PB0953 - Free protein S antigen represents more reliable assay for protein S deficiency testing compared with protein S activity and should be used as the first and main test in the diagnostic protocol

Background: Heterozygous protein S (PS) deficiency is a well known risk factor for thrombophilia with plasma levels of PS of 35-60%. However, diagnostics of PS deficiency using the most common PS activity (PS:Ac) assays is difficult due to interfering preanalytical and analytical factors leading to false positive results.

Aims: To investigate whether free PS antigen (fPS:Ag) assay could be used as an initial assay to determine hereditary PS deficiency in order to improve current diagnostic protocol with PS:Ac as first test

Methods: PS:Ac (functional clot-based test) and fPS:Ag (immunological test with monoclonal antibody to unbound PS) were measured with commercial assays (Protein S Ac and Innovance Free PS Ag, Siemens Healthineers, Germany) in 133 consecutive patients referred for testing to our laboratory.

Results: Results of protein PS:Ac and fPS:Ag testing are presented in Table 1. In 88 (66.2%) patients, both fPS:Ag and PS:Ac were within reference ranges. In 12 (9%) patients both fPS:Ag and PS:Ac were decreased, among which in 11/133 (8.3%) due to pregnancy or warfarin therapy. PS deficiency was confirmed in 1 (0.8%) patient with decreased both PS:Ac and fPS:Ag at two separate occasions. FPS:Ag assay correctly classified all 133 samples as normal and abnormal. In contrast, in 31/133 (24.1%) samples, PS:Ac levels were slightly decreased and confirmed as false positive in retesting, with fPS:Ag levels within reference range.

Conclusion(s): This study confirmed that fPS:Ag should be used as first diagnostic step in hereditary protein S testing due to its much lower falsely decreased values and unclear results and less susceptibility to interferences compared to PS:Ac. In the vast majority of patients, in case of normal fPS:Ag result, no further testing is needed. Based on the results obtained in our laboratory we changed our previous practice with PS:Ac as first diagnostic step and applied fPS:Ag as initial and main diagnostic assay (Figure 1).