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Living FRIendly Summaries of the Body of Evidence using Epistemonikos (FRISBEE)
Medwave 2016;16(Suppl3):e6528 doi: 10.5867/medwave.2016.6528
Does Helicobacter pylori eradication play a role in immune thrombocytopenia?
Valentina Llovet , Gabriel Rada
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Abstract

Helicobacter pylori infection has been implicated as trigger or disease modifier in immune thrombocytopenia (ITP). So, eradication treatment for this agent could have clinical benefits. Searching in Epistemonikos database, which is maintained by screening 30 databases, we identified four systematic reviews comprising 40 studies addressing the question of this article overall, including one randomized controlled trial. We combined the evidence using meta-analysis and generated a summary of findings following the GRADE approach. We concluded Helicobacter eradication might decrease risk of bleeding in patients with immune thrombocytopenia but the certainty of the evidence is low.


 
Problem

Helicobacter pylori is known for its influence on the development of gastrointestinal diseases. However, it could also play a role in diseases outside the digestive system such as immune thrombocytopenia (also called idiopathic or immune thrombocytopenic purpura - ITP). This condition is characterized by the presence of antibodies against platelets, and it has been postulated Helicobacter might act as a trigger, and also as a disease modulator by a mechanism not completely understood.

For this reason, it has been suggested eradication of Helicobacter could be beneficial. However, it is unclear whether this actually translates into clinical benefits.

Methods

We used Epistemonikos database, which is maintained by screening more than 30 databases, to identify systematic reviews and their included primary studies. With this information we generated a structured summary using a pre-established format, which includes key messages, a summary of the body of evidence (presented as an evidence matrix in Epistemonikos), meta-analysis of the total of studies, a summary of findings table following the GRADE approach and a table of other considerations for decision-making.

Key messages

  • Helicobacter eradication might decrease bleeding risk in immune thrombocytopenia, but the certainty of the evidence is low.
  • Adverse effects of Helicobacter eradication therapy are common but self-limiting and not severe.
  • There is a substantial number of published and ongoing trials that have not yet been incorporated into systematic reviews in this topic, so a new review could provide further information on the matter. 
About the body of evidence for this question

What is the evidence.
See evidence matrix  in Epistemonikos later

We found four systematic reviews [1][2][3][4], including 40 studies addressing the question of interest [5][6][7][8] ,[9][10][11][12],[13][14][15][16], [17][18][19][20][21][22][23][24][25][26], [27][28][29][30][31][32][33][34][35][36],
[37],[38][39][40][41][42][43][44]. However, only one corresponds to a randomized controlled trial [32]. This table and the summary in general are based on the latter, because the inclusion of the non-randomized studies did not provide additional relevant information or increase the certainty of the existing evidence.

What types of patients were included

The trial included adult patients between 18 and 75, with chronic immune thrombocytopenia and Helicobacter pylori infection confirmed with urea breath test.

Patients were included only if secondary causes of thrombocytopenia had been clearly ruled out, including hepatitis B or C virus infection, HIV infection, lupus, antiphospholipid antibody syndrome, bone marrow failure syndromes, drug-induced thrombocytopenia, and malignancies such as chronic lymphocytic leukemia and malignant lymphoma.
Patients with renal failure, severe liver failure, allergic to amoxicillin, clarithromycin or lansoprazole and patients with platelet counts below 20 x 103/µl or above 100 x 103/µl were also excluded.

What types of interventions were included

The trial evaluated eradication of Helicobacter pylori with amoxicillin 750 mg, clarithromycin 200 mg and lansoprazole 30 mg bid for one week.

The trial compared against placebo.

What types of outcomes
were measured

All of the systematic reviews evaluated only considered the outcome platelet response, measured in different ways.

The randomized trial defined a platelet count of 150 x 103/µl as complete response and a partial response over 50 x 103/µl.
Summary of findings

The Information on the effects of Helicobacter pylori eradication in patients with immune thrombocytopenia is based in only one randomized trial including 25 participants [32]. The trial measured increase in platelet count after the eradication of Helicobacter pylori, which was used as indirect evidence of the effect on the risk of bleeding. The summary of findings is as follows:

  • Helicobacter eradication might decrease bleeding risk in immune thrombocytopenia, but the certainty of the evidence is low.
  • Adverse effects of Helicobacter eradication therapy are common but self-limiting and not severe. The certainty of the evidence is high.

