title: Marked discrepancy between coagulometric protein C activity assays with the pro-thrombotic protein C Asn2Ile substitution.
abstract: BACKGROUND
  Protein C (PC) Asn2Ile is a rare pro-thrombotic variant in which loss of anticoagulant function in vivo is likely to result from defective PC binding to the endothelial PC receptor and phospholipid.
  
  
  METHODS
  To characterize the consequences of this functional defect on the diagnostic performance of commercial PC activity assays, we performed one antigen, three chromogenic and three coagulometric assays on plasma from a subject who was heterozygous for the PC Asn2Ile substitution.
  
  
  RESULTS
  As anticipated, the PC antigen (96.2 IU/dl) and chromogenic PC activity assays (98.4 IU/dl) were insensitive to PC Asn2Ile, which has intact enzymatic activity and is secreted normally. There was a marked reduction in apparent PC activity by STACLOT coagulometric assay (50.4 IU/dl). However, there was only a small reduction in apparent PC activity by CRYOcheck Clot C assay (69.5 IU/dl) and by HemosIL ProClot assay, the PC activity was within the laboratory reference range (91 IU/dl). This discrepancy between coagulometric assays could not be explained by lupus anticoagulant, activated PC resistance or elevated plasma factor VIII activity.
  
  
  CONCLUSIONS
  We demonstrate that coagulometric assays are not equally sensitive to clinically important functional defects of PC and that multiple assays may be required to identify all variants.
authors.affiliation: Department of Coagulation, Sheffield Haemophilia and Thrombosis Centre, Sheffield, UK. Peter.Cooper@sth.nhs.uk
authors.forename: P C
authors.initials: PC
authors.lastname: Cooper
authors.forename: S
authors.initials: S
authors.lastname: Siddiq
authors.forename: C
authors.initials: C
authors.lastname: Morse
authors.forename: J
authors.initials: J
authors.lastname: Nightingale
authors.forename: A D
authors.initials: AD
authors.lastname: Mumford
mesh_terms: D000328:Adult; D019943:Amino Acid Substitution / Q000235:genetics; D001780:Blood Coagulation Tests; D005260:Female; D006579:Heterozygote; D006801:Humans; D011486:Protein C / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D020151:Protein C Deficiency / Q000097:blood* / Q000175:diagnosis*
chemical_list: D011486:Protein C