Impact of helicobacter pylori infection on clinical outcomes in patients with immune thrombocytopenia: A propensity-matched analysis from a national cohort

Abstract Backgorund Over the past two decades, numerous international studies have explored a potential link between Helicobacter pylori (H. pylori) infection and Immune thrombocytopenia (ITP), with some reports suggesting that eradication therapy can result in partial or complete platelet count recovery in a subset of patients. However, the response to H. pylori eradication has been shown to vary significantly by geography and ethnicity, with the strongest associations observed in East Asian and Southern European populations. In contrast, U.S.-based data on the impact of H. pylori on ITP outcomes remain limited and inconclusive. Furthermore, while the potential for platelet count improvement following eradication has been examined, few studies have evaluated whether H. pylori status influences clinically meaningful outcomes such as bleeding risk, hospitalization, or overall survival. Methods: We conducted a retrospective, multicenter cohort study using the TriNetX US Collaborative Network, a federated health research platform encompassing electronic medical records from 68 healthcare organizations across the United States. Adults (≥18 years) with a diagnosis of ITP were identified and stratified into two cohorts: those with a concurrent diagnosis of H. pylori infection (Cohort 1, n=1,367) and those without (Cohort 2, n=101,632 prior to matching; n=1,367 after matching). Propensity score matching (1:1) was performed to control for potential confounding variables, including age, sex, race/ethnicity, and comorbidities such as autoimmune diseases, liver disease, diabetes, and HIV. The index event was the earliest recorded diagnosis meeting inclusion criteria, and outcomes were tracked over a 5-year follow-up period. Outcomes of interest included all-cause mortality, hospitalization, non-traumatic intracranial hemorrhage (ICH), gastrointestinal (GI) bleeding, and platelet nadir <10 x 10³/μL. Time-to-event analyses were performed using Kaplan-Meier curves, and hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated. Results: After propensity score matching, the study included 1,367 patients in each cohort, with baseline characteristics well-balanced between groups. Over a 5-year follow-up period, all-cause mortality was comparable in H. pylori-positive and H. pylori-negative ITP patients, with survival probabilities of 77.7% and 76.5%, respectively (HR 0.92; 95% CI 0.76–1.11; p=0.46), indicating no significant difference in overall survival. Similarly, hospitalization rates did not differ significantly between groups (HR 0.96; 95% CI 0.86–1.07; p=0.48). Intracranial hemorrhage, a rare but severe complication, occurred less frequently in the H. pylori-positive group (1.3% vs. 1.8%), though the difference did not reach statistical significance (HR 0.68; 95% CI 0.37–1.25; p=0.21). Notably, gastrointestinal bleeding was significantly more common in patients with H. pylori infection (13.0% vs. 7.0%; HR 1.81; 95% CI 1.41–2.32; p<0.001), suggesting an increased bleeding risk specific to the gastrointestinal tract. In addition, severe thrombocytopenia—defined as a platelet nadir <10 × 10³/μL—was more frequently observed in the H. pylori-positive group (18.1% vs. 14.7%; HR 1.21; 95% CI 1.00–1.46; p=0.045), pointing to a potential association between H. pylori infection and more profound platelet suppression in ITP. Conclusion: In this large, national, propensity-matched cohort analysis, H. pylori infection in patients with immune thrombocytopenia was not associated with improved survival, decreased hospitalizations, or reduced incidence of major hemorrhagic events such as intracranial bleeding. On the contrary, H. pylori–positive ITP patients had significantly higher rates of gastrointestinal bleeding and were more likely to experience critically low platelet counts. These findings challenge earlier assumptions that H. pylori may confer a favorable or benign clinical course in ITP and underscore the importance of careful monitoring for bleeding complications and thrombocytopenia severity in this subgroup. Future studies should explore the mechanisms underlying this association and evaluate whether targeted H. pylori eradication therapy modifies risk in affected individuals.