Marked discrepancy between coagulometric Protein C activity assays with the pro-thrombotic Protein C Asn2Ile substitution

PC Cooper, S Siddiq, C Morse, J Nightingale, A Mumford

Research output: Contribution to journalArticle (Academic Journal)peer-review

13 Citations (Scopus)

Abstract

Introduction:  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. Conclusion:  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.
Translated title of the contributionMarked discrepancy between coagulometric Protein C activity assays with the pro-thrombotic Protein C Asn2Ile substitution
Original languageEnglish
Pages (from-to)451 - 456
JournalInternational Journal of Laboratory Haematology
Volume33
Publication statusPublished - 2011

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