Establishment of Reference Intervals for Thrombus Biomarkers in a Single-Center Chinese Population Using Indirect Methods.

BACKGROUND: Thrombin-antithrombin complex (TAT), plasmin-α2-antiplasmin complex (PIC), thrombomodulin (TM), and tissue plasminogen activator-inhibitor complex (t-PAIC) are key biomarkers reflecting coagulation/fibrinolysis activation and endothelial injury. Population-specific reference intervals (RIs) are essential for accurate diagnosis, but Chinese-specific RIs remain limited. This study aimed to establish reliable RIs for these four markers in a Chinese population using indirect methods applied to clinical big data. METHODS: Anonymized clinical data for TAT, PIC, TM, and t-PAIC from 2020 to 2024 at Beijing Anzhen Hospital, Capital Medical University, were collected. After data reduction, deduplication, and outlier removal, RIs were calculated for the overall population and stratified by sex and age using indirect methods (Hoffmann and Bhattacharya). Reliability was verified by comparing the derived RIs with manufacturer-provided ranges using reference change value (RCV) criteria. RESULTS: Overall RIs determined by the Hoffmann method for TAT, PIC, TM, and t-PAIC were 0.64-3.57 ng/mL, 0.25-1.08 μg/mL, 5.64-13.42 TU/mL, and 3.22-15.88 ng/mL, respectively. Those determined by the Bhattacharya method were 0.58-2.84 ng/mL, 0.25-1.11 μg/mL, 5.60-14.53 TU/mL, and 3.46-15.44 ng/mL, respectively. TAT and PIC levels were higher in females, whereas TM and t-PAIC were higher in males. All four markers increased with age. Relative differences between method-derived RIs and manufacturer ranges were within RCV limits. CONCLUSION: Both Hoffmann and Bhattacharya's indirect methods are reliable for establishing RIs for TAT, PIC, TM, and t-PAIC. The study provides population-specific RIs for a Chinese cohort, supporting accurate early detection and risk assessment of thrombotic diseases.