Factor V Leiden

A genetic disorder affecting blood clotting

Factor V Leiden

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Diagram illustrating the mutation in Factor V Leiden.

Factor V Leiden is a genetic mutation of one of the clotting factors in the blood, known as Factor V. This mutation results in a variant of Factor V that is resistant to inactivation by activated protein C, leading to an increased risk of venous thromboembolism.

Genetics

Factor V Leiden is caused by a single nucleotide polymorphism (SNP) in the F5 gene, which encodes the Factor V protein. The mutation involves a substitution of adenine for guanine at nucleotide position 1691, resulting in the replacement of the amino acid arginine with glutamine at position 506 in the protein. This specific mutation is referred to as R506Q.

Pathophysiology

The Factor V Leiden mutation leads to a form of Factor V that is resistant to cleavage by activated protein C (APC). Normally, APC inactivates Factor V, thus regulating the clotting process. However, in individuals with Factor V Leiden, this regulation is impaired, leading to a hypercoagulable state. This increases the risk of developing abnormal blood clots, particularly in the veins, a condition known as thrombophilia.

Epidemiology

Factor V Leiden is the most common inherited form of thrombophilia. It is particularly prevalent in individuals of European descent, with approximately 5% of Caucasians carrying the mutation. The prevalence is lower in other populations.

Clinical Manifestations

Individuals with Factor V Leiden have an increased risk of developing deep vein thrombosis (DVT) and pulmonary embolism (PE). The risk is higher in those who are homozygous for the mutation compared to those who are heterozygous. Other risk factors, such as oral contraceptive use, pregnancy, and surgery, can further increase the risk of thrombotic events in affected individuals.

Diagnosis

Diagnosis of Factor V Leiden is typically made through genetic testing. A blood test can identify the presence of the Factor V Leiden mutation. In some cases, functional assays that measure the resistance of Factor V to inactivation by APC may also be used.

Management

Management of Factor V Leiden involves reducing the risk of thrombosis through lifestyle modifications and, in some cases, anticoagulant therapy. Individuals with a history of thrombotic events may require long-term anticoagulation. Those without a history of thrombosis may be advised to avoid additional risk factors, such as smoking and prolonged immobility.

Related pages

• Thrombophilia
• Deep vein thrombosis
• Pulmonary embolism
• Protein C