Leidenmutatie

Leidenmutatie, commonly known as Factor V Leiden, is the most common inherited form of thrombophilia in people of European descent. It refers to a single nucleotide change in the F5 gene (G1691A) that causes an arginine-to-glutamine substitution at position 506 (R506Q) in coagulation factor V, making factor V resistant to inactivation by activated protein C.

The mutation is inherited in an autosomal dominant pattern with incomplete penetrance. Heterozygous carriers have a substantially increased risk of venous thromboembolism (VTE) compared with noncarriers, while homozygous individuals have an even higher risk. The prevalence is highest in Europe and ranges around 2–7% in many populations of European ancestry; it is far less common in other groups.

Pathophysiologically, APC resistance due to Factor V Leiden promotes continued thrombin generation and a prothrombotic state, particularly in situations that activate coagulation such as surgery, reduces mobility, pregnancy, or estrogen-containing medications. Many carriers never develop thrombosis, and the mutation is typically discovered after a VTE event or through familial screening.

Diagnosis can be made by genetic testing for F5 G1691A or, less specifically, by functional tests that assess activated protein C resistance. Management focuses on risk reduction and treatment of thrombosis. Carriers without VTE generally do not require long-term anticoagulation but should be informed about risk factors. Hormonal contraception or hormone replacement therapy may be discussed with caution, and prophylactic anticoagulation may be considered in high-risk settings (e.g., major surgery, prolonged immobilization) for individuals with VTE or strong family history.