George participates in CLSC5124E-Sp14; Advanced Hemostasis, a graduate course offered by Drs. Nadine Fydryszewski and Elaine Keohane of Rutgers University School of Biomedical and Health Sciences. The faculty also include Dr. Larry Smith and Prof.Donna Castellone. This course attracts experienced medical laboratory scientists from around the world who raise interesting questions, including this one about transient gestations protein S deficiency:
A surfeit of studies have linked gestational thrombophilia and fetal loss with factor V Leiden and prothrombin 20210 mutations, congenital antithrombin, protein C, and protein S deficiency, antiphospholipid syndrome, and in particular, eclampsia. We also know that for many women, the free protein S concentration drops, often to below the lower limit of the reference interval, during pregnancy. This is a transient, perhaps inflammation-related occurrence, and does not imply an inherited thrombosis risk factor. However, is the temporary free protein S deficiency an independent risk factor for thrombosis? Should the obstetrician consider anticoagulant therapy while the protein S is low? Have any of our Fritsma Factor participants seen studies linking transient gestational protein S deficiency with thrombosis or fetal loss? The inquiring minds of our graduate students want to know.
Different PS assays may have different diagnostic cut off le
Different PS assays may have different diagnostic cut off levels:
…In this study we assessed the diagnostic performance of two total PS antigen assays, four free PS assays and three PS activity assays in a group of 28 heterozygous carriers of mutations in PROS1 and 165 control subjects. Several control groups were formed, one of healthy volunteers and–because PS levels are influenced by oral contraception and pregnancy, and assays measuring PS activity may be influenced by the presence of the factor V Leiden mutation–we also investigated the influences of these factors. All nine PS assays detected significantly reduced PS levels in subjects with a PROS1 mutation. Eight out of nine PS assays showed a 100% sensitivity and 100% specificity to detect heterozygous carriers of mutations in PROS1 with values far below the lower limit of the reference values obtained from healthy volunteers. Low specificities were found in subjects with a factor V Leiden mutation and in pregnant women. At lower cut-off levels, equal to the highest PS value found in heterozygous carriers of mutations in PROS1, the specificity considerably increased in these subjects. When using low cut-off levels equal to the highest PS value found in heterozygous carriers of mutations in PROS1, ensuring 100% sensitivity, the specificity in all study groups increases considerably, by which misclassification can be maximally avoided…
Mulder R et al. Low cut-off values increase diagnostic performance of protein S assays.
Thromb Haemost. 2010;104: 618-25.
It looks like only severe deficiency of free protein S (<
It looks like only severe deficiency of free protein S (<33-41 IU/dL) associates with increased risk of venous thromboembolism (including the acute settings): Clinical relevance of decreased free protein S levels: results from a retrospective family cohort study involving 1143 relatives.
Mulder R, et al. Decreased free protein S levels and venous thrombosis in the acute setting, a case-control study. Thromb Res. 2011; 128:5012.
Protein S levels and the risk of venous thrombosis: results from the MEGA case-control study.