FV and APC resistance: the plot thickens.
نویسنده
چکیده
In this issue of Blood, Nogami et al report on a novel factor V (FV) gene mutation (FV Trp1920→Arg, FVNara) associated with activated protein C (APC) resistance and a severe thrombotic phenotype in a young Japanese patient. Since the affected amino acid residue is located in the light chain of FV, far from the known APC-cleavage sites, this discovery may afford new insights into the molecular mechanisms of APC resistance.
منابع مشابه
Impaired APC cofactor activity of factor V plays a major role in the APC resistance associated with the factor V Leiden (R506Q) and R2 (H1299R) mutations.
Activated protein C (APC) resistance is a major risk factor for venous thrombosis. Factor V (FV) gene mutations like FV(Leiden) (R506Q) and FV(R2) (H1299R) may cause APC resistance either by reducing the susceptibility of FVa to APC-mediated inactivation or by interfering with the cofactor activity of FV in APC-catalyzed FVIIIa inactivation. We quantified the APC cofactor activity expressed by ...
متن کاملFactor V is an anticoagulant cofactor for activated protein C during inactivation of factor Va.
Coagulation factor V (FV) promotes inactivation of activated factor VIII (FVIIIa) by activated protein C (APC) and protein S. Loss of this APC cofactor activity is proposed to be partially responsible for the APC resistance phenotype of FV(Leiden). However, FVIIIa loses activity rapidly due to dissociation of the A2 domain, and this may be the primary mechanism of FVIIIa inactivation. APC/prote...
متن کاملMolecular mechanisms of activated protein C resistance. Properties of factor V isolated from an individual with homozygosity for the Arg506 to Gln mutation in the factor V gene.
Resistance to activated protein C (APC), which is the most prevalent pathogenetic risk factor of thrombosis, is linked to a single point-mutation in the factor V (FV) gene, which predicts replacement of Arg (R) at position 506 with a Gln (Q). This mutation modifies one of three APC-cleavage sites in the heavy chain of activated FV (FVa), suggesting that mutated FVa (FVa:Q506) is at least partia...
متن کاملActivated Protein C Resistance : Molecular Mechanisms Based on Studies Using Purified G 1 n 5 O 6 - Factor
Gln=-factor V (W) was purified from plasma of an individual homozygous for an Arg506Gln mutation in FV that is associated with activated protein C (APC) resistance. Purified GlnW-FV, as well as Glnm-FVa generated by either th ombin or FXa, conveyed APC resistance to FV-deficient plasma in coagulation assays. Clotting assay studies also suggested that APC resistance does not involve any abnorm...
متن کاملFactor V Is an Anticoagulant Cofactor for Activated Protein C during Inactivation of Factor Va
Coagulation factor V (FV) promotes inactivation of activated factor VIII (FVIIIa) by activated protein C (APC) and protein S. Loss of this APC cofactor activity is proposed to be partially responsible for the APC resistance phenotype of FV Leiden . However, FVIIIa loses activity rapidly due to dissociation of the A2 domain, and this may be the primary mechanism of FVIIIa inactivation. APC/prote...
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عنوان ژورنال:
- Blood
دوره 123 15 شماره
صفحات -
تاریخ انتشار 2014