Frequency of Polymorphisms in the B-domain of Factor V Gene in APC-resistant Patients

Joint effects of cancer and variants in the factor 5 gene on the risk of venous thromboembolism

“…Both FVL and F5 rs4524 have been reported to exhibit their prothrombotic actions by attenuated down-regulation of activated FV by APC. 19 Previous studies have also found an increased prevalence of acquired APC resistance in patients with cancer. [46][47][48] It is licit to assume that two sources of APC resistance (i.e.…”

“…18 The rs4524 single nucleotide polymorphism (169542517T>C) is the result of a missense mutation (lysine to arginine) at position 2684 in the B-domain of F5 which is thought to result in APC resistance. 19 A missense mutation (arginine to glutamine) at position 506 results in the well-known factor V Leiden (FVL) (1691G>A, rs6025) single nucleotide polymorphism. FVL is pro-thrombotic by two mechanisms: its APC-resistant properties and its abnormal factor VIII degradation by APC.…”

Inherited and Acquired Thrombophilia in Pregnancy

“…Although Factor V and factor VIII share homologous A and C domains, the B domain of factor V is not homologous to that in factor VIII. Cleavage of the B domain from factor V results in an inert factor V. This suggests that the B domain is of vital importance in activated protein C cofactor activity, and that mutations in this domain may contribute to an impaired activated protein C response (Kostka, 2000). Activated factor V (factor Va) is a cofactor protein in the prothrombinase complex that, together with the serine protease factor Xa, is responsible for conversion of prothrombin to the active enzyme thrombin.…”

Venous Thromboembolism and Cancer

“…94 Previous studies have also reported that cancer is associated with an acquired APC resistance. [246][247][248] Therefore, it would be likely to assume that two sources of APC resistance, acquired and inherited sources, would greatly increase the risk of a VTE.…”

“…92,93 FVL is thought to be prothrombotic by its resistance to activated protein C (APC) and also by the abnormal breakdown of FVIII by APC. 94 Heterozygous carriers have a 2 to 5-fold higher risk of VTE, while the risk is 10-to 80-fold higher in homozygous carriers. 92 The prothrombin (PT) 20210A mutation on the prothrombin (F2) gene is characterized by high plasma levels of prothrombin.…”