Frequency of Helicobactor pylori infection among adult patients with chronic immune thrombocytopenia: A Pakistani Perspective

Jamal Uddin Kakar; Sadia Sultan; Syed Muhammad Irfan; Rozina Zeeshan; Unaib Rabbani

doi:10.4103/1658-5127.137144

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ORIGINAL ARTICLE

Year : 2014 | Volume : 5 | Issue : 2 | Page : 54-57

Frequency of Helicobactor pylori infection among adult patients with chronic immune thrombocytopenia: A Pakistani Perspective

Jamal Uddin Kakar¹, Sadia Sultan¹, Syed Muhammad Irfan¹, Rozina Zeeshan¹, Unaib Rabbani²
¹ Department of Hematology, Liaquat National Hospital, Karachi, Pakistan
² Department of Community Health Sciences, Agha Khan University, Karachi, Pakistan

Date of Web Publication

19-Jul-2014

Correspondence Address:
Sadia Sultan
Department of Hematology, Liaquat National Hospital, Stadium Road, Karachi - 74800
Pakistan

Source of Support: None, Conflict of Interest: None

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DOI: 10.4103/1658-5127.137144

Abstract

Objective: Many studies have reported an association between chronic immune thrombocytopenia and Helicobactor pylori infection. Significant improvement in platelet count is seen after eradication therapy. We looked for the frequency of H. pylori infection in immune thrombocytopenia and clinico-hematological features. Material and Method: A prospective case-control study was conducted from January 2009 to December 2011. One hundred and ten chronic immune thrombocytopenic patients and 40 control subjects were enrolled. H. pylori infection was documented by H. pylori stool antigen enzyme immunoassay method. Results: H. pylori infection in immune thrombocytopenic patients was seen in 45 cases (40.9%) and in 24 (60%) controls; not significant statistically. No significant differences were seen in H. pylori positive and negative patients with respect to maternal characteristics and clinical features except for mean platelet count, which was lower in H. pylori negative group (P = 0.035). Conclusion: Unlike many related studies, we found no significant difference between the frequencies of cases versus controls. Degree of thrombocytopenia appears more marked in H pylori negative patients.

Keywords: Chronic immune thrombocytopenia, Helicobactor pylori, platelet counts

How to cite this article:
Kakar JU, Sultan S, Irfan SM, Zeeshan R, Rabbani U. Frequency of Helicobactor pylori infection among adult patients with chronic immune thrombocytopenia: A Pakistani Perspective. J Appl Hematol 2014;5:54-7

How to cite this URL:
Kakar JU, Sultan S, Irfan SM, Zeeshan R, Rabbani U. Frequency of Helicobactor pylori infection among adult patients with chronic immune thrombocytopenia: A Pakistani Perspective. J Appl Hematol [serial online] 2014 [cited 2023 Mar 24];5:54-7. Available from: https://www.jahjournal.org/text.asp?2014/5/2/54/137144

Introduction

Autoimmune thrombocytopenic purpura is an acquired bleeding disorder in which autoantibodies bind to platelet surface, leading to platelet destruction. ^[1] The mechanism triggering the production of platelet autoantibodies are poorly understood. ^[2] Immune thrombocytopenic purpura (ITP) can be classified based on the absence or presence of other diseases (primary or secondary), patient age (adult or childhood ITP) and duration of thrombocytopenia (acute or chronic). ^[3] ITP in childhood is usually an acute self-limiting problem, however in adults it is often chronic and up to 25% of cases of chronic ITP are refractory to standard therapy. ^[2]

The Gram-negative bacterium Helicobacter pylori are widely known as a causative agent of gastritis and peptic ulcers and as a high-risk factor for the development of gastric cancer and mucosa-associated lymphoid tissue lymphoma. ^[4] The infection has also been implicated in the pathogenesis of extra digestive diseases, such as coronary heart disease, acne rosacea, idiopathic chronic urticaria and also autoimmune diseases such as rheumatoid arthritis, autoimmune thyroiditis, Sjoegren syndrome and Schoenlein-Henoch purpura. ^[5]

In recent times, it was suggested that H. pylori may play a role in ITP pathogenesis, as partial or complete remission of thrombocytopenia has been reported in some studies after eradication of H. pylori. ^{[6],[7],[8],[9],[10],[11]} These studies are mainly from Italy and Japan, whereas studies from North America and some European countries are not supportive of the association. ^{[2],[12],[13]} Kurtoglu et al. from Turkey reported the same prevalence of H. pylori in the ITP patients and the controls, where platelet response was seen after eradication therapy. ^[14] Good platelet response has also been described after eradication of H. pylori in studies from Iran. ^[15],[16]

We, therefore, conducted a study to look for the role of H. pylori infection in adult patients with chronic ITP by comparing with normal control subjects and by clinico-haematological features in H. pylori positive and H. pylori negative groups.

Materials and methods

Study Setting

This prospective case-control study was conducted at Liaquat National Hospital, Karachi, Pakistan.

Patients

All adult individuals of either sex diagnosed as chronic ITP who attended the haematology clinic at our hospital from January 2009 to December 2011 were enrolled. An informed consent was attained from the patients aged ≥16 years. Chronic ITP was defined as per guidelines of the American Society of Hematology: ^[17] Thrombocytopenia (platelets < 100 × 10 ⁹ /L) persistent for more than 6 months, with normal or increased megakaryocytes in the bone marrow and when other causes had been excluded, such as hepatitis C virus and HIV infections, drugs, lymphoproliferative disorders, other autoimmune diseases and pseudo thrombocytopenia.

Patients were excluded from the study if they were younger than 16 years, had been treated for H. pylori, positive for other viral markers like hepatitis -B and C etc., Patients with a history of autoimmune disease or positivity for rheumatoid factor or anti-nuclear antibody were also excluded.

Twenty-seven of the 137 patients were ineligible and, therefore, excluded from the study for various reasons. One female patient with chronic renal failure is included in the study after excluding the other relevant thrombocytopenia causes. Similarly, a patient with breast cancer after 1 year of completion of chemotherapy cycles is also included.

At the time of presentation, few patients were symptomatic and managed accordingly, and others came for thrombocytopenia workup only. Out of 110 patients 9 were splenectomized. All the symptomatic patients were treated with standard dose of steroids.

Controls

Forty normal healthy individuals of both genders with same ethnicity and socioeconomic status were selected as controls. None of these had been treated for H. pylori and their platelet counts and H. pylori status were not known. They were investigated by the same method (stool for H. pylori antigen) and at the same hospital.

Helicobactor Pylori Infection Testing

Helicobactor pylori infection was documented by detecting H. pylori antigens in stool specimens through H. pylori stool antigen enzyme immunoassay method of all the patients who fulfilled the inclusion criteria. The sensitivity and specificity of the test are around 96% and 83%, respectively. Test is qualitative, and results were reported as positive or negative. The test was done at the same time on presentation if patients were asymptomatic and suspected of having chronic ITP. Symptomatic patients were provided emergency cover, before relevant workup was done.

Ethical Approval

Ethical approval for this study was obtained from the Hospital Ethical Committee and Research Committee prior to the study.

Data Management and Analysis

Data were entered and analyzed using SPSS (IBM corporation version 19.0, Chicago, Illinois, USA). Data were expressed as mean and standard deviation (SD) or as median (range) and proportions. T-test was used to compare means between cases and controls, and Chi-square or Fischer exact test were used to see significant differences in proportion between cases and controls. A two-tailed P < 0.05 was considered as significant.

Results

Patient Characteristics

One hundred ten patients were enrolled as cases. Sixty-eight were females (61.8%) and 42 males (38.2%), with a mean age of 40.5 years (SD ± 16.7). The mean age of the H. pylori positive patients was 42.04 years (SD ± 14.8) and 39.55 years (SD ± 17.9) for H. pylori negative ones (P = 0.44) [Table 1]. Only 8.1% patients were splenectomized.

Table 1: Patient characteristics

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Forty individuals were selected as controls, 12 (30%) were females and 28 (70%) were males. The higher number of male controls was because of easy availability. The mean age of controls were 37.4 (SD ± 8), not significantly lower than patients (P = 0.128) [Table 2].

Table 2: Comparison between patients and controls regarding mean age, gender and H. pylori infection

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Analysis

Prevalence of Helicobactor Pylori Infection

Forty-five of the 110 patients (40.9%) were positive of H. pylori, the difference seen is statistically insignificant (P = 0.12) when compared with control group 24/40 (60%) [Figure 1]. No statiscally significant difference was noted between splenectomized and nonsplenectomized patients.

Figure 1: Comparison of prevalence of Helicobactor pylori between patients and controls (%)

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Clinico-Hematological Features

Among the patients, 52 (47%) cases were symptomatic and 58 (53%) were asymptomatic at the time of presentation. Symptomatic patients had mild mucosal bleeds and none had life-threatening bleeds. Of the symptomatic and asymptomatic cases, 20 and 25 were positive for H. pylori in each group. The difference between the symptoms of H. pylori positive and negative group is also statistically insignificant (P = 0.382).

Regarding the severity of thrombocytopenia, patients were categorized as having platelet counts below 20 × 10 ⁹ /L, between 20 × 10 ⁹ /L and 50 × 10 ⁹ /L and more than 51 × 10 ⁹ /L; individual difference in each category is statistically not significant, but as a whole, lower mean platelet count was seen in H. pylori negative patients (P = 0.035) [Table 1].

No statistically significant difference was noted in the two groups as far as treatment and response to steroids are concerned.

Discussion

The association of H. pylori with chronic ITP was reported 1 ^st time by Gasbarrini et al. from Italy in 1998, in which significant increase in platelet count was seen in 8 of the 11 ITP patients in whom the bacterium was eradicated. After that many studies mainly from Japan and Italy reported the causative role of H. pylori in immune mediated thrombocytopenia and platelet increment were seen in these studies after eradication. ^{[6],[7],[8],[9],[10],[11]} Some studies from Turkey, Iran, and Korea also favor the association. ^{[14],[15],[16],[18]} A local study from Pakistan shows the association, where H. pylori infection was found high when compared with controls. ^[19] Contrary to this we could not establish a correlation of H. pylori infection in our ITP patients in comparison to controls. The association between the two is also not seen in studies from France, Spain and Northern America, where the prevalence in general population is also similar as in our series of patients. ^{[9],[2],[12],[13]}

Helicobacter pylori infection is demonstrated by various methodologies includes stool antigen test, urea breath test, rapid urease test, serology and histology. ^[20] The sensitivity, specificity, positive predictive value, negative predictive value and accuracy are highly variable. ^[20] However, by stool antigen test method sensitivity and specificity are 96% and 83% respectively, in comparison with urea breath test it is 89% and 73% for sensitivity and specificity, respectively. ^[20]

The mechanism by which H. pylori can cause thrombocytopenia is unclear, but the pathogenetic virulence factors of H. pylori such as CagA and VacA are known to play the main role. ^[7],[21] In this regard, it should be noted that most Japanese H. pylori strains were positive for CagAand had the intact cag pathogenicity island. Although the prevalence of H. pylori is much higher in developing countries including India, Bangladesh and Pakistan, but we are not aware of the strain of bacterium in our population. ^{[22],[23],[24],[25]}

In our patients, no difference in maternal characteristics includes age and gender were seen in H. pylori positive and negative groups. Findings of many related studies are similar to us but increased prevalence of H. pylori with increasing age is seen in some of the studies mainly from Japan. ^[6]

In our patients, low mean platelet count is seen in H. pylori negative group (P = 0.035), but if we compare the thrombocytopenia of the two group according to the severity then no difference is seen [Table 1].

Limitations

We could not do strain identification testing because of lack of molecular facilities in our center. Data of the patients regarding H. pylori eradication therapy and their response was not obtained. Hence mainly we looked at the role of H. pylori in chronic ITP on the basis of comparison of the patients with controls and clinico-hematological features comparing the H. pylori positive and negative groups.

Conclusion and future directions

No significant association was observed in this study, which can tell us the role of H. pylori infection in chronic ITP in our population, which may be attributed to the high prevalence in our general population. Future studies with strain identification and eradication of H. pylori infection will definitely be required to ascertain the association between the specific strain and H. pylori and also to establish the role of eradication treatment whether to offer it as a first line treatment to all ITP patients or selected patients with a specific strain.

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