Factor V Leiden is a specific, inherited change in a gene involved in the blood clotting process. This genetic variation makes the factor V protein, a component of the clotting system, more resistant to inactivation by a natural anticoagulant protein called activated protein C (APC). This resistance means that blood clotting can continue for longer than usual, increasing the likelihood of abnormal clot formation. It is considered the most common inherited disorder affecting blood coagulation. This article focuses on what it means to inherit one copy of this genetic change, a condition known as heterozygous Factor V Leiden.
The Genetics of Heterozygous Factor V Leiden
Being heterozygous for Factor V Leiden means an individual has inherited one copy of the mutated F5 gene from one parent and one normal copy of the F5 gene from the other parent. Think of it like receiving one instruction manual with a slight error and another manual that is perfectly normal. In the body, this results in having a mix of both the altered Factor V protein and the normal Factor V protein, typically around 50% of each.
In contrast, being homozygous for Factor V Leiden involves inheriting two copies of the mutated gene, one from each parent, leading to a much higher proportion of the altered protein. The inheritance pattern for Factor V Leiden is autosomal dominant, meaning only one copy of the mutated gene is sufficient for the trait to be expressed. If a parent is heterozygous for Factor V Leiden, each of their children has a 50% chance of inheriting the mutated gene and also being heterozygous. While heterozygous individuals have an increased tendency for clotting compared to those without the mutation, their risk is significantly lower than those who are homozygous.
Associated Health Risks
The primary health concern for individuals with heterozygous Factor V Leiden is an increased tendency to form abnormal blood clots, particularly in the veins. These clots commonly manifest as venous thromboembolism (VTE), which encompasses deep vein thrombosis (DVT) and pulmonary embolism (PE). DVT involves a blood clot forming in a deep vein, often in the leg. A PE occurs when part of that clot breaks off and travels to the lungs, potentially causing a life-threatening blockage.
For a heterozygous individual, the risk of developing a blood clot is approximately 3 to 8 times higher than for someone without the mutation. Despite this relative increase, the overall absolute risk of developing a clot remains low for most heterozygous individuals. Additional factors can further elevate this risk, triggering clot formation. These include major surgery, prolonged immobility (e.g., long flights, bed rest), and lifestyle factors like smoking and obesity.
Diagnosis and Management
Diagnosis of Factor V Leiden typically begins if a person has experienced unexplained blood clots or has a family history of such events. Diagnosis involves an initial activated protein C (APC) resistance screening test. If this suggests resistance, a genetic test confirms the Factor V Leiden mutation and determines if the individual is heterozygous or homozygous.
Most individuals who are heterozygous for Factor V Leiden and have never experienced a blood clot do not require ongoing anticoagulant medication. Management focuses on reducing other risk factors and implementing preventive measures.
During situations that temporarily heighten clotting risk, such as major surgery or extended immobility, a doctor might recommend a short course of blood thinners or precautions like compression stockings. Anticoagulant therapy is reserved for those who have already experienced a blood clot or are facing a high-risk medical situation.
Pregnancy and Contraception Considerations
Pregnancy naturally increases a woman’s risk of blood clots, and heterozygous Factor V Leiden adds to this baseline risk. The risk of venous thromboembolism (VTE) during pregnancy is estimated to be about 1% for Factor V Leiden heterozygotes, increasing to 3% if there is also a family history of VTE.
Management during pregnancy often involves close monitoring. For some women, particularly those with a history of clots, preventative treatment with blood thinners like low molecular heparin may be recommended throughout pregnancy and for about six weeks postpartum.
Regarding contraception, estrogen-containing methods, such as combination birth control pills, patches, and vaginal rings, should be avoided by individuals with Factor V Leiden. Estrogen significantly increases blood clot risk, compounded by the Factor V Leiden mutation, potentially increasing it by 27 to 35 times compared to women without the mutation not using these contraceptives.
Safer alternatives include progestin-only methods (e.g., pills, implants, injections, IUDs) and non-hormonal options like the copper IUD. Discuss these choices with a healthcare provider to determine the most suitable and safest option.