Factor V Leiden mutation

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. more...

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.

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