Factor V Leiden (sometimes Factor V_Leiden) is a hypercoagulability disorder in which Factor V, one of the coagulation factors, cannot be deactivated. Factor V Leiden is the most common hereditary hypercoagulability clotting disorder amongst Eurasians, possibly affecting up to 5% of the population of the U.S. It is named after the city Leiden (The Netherlands), where it was first identified in 1994 by Prof R. Bertina et al.

Contents

1 Pathophysiology 2 Epidemiology 3 Diagnosis 4 References

Pathophysiology

It is an autosomal dominant condition in which the coagulation factor has a mutation and cannot be destroyed by activated protein C (aPC). It is a single nucleotide substitution of adenine for guanine - which causes an amino acid substitution of glutamine for arginine at position 506, the cleavage site for protein C.

As factor V cannot be inactivated, it continues to facilitate production of thrombin, and so thrombi form in the veins.

Epidemiology

Up to 30% of patients who present with venous thrombosis or pulmonary embolism have this mutation.

Diagnosis

Suspicion of Factor V Leiden being the cause for any thrombotic event should be considered in any white patient below the age of 45, or in any person with a family history of thrombosis.

This disease can be diagnosed by watching the APTT (the time it takes for blood to clot) as activated protein C is added. With a normal patient, adding aPC increases the APTT. With patients suffering from Factor V Leiden, adding aPC will barely affect the time it takes for blood to clot.

There is also a simple genetic test that can be done for this disorder. The mutation (a 1691G→A substitution) removes a cleavage site of the restriction endonuclease MnlI, so simple PCR, treatment with MnlI, and then DNA electrophoresis will give a quick diagnosis.

References

• Bertina RM, Koeleman BP, Koster T, Rosendaal FR, Dirven RJ, de Ronde H, van der Velden PA, Reitsma PH. Mutation in blood coagulation factor V associated with resistance to activated protein C. Nature 1994;369:64-7. PMID 8164741.