Clinical relevance of low free protein S levels
PhD ceremony: Mr. R. Mulder, 11.00 uur, Academiegebouw, Broerstraat 5, Groningen
Dissertaion: Clinical relevance of low free protein S levels
Promotor(s): prof. J.C. Kluin-Nelemans
Faculty: Medical Sciences
Protein S is a vitamin K-dependent glycoprotein that functions as a cofactor for both activated protein C and Tissue Factor Pathway Inhibitor (TFPI) in the down regulation of coagulation. Hereditary protein S deficiency is a relatively rare coagulation disorder with an estimated prevalence of 0.03 to 0.13% in the general population. Whereas hereditary protein S deficiency predisposes for deep vein thrombosis in the legs or pulmonary embolism, conflicting data have been reported on the risk of thrombosis associated with low free protein S levels. Protein S levels are influenced by age, gender, and several acquired conditions. Moreover, protein S assays have a low specificity due to interferences with many factors, including elevated factor VIII levels and factor V Leiden. This results in the measurement of falsely low protein S levels. This thesis describes that low free protein S levels, far below the normal range measured in healthy volunteers, i.e., below the 5th percentile, can identify subjects who are at risk of a first venous thrombosis and its recurrence. Moreover, our results suggest that low free protein S levels also seem to be a mild risk factor for arterial thrombosis. Using low cut-off levels equal to the highest protein S level found in heterozygous carriers of mutations in PROS1 gene, ensures 100% sensitivity, the specificity of protein S assays increases considerably, and misclassification can be avoided. Finally, our results suggest that high free TFPI levels might counteract the prothrombotic effects of low free protein S levels and contribute to a less-thrombotic phenotype in subjects with a protein S Heerlen variant.
Last modified: | 13 March 2020 01.01 a.m. |
More news
-
24 May 2024
Lustrum 410 in pictures
Lustrum 410 in pictures: We are already over half way through our lustrum! Enjoy a few photos of the lustrum so far.
-
21 May 2024
Results of 2024 University elections
The votes have been counted and the results of the University elections are in!
-
15 May 2024
Part of the children with ADHD can stop using Ritalin sooner
A part of children with ADHD could stop taking Ritalin after two years. This is the conclusion of Anne-Flore Matthijssen's PhD research.