Journal of Current Medical Research and Practice

ORIGINAL ARTICLE
Year
: 2020  |  Volume : 5  |  Issue : 1  |  Page : 32--35

Helicobacter pylori eradication therapy in patients with immune thrombocytopenic purpura: a single-center experience


Nabila Faiek, Safinaz Hussein, Reham Badr 
 Department of Internal Medicine, Clinical Hematology Unit, Faculty of Medicine, Assiut University, Assiut, Egypt

Correspondence Address:
Safinaz Hussein
Clinical Hematology, Department of Internal Medicine, Assiut University, Assiut, 71516
Egypt

Abstract

Objective: The aim was to determine the frequency of Helicobacter pylori infection in patients with immune thrombocytopenic purpura (ITP) and to detect the effect of its eradication therapy on platelet count response in H. pylori-positive patients. Patients and methods: H. pylori stool antigen enzyme immunoassay test was done for 54 patients with ITP. H. pylori-positive patients received standard triple therapy for 2 weeks. Platelet count response to H. pylori eradication therapy was evaluated 2 and 3 months after the treatment. Results: H. pylori infection was positive in 38 (70.4%) patients with ITP. Eradication of H. pylori was achieved in 30 (78.9%) patients (responder group). There were statistically significant increases in platelet count (among the responder group) after H. pylori eradication therapy at 2 and 3 months (P < 0.05). Conclusion: Eradication of H. pylori infection in patients with ITP is associated with significant increase in platelet counts.



How to cite this article:
Faiek N, Hussein S, Badr R. Helicobacter pylori eradication therapy in patients with immune thrombocytopenic purpura: a single-center experience.J Curr Med Res Pract 2020;5:32-35


How to cite this URL:
Faiek N, Hussein S, Badr R. Helicobacter pylori eradication therapy in patients with immune thrombocytopenic purpura: a single-center experience. J Curr Med Res Pract [serial online] 2020 [cited 2021 Apr 18 ];5:32-35
Available from: http://www.jcmrp.eg.net/text.asp?2020/5/1/32/277491


Full Text



 Introduction



Helicobacter pylori is a gram-negative microaerophilic bacterium that colonizes the human stomach of more than 50% of the world population[1]. H. pylori is considered as the main agent of gastritis and peptic ulcer, and it has been connected with gastric cancer development[2]. H. pylori was considered as a class I carcinogen by the WHO[3].

H. pylori infection is associated with several extragastrointestinal diseases, such as neurological (stroke, Parkinson's disease, and Alzheimer's disease), obesity, cardiovascular (ischemic heart diseases), skin disorders, and hematological diseases [unexplained iron-deficiency anemia (IDA) and immune thrombocytopenic purpura (ITP)][4].

ITP, an acquired immune condition, is caused by autoantibody-mediated platelet destruction. ITP is diagnosed by a low platelet count (<100 × 109/l) after exclusion of secondary causes of thrombocytopenia[5],[6], such as lymphoproliferative diseases, autoimmune disorders, drugs, and infectious diseases[7].

Helicobactor pylori is an important infectious agent and can cause persistence of thrombocytopenia[8]).

The association between H. pylori and ITP has been explained by several mechanisms. One of them, antibodies against H. pylori, against cytotoxinassociated gene A (cagA) protein have been cross-reacting with platelet antigens, leading to platelet clearance[9]. Variations in platelets response to eradication of H. pylori infection can be explained by increasing the frequency of CagA-positive strains of H. pylori in Japan than in North America[10].

Following colonization by H. pylori, modulation of host immunity leads to overproduction of autoreactive B cells (antiplatelets)[11] and increases the phagocytic capacity of monocytes together with low levels of the inhibitory Fc++ receptor IIB[12].

After the results of Gasbarrini et al.[13] which have shown improvement in platelet counts in H. pylori-positive patients with ITP after successful H. pylori eradication therapy, several studies from different geographical areas have evaluated this effect with highly variable results (0–100%)[14].

The aim of this study was to determine the frequency of H. pylori infection in patients with ITP and to detect the effect of its eradication therapy on platelet count response in H. pylori-positive patients.

