title: An evaluation of screening tests for defects in the protein C pathway: commercial kits lack sensitivity and specificity.
abstract: A comparative evaluation of four commercial coagulation test kits for screening the protein C pathway kits was performed at two centres. The tests were Acticlot V-OUT (V-OUT), the PCA test (PCA), the GradiThrom PCP test (PCP) and ProC Global (ProC). Reference ranges were established in 40 normal subjects and, with the exception of V-OUT and ProC, significant differences were observed between males and females. Consequently, sex-specific normal cut-off values (fifth percentile) were used that led to greatly improved sensitivity when compared with the manufacturers' recommended cut-off values. Plasma from patients with factor V Leiden (n = 23), congenital protein S deficiency (n = 19), congenital protein C deficiency (n = 11), lupus anticoagulant (n = 17) and thrombophilia with no demonstrable protein C pathway defect (n = 20) were tested. All kits showed 100% sensitivity to factor V Leiden, but sensitivity was variable for protein C deficiency (27-73%), and poor for protein S deficiency (29-35%). The lupus anticoagulant affected all kits to some degree, with 29-35% giving values below the fifth percentile of normal, whereas all kits gave 1/20 unexpected abnormal results in the thrombophilia group, with the same sample accounting for the abnormal results in three of the four kits. Overall sensitivity and specificity, respectively, for defects in the protein C pathway were: V-OUT, 60 and 91%; PCA, 70 and 86%; PCP 75 and 94%; and ProC, 66 and 88%. We conclude that all four kits lack the sensitivity and specificity required for routine laboratory screening for defects in the protein C pathway and cannot replace assays for the individual proteins of this system.
authors.affiliation: Department of Haematology, University College London Hospital, London, UK. c_gardiner@btconnect.com
authors.forename: C
authors.initials: C
authors.lastname: Gardiner
authors.forename: P C
authors.initials: PC
authors.lastname: Cooper
authors.forename: M
authors.initials: M
authors.lastname: Makris
authors.forename: I J
authors.initials: IJ
authors.lastname: Mackie
authors.forename: R G
authors.initials: RG
authors.lastname: Malia
authors.forename: S J
authors.initials: SJ
authors.lastname: Machin
mesh_terms: D001780:Blood Coagulation Tests / Q000592:standards; D005260:Female; D006801:Humans; D008297:Male; D008403:Mass Screening / Q000379:methods; D011486:Protein C / Q000378:metabolism*; D011933:Reagent Kits, Diagnostic / Q000592:standards*; D012016:Reference Values; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D019851:Thrombophilia / Q000175:diagnosis*
chemical_list: D011486:Protein C; D011933:Reagent Kits, Diagnostic