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 a family history of recurrent thombosis. 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.