escherichia coli bacteria at petri plate. Inoculating loop for spreading bacteria.

We begin our article with a story—an incredulous one that began a scientist’s journey towards the Nobel Prize in Medicine. For years, (arguably centuries), people believed that gastritis and peptic ulcer disease were caused by a mixture of internal and external factors. The external factors were thought to be fiery, fried food, deemed unsuited to the delicate environment of the stomach; the internal factors were thought to be stress or life events that evoke worry. 

At the time Barry Marshall and Robin Warren were studying a curious bacteria called H. pylori in the stomach, no one had seriously entertained the possibility that gastritis and peptic ulcer disease could be driven by a biological entity. It simply went against the grain of human wisdom accumulated thus far. 

Not one to be deterred, Barry Marshall made an extraordinary personal sacrifice by downing a specimen containing H. pylori to test the hypothesis that it causes gastric disease. As expected, he soon developed gastritis and peptic ulcer disease. This took the medical world by storm and caused a profound paradigm shift in how we understand gastric disease. Today, H. pylori is routinely tested for in patients who have persistent gastric disease despite over-the-counter medication. 

This discovery, along with the way the discovery was made, has become a much-discussed anecdote. It has been compared to how Marie Curie risked her personal health by continuing her research into radiation. 

We can now safely conclude that H. pylori can play a central role in the development of gastritis and peptic ulcer disease. However, is there more to uncover? 

H. Pylori in Other Biological Processes 

In the Journal of Clinical Medicine, Takeuchi and Okamoto proposed that H. pylori infection is associated with chronic immune thrombocytopenia

In the years since Marshall and Warren discovered that H. pylori causes gastritis/peptic ulcer disease, further studies have found that nearly half of the world’s population is infected with this organism. Epidemiological studies report that East Asian strains of H. pylori are more pathogenic compared to Western strains. 

In addition, scientists have found a link between H. pylori infection and a number of extragastric diseases. These include diabetes, metabolic syndrome, iron deficiency anemia, vitamin B12 deficiency, and chronic immune thrombocytopenia. 

Read more about immune thrombocytopenia etiology 

Immune thrombocytopenia is characterized by the autoimmune destruction of platelets; this can either be a primary disease or exist secondary to infection (such as H. pylori infection). If thrombocytopenia is observed over a period of 12 months or more, it can be considered “chronic.”

How does H. pylori infection cause chronic immune thrombocytopenia? There are a number of proposed mechanisms, and suffice to say, theories abound.

“The mechanistic pathways by which H. pylori promotes [chronic immune thrombocytopenia] development are postulated to include molecular mimicry, increased plasmacytoid dendritic cell count, and the host immune response to virulence factors such as vacuolating-associated cytotoxin gene A (VacA) and cytotoxin-associated gene A (CagA),” the study authors wrote.  

The Role of Eradication Therapy

Although the exact pathophysiology underpinning extragastric manifestations of H. pylori infection remains poorly defined, there is global consensus that it can cause more than just gastric disease. In Japan, for example, the extragastric component of H. pylori infection is officially recognized, with eradication therapy recommended for patients with symptomatic infection. 

Scientists are still studying the exact components of eradication therapy that yield the best results in the shortest amount of time. In Gastroenterology, Chey and colleagues studied the use of vonoprazan (a potassium-competitive acid inhibitor) against standard proton pump inhibitor-based triple therapy. They tested the use of either vonoprazan dual therapy (vonoprazan + amoxicillin) or vonoprazan triple therapy (vonoprazan + amoxicillin + clarithromycin) against traditional lansoprazole triple therapy, which consists of lansoprazole, amoxicillin, and clarithromycin. 

In their study, a total of 1046 patients were randomized 1:1:1 according to the treatment regime described above. Patients were recruited from multiple sites across the United States and Europe. The research team discovered that both vonoprazan-based regimes were superior to traditional lansoprazole triple therapy in the study population. 

Read more about immune thrombocytopenia treatment 

“In the entire study population and in study participants with clarithromycin-resistant strains of H. pylori, the observed eradication rates were significantly higher with vonoprazan than with lansoprazole,” the authors of the study wrote. 

Regardless of the choice of eradication therapy used, it is clear from a number of studies that this form of therapy can alleviate chronic immune thrombocytopenia to some degree. The most common outcome upon initiation of eradication therapy is that patients experience platelet count recovery. 

Nevertheless, more studies are needed for us to understand the kinds of H. pylori strains that are more highly associated with platelet activation/aggregation in chronic immune thrombocytopenia—it is important to recognize that there is considerable diversity in the spectrum of H. pylori strains found in stomachs. In addition, we need a better grasp on how H. pylori interacts with organs/systems outside the stomach in order to better treat extragastric manifestations of H. pylori infection.


Takeuchi H, Okamoto A. Helicobacter pylori infection and chronic immune thrombocytopeniaJ Clin Med. Published online August 17, 2022. doi:10.3390/jcm11164822

Chey WD, Mégraud F, Laine L, López LJ, Hunt BJ, Howden CW. Vonoprazan triple and dual therapy for Helicobacter pylori infection in the United States and Europe: randomized clinical trialGastroenterology. Published online June 6, 2022. doi:10.1053/j.gastro.2022.05.055