H. pylori detection, eradication effective for people with ITP

The detection and eradication of Helicobacter pylori infection should be considered in the work-up of patients with what seems to be normal immune thrombocytopenic purpura, according to data from a systematic review.

Researchers performed a systematic review of published studies that reported on randomized, cohort, case-control or retrospective studies and evaluated the effects of H. pylori eradication on the platelet count in adult patients with ITP.

Twenty-five studies met the inclusion criteria and included 696 participants who were able to be measured for the effects of H. pylori eradication on platelet count.

Data indicated that the weighted mean complete response (platelet count ≥100 x 10⁹/L) was 42.7% (95% CI, 31.8%-53.9%) and the overall response (platelet count ≥30 x 10⁹/L and at least doubling of the basal count) was 50.3% (95% CI, 41.6%-59.0%).

Of the 222 participants with a baseline platelet count <30 x 10⁹/L the complete response rate was 20.1% (95% CI, 13.5%-26.7%); the overall response rate was 35.2% (95% CI, 28.0%-42.4%).

In addition, the response rate was more likely to be higher in countries with a high background prevalence of H. pylori infection and in patients with milder degrees of thrombocytopenia.

“When looking at the results of the pooled analysis, it is important to note that most of the studies were from Japan and that Japanese participants accounted for almost two-thirds of the immune thrombocytopenic purpura population analyzed in this review,” the researchers wrote. “The preponderance of reports from one country where infection rates and response to eradication therapy are consistently higher than in other countries adds a potential element of bias to our analysis and suggests caution in the generalizability of results.” – by Jennifer Southall

Blood. 2009;113:1231-1240.

I first read this paper as one of the journal’s peer reviewers, and I was very impressed by their methodology. It is a beautiful example of the methodology of systematic literature reviews. The authors comprehensively identified all relevant publications and used very sophisticated methods to analyze the data. The association of H. pylori infection and ITP is kind of a will-o’-the-wisp in the United States; there is no consistent understanding of how to interpret these data. There is remarkable geographical diversity in the relation of H. pylori infection to ITP. The relationship of H. pylori to ITP was first described in Italy — which is the country where four of these 25 papers came from. Fourteen of the articles, nearly 60%, are from Japan, which is a country where H. pylori infection is endemic. Only two of these references came from the United States, because in the United States fewer people have H. pylori infection and among ITP patients treated for H. pylori infection, relatively few have platelet count responses. Therefore, investigation for and treatment of H. pylori infection as a treatment for ITP remains uncommon in the United States.

The question stimulated by this review is, 'Where does investigation and treatment of H. pylori infection fit in the management scheme of ITP?' The major advantage is that the test for H. pylori infection is simple and inexpensive and the treatment is essentially risk free. When measuring this against other treatments for ITP, it’s like eating ice cream — it just seems so easy that maybe we should do it all the time. The major reason why, as a reviewer, I advocated for this to be published is that I think investigation and treatment of H. pylori infection as a treatment for ITP needs more attention in this country. If it is found to be effective for treatment of patients with ITP, it will be noticed and use will increase.

A downside to the data on investigation and treatment of H. pylori infection as a treatment for ITP is that many patients reported in these articles did not have very low platelet counts and may not have needed any treatment at all. Another systemic review of treatment of H. pylori infection as treatment for ITP by Arnold et al will be published in Haematologica. Their focus was different from the review by Stasi et al because they restricted their analysis to studies reporting treatment of ITP patients both with and without H. pylori infection. Arnold et al found that when the H. pylori eradication regimen was used for patients with ITP who had no H. pylori infection, there was no platelet count response. Their conclusion was clear, that it was the eradication of the infection and not the drugs themselves that have an effect. Therefore, there is something about H. pylori infection that triggers or sustains the autoimmune reaction that is the etiology of ITP. Both of these reviews document that there is a significant platelet count response when H. pylori infection is eradicated. The remaining uncertainty is the frequency and durability of responses, and whether responses occur in patients who most need treatment — patients who have severe and symptomatic thrombocytopenia.

– James N. George, MD

Departments of Medicine, Biostatistics and Epidemiology
University of Oklahoma Health Sciences Center

This adds to our increasing insight that chronic immune stimulation by extraneous microbial agents, such as H. pylori, can foster 'innocent bystander' autoimmune cytopenias — especially ITP. In the case of H. pylori, recent evidence supports the impression that eradication of the microbe may ameliorate the thrombocytopenia.

– Harry S. Jacob, MD

HemOnc Today Chief Medical Editor