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Thromb Haemost 1993; 70(06): 0946-0950
DOI: 10.1055/s-0038-1649705
Original Article
Coagulation
Schattauer GmbH Stuttgart

Comparison of Functional Assays for Protein S: European Collaborative Study of Patients with Congenital and Acquired Deficiency

C Boyer-Neumann
1   The Laboratoire d'Hématologie and INSERM U. 143, Hôpital Bicêtre, Le Kremlin-Bicêtre, France
,
R M Bertina
2   Haemostasis and Thrombosis Research Unit, Dept of Haematology, Leiden University Hospital, Leiden, The Netherlands
,
A Tripodi
3   The A. Bianchi Bonomi Hemophilia and Thrombosis Center and the Institute of Internal Medicine, IRCCS Ospedale Maggiore and University of Milan, Milan, Italy
,
A D'Angelo
4   The Servizio di coagulazione, IRCCS H S Raffaele, Milan, Italy
,
M Wolf
1   The Laboratoire d'Hématologie and INSERM U. 143, Hôpital Bicêtre, Le Kremlin-Bicêtre, France
,
S Vigano D'Angelo
4   The Servizio di coagulazione, IRCCS H S Raffaele, Milan, Italy
,
P M Mannucci
3   The A. Bianchi Bonomi Hemophilia and Thrombosis Center and the Institute of Internal Medicine, IRCCS Ospedale Maggiore and University of Milan, Milan, Italy
,
D Meyer
1   The Laboratoire d'Hématologie and INSERM U. 143, Hôpital Bicêtre, Le Kremlin-Bicêtre, France
,
M J Larrieu
1   The Laboratoire d'Hématologie and INSERM U. 143, Hôpital Bicêtre, Le Kremlin-Bicêtre, France
› Author Affiliations
Further Information

Publication History

Received 09 February 1993

Accepted after revision 04 August 1993

Publication Date:
06 July 2018 (online)

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Summary

Four functional assays for protein S were evaluated by 4 different laboratories, each center using its own method. The aim of this study was to compare these different assays and to establish a relationship with results of immunological assays of total and free protein S antigen and C4bBP. The same plasma samples were distributed to each center and tested in blind. In 47 normal subjects, there was no significant difference between the 4 functional assays, with mean values ranging from 93 to 100%. These values were in good agreement with those of free and total protein S antigen. In 34 patients with a quantitative congenital deficiency of protein S the mean values of protein S activity were decreased with the 4 assays, ranging from 25 to 40%. Free protein S antigen was reduced to a similar extent, whereas total antigen was either normal or decreased. The correlation of protein S activity with free protein S antigen was satisfactory for 3 methods, with coefficients of correlation varying from 0.84 to 0.92 whereas it was only 0.70 in one lab. When total protein S antigen was reduced, protein S activity was decreased in all the patients with the 4 assays. In contrast when total protein S antigen was normal an important overlap of protein S activity between normals and patients was observed in one lab with 12 patients misclassified. In 8 patients with a functional defect, results of protein S activity differed substantially according to the assay used and about half of these patients were misclassified. In patients with inflammatory disease, protein S activity was normal with the 4 assays, in good correlation with free antigen, despite high levels of both C4bBP and total protein S antigen. In patients with oral anticoagulants, protein S activity was low with all assays. Only with one assay, protein S activity was significantly lower than free antigen, suggesting that this assay is sensitive to the hypo-carboxylated protein. Variable values of protein S activity were observed in patients with liver cirrhosis, with relatively little agreement between methods. As discordant results were obtained in some patients with dysfunctional protein S deficiency and acquired disorders, these methods do not necessarily measure the same cofactor of activated protein C. However this study indicates that all 4 functional protein S assays give similar results in normals, and almost all patients with a quantitative congenital deficiency.

 

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