E-ISSN:2320-8686
P-ISSN:2321-127X

Research Article

Thrombocytopenic

International Journal of Medical Research and Review

2019 Volume 7 Number 6 November-December
Publisherwww.medresearch.in

Prevalence of H. pylori in Immune Thrombocytopenic Purpura (ITP) in a tertiary care center, South India

Antony A.1, Margaret C.2*, Karthick R.3, Ali M.4, Chenthil K.5
DOI: https://doi.org/10.17511/ijmrr.2019.i06.12

1 Anny Antony, Department of Hematology, Madras Medical College, Chennai, Tamil Nadu, India.

2* C. Margaret, Department of Hematology, Madras Medical College, Chennai, Tamil Nadu, India.

3 R. Karthick, Multidisciplinary Research Unit (MRU), Madras Medical College, Chennai, Tamil Nadu, India.

4 Mohammed Ali, Department of Medical Gastroenterology, Madras Medical College, Chennai, Tamil Nadu, India.

5 K.S. Chenthil, Department of Hematology, Madras Medical College, Chennai, Tamil Nadu, India.

Introduction: Immune thrombocytopenic purpura (ITP) has been linked with Helicobacter Pylori infection. Objectives: The objective of the present study was to determine the prevalence of H pylori infection in adult ITP patients in a tertiary care center in South India. Methods: 50 adult patients with ITP in the Department Hematology, Madras Medical College were recruited for a cross -sectional study over a period of 6 months. Biopsy from the antrum was subjected to Rapid urease test to detect H. pylori. A total of 50 patients participated in the study. Result: The prevalence of H. pylori infection in ITP patients was 36%. The majority of patients were male (78%). Conclusion: The diagnosis of H. pylori in ITP patients may be considered in high prevalent areas.

Keywords: Immune thrombocytopenic purpura, Helicobacter Pylori, Urease test

Corresponding Author How to Cite this Article To Browse
C. Margaret, Department of Hematology, Madras Medical College, Chennai, Tamil Nadu, India.
Email: 		Antony A, Margaret C, Karthick R, Ali M, Chenthil KS. Prevalence of H. pylori in Immune Thrombocytopenic Purpura (ITP) in a tertiary care center, South India. Int J Med Res Rev. 2019;7(6):520-525.
Available From
https://ijmrr.medresearch.in/index.php/ijmrr/article/view/1110

Manuscript Received Review Round 1 Review Round 2 Review Round 3 Accepted
2019-03-24 2019-04-04 2019-04-10 2019-04-15
Conflict of Interest Funding Ethical Approval Plagiarism X-checker Note
No Nil Yes 7%

© 2019 by Anny Antony, C. Margaret, R. Karthick, Mohammed Ali, K.S. Chenthil and Published by Siddharth Health Research and Social Welfare Society. This is an Open Access article licensed under a Creative Commons Attribution 4.0 International License https://creativecommons.org/licenses/by/4.0/ unported [CC BY 4.0].

International Journal of Medical Research and Review 2019;7(6)520
Antony A. et al: Prevalence of H. pylori in Immune Thrombocytopenic

Introduction

Immune thrombocytopenic purpura (ITP) commonly called as idiopathic thrombocytopenic purpura, is an acquired disease of adults and children which is immune mediated and is characterized by transient or persistent decrease of the platelet count. The risk of bleeding increases depending upon the degree of thrombocytopenia.

When ITP occurs in the absence of an evident predisposing etiology it is known as primary ITP and when it occurs secondary to an identifiable cause it is known as secondary ITP. Pseudo thrombocytopenia should also be ruled out.

Helicobacter pylori have been clearly recognized as the main cause of gastritis and most of gastric adenocarcinoma and mucosa associated lymphoid tissue (MALT) lymphoma. It has also been implicated in the pathogenesis of some autoimmune diseases such as rheumatoid arthritis, autoimmune thyroid disease and ITP. Many studies have well documented that there is an association between ITP and H. pylori infection and showed a high prevalence of H. pylori infection in patients with ITP [1-4].

Recently, Khan Sheema et al conducted an interventional and prospective study and reported a good response to bacterium eradication in most of the cases. However discrepant reports have been produced by earlier studies from France and Spain where the prevalence of H. pylori was high, but there was no significant improvement in platelet count after eradication therapy [5, 6,7].

