Characteristics of Protein S in Koreans by Age and Gender: a Retrospective Analysis based on Results from Korean Referral Laboratories

BACKGROUND: Protein S, a vitamin K-dependent protein, is crucial in inhibiting blood clotting, and its deficiency increases the risk of thrombotic disease. However, most studies have focused on Western populations. Although Koreans have a lower incidence of thrombotic diseases, the risk is rising due to aging and Westernized lifestyle habits. Therefore, protein S levels should be investigated in Koreans for developing strategies to prevent and manage thrombotic diseases. This study aimed to analyze protein S-related data according to age and gender in Korean adults. METHODS: This retrospective study examined protein S activity and free protein S levels from January 2017 through December 2023 in Korean adults, using data from commissioned inspection institutions in Korea. Protein S activity was measured using a coagulation-based assay, while free protein S levels were determined via immunoturbidimetric analysis. Data were categorized by year, gender, age group, and type of protein S deficiency, and trends in test values and frequency were analyzed. RESULTS: A total of 2,470 individuals (907 men and 1,563 women) were included. Protein S activity increased with age until 50 - 59 years, then declined, whereas free protein S levels peaked at 70 - 79 years before slightly decreasing. The number of protein S tests increased steadily over the years, with consistently more tests performed in women than in men throughout. Women showed significantly lower levels of both protein S activity and free protein S than men (p < 0.001), and a strong significant positive correlation was observed between the two protein S activity and free protein S tests (R = 0.543, p < 0.001). Deficiency patterns were classified into three groups based on test results. Among these, the most prevalent group (39.3%) had decreased protein S activity with normal free protein S, particularly among women and individuals aged 20 - 39 years. CONCLUSIONS: This study provides critical reference data on protein S levels in Koreans, highlighting significant age- and gender-related differences. These findings contribute to refining thrombotic risk assessment in Korean populations and complement existing Western-based studies. Further research incorporating clinical histories is warranted to enhance the clinical applicability of protein S testing.