Elucidating the Pathogenic Role of Helicobacter pylori Infection in Hematologic Disorders: Mechanistic Insights and Future Perspectives.

Abstract

Helicobacter pylori (H. pylori), a helical, flagellated Gram-negative bacterium, exhibits remarkable adaptability within the human gastric niche, enabling survival under acidic, nutrient-limited, and oxidative stress conditions. Beyond its established role in gastritis, peptic ulcer disease, and gastric adenocarcinoma, accumulating evidence implicates H. pylori in a spectrum of hematologic disorders. Iron deficiency anemia (IDA), vitamin B12 deficiency, immune thrombocytopenic purpura (ITP), and gastric mucosa-associated lymphoid tissue (MALT) lymphoma represent the most substantiated associations. Pathogenesis is multifactorial, encompassing chronic inflammation, cytokine dysregulation, molecular mimicry, impaired micronutrient absorption, and virulence factor-mediated disruption of host cellular processes, notably through CagA, VacA, SabA, and BabA components. In IDA and vitamin B12 deficiency, H. pylori-induced hypochlorhydria, altered gastric ascorbate levels, and hepcidin upregulation compromise systemic iron and cobalamin homeostasis. In contrast, in ITP, cross-reactivity between bacterial antigens and platelet epitopes triggers the production of autoantibodies and accelerates platelet clearance. Chronic antigenic stimulation and epigenetic modifications underpin lymphomagenesis in gastric MALT lymphoma, with treatment response modulated by strain-specific virulence, host genetics, and somatic translocations affecting NF-κB signaling. Clinical evidence demonstrates that targeted eradication therapy, often in combination with micronutrient supplementation, significantly restores hematologic parameters and mitigates systemic sequelae, yet patient-specific variability necessitates individualized management strategies. This review integrates current mechanistic and clinical insights into H. pylori-associated hematologic manifestations, highlighting the bacterium's systemic impact, elucidating therapeutic implications, and identifying critical gaps for future research aimed at optimizing diagnostic precision, intervention efficacy, and prognostic outcomes in affected populations.