NOVEL THROMBOTIC BIOMARKERS IN HEMODIALYSIS: FLUCTUATION PATTERNS AND CLINICAL UTILITY

The four thrombotic biomarkers [thrombin-antithrombin complex (TAT), tissue plasminogen activator-plasminogen activator inhibitor-1 complex (t-PAIC), plasmin-α2 plasmin inhibitor complex (PIC), and thrombomodulin (TM)] are novel coagulation markers that have demonstrated significant prognostic value in various diseases. This study aimed to investigate their fluctuation patterns during hemodialysis (HD) and their predictive value for short-term prognosis.

Maintenance HD patients from Peking University People's Hospital in March 2025, who received heparin/low molecular weight heparin (LMWH) anticoagulation and had an autogenous arteriovenous fistula as vascular access, were enrolled. Baseline data collection included: ① The four thrombotic biomarkers: Blood samples were drawn from the arterial side of the vascular access at four time points: pre-dialysis (i.e., 68 hours after the previous HD session), 5 minutes into dialysis, post-dialysis, and pre-next dialysis (i.e., 44 hours after the current HD session). These samples were analyzed for coagulation parameters, antithrombin, anti-Factor Xa activity, and the four thrombotic biomarkers. ② Demographic data, medical history, dialysis-related parameters, and laboratory results. Patients were followed for 180 days, with the composite endpoint being all-cause mortality, acute coronary syndrome, ischemic stroke, arteriovenous fistula thrombosis, and pulmonary embolism. Paired sample t-tests/non-parametric tests were used for intra-individual comparisons of coagulation parameters. The impact of heparin versus LMWH on the fluctuations of the four biomarkers was analyzed. Logistic regression analysis was employed to determine the predictive value of these biomarkers for the short-term prognosis of HD patients.

A total of 133 HD patients were enrolled, including 73 receiving heparin and 60 receiving LMWH anticoagulation. There were 89 males (67%), with a median age of 61 (IQR: 45.5, 70) years and a median dialysis vintage of 84 (IQR: 30, 154) months. (1) Among the four biomarkers, TM levels were significantly elevated above the normal range in HD patients. Nearly half of the patients had PIC levels above normal, while TAT and t-PAIC were generally within normal limits (Table 1). (2) The four biomarkers exhibited significant fluctuations during HD: Compared to pre-dialysis levels, TM, TAT, PIC, and t-PAIC increased significantly post-dialysis and decreased by the next pre-dialysis measurement. At 44 hours post-dialysis compared to 68 hours post-dialysis (i.e., pre-next vs. pre-current dialysis), TAT and t-PAIC levels still showed statistically significant differences, whereas the differences for TM and PIC were not significant, suggesting varying thrombotic risks associated with different interdialytic intervals (Table 2). (3) Compared to heparin, LMWH anticoagulation significantly attenuated the intradialytic fluctuations of TAT, PIC, and t-PAIC. No statistically significant difference was observed in TM fluctuations between the two anticoagulant groups (Table 1). (4) During the 180-day follow-up, 11 patients (8.3%) reached the composite endpoint. Univariate analysis identified age, post-dialysis PIC, reticulocyte percentage, neutrophil percentage, and post-dialysis mean diastolic blood pressure as statistically significant factors. Subsequent multivariate logistic regression analysis revealed that post-dialysis PIC (OR 12.179, 95% CI 1.521–97.347, p=0.018) and reticulocyte percentage (OR 10.012, 95% CI 1.638–61.206, p=0.013) were independent predictors of short-term prognosis in HD patients (Table 3).

The four thrombotic biomarkers exhibit substantial fluctuations during hemodialysis. LMWH anticoagulation, compared to unfractionated heparin, significantly mitigates these fluctuations for TAT, PIC, and t-PAIC. Post-dialysis PIC level and reticulocyte percentage are strong predictors of short-term prognosis in hemodialysis patients.