title: Resistance to activated protein C due to mutated factor V as a novel cause of inherited thrombophilia.
abstract: Inherited resistance to activated protein C (APC) was recently recognized as a novel cause underlying venous thrombophilia. In most cases APC-resistance is due to a single point mutation in the factor V gene leading to a replacement of Arg506 with Gln (factor V Leiden). Amino acid substitution occurs at one of the APC cleavage sites of factor Va, rendering it resistant to APC inactivation. Plasma anticoagulant response to exogenous APC as a simple diagnostic assay of APC- resistance shows good sensitivity and specificity as compared to gene analysis, yet standardization of the results needs to be improved. The APC-resistance trait is present in 2%-6% of the general population and was found to be associated with venous thrombophilia in about 20% of patients with unexplained thrombosis. Clinical features are substantially similar to other congenital plasma abnormalities predisposing to thrombosis (antithrombin III, protein C, protein S deficiencies); yet the overall clinical penetrance of the defect seems lower, at least for the heterozygous condition. 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. To date, genetically determined APC-resistance does not seem to play a significant role in the development of arterial thrombotic disease.
authors.affiliation: Divisione di Ematologia, Università Cattolica, Rome, Italy.
authors.forename: V
authors.initials: V
authors.lastname: De Stefano
authors.forename: G
authors.initials: G
authors.lastname: Leone
mesh_terms: D000328:Adult; D000925:Anticoagulants / Q000494:pharmacology; D016477:Artifacts; D015331:Cohort Studies; D004789:Enzyme Activation; D005165:Factor V / Q000235:genetics*; D005166:Factor V Deficiency / Q000150:complications / Q000453:epidemiology / Q000235:genetics*; D015943:Factor Va / Q000378:metabolism; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006493:Heparin / Q000494:pharmacology; D006801:Humans; D008297:Male; D008875:Middle Aged; D010314:Partial Thromboplastin Time; D017354:Point Mutation; D011247:Pregnancy; D011250:Pregnancy Complications, Hematologic; D015995:Prevalence; D011486:Protein C / Q000378:metabolism*; D017293:Protein S / Q000032:analysis; D012680:Sensitivity and Specificity; D013923:Thromboembolism / Q000097:blood / Q000235:genetics*
chemical_list: D000925:Anticoagulants; D011486:Protein C; D017293:Protein S; C095381:factor V Leiden; D015943:Factor Va; D005165:Factor V; D006493:Heparin