D-Dimer: A Mediator of the Association Between Lymphocyte and Dissemination of Pulmonary Tuberculosis: A Retrospective Cohort Study.

INTRODUCTION

This study aimed to examine whether D-dimer and lymphocyte counts predict the risk of concurrent pulmonary tuberculosis (PTB) and extrapulmonary tuberculosis (EPTB) and to identify critical thresholds for clinical use. We also investigated whether D-dimer mediates the protective effect of lymphocytes against tuberculosis (TB) dissemination.

METHODS

One thousand nine hundred (1318 PTB and 582 PTB + EPTB) patients diagnosed between 2022 and 2024 were analyzed. Multiple regression analysis, smooth curve fitting, threshold effect analysis, and causal mediation analysis were conducted using EasyStat and R software to evaluate the association between lymphocyte counts (exposure), D-dimer (mediator), and PTB + EPTB risk (outcome) and to determine the critical value of lymphocyte counts and D-dimer.

RESULTS

PTB + EPTB patients had higher D-dimer and lower lymphocyte counts. Elevated D-dimer increased the risk of PTB + EPTB (adjusted OR = 2.28, 95% CI: 1.99-2.60). High lymphocyte counts reduced the risk (adjusted OR = 0.25, 95% CI: 0.13-0.46). Threshold effects showed increased risk when D-dimer exceeded 0.170 mg/L (OR = 2.35, 95% CI: 2.05-2.70) and reduced risk when lymphocyte counts exceeded 750 cells/μL (OR = 0.15, 95% CI: 0.07-0.32). D-dimer mediated 36.473% (95% CI: 25.469-53.168) of the protective effect of lymphocytes.

CONCLUSIONS

D-dimer is an independent risk factor and lymphocyte counts a protective factor for PTB + EPTB, with D-dimer mediating 36.473% of the lymphocyte effect. Clinically actionable thresholds (D-dimer > 0.170 mg/L and lymphocytes < 750 cells/μL) provide concrete targets for early intervention to prevent TB dissemination and improve outcomes.