Factor II-related thrombophilia or prothrombin thrombophilia is characterized by venous thromboembolism (VTE). Deep-vein thrombosis (DVT) in the legs is the most common VTE in adults, followed by pulmonary embolism. Prothrombin related thrombophilia is suspected in individuals with unprovoked VTE before fifty, with a history of recurrent VTE, for women with VTE during pregnancy or associated with the use of oral contraceptives, and in individuals with a personal or family history of recurrent thrombosis. Predisposing factors to thrombosis are the number of mutated alleles, the presence of coexisting genetic abnormalities and acquired thrombophilic disorders. The mutant allele is associated with elevated plasma levels of prothrombin. As the mutation is located in the 3’untranslated region of FII it is suggested that the mutation increases the efficiency and accuracy of processing of the 3’ end of the mRNA, resulting in an accumulation of mRNA and increased synthesis of prothrombin. Diagnosis of prothrombin related thrombophilia requires molecular genetic analysis of FII, which encodes prothrombin, to identify the specific G-to-A substitution at nucleotide 20210.
Factor V Leiden polymorphism
Factor V Leiden thrombophilia is characterized by a poor anticoagulant response to activated protein C (APC) and an increased risk for venous thromboembolism (VTE). Deep venous thrombosis (DVT) is the most common VTE, with the legs being the most common site. Factor V Leiden thrombophilia is suspected in individuals with a history of venous thromboembolism (VTE) manifest as deep vein thrombosis (DVT) or pulmonary embolism, in women with a history of VTE during pregnancy or in association with oral contraceptive use, and in individuals with a personal or family history of recurrent thrombosis. The variant Factor V Leiden is inactivated by APC at a rate approximately ten times slower than normal Factor V and persists longer in the circulation, resulting in increased thrombin generation and a mild hypercoagulable state, reflected by elevated levels of prothrombin fragment F1+2 and other activated coagulation markers. The diagnosis of Factor V Leiden thrombophilia is made either using a coagulation screening test (APC resistance assay) or by DNA analysis of the F5 gene which encodes the Factor V protein, the only gene associated with Factor V Leiden thrombophilia. The term "Factor V Leiden" refers to the specific G-to-A substitution at nucleotide 1691 in the gene for Factor V that predicts a single amino-acid replacement (Arg506Gln) at one of three APC cleavage sites in the Factor V molecule.
- Desjonquères, A., Ménard, A., Detemmerman, L., Ternisien, C., Fouassier, M., Gillet, B., … Le Bris, Y. (2019). Confirmed validation of an innovative PCR-assay without DNA extraction for multiplex diagnosis of factor V Leiden and prothrombin gene variants. Thrombosis Research, 183, 143–145. Available from : Thrombosis Research