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Prepublished online as a Blood First Edition Paper on May 1, 2003; DOI 10.1182/blood-2003-02-0620.
Submitted February 26, 2003
Accepted December 31, 1969
The APC-independent anticoagulant activity of protein S in plasma is decreased by elevated prothrombin levels due to the prothrombin G20210A mutation
Rory R Koenen, Guido Tans, Rene van Oerle, Karly Hamulyak, Jan Rosing, and Tilman M Hackeng*
Biochemistry, Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, The Netherlands
* Corresponding author; email: t.hackeng{at}bioch.unimaas.nl.
Protein S exhibits anticoagulant activity independent of activated protein C (APC). An automated factor Xa-based one-stage clotting assay was developed which enables quantification of the APC-independent activity of protein S in plasma from the ratio of clotting times (protein S Ratio: pSR) determined in the absence and presence of neutralizing antibodies against protein S. The pSR was 1.62 ± 0.16 (mean ± SD) in a normal population (n=60), independent of the plasma levels of factors V, VIII, IX, X, protein C, antithrombin, and not affected by the presence of factor VLeiden. The pSR strongly correlates with the plasma level of protein S and is modulated by the plasma prothrombin concentration. In a group of 16 heterozygous protein S-deficient patients, the observed mean pSR (1.31 ± 0.09) was significantly lower than the mean pSR of the normal population (1.62 ± 0.16). The pSR of plasma from carriers of the prothrombin G20210A mutation (n = 46) was significantly lower (1.47 ± 0.21) than the pSR of the 60 controls (1.62 ± 0.16). We propose that the decreased APC-independent anticoagulant activity of protein S in plasma with elevated prothrombin levels may contribute to the thrombotic risk associated with the prothrombin G20210A mutation.
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