However, several point mutations in the F5 gene causing APC resistance have been identified in different populations.231Recently, severe thrombophilia in a factor V-deficient patient homozygous for the Ala2086Asp mutation (FV Besançon) has been described that affects anticoagulant pathways more strongly than the prothrombinase activity of FVa.232It can also occur that heterozygous FVL carriers present with a concomitant heterozygous F5 gene mutation responsible for FV deficiency, resulting in the 50% of FV plasma levels being all FVL. Here, F5 is linked to Rare hereditary thrombophilia.