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Marked discrepancy between coagulometric protein C activity assays with the pro-thrombotic protein C Asn2Ile
P C Cooper1, S Siddiq, C Morse
1Department of Coagulation, Sheffield Haemophilia and Thrombosis Centre, Sheffield, UK. Peter.Cooper@sth.nhs.uk
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.
