Application of thrombosis-related biomarkers in the diagnosis and thrombosis risk stratification of heparin-induced thrombocytopenia patients

OBJECTIVE To evaluate thrombomodulin (TM), thrombin-antithrombin complex (TAT), plasmin-α2-plasmin inhibitor complex (PIC), tissue-plasminogen activator-inhibitor complex (t-PAIC), and D-dimer for diagnosing heparin-induced thrombocytopenia (HIT) and stratifying thrombosis risk. METHODS A total of 221 patients with suspected HIT were classified as HIT-positive (HIT+) or HIT-negative (HIT-), with HIT+ further stratified by thrombosis (HITT+/HITT - ). We collected clinical variables and identified HIT risk factors using multivariable logistic regression. Group differences in TM, TAT, PIC, t-PAIC, and D-dimer were assessed, diagnostic performance was examined using receiver operating characteristic (ROC) curves, and correlations were tested with Spearman's rank correlation. Kaplan-Meier analysis estimated the 15-day cumulative incidence of thrombosis in HIT patients stratified by TAT. RESULTS Elevated 4 T scores and HIT antibody levels were independent risk factors for HIT. TM, TAT, and D-dimer levels were higher in HIT+ versus HIT-. Only TAT was elevated in HITT+ versus HITT-, correlating positively with HIT antibodies. For diagnosing HIT, the areas under the curve (AUCs) for TM, TAT, and D-dimer were 0.712, 0.735, and 0.721, respectively. The combination of these three markers yielded the highest efficacy (AUC = 0.807). TAT showed predictive value for thrombosis among HIT patients; a threshold of 12.11 µg/L yielded the best performance. Kaplan-Meier analysis demonstrated a significantly higher 15-day thrombosis risk for patients with TAT ≥ 12.11 µg/L vs. < 12.11 µg/L. CONCLUSION TM, TAT, and D-dimer can serve as auxiliary biomarkers for HIT diagnosis, with combined use improving accuracy. Notably, TAT may be useful in guiding risk-stratified anticoagulation therapy based on thrombotic risk.