OBJECTIVE  To investigate the association between changes in clearance rate of serum heparin-binding protein （HBP） and the 28-day in-hospital mortality risk in patients with septic.

METHODS  A total of 206 septic patients admitted to Shenzhou Hospital in Hebei Province from May 2022 to May 2025 were enrolled. A latent class growth model （LCGM） was established based on serum HBP changes within 1–7 days of admission, categorizing patients into three trajectory groups: low-level decline （n=58）, medium-level decline （n=56） and high-level stability （n=92）. Clinical data and laboratory indicators were compared among the groups. Multivariate logistic regression analysis was employed to identify influencing factors of trajectory categories. Kaplan-Meier survival curves were plotted to compare cumulative survival rates among the groups. Cox regression was employed to assess the relationship between trajectories and 28-day mortality risk. Receiver operating characteristic （ROC） curve analysis was adopted evaluated the predictive efficacy of trajectories for mortality, followed by subgroup analysis.

RESULTS  The low-level decline group exhibited a high proportion of septic shock, as well as high levels of white blood cell count （WBC）, procalcitonin （PCT）, C-reactive protein （CRP）, prothrombin time （PT）, activated partial thromboplastin time （APTT） and D-dimer （D-D） compared to the other two groups, while the high-level stability group showed high platelet （PLT） and fibrinogen （FIB） levels compared to the other two groups （P＜0.05）. PLT, PCT, CRP and D-D were identified as influencing factors for HBP clearance rate trajectory categories （P＜0.05）. The high-level stability group demonstrated a higher 28-day survival rate than the low- and medium-level decline groups （P＜0.05）. After adjusting for confounders, the medium- and low-level decline groups had 2.866-fold and 5.541-fold increased in mortality risks, respectively （P＜0.05）. ROC analysis revealed an area under the curve （AUC） of 0.836 （95%CI: 0.764–0.887） for predicting 28-day in-hospital mortality when HBP clearance followed a low-level decline trajectory. Subgroup analysis confirmed associations between HBP clearance rate and mortality risk across all subgroups （P_trend＜0.05）.

CONCLUSIONS  A low-level decline trajectory in serum HBP clearance rate is a risk factor for 28-day mortality in septic patients, demonstrating strong predictive value for mortality risk. Dynamic monitoring of HBP clearance provides critical insights for early identification of high-risk patients and risk stratification.