Other considerations for decision-making

To whom this evidence does and does not apply

  • The evidence presented in this summary is widely applicable to Helicobacter pylori positive adults with immune thrombocytopenia.
  • While some observational studies have suggested a role in patients without demonstrated Helicobacter infection, it does not seem reasonable to extrapolate to this group in the absence of more certain evidence.
  • This evidence does not apply to secondary immune thrombocytopenia, since there is no role of Helicobacter in these cases.
About the outcomes included in this summary
  • Bleeding and adverse effects were considered as critical outcomes for decision-making according to the opinion of the authors of this summary.
  • Platelet count corresponds to a surrogate outcome that allegedly has good correlation with bleeding, so we considered it as indirect evidence for bleeding risk.
Balance between benefits and risks, and certainty of the evidence
  • From other studies we know adverse events related to Helicobacter eradication treatment are frequent, but self-limiting and mild [36]. In addition, there may be benefits in relation to the decrease of bleeding risk, although the certainty of the evidence is low.
  • Eventually, other benefits associated with the eradication of Helicobacter not related to immune thrombocytopenia could be considered, which could tip the balance in favor of treatment.
What would patients and their doctors think about this intervention
  • Considering the nature of the adverse effects, some patients and their doctors may be inclined to use this intervention, despite doubts about benefits.
  • Other patients may not want to be exposed to adverse effects from an intervention whose effectiveness has low level of certainty.
Resource considerations
  • It is a relatively low-cost intervention, so probably this factor is not determinant in the decision.

Differences between this summary and other sources

  • The conclusions of this article partially agree with the identified systematic reviews, noting eradication could have benefits. However, our summary puts more emphasis on the limitations of the existing evidence
  • The conclusions of this summary do not agree with one of the main guidelines on this subject [46], which recommends against routine eradication in asymptomatic patients with chronic immune thrombocytopenia. Importantly, the guideline does not include most of the evidence discussed in this summary.
Could this evidence change in the future?
  • The probability that the conclusions of this summary change with future evidence is high, due to the existing uncertainty.
  • We identified at least three ongoing studies evaluating this question [47],[48],[49], and some already published but not yet incorporated into systematic reviews [50],[51],[52],[53]. So, it is very likely that a new systematic review would offer relevant information.

How we conducted this summary

Using automated and collaborative means, we compiled all the relevant evidence for the question of interest and we present it as a matrix of evidence.

Follow the link to access the interactive version: Helicobacter pylori eradication for immune thrombocytopenia (ITP)

 

Notes

The upper portion of the matrix of evidence will display a warning of “new evidence” if new systematic reviews are published after the publication of this summary. Even though the project considers the periodical update of these summaries, users are invited to comment in Medwave or to contact the authors through email if they find new evidence and the summary should be updated earlier. After creating an account in Epistemonikos, users will be able to save the matrixes and to receive automated notifications any time new evidence potentially relevant for the question appears.

The details about the methods used to produce these summaries are described here http://dx.doi.org/10.5867/medwave.2014.06.5997.

Epistemonikos foundation is a non-for-profit organization aiming to bring information closer to health decision-makers with technology. Its main development is Epistemonikos database (www.epistemonikos.org).

These summaries follow a rigorous process of internal peer review.

Conflicts of interest
The authors do not have relevant interests to declare.

Licencia Creative Commons Esta obra de Medwave está bajo una licencia Creative Commons Atribución-NoComercial 3.0 Unported. Esta licencia permite el uso, distribución y reproducción del artículo en cualquier medio, siempre y cuando se otorgue el crédito correspondiente al autor del artículo y al medio en que se publica, en este caso, Medwave.

 

Se ha planteado que el Helicobacter pylori tendría un rol etiopatogénico en la trombocitopenia inmune (PTI), y que la erradicación de este podría tener beneficios clínicos. Utilizando la base de datos Epistemonikos, la cual es mantenida mediante búsquedas en 30 bases de datos, identificamos cuatro revisiones sistemáticas que en conjunto incluyen 40 estudios, entre ellos un estudio controlado aleatorizado, que responden la pregunta de interés. Realizamos un metanálisis y tablas de resumen de los resultados utilizando el método GRADE. Concluimos que la erradicación de Helicobacter podría disminuir el riesgo de sangrado en pacientes con trombocitopenia inmune, pero la certeza de la evidencia es baja.

