Helicobacter pylori: An Underrated Cause of Immune Thrombocytopenic Purpura. A Comprehensive Review

Abstract

Idiopathic thrombocytopenic purpura (ITP) is the autoimmune-mediated destruction of platelets. ITP is a diagnosis of exclusion after other identifiable etiologies have been ruled out. After the first report by Gasbarrini et al. (1998) showing rising platelet counts in ITP patients following Helicobacter pylori (HP) eradication therapy, there is growing evidence that highlights the role of HP in triggering ITP. However, the exact pathophysiology of HP-associated ITP is still unclear, but many theories have been implicated in this regard. According to various reports, the postulated mechanisms for the role of HP in cITP include molecular mimicry, increased plasmacytoid dendritic cell numbers, phagocytic perturbation, and variable host immune response to HP virulence factors. One famous theory suggested molecular mimicry between platelet surface antigen and bacterial virulence factor, i.e. cytotoxin-associated gene A (CagA). It is thought that a chronic inflammatory response following an HP infection induces the host autoantibodies' response against CagA, which cross-reacts with platelet surface glycoproteins; therefore, it may accelerate platelet destruction in the host reticuloendothelial system. However, further studies are mandated to better understand the causal link between ITP and HP and study the role of biogeography. Nowadays, it is recommended that every patient with ITP should undergo HP diagnostic testing and triple therapy should be administered in all those candidates who test positive for HP infection. In our review, there were a few pregnant female ITP patients who took HP eradication therapy mainly after 20 weeks of gestation without maternal or fetal worst outcomes. However, large-scale studies are advisable to study the adverse fetal outcomes following triple therapy use.

Effect of Helicobacter Pylori eradication on patients with ITP: a meta-analysis of studies conducted in the Middle East

“…Another aspect of this association is mediated by the vacuolating cytotoxin A gene (VacA), which is another important virulence factor of H. pylori. VacA perturbs IL-2 signaling, inhibits proliferation of helper T cells, and mediates adherence to platelets [33]. In addition, H. pylori can use the von Willebrand factor (VWF) to increase adherence to platelets [37], resulting in the activation and consumption of platelets, which is another This study has several limitations, including the following: i) The number of studies and patients involved was small; ii) the included studies only examined chronic ITP in adults, and therefore, the results cannot be generalized to patients with acute ITP, especially children; iii) the studies showed heterogeneity in the method used for H. pylori infection; iv) the thresholds for complete response (CR) and partial response (PR) varied among the included studies; and v) some data were missing (such as the duration of ITP).…”

“…Using different mechanisms, it is believed that H. pylori escapes from innate immune mediators and attaches to gastric epithelial cells. After attachment, one of the important virulence factors of H. pylori , cytotoxin-associated gene A (CagA), induces inflammation through NF-κB signaling and interleukin (IL)-8 stimulation [ 33 , 34 ]. In addition, CagA activates SHP-2 phosphatase and ERK (a mediator of the MPK signaling pathway), which results in the perturbation of gastric epithelial cell signaling [ 33 ].…”

“…After attachment, one of the important virulence factors of H. pylori , cytotoxin-associated gene A (CagA), induces inflammation through NF-κB signaling and interleukin (IL)-8 stimulation [ 33 , 34 ]. In addition, CagA activates SHP-2 phosphatase and ERK (a mediator of the MPK signaling pathway), which results in the perturbation of gastric epithelial cell signaling [ 33 ]. CagA is an immunogenic protein that stimulates the production of antibodies.…”

“…Another aspect of this association is mediated by the vacuolating cytotoxin A gene (VacA), which is another important virulence factor of H. pylori . VacA perturbs IL-2 signaling, inhibits proliferation of helper T cells, and mediates adherence to platelets [ 33 ]. In addition, H. pylori can use the von Willebrand factor (VWF) to increase adherence to platelets [ 37 ], resulting in the activation and consumption of platelets, which is another possible cause of thrombocytopenia in H. pylori - induced ITP.…”

Impact of eradication therapy of Helicobacter pylori in children with chronic immune thrombocytopenic purpura

“…Although the pathogenesis of H. pylori-associated ITP is still not confirmed, several studies have mentioned that cytotoxin-associated gene A (cagA), a virulence factor of H. pylori, elicits the production of anti-cagA antibodies that cross react with platelet surface antigens resulting in thrombocytopenia. However, there is a debate about whether the eradication of H. pylori in chronic ITP results in an improvement in platelet count or not [6][7][8]. This study was performed to investigate the impact of treatment of H. pylori infection on platelet count response in chronic ITP children.…”