Thrombophilia is a multifactorial disorder of inappropriate clot formation (venous thrombosis) resulting from an interaction of genetic, acquired, and circumstantial predisposing factors. Resistance to Activated Protein C (APC) due to heterozygosity or homozygosity for the Factor V Leiden (FVL) variant, or an increased prothrombin level due to heterozygosity or homozygosity for the prothrombin 20210G>A variant, are regarded as the most prevalent heritable abnormalities predisposing to venous thrombosis.

The FVL variant is a G>A transition at nucleotide 1691 of the factor V (F5) gene, which results in the substitution of arginine by glutamine p.(R506Q), inactivating the APC cleavage site and thus rendering factor V resistant to cleavage by APC. Homozygotes are 30 to 40 times more likely to suffer deep vein thrombosis (DVT) or pulmonary embolism (PE). The prothrombin 20210A variant is a G>A transition at nucleotide 20210 of the Factor II (F2) gene.

Analysis involves amplification of the Factor II/ Factor V genes and discrimination of the normal and mutant alleles using a Taqman® Genotyping assay. Testing within the Royal Devon & Exeter Hospital is provided as part of a combined thrombophilia screen. Please see link for sample requirements for internal and external requests. 

Queries regarding heritable risk factors for thrombophilia should be directed to Consultant Haematologists, Dr Jason Coppell (e-mail JCoppell@nhs.net) or Dr Jackie Ruell (e-mail Jackie.Ruell@nhs.net). Both can be contacted by telephone on 01392 402468.