is at risk?
The Factor V Leiden mutation occurs when offspring inherit a copy of the factor V mutation from one or both parents. Factor V Leiden gene mutations have a higher prevalence among individuals with Northern European family members compared to the general population.
The genetic disorder involves a point mutation in the factor V (f5) gene, which makes up one of the proteins in the coagulation system. Because two different genes (one from each parent) make up each protein in the human body, two types of factor V Leiden exist: heterozygous factor V Leiden, in which only one copy of the factor V gene mutation was inherited through Mendelian inheritance, and homozygous factor V Leiden, in which two copies of the factor V Leiden mutation were inherited through Mendelian inheritance.
Normal pregnancies involve changes in the coagulation system, including an increase in clotting factors and the decreased activity of APC, an important anticoagulant. These factors can lead to a higher risk of thrombotic events during childbirth in pregnant women with the Leiden variant.
According to a case-control study by NCBI, the prevalence of factor V Leiden was 44 percent among pregnant women with venous thromboembolism. Venous thrombosis can lead to pregnancy loss in the first trimester, placental abruption, placental infarction, and recurrent miscarriage. A screening test for the Leiden variant is recommended for pregnant women with familial thrombophilia and women with a history of VTE.
How common is factor V Leiden (FVL)?
In the U.S., the f5 gene mutation is present among approximately five percent of the general population. The Leiden mutation has a lower prevalence among Native Americans and African Americans and is a more common mutation in Caucasian and European populations.
In some parts of Northern Europe, factor V Leiden gene mutations are present in approximately 10–15 percent of the general population. The prevalence of Factor V Leiden is lower in South America, Africa, and Asia, where the mutation is present in less than one to three percent of the general population.
What causes factor V Leiden (FVL)?
Factor V Leiden is caused by a point mutation in the factor V gene, which encodes a substitution of arginine and glutamine at position 506 of the factor V molecule where activated protein C cleaves factor VA. The f5 gene produces the coagulation factor V protein, one of the proteins in the coagulation system that helps blood to clot. The factor V Leiden mutation makes factor VA, a cofactor in thrombin activation, resistant to the anticoagulant effects of activated protein C, causing a genetic predisposition to thrombotic events.
In other words, the mutation causes an increased tendency of blood to clot, leaving individuals with a copy of the mutation at a higher risk of abnormal blood clots, recurrent miscarriages, stillbirths, and thrombophilic defects.