title: Detection of protein S deficiency: a new functional assay compared to an antigenic technique.
abstract: Congenital protein S (PS) deficiency is associated with increased risk of venous thrombosis. To investigate the possibility of automating PS testing with decreased turnaround time, a clotting-based functional protein S assay was evaluated and compared to an antigenic method. Samples were collected from 126 patients within 5 days of their first acute cerebral infarction, from 62 controls and from 47 consecutive samples for thrombophilia investigation. The normal range for the clotting-based kit, calculated from the results of 20 healthy controls, was 62-136% (mean +/- 2 SD). Intra- and inter-assay co-efficients of variation were < 3.0 and 10.0% respectively. There was no significant correlation between the two methods (r = 0.30, P > 0.05). Two patients had low PS antigen results with normal functional levels. Both techniques were used to compare a further group of 53 patients with defined abnormalities which included nine antigenic protein S deficiencies, five protein C deficient patients, 10 patients with a lupus anticoagulant (LA), 17 Factor V Leiden (FVL) heterozygotes, two FVL homozygotes and 10 patients on therapeutic levels of heparin. In this group we found that four of nine antigenic PS deficient patients had normal functional PS levels. The test was susceptible to the FVL mutation with four of 17 FVL heterozygotes and both of two FVL homozygotes giving low levels. One of five protein C-deficient patients also had a low functional PS result with a normal antigenic level. Normal results were obtained by both methods for all of the LA and patients on therapeutic heparin. We concluded that the automated protein S clotting assay was rapid and simple to perform but appeared to be influenced by factors other than PS deficiency. Results need to be interpreted with caution but may be useful as part of a full thrombophilia investigation.
authors.affiliation: Coagulation Unit, Royal Perth Hospital, University of Western Australia, Perth, Western Australia.
authors.forename: C
authors.initials: C
authors.lastname: Moraes
authors.forename: E
authors.initials: E
authors.lastname: Lofthouse
authors.forename: J
authors.initials: J
authors.lastname: Eikelboom
authors.forename: J
authors.initials: J
authors.lastname: Thom
authors.forename: R
authors.initials: R
authors.lastname: Baker
mesh_terms: D002544:Cerebral Infarction / Q000175:diagnosis; D004247:DNA / Q000302:isolation & purification; D005260:Female; D006801:Humans; D007122:Immunoelectrophoresis; D008297:Male; D017293:Protein S / Q000276:immunology*; D018455:Protein S Deficiency / Q000097:blood / Q000145:classification / Q000151:congenital / Q000175:diagnosis*; D011933:Reagent Kits, Diagnostic; D012016:Reference Values; D015203:Reproducibility of Results; D014914:Whole Blood Coagulation Time
chemical_list: D017293:Protein S; D011933:Reagent Kits, Diagnostic; D004247:DNA