 Patients and Methods



This prospective, observational, study was done at Clinical Hematology Unit, Internal Medicine Department, Assiut University, during the period between May 2018 and May 2019. Written informed consent was taken from all participants, and this study was approved by the Ethical Committee of Assiut University.

It included 54 patients with persistent ITP (platelet count <100 and >30 × 109/l), in the absence of secondary causes of thrombocytopenia, and previous therapy with prednisone.

H. pylori infection was detected among studied group by H. pylori stool antigen enzyme immunoassay test.

H. pylori-positive patients were given triple eradication therapy for 2 weeks (amoxicillin 1 g twice daily; clarithromycin 500 mg twice daily; proton pump inhibitor 20 mg twice daily).

Assessment of response, eradication, or persistence of H. pylori was done after 8 weeks using the H. pylori stool antigen enzyme immunoassay method.

To evaluate platelet count response to H. pylori eradication therapy, platelet counting was performed at 2 and 3 months after the treatment.

Statistical analysis

Data entry and data analysis were done using SPSS version 19 (Statistical Package for the Social Sciences, IBM corp., Armonk, NY). Data were presented as number, percentage, mean, and SD. Independent samples t-test was used to compare quantitative variables between groups. Paired samples t-test was done to compare quantitative data between before and after treatment. P value considered statistically significant when less than 0.05.

 Results



Between May 2018 and May 2019, 54 patients (34 female, 20 male), with ages ranging from 19 to 55 years (mean: 34.07 ± 8.95 years) were enrolled in the study. Overall, 38 (70.4%) were positive for H. pylori and 16 (29.6%) were negative [Figure 1].{Figure 1}

At the beginning of the study, platelets counts at the beginning of the study, platelet counts in H. pylori-positive patients ranged from 30.0 to 77.0 × 109/l, with a mean of 41.38 ± 12.68, and platelet counts in H. pylori-negative patients ranged from 31.0 to 77.0 × 109/l, with a mean of 40.44 ± 11.64. There were no statistically significant difference in baseline platelet count between H. pylori-positive and H. pylori-negative patients (P = 0.799) [Table 1].{Table 1}

Overall, 30 (78.9%) of the 38 H. pylori-positive patients responded to eradication therapy (responder group) and eight (21.1%) did not respond (nonresponder group) [Figure 2].{Figure 2}

Assessment of platelet count in response to the eradication therapy

Among 30 patients (responder group) who responded to H. pylori eradication therapy, there were statistically significant increase in platelet count before and after the treatment at 2 and 3 months (P< 0.05).

Platelet count before the therapy ranged from 30.0 to 77.0 × 109/l, with mean of 42.13 ± 12.98; at 2 months after treatment, ranged from 33.0 to 96.6 × 109/l, with mean of 63.87 ± 19.97; and at 3 months after treatment were, ranged 39.0 to 110.0 × 109/l, with a mean of 76.38 ± 22.11 [Table 2].{Table 2}

On the contrary, among eight patients (nonresponders) who did not respond to H. pylori eradication therapy, there were statistically significant decreases in platelet count before and after the treatment at 2 and 3 months (P< 0.05).

Platelet count before the therapy ranged from 30.0 to 60.0 × 109/l, with a mean of 38.56 ± 11.84, at 2 months after treatment ranged from 11.0 to 55.0 × 109/l, with a mean of 26.54 ± 16.53; and at 3 months after treatment ranged from 10.0 to 50.0 × 109/l, with a mean of 24.73 ± 15.57 [Table 3].{Table 3}

 Discussion



Since its discovery in the 1980s, the relation between H. pylori infection and peptic ulcer and gastric cancer has been established by extensive research[15]. In the past few years, various studies have supported the link between H. pylori and ITP[16].

In our study, a high frequency of H. pylori infection in patients with ITP 38/54 (70.4%) was found. In concordance with our study, Ando et al.[17] and some Pakistani studies have also reported 83 and 63%, respectively, of H Pylori infection in patients with chronic ITP[18]. However, other studies reported a low frequency of H. pylori infection in France[19] and USA[20]. This might be related to the low prevalence of H. pylori in local population as the socioeconomic status affected the prevalence of H. pylori infection[21].