Autores: Valentina Llovet [1,2 ], Gabriel Rada [2,3,4,5,6 ]

Affiliation:
[1] Facultad de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile
[2] Proyecto Epistemonikos, Santiago, Chile
[3] Departamento de Medicina Interna, Facultad de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile
[4] Programa de Salud Basada en Evidencia, Facultad de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile
[5] GRADE working group
[6] The Cochrane Collaboration

E-mail: radagabriel@gmail.com

Author address:
[1] Facultad de Medicina
Pontificia Universidad Católica de Chile
Lira 63
Santiago Centro
Chile

Citation: Llovet V, Rada G. Does Helicobacter pylori eradication play a role in immune thrombocytopenia?. Medwave 2016;16(Suppl3):e6528 doi: 10.5867/medwave.2016.6528

Publication date: 5/9/2016

PubMed record

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Arnold DM, Bernotas A, Nazi I, Stasi R, Kuwana M, Liu Y, et al. Platelet count response to H. pylori treatment in patients with immune thrombocytopenic purpura with and without H. pylori infection: a systematic review. Haematologica. 2009 Jun;94(6):850-6. | CrossRef | PubMed |

Franchini M, Cruciani M, Mengoli C, Pizzolo G, Veneri D. Effect of Helicobacter pylori eradication on platelet count in idiopathic thrombocytopenic purpura: a systematic review and meta-analysis. J Antimicrob Chemother. 2007 Aug;60(2):237-46. | PubMed |

Stasi R, Sarpatwari A, Segal JB, Osborn J, Evangelista ML, Cooper N, et al. Effects of eradication of Helicobacter pylori infection in patients with immune thrombocytopenic purpura: a systematic review. Blood. 2009 Feb 5;113(6):1231-40. | CrossRef | PubMed |

Franchini M, Veneri D. Helicobacter pylori infection and immune thrombocytopenic purpura: an update. Helicobacter. 2004 Aug;9(4):342-6. | PubMed |

Ahn ER, Tiede MP, Jy W, Bidot CJ, Fontana V, Ahn YS. Platelet activation in Helicobacter pylori-associated idiopathic thrombocytopenic purpura: eradication reduces platelet activation but seldom improves platelet counts. Acta Haematol. 2006;116(1):19-24. | PubMed |

Ando K, Shimamoto T, Tauchi T, Ito Y, Kuriyama Y, Gotoh A, et al. Can eradication therapy for Helicobacter pylori really improve the thrombocytopenia in idiopathic thrombocytopenic purpura? Our experience and a literature review. Int J Hematol. 2003 Apr;77(3):239-44. | PubMed |

Ando T, Tsuzuki T, Mizuno T, Minami M, Ina K, Kusugami K, et al. Characteristics of Helicobacter pylori-induced gastritis and the effect of H. pylori eradication in patients with chronic idiopathic thrombocytopenic purpura. Helicobacter. 2004 Oct;9(5):443-52. | PubMed |

Asahi A, Kuwana M, Suzuki H, Hibi T, Kawakami Y, Ikeda Y. Effects of a Helicobacter pylori eradication regimen on anti-platelet autoantibody response in infected and uninfected patients with idiopathic thrombocytopenic purpura. Haematologica. 2006 Oct;91(10):1436-7. | PubMed |

Campuzano-Maya G. Proof of an association between Helicobacter pylori and idiopathic thrombocytopenic purpura in Latin America. Helicobacter. 2007 Jun;12(3):265-73. | PubMed |

Emilia G, Longo G, Luppi M, Gandini G, Morselli M, Ferrara L, et al. Helicobacter pylori eradication can induce platelet recovery in idiopathic thrombocytopenic purpura. Blood. 2001 Feb 1;97(3):812-4. | PubMed |

Emilia G, Luppi M, Zucchini P, Morselli M, Potenza L, Forghieri F, et al. Helicobacter pylori infection and chronic immune thrombocytopenic purpura: long-term results of bacterium eradication and association with bacterium virulence profiles. Blood. 2007 Dec 1;110(12):3833-41. | PubMed |

Estrada-Gómez RA, Parra-Ortega I, Martínez-Barreda C, Ruiz-Argüelles GJ. Helicobacter pylori infection and thrombocytopenia: a single-institution experience in Mexico. Rev Invest Clin. 2007 Mar-Apr;59(2):112-5. | PubMed |

Fujimura K, Kuwana M, Kurata Y, Imamura M, Harada H, Sakamaki H, et al. Is eradication therapy useful as the first line of treatment in Helicobacter pylori-positive idiopathic thrombocytopenic purpura? Analysis of 207 eradicated chronic ITP cases in Japan. Int J Hematol. 2005 Feb;81(2):162-8. | PubMed |

Gasbarrini A, Franceschi F, Tartaglione R, Landolfi R, Pola P, Gasbarrini G. Regression of autoimmune thrombocytopenia after eradication of Helicobacter pylori. Lancet. 1998 Sep 12;352(9131):878. | PubMed |

Hashino S, Mori A, Suzuki S, Izumiyama K, Kahata K, Yonezumi M, et al. Platelet recovery in patients with idiopathic thrombocytopenic purpura after eradication of Helicobacter pylori. Int J Hematol. 2003 Feb;77(2):188-91. | PubMed |

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