Factor V Leiden thrombophilia is characterized by a poor anticoagulant response to activated protein C (APC) and an increased risk for venous thromboembolism (VTE).
The p.R147W mutation, the c.C6152T in exon 7, causing a change in amino acid from arginine to tryptophan of the PROC gene has been reported as a common mutation in Taiwanese populations with venous thromboembolism (VTE).
Seven SNPs (F5 rs6025, F2 rs1799963, ABO rs514659, FGG rs2066865, F11 rs2289252, PROCrs1799810 and KNG1 rs710446) with four SNP-SNP interactions contributed to the genetic risk score for VTE, with an AUC of 0.66 (95% CI, 0.64-0.68).
Several low-frequency genetic mutations, PROS1 p.Lys196Glu in Japanese and PROCp.Arg189Trp and p.Lys193del in Chinese, are significantly associated with increased risk for VTE, with odds ratio more than 2 through the reduced protein C anticoagulant activity.
The endogenous thrombin potential (ETP) showed a striking inter-individual variability among different FV Leiden carriers and, especially when measured in the presence of APC, correlated with VTE risk.
The THBD 1418T allele is associated with lower soluble TM, both in plasma and in HUVEC-conditioned medium, and with an increase in functional membrane-bound TM in HUVEC, which could explain the increased activated protein C levels and the reduced VTE risk observed in individuals carrying this allele.
Factor V Leiden is a genetic disorder characterized by a poor anticoagulant response to activated Protein C and an increased risk for venous thromboembolism.
In conclusion, high thrombin generation in the presence of APC, in women after a first event of VTE is indicative for an increased risk of a recurrence.
Among them, the factor V (FV) Leiden mutation causes a reduced ability of activated protein C to inactivate activated FV and is the most frequent genetic predisposing factor for venous thromboembolism.
The levels of circulating activated protein C reflect in-vivo protein C activation, and a low level of activated protein C is a risk factor for venous thromboembolism.
The complex between activated protein C (APC) and the protein C inhibitor (PCI) is a sensitive indicator of the degree of activation of blood coagulation and higher concentrations have been measured in carriers of the FV Leiden mutation who were in the recovery phase after treatment for venous thromboembolism (VTE).
We investigated in case-control studies both biological effects (FVIII levels and activated protein C sensitivity ratio) and clinical associations (venous thromboembolism) of the D1241E change.
These data indicate that individuals carrying the 4600AG genotype have high sEPCR levels but do not have an increased risk of thrombosis, whereas individuals carrying the 4678CC genotype have higher APC levels and lower risk of venous thromboembolism.
Resistance to activated protein C (APC) has been demonstrated to be a risk factor for venous thromboembolism, but it is not known whether this phenotype is consistent over time.
These data indicate that individuals carrying the 4600AG genotype have high sEPCR levels but do not have an increased risk of thrombosis, whereas individuals carrying the 4678CC genotype have higher APC levels and lower risk of venous thromboembolism.
Activated protein C (APC) resistance is a common risk factor for venous thromboembolism (VTE) attributed to various mechanisms, including factor V Leiden (FVL) polymorphism.