In our study, the H. pylori eradication rate was 78.9% (30/38). In agreement with our results, several studies reported eradication rates above 70%[22],[23], except one study from Japan (42.9%)[24].

The link between H. pylori and ITP was firstt studied by Gasbarrini et al.[13] by evaluating platelet count improvement in 8 of 11 patients following eradication of H. pylori.

In this study, there were statistically significant increase in platelet count after H. pylori eradication therapy (P< 0.001). In this regard, multiple studies evaluated the effect of eradication therapy on platelet count [25–27]. In concordance with our results, Suzuki et al.[28] in Japan and Rostami et al.[29] showed a significantly increased platelet count in response to H. pylori eradication therapy.

In contrast with our results, the study by Jarque et al.[30] and other multicenter trials in Thailand[31] showed lower platelet response to the eradication therapy.

In our opinion, this variability in the results of studies are related to multiple factors that affect the interaction between host (age, duration of thrombocytopenia, and socioeconomic status) and infectious agent (prevalence and bacterial strains), and in particular, prevalence of infection, which varies in different regions and generations.

 Conclusion



Regarding our results, H. pylori eradication therapy patients with in ITP showed significant improvement of platelet count in most patients. So, it is important to include a screening tests for H. pylori in patients with ITP and initiate treatment in the infected cases. However, Further studies are required to understand the mechanism underlying the response to eradication therapy with longer follow-up duration.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

