The APC-independent anticoagulant activity of protein S in plasma is decreased by elevated prothrombin levels due to the prothrombin G20210A mutation.
Protein S exhibits anticoagulant activity independent of activated protein C (APC). An automated factor Xa-based one-stage clotting assay was developed that 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 healthy population (n = 60), independent of plasma levels of factors V, VIII, IX, and X; protein C; and antithrombin, and not affected by the presence of factor V Leiden. 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 healthy population, as was the pSR of plasma from carriers of the prothrombin G20210A mutation (1.47 +/- 0.21; n = 46). 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.
Department of Biochemistry, Cardiovascular Research Institute Maastricht, University Maastricht, 6200 MD Maastricht, The Netherlands.
Rory R
RR
Koenen
Guido
G
Tans
René
R
van Oerle
Karly
K
Hamulyák
Jan
J
Rosing
Tilman M
TM
Hackeng
D000906:Antibodies; D000925:Anticoagulants / Q000494:pharmacology; D001777:Blood Coagulation / Q000187:drug effects / Q000502:physiology; D001780:Blood Coagulation Tests; D015951:Factor Xa / Q000378:metabolism / Q000494:pharmacology; D005260:Female; D006493:Heparin / Q000494:pharmacology; D006579:Heterozygote; D006801:Humans; D008297:Male; D010743:Phospholipids / Q000494:pharmacology; D017354:Point Mutation; D011486:Protein C / Q000378:metabolism; D017293:Protein S / Q000235:genetics* / Q000276:immunology / Q000378:metabolism*; D011516:Prothrombin / Q000235:genetics* / Q000378:metabolism*
D000906:Antibodies; D000925:Anticoagulants; D010743:Phospholipids; D011486:Protein C; D017293:Protein S; D011516:Prothrombin; D006493:Heparin; D015951:Factor Xa