Measuring protein S activity with an automated calcium-thromboplastin-based protein S activity assay, a significant correlation (P < 0.0001) between the results of this functional protein S assay and APC resistance (represented by the ratio (Rs value) of clotting time with and without addition of activated protein C) was observed.
Here we demonstrate that the phenotype of APC resistance is associated with heterozygosity or homozygosity for a single point mutation in the factor V gene (at nucleotide position 1,691, G-->A substitution) which predicts the synthesis of a factor V molecule (FV Q506, or FV Leiden) that is not properly inactivated by APC.
This suggests that homozygous FV-deficient plasma completely lacks the cofactor, i.e. the second APC cofactor, which can correct APC resistance in plasma.
Because the APC-resistant plasma contained normal levels of factor V procoagulant activity, the results indicated APC resistance to be due to a selective defect in the anticoagulant function of factor V. The present results show factor V not only to express procoagulant properties after its activation by thrombin but also to play an important part in the anticoagulant system as cofactor to APC.
Resistance to activated protein C (APC) is a major cause of familial thrombophilia, and can be corrected by an anticoagulant activity expressed by purified factor V. We investigated linkage between APC resistance and the factor V gene in a large kindred with familial thrombophilia.
Evidence against heterozygous coagulation factor V 1691 G-->A mutation with resistance to activated protein C being a risk factor for coronary artery disease and myocardial infarction.
The level of antibodies to anionic phospholipids (PLa), a response to activated protein C (APC), and the presence for the mutation in the coagulation factor V gene causing APC resistance were studied.
The factor V Leiden variant, responsible for the phenomenon of activated protein C resistance, was found to be less frequent among British (0.06) and Swedish/Danish (0.15) protein C deficiency patients than previously reported in a Dutch study (0.19).
This reduced but measurable susceptibility of Gln506-FVa to APC inactivation may help explain why APC resistance is a mild risk factor for thrombosis because APC can inactivate both normal FVa and variant Gln506-FVa.
APC-resistance is in more than 90% of the cases caused by a single point mutation in the gene for factor V (G to A transition at nucleotide position 1691), which predicts replacement of Arg(R)506 in the APC-cleavage site with a Gln(Q).
The patient, her mother, and her brother were found to have resistance to activated protein C (APC), and the congenital thrombophilia in this family was verified by the finding of the Arg506 Gln mutation in factor V. This is the first case of HIT and APC resistance.
Preliminary data suggest a higher risk of thrombosis in APC-resistant homozygous individuals or in patients exhibiting APC-resistance together with other thrombophilic genetic defects.
In the present study we found no difference between the prevalence of APC resistance (assessed by the ratio of the aPTT with and without added APC) in 134 non-anticoagulated survivors of myocardial infarction and that in 100 controls of similar age and sex distribution (2.2% and 2.0%, respectively).
The level of antibodies to anionic phospholipids (PLa), a response to activated protein C (APC), and the presence for the mutation in the coagulation factor V gene causing APC resistance were studied.
This reduced but significant susceptibility of Gln506-FVa to APC inactivation may help explain why APC resistance, especially for heterozygotes, is a relatively moderate risk factor for venous thrombosis.
Two APC-resistant women without the Leiden mutation subsequently discontinued OC and both then normalized their APC-SR. We conclude that acquired factors, i.e. oral contraceptives, may play an important role in determining plasma APC resistance.
Since the presence of activated protein C (APC) resistance has been reported to interfere with PS activity assays resulting in an apparent type II PS deficiency, we retrospectively tested a pre-transplantation frozen plasma sample for APC resistance.