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Helicobacter pylori eradication: a novel therapeutic option in chronic immune thrombocytopenic purpura

Vanaja Sivapathasingam, Michael P Harvey and Robert B Wilson
Med J Aust 2008; 189 (7): 367-370. || doi: 10.5694/j.1326-5377.2008.tb02080.x
Published online: 6 October 2008

Abstract

Objective: To determine whether Helicobacter pylori eradication is an effective treatment for Australian patients with chronic immune thrombocytopenic purpura (ITP).

Design, setting and patients: Retrospective analysis of clinical records of a consecutive series of ITP patients referred to a gastrointestinal surgeon in a tertiary referral hospital for laparoscopic splenectomy between August 2005 and November 2007.

Main outcome measures: Platelet response (measured at least 3-monthly) following successful H. pylori eradication therapy (confirmed by urea breath test 4 weeks later).

Results: Of 16 patients, seven were H. pylori-negative and underwent laparoscopic splenectomy. Nine were H. pylori-positive and successfully underwent H. pylori eradication therapy; five of the nine had an initial platelet response. Four patients had platelet counts > 100 × 109/L (reference range, 140–450 × 109/L) and were off all immunosuppression at 9 months; three had a sustained response beyond 12 months. One patient had an initial response at 3 months (15 × 109/L to 208 × 109/L), but relapsed 4 months after H. pylori eradication and underwent splenectomy with platelet count recovery. The remaining four patients showed no platelet response and subsequently underwent splenectomy.

Conclusion: Larger prospective studies are needed to fully ascertain the role of H. pylori in Australian patients with ITP. However, H. pylori eradication is simple and safe. H. pylori screening and eradication should be considered before immunosuppression or splenectomy.

Immune thrombocytopenic purpura (ITP) is the most common autoimmune-mediated haematological disorder, characterised by antibodies against platelet surface antigens.1 Its aetiology, pathogenesis and molecular receptor targets remain unclear. It has been associated with HIV infection and hepatitis C.1

Helicobacter pylori is a causative agent in a spectrum of gastrointestinal diseases, including peptic ulcer disease, gastric cancer and MALToma (mucosa-associated lymphoid tissue lymphoma). There is growing evidence of an association between H. pylori eradication and platelet recovery in patients with ITP.2-6 The evidence is strongest in Japan, where H. pylori eradication is now recommended as an initial treatment for infected ITP patients.7 Screening and eradication may be a simpler and safer therapeutic option than immunosuppression or splenectomy in certain ITP patients.8,9 Most studies of H. pylori and ITP are from Japan, Spain and Italy; however, the British Society for Haematology now recommends H. pylori screening and eradication as a treatment in ITP (evidence level, III).10 To date, there have been no published reports of such therapy in Australian patients. Local experience is important, given the potential regional variation in strains of H. pylori.

Discussion

This study found that H. pylori eradication was of long-term benefit in three of nine patients with ITP who were H. pylori-positive, leading to a sustained platelet response. Two other patients had a short-term response. H. pylori eradication appeared to be least successful in the context of severe ITP that had already been extensively treated. To our knowledge, this is the first published study of H. pylori eradication therapy in Australian ITP patients.

The association between ITP and H. pylori was first reported in 1998.12 Possible aetiological links include molecular mimicry and cross-reactivity of bacterial and platelet antigens, in association with host factors such as specific human leukocyte antigen (HLA) class II alleles.13,14 A recent Italian study found that the HLA-DRB1*11, -DRB1*14 and -DQB1*03 alleles occur significantly more often in H. pylori-infected ITP patients and indicate a higher probability of platelet response to eradication therapy.15 ITP patients who had successful H. pylori eradication showed significantly decreased serum platelet-associated IgG levels, suggesting that removal of the H. pylori antigenic stimulus leads to platelet recovery.9

However, response rates have varied. A literature review of 13 major studies published between 1998 and 2004 revealed an overall platelet response rate of 52% following H. pylori eradication therapy when used as an adjunct to standard ITP therapy or in otherwise untreated cases.5 Another review concluded that 58% of 482 patients with ITP were H. pylori-positive and, of these, more than 50% showed a significant platelet response to successful H. pylori eradication.13 Long-term follow-up studies, including one with a median follow-up of 31 months, have also shown good results.2,16,17 A large retrospective analysis in Japan yielded a platelet response rate as high as 63%, with remission sustained after 12 months, even among patients whose ITP was refractory to splenectomy.7 A small randomised controlled trial, also in Japan, showed a significant increase in platelet count in the group who had successful eradication therapy.3 Some studies showed that platelet recovery was better in less severe or recent-onset ITP,18,19 or in the absence of concurrent steroid therapy.20

In contrast, several studies have refuted a significant association between H. pylori and ITP.21-23 For example, a prospective study in the United States found that only one of 14 patients who responded to H. pylori eradication had a rise in platelet count.21

There is substantial variability in ITP response to H. pylori eradication in different countries.5,18,20,24 This may be due to variations in bacterial virulence factors, such as CagA expression or host immunological class II HLA factors.2,24 Most Japanese H. pylori strains are CagA-positive, unlike most American strains.9 Patients infected with CagA-positive strains (as measured by anti-CagA IgG antibodies) are thought to have increased platelet response to H. pylori eradication compared with those who are CagA-negative or who have low serum titres of CagA antibodies.3,5 Serum levels of anti-CagA IgG may be used as a predictor of response to H. pylori treatment.2,25

The prevalence of H. pylori infection in ITP patients varies from 22% in a US study21 to 47% in a study from the United Kingdom and Italy19 to 71% in a Spanish study.23 In a comparison of H. pylori and ITP data from the UK and Italy, the prevalence of H. pylori infection in patients with ITP appeared to be similar to that in the general population.19 The prevalence of H. pylori infection in the general Australian population is 25%–38%,26 but its prevalence in Australians with ITP is yet to be determined. In our series, 56% of ITP patients were H. pylori-positive.

The results in this small series support a role for H. pylori eradication in the treatment of patients with ITP in Australia. H. pylori screening and eradication should be considered in patients presenting with ITP, given the low cost and potential for avoidance of immunosuppression and splenectomy. Larger prospective studies are needed to fully ascertain the role of H. pylori in Australian patients with ITP.

Received 12 October 2007, accepted 2 March 2008

  • Vanaja Sivapathasingam1,2
  • Michael P Harvey1
  • Robert B Wilson1

  • 1 Liverpool Hospital, Sydney, NSW.
  • 2 Monash Medical Centre, Melbourne, VIC.


Correspondence: Rbwilson52@hotmail.com

Competing interests:

None identified.

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