C. Boyerneumann et al., COMPARISON OF FUNCTIONAL ASSAYS FOR PROTEIN-S - EUROPEAN COLLABORATIVE STUDY OF PATIENTS WITH CONGENITAL AND ACQUIRED DEFICIENCY, Thrombosis and haemostasis, 70(6), 1993, pp. 946-950
Four functional assays for protein S were evaluated by 4 different lab
oratories, each center using its own method. The aim of this study was
to compare these different assays and to establish a relationship wit
h 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 diff
erence 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 congenita
l deficiency of protein S the mean values of protein S activity were d
ecreased with the 4 assays, ranging from 25 to 40%. Free protein S ant
igen 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 tot
al protein S antigen was normal an important overlap of protein S acti
vity between normals and patients was observed in one lab with 12 pati
ents 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 C
4bBP and total protein S antigen. In patients with oral anticoagulants
, protein S activity was low with all assays. Only with one assay, pro
tein S activity was significantly lower than free antigen, suggesting
that this assay is sensitive to the hypo-carboxylated protein. Variabl
e values of protein S activity were observed in patients with liver ci
rrhosis, with relatively little agreement between methods. As discorda
nt results were obtained in some patients with dysfunctional protein S
deficiency and acquired disorders, these methods do not necessarily m
easure the same cofactor of activated protein C. However this study in
dicates that all 4 functional protein S assays give similar results in
normals, and almost all patients with a quantitative congenital defic
iency.