Background:

Tuberculosis (TB) induces a significant systemic hypercoagulable state driven by chronic inflammation, endothelial dysfunction, immobility, and frequent comorbidities (e.g., HIV, malnutrition). This pathophysiology substantially elevates the theoretical risk of venous thromboembolism (VTE) in hospitalized patients. Despite established links between TB and coagulation abnormalities, robust epidemiological data quantifying the incidence, predictors, and clinical consequences of VTE within the large-scale inpatient TB population remain notably scarce. This gap impedes effective risk stratification and prophylactic strategy development. While relatively low-incidence in the United States (~8,000 cases/year), this study leverages a national database to characterize the real-world burden, identify independent predictors, and determine the impact of VTE on critical outcomes (mortality, resource utilization) among hospitalized TB patients in the US. Its findings may have implications for similar settings.

Methods

A retrospective cohort study was conducted using the Healthcare Cost and Utilization Project-Inpatient database (HCUP-NIS) from 2018 to 2020. This database represents >95% of US hospitalizations. Adult patients (≥18 years) with a primary or secondary TB diagnosis (ICD-10 codes A15.x-A19.x) were included. Elective admissions were excluded to capture acute VTE events. The cohort was stratified into TB patients with VTE (TB+VTE) and without VTE (TB Only). Outcomes studied were incidence of VTE, in-hospital mortality, length of stay (LOS), and inflation-adjusted hospitalization costs. Weighted multivariable logistic regression was used to identify predictors of VTE and mortality. Negative binomial and gamma regressions were used for LOS and costs, respectively. Analyses adjusted for demographics, insurance, comorbidities (including HIV/AIDS), TB severity (miliary TB, respiratory failure, sepsis), and year.

Results

Among a 33,630 weighted hospitalizations for TB, 815 patients (2.4%) had a concurrent diagnosis of VTE. Mean age of participants was 54.32 (SD 20.07, p<0.001 among VTE vs Non-VTE group). Females were 12,875 (38.3%, p<0.001, chi-square among VTE vs Non-VTE group).

  • Predictors of VTE in TB: Multivariable logistic regression identified the following independent predictors significantly associated with increased odds of developing VTE during TB hospitalization: Black Race: (aOR = 3.058, p=0.006), Older Age: (aOR = 1.019 per year increase, p<0.001), Miliary TB: (aOR = 2.02, p=0.004), Sepsis: (aOR = 2.01, p=0.001).

  • Impact of VTE on Mortality in TB: After adjusting for covariates, the presence of VTE was independently associated with significantly higher odds of in-hospital mortality (aOR = 2.24, 95% CI: [Implied by p-value], p=0.002).

  • Other Predictors of In-Hospital Mortality: Significant independent predictors of in-hospital mortality among the cohort included: Respiratory Failure: (aOR = 8.0, p<0.001), Sepsis: (aOR = 6.13, p<0.001), HIV Infection: (aOR = 1.88, p<0.001), Older Age: (aOR = 1.030 per year increase, p<0.001).

Conclusion:

This study highlights that VTE complicates a significant proportion (2.4%) of TB hospitalizations and is an independent predictor of doubled in-hospital mortality. These findings underscore the clinical and prognostic burden imposed by VTE in hospitalized TB patients. Prophylactic strategies should be considered, especially for high-risk subgroups defined by older age, miliary disease, sepsis, and race. Future research may be focused on validating risk models and evaluating the efficacy and safety of targeted thromboprophylaxis in TB patients.

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