The discovery of the factor V Leiden (FVL) missense mutation (Arg506Gln) causing factor V resistance to the anticoagulant action of activated protein C was a landmark that allowed a better understanding of the basis of inherited thrombotic risk.
PC activity ranged from 5% to 9%, and PC antigen levels were 5,3% in two homozygous for PROC missense mutation Arg32Cys; PC activity ranged from 18% to 60% and antigen levels from 21% to 64%, respectively, in 11 heterozygous for Arg32Cys; PC activity was 99% and 120% in two wild type.Of 15, eight were heterozygous for FVL.
The laboratory diagnosis is based on two tests: a phenotypic test based on APTT with and without APC and a genotypic test based on detection of a Factor V Leiden mutation.
Resistance to activated protein C (aPC) is most commonly due to the F5 rs6025 (factor V Leiden) polymorphism, which increases the risk of venous thrombosis.
The presumed cause of congenital thrombophilia can now be explained in ~50% of familial thrombosis cases following evaluation of a range of markers, primarily comprising factor V Leiden (FVL), activated protein C resistance (APCR), protein C (PC), protein S (PS) and antithrombin (AT).
Thrombophilia screening is aimed at detecting the most frequent and well-defined causes of venous thrombosis, such as activated protein C resistance/factor V Leiden mutation, prothrombin G20210A gene mutation, deficiencies of natural anticoagulants, such as antithrombin, protein C and protein S, the presence of antiphospholipid antibodies, hyperhomocysteinemia and increased factor VIII activity.
One of the most common hereditary thrombophilias is the factor V Leiden mutation, which is identified with a screening assay for activated protein C (APC) resistance and confirmed by DNA analysis.
Although the propensity to thrombosis is increased in individuals with type 1 diabetes, activated protein C sensitivity ratio and factor V Leiden mutation do not appear to be significant determinants.
The efficiency of a new prothrombin-based activated protein C (APC) resistance test to detect factor V Leiden (FVL) was clinically evaluated in 150 Italian patients with deep venous thrombosis.
If we had sequenced the F5 gene in patients homozygous for this haplotype, in order to locate the possible causal polymorphism, we would have found that 16 (76%) patients were homozygous or heterozygous for a missense mutation in exon 10 (1691G --> A), which predicts the replacement of Arg506 by Gln in one of the cleavage sites for activated protein C, a mutation that we now know as the FVL mutation.
We sought to confirm that carriers of this prothrombotic factor V Leiden mutation do not have an increased risk of developing severe sepsis and that carriers with severe sepsis derive similar treatment benefit from recombinant human activated protein C (drotrecogin alfa [activated]) as non-factor V Leiden carriers.
Activated protein C (APC) resistance is a common risk factor for venous thromboembolism (VTE) attributed to various mechanisms, including factor V Leiden (FVL) polymorphism.
It is caused by a single point mutation in the FV gene (factor V(Leiden)) that not only renders FVa less susceptible to the proteolytic inactivation by APC but also impairs the anticoagulant properties of FV.
The activated protein C (APC) resistance phenotype associated with an abnormal factor V Leiden (FVL), and the G20210A prothrombin gene mutation are the most common findings in patients with venous thromboembolism (VTE).
The most common inherited thrombotic disorders include activated protein C (APC) resistance (factor V Leiden), hyperhomocysteinemia, the prothrombin gene variant G20210A, elevated factor VIII levels, and deficiencies of thrombomodulin, protein C, protein S, and antithrombin.
Activated protein C (APC) resistance, both in its congenital form, due to the factor V Leiden mutation, and in its acquired form, are important risk factors for systemic venous thrombosis.
The activated protein C (APC) resistant-factor V (factor V Leiden) has emerged as the most common inherited risk factor for thrombosis in the Caucasian population.
Because activated protein C resistance is a common risk factor for venous thromboembolism, we prospectively evaluated the activated protein C sensitivity ratio and factor V Leiden mutation in cancer patients with and without venous thromboembolism.