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.
Koenen
Rory R
RR
Department of Biochemistry, Cardiovascular Research Institute Maastricht, University Maastricht, 6200 MD Maastricht, The Netherlands.
Tans
Guido
G
van Oerle
René
R
Hamulyák
Karly
K
Rosing
Jan
J
Hackeng
Tilman M
TM
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