References

1Suerbaum S, Michetti P. Helicobacter pylori infection. N Engl J Med 2002; 347:1175–1186.
2Parsonnet J, Friedman GD, Vandersteen DP, Chang Y, Vogelman JH, Orentreich N, et al. Helicobacter pylori infection and the risk of gastric carcinoma. N Engl J Med 1991; 325:1127–1131.
3Roberto S, Drew P. Helicobacter pylori and chronic ITP. ASH Education Book 2008; 1:206–211.
4Huck JT, Khean LG. Extragastrointestinal manifestations of Helicobacter pylori infection: Facts or myth? A critical review. JDig Dis2012; 13:342–349.
5Lichtman MA, Beutler E, Seligsohn V, Kaushansky K, Kipps TO. Williams Hematology. 7th ed.: New York, NY: McGraw-Hill,2008:2231–2236
6Liebman HA, Pullarkat V. Diagnosis and management of immune thrombocytopenia in the era of thrombopoietinmimetics. Hematol Am Soc Hematol Educ Program 2011; 2011:384–390.
7Kühne T, Berchtold W, Michaels LA, Wu R, Donato H, Espina B, et al. Intercontinental Cooperative ITP Study Group. Newly diagnosed immune thrombocytopenia in children and adults: a comparative prospective observational registry of the Intercontinental Cooperative Immune Thrombocytopenia Study Group. Haematological. 2011; 96:1831–1837.
8Cines DB, Liebman H, Stasi R. Pathobiology of secondary immune thrombocytopenia. Semin Hematol 2009; 46 (Suppl 2):S2–S14.
9Franceschi F, Christodoulides N, Kroll MH, Genta RM. Helicobacter pylori and idiopathic thrombocytopenic purpura. Ann Intern Med 2004; 140:766–767.
10Perez-Perez GI, Bhat N, Gaensbauer J, Fraser A, Taylor DN, Kuipers EJ, et al. Country-specific constancy by age in cagA+ proportion of Helicobacter pylori infections. Int J Cancer 1997; 72:453–456.
11Yamanishi S, Iizumi T, Watanabe E, Shimizu M, Kamiya S, Nagata K, et al. Implications for induction of autoimmunity via activation of B-1 cells by Helicobacterpylori urease. Infect Immun 2006; 74:248–256.
12Asahi A, Nishimoto T, Okazaki Y, Suzuki H, Masaoka T, Kawakami Y, et al.Helicobacterpylori eradication shifts monocyte Fc gamma receptor balance toward inhibitory Fc gamma RIIB in immune thrombocytopenic purpura patients. J Clin Invest 2008; 118:2939–2949.
13Gasbarrini A, Franceschi F, Tartaglione R, Landolfi R, Pola P, Gasbarrini G. Regression of autoimmune thrombocytopenia after eradication of Helicobacter pylori. Lancet 1998; 352:878.
14Frydman GH, Davis N, Beck PL, Fox JG. Helicobacter pylori eradication in patients with immune thrombocytopenicpurpura: a review and the role of biogeography. Helicobacter 2015; 20:239–251.
15Kandulski A, Selgrad M, Malfertheiner P. Helicobacterpylori infection: a clinical overview. Dig Liver Dis 2008; 40:619–626.
16Emilia G, Luppi M, Zucchini P, Morselli M, Potenza L, Forghieri F, et al.Helicobacterpylori infection and chronic immune thrombocytopenic purpura. Blood 2007; 12:3833–3841.
17Ando K, Shimamoto T, Tauchi T, Ito Y, Kuriyama Y, Gotoh A, et al. Can eradication therapy for Helicobacterpylori really improve the thrombocytopenia in idiopathic thrombocytopenic purpura? Our experience and a literature review. Int J Hematol 2003; 77:239–244.
18Shaikh KH, Ahmed S, Ayyub M, Anwar J. Association of Helicobacterpylori infection with idiopathic thrombocytopenic purpura. J Pak Med Assoc 2009; 59:660–663.
19Michel M, Khellaf M, Desforges L, Lee K, Schaeffer A, Godeau B, et al. Autoimmune thrombocytopenic purpura and Helicobacter pylori infection. Arch Intern Med 2002; 162:1033–1036.
20Michel M, Cooper N, Jean C, Frissora C, Bussel JB. Does Helicobacterpylori initiate or perpetuate immune thrombocytopenic purpura? Blood 2004; 103:890–896.
21Webb PM, Knight T, Greaves S, Wilson A, Newell DG, Elder J, et al. Relation between infection with Helicobacterpylori and living conditions in childhood: evidence for person to person transmission in early life. Br Med J 1994; 308:750–753.
22Alzira MCB, Rosangela AR, Ccero SMS, Francisco WSC, Orleancio GRA, Maria HSP, et al. Platelet count response to Helicobacter pylori eradication for idiopathic thrombocytopenic purpura in northeastern. Brazil Hematol Transfus Cell Ther 2018; 40:12–17.
23Campuzano MG. Proof of an association between Helicobacterpylori and idiopathic thrombocytopenic purpura in Latin America. Helicobacter 2007; 12:265–273.
24Stasi 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; 113:1231–1240.
25Emilia G, Longo G, Luppi M, Gandini G, Morselli M, Ferrara L, et al.Helicobacterpylori eradication can induce platelet recovery in idiopathic thrombocytopenic purpura. Blood 2001; 97:812–814.
26Franchini M, Cruciani M, Mengoli C, Pizzolo G, Veneri D. Effect of Helicobacterpylori eradication on platelet count in idiopathic thrombocytopenic purpura: a systematic review and meta-analysis. J Antimicrob Chemother 2007; 60:237–246.
27Stasi R, Rossi Z, Stipa E, Amadori S, Newland AC, Provan D. Helicobacterpylori eradication in the management of patients with idiopathic thrombocytopenic purpura. Am J Med 2005; 118:414–419.
28Suzuki T, Matsushima M, Masui A, Watanabe K, Takagi A, Ogawa Y, et al. Effect of Helicobacterpylori eradication in patients with chronic idiopathic thrombocytopenic purpura-a randomized controlled trial. Am J Gastroenterol 2005; 100:1265–1270.
29Rostami N, Keshtkar JM, Rahnavardi M, Keshtkar JM, Esfahani FS. Effect of eradication of Helicobacterpylori on platelet recovery in patients with chronic idiopathic thrombocytopenic purpura: a controlled trial. Am J Hematol 2008; 83:376–381.
30Jarque I, Andreu R, Llopis I, De la Rubia J, Gomis F, Senent L, et al. Absence of platelet response after eradication of Helicobacterpylori infection in patients with chronic idiopathic thrombocytopenic purpura. Br J Haematol 2001; 115:1002–1003.
31Treepongkaruna S, Sirachainan N, Kanjanapongkul S, et al. Absence of platelet recovery following Helicobacter pylori eradication in childhood chronic idiopathic thrombocytopenic purpura: a multi-center randomized controlled trial. Pediatr Blood Cancer2009; 53:72–77.