Summary
To study the physiological importance of the activated protein C (APC)-independent
anticoagulant activity of protein S, we developed an assay specific for this activity.
The ability of protein S to prolong the clotting time in an APC-independent way was
expressed as the ratio of the clotting time in a plasma sample divided by the clotting
time in the presence of a polyclonal antibody against human protein S (both after
1:1 dilution in protein S-C4BP deficient plasma). The mean protein S-dependent anticoagulant
ratio (PSdAR) was 1.53 ± 0.18 in 34 healthy controls, and was significantly lower
in 16 heterozygous protein S deficient patients (PSdAR = 1.15 ± 0.09). In plasmas
from patients under oral anticoagulant therapy the mean PSdAR was within the range
of the control population (1.50 ± 0.18). The mean total protein S antigen level in
these plasmas was 58%, suggesting a higher specific APC-independent anticoagulant
activity of protein S in these patients than in normals.
This functional protein S assay can be used for the laboratory diagnosis of protein
S deficiency, and to study the mechanism of the APC-independent anticoagulant activity
in plasma.