title: Activated protein C resistance assay detects thrombotic risk factors other than factor V Leiden.
abstract: Activated protein C (APC) resistance is a common risk factor for venous thromboembolism (VTE) attributed to various mechanisms, including factor V Leiden (FVL) polymorphism. FVL is considered responsible for up to 95% of APC resistance; however, other factor V polymorphisms and elevated factor VIII levels also have been implicated. We assessed whether additional mechanisms contribute to APC resistance in a blinded case-control study of 65 subjects by measuring APC resistance using 3 methods: 2 activated partial thromboplastin time-based methods with and without dilution in factor V-deficient plasma and 1 Russell viper venom-based assay (RVV). Without factor V-deficient plasma, 24 subjects were APC resistant; with factor V-deficient plasma, the assay identified fewer APC-resistant subjects, as did RVV. All assays detected the 7 heterozygous FVL subjects. Thirteen subjects had factor VIII levels above 150% (1.50). After excluding subjects with FVL or elevated factor VIII levels, 4 subjects still had APC resistance. VTE risk trended higher for subjects with APC resistance in the absence of FVL. Measurement of APC resistance without dilution in factor V-deficient plasma is needed to assess for potentially important thrombotic risk factors other than FVL.
authors.affiliation: Pathology Research Laboratory, Research Service, Denver Veterans Affairs Medical Center, 1055 Clermont St, Denver, CO 80220, USA.
authors.forename: Laurie L
authors.initials: LL
authors.lastname: Graf
authors.forename: Carolyn H
authors.initials: CH
authors.lastname: Welsh
authors.forename: Zainab
authors.initials: Z
authors.lastname: Qamar
authors.forename: Richard A
authors.initials: RA
authors.lastname: Marlar
mesh_terms: D020016:Activated Protein C Resistance / Q000097:blood / Q000235:genetics*; D001780:Blood Coagulation Tests / Q000379:methods; D016022:Case-Control Studies; D004247:DNA / Q000032:analysis; D005165:Factor V / Q000032:analysis / Q000235:genetics*; D005169:Factor VIII / Q000032:analysis; D020022:Genetic Predisposition to Disease; D015894:Genome, Human; D006239:Haplotypes; D006801:Humans; D008875:Middle Aged; D011110:Polymorphism, Genetic; D012307:Risk Factors; D016037:Single-Blind Method; D020246:Venous Thrombosis / Q000209:etiology* / Q000473:pathology
chemical_list: C095381:factor V Leiden; D005165:Factor V; D005169:Factor VIII; D004247:DNA