Studies from India pointed out that almost 80% to 90% of the population is infected with H. pylori in all age groups [8-11]. There is a relationship of H. pylori infection with hygiene lifestyle and socioeconomic conditions with a 45% yearly increase in incidence rate of H. pylori infection in developing nations compared to approximately 0.5% in developed and industrialized countries [12].

Thus H. pylori prevalence in ITP patients mirrored the prevalence of H. pylori in the general population. However, It is still not clear if H. pylori should be implicated as a secondary cause of ITP or it is just an alternative, additional or incidental finding in patients with ITP in our country particularly South India. In this study, authors aimed to find the prevalence of H. pylori in ITP patients and its association with clinical and demographic profiles.

Materials and Methods

Type of study: This was a prospective, cross sectional study where all adult patients with ITP in the Department of Hematology, Madras Medical College were reviewed and recruited over a period of 6 months.

Inclusion and exclusion criteria: The inclusion criteria included patients with ITP in whom the secondary causes of ITP had been ruled out. Patients who were previously included were not recruited again. Patients were not eligible if they had anti-phospholipid antibody syndrome, systemic lupus erythematous, lymphoproliferative disorders, chronic renal disease or drug induced thrombocytopenia. Patients who are HIV positive, Hepatitis C virus positive or pregnant were also excluded.

Ethical consideration and permission: Informed consent was obtained from all patients and the study was approved by the Institute Ethics Committee.

Patients were asked questions as per a questionnaire and subjected to clinical examination. All the secondary causes of ITP were ruled out using appropriate tests. Patients were grouped as per age, sex and platelet counts. Patients who have dyspeptic symptoms were identified. Routine lab investigations were done. Platelets counts were done before endoscopy. Patients with stable platelet counts and no active bleeding were subjected to upper GI endoscopy in the Medical Gastroenterology Department and the findings were recorded. A biopsy was taken from the antrum and it was subjected to Rapid urease test to detect H. pylori. Patients who turn out to be positive were put on H. pylori regimen.

Statistical analysis: Shapiro-Wilk Test was used for normality of data for parametric variable analysis. Continuous variables were analyzed by Mann-Whitney U and categorical variables were analyzed by Chi-square test. 𝑃 level of significance was considered at 5% level. Data analysis was performed on SPSS version 17.0.

Results

A total of 50 patients participated in the study. The patients’ characteristics were analyzed. The median age was 30 years, 16 were in the third decade and 13 in the fourth decade.

International Journal of Medical Research and Review 2019;7(6)521
Antony A. et al: Prevalence of H. pylori in Immune Thrombocytopenic

The majority of patients were male (78%) (Table 1).

Table-1: Baseline demographic and clinical characteristics of study patients.

Variables H. Pylori Negative H.Pylori Positive P value
Age 30.0 (21- 40) 30.0 (24.75 - 40.75) 0.671
Economic status     0.609
Upper 5 (62.5%) 3 (37.5%)
Lower 27 (64.3%) 15 (35.7%)
Gender     0.621
Male 25 (64.1%) 14 (35.9%)
Female 7 (63.6%) 4 (36.4%)
Platelet count 31000 (16250 - 46500) 20000 (9750 - 24250) 0.009
Bleeding     0.285
Yes 27 (61.4%) 17 (38.6%)
No 5 (83.3%) 1 (16.7%)
Skin rash     0.049
Yes 18 (54.5%) 15 (45.5%)
No 14 (82.4%) 3 (17.6%)
Dyspepsia Yes 10 (76.9%) 3 (23.1%) 0.216
No 22 (59.5%) 15 (40.5%)
Endoscopy (gastritis)     0.124
Yes 11 (52.4%) 10 (47.6%)
No 21 (72.4%) 8 (27.6%)
Blood group     0.053
A Positive 6 (85.7%) 1 (14.3%)
AB Positive 2 (100%) 0 (0%)
B Negative 1 (50%) 1 (50%)
B Positive 10 (90.9%) 1 (9.1%)
O Negative 0 (0%) 1 (100%)
O Positive 13 (48.1%) 14 (51.9%)
Duration 20.0 (12.25 - 39.0) 17.0 (7.5 - 46.5) 0.793

Prevalence of H. pylori in ITP patients: Analysis of patient's clinical profile was done and an antral biopsy and was subjected the specimen to rapid urease test, to detect the H. pylori status of the ITP patients. Out of the 50 ITP patients 18 were H. pylori positive that is the prevalence was 36%. The frequency of H. pylori infection was equal among females (35.89%) and males (36%) although ITP was more common among females.

Demographic profile of ITP patients: Applying the Kuppusamy’s criteria it was found that higher percentage of people (84%) were from the lower economic class and 16% from upper economic class. The frequency of H. pylori positivity was almost equal in both the upper class (37.5%) and lower class (35.7%).

In the present study, most of the patients were from urban area (76%). However, H. pylori positivity was more common in rural population, 41% (5 positives among 12) in ITP patients from rural areas and 34% (13 positives among 38) in urban area. Median platelet count was 21000 cells/cu mm in H. pylori positive individuals from both urban and rural population.

Among demographic profile of ITP patients, there was no significant difference between H. pylori positive and negative patients in terms of age, gender, economic status.

Clinical profile of ITP patients

Bleeding: 88% (44 of 50) presented with bleeding and 12% (6 of 50) were asymptomatic. Among the patients with bleeding 50% had major bleed (GI bleed, genitor-urinary and intra cranial) and 50% presented with minor bleed (skin and mucous bleed).

H.pylori positivity was more frequent in patients with bleeding 38% (17 of 44 positive) than patients without bleeding 16% (1 of 6). Median platelet in ITP patients with bleeding and H. pylori infection was 20000 cells/cmm.

Skin rash: Among 64% (32 of 50) of ITP patients with skin rash H. pylori positivity was seen in 47% (15 positives of 32) of these patients. H. pylori positivity among patients without skin rash was only 16.6%.

Dyspepsia: Out of 50 patients, only 13(26%) had dyspepsia and 74% had no dyspepsia. H. pylori positivity was only 7% among patients with dyspepsia as compared to 46% positivity in patients without dyspepsia.

Platelet count: All the 18 H. pylori positive patients had platelet counts less than 60000, out of these 77% (14 of 18) had platelet < 30000 and 23% (4 of 18) had platelet counts between 31000 and 600000. Significant low median platelet count (20000 cells/cmm) in ITP patients with H.pylori positivity was observed compared to ITP patients who were H.pylori negative (31000 cells/cmm) (P < 0.009).

Endoscopy (Gastritis): Out of 50 patients, 21 (42%) had gastritis on endoscopy and of these 47% (10 of 21) were positive for H.pylori. the remaining 29 (58%) patients did not have gastritis on endoscopy and only 27% (8 of 29) were H.pylori positive.

International Journal of Medical Research and Review 2019;7(6)522
Antony A. et al: Prevalence of H. pylori in Immune Thrombocytopenic

Out of 18 ITP patients positive for H.pylori, 55% (10 patients) had gastritis on endoscopy.

Blood group: In the present study majority of the patients had O positive (54%) and B positive blood groups (22%). 14% were A positive, 4% AB positive, 4% B negative and 2% O negative respectively. 14 out of the 18 H. pylori positive patients were O positive (77%).

Duration of ITP: In the present study, 66% (33 of 50) had chronic ITP, 22% (11 of 50) had persistent ITP, 6% (3 of 50) had ITP of less than 3 months duration and 6% (3 of 50) had spleenectomy done for refractory ITP. The median duration of ITP patients included in the present study was 18 months.

61% (11 of 18) H. pylori positive ITP patients had chronic ITP, 22% (4 of 18) had persistent ITP 11% (2 of 18) had acute ITP and 6% (1 of 18) had steroid refractory ITP.

H.pylori frequency was more among patients with acute ITP (66.66%) when compared to patients with persistent ITP (36.66%), chronic ITP (33.33%) and refractory ITP (33.33%).

In analyzing the clinical profile there was no significant difference between H. pylori positive and negative patients in terms of bleeding risk, dyspepsia, endoscopic findings and duration of ITP. However, a statistically significant difference between H. pylori positive and negative patients in terms of platelet counts were observed.

Discussion

Several studies have shown that ITP patients infected with H. pylori were found to be significantly older than ITP patients not infected with H. pylori [13-15]. Prevalence of H. pylori increases with increasing age and is mostly seen in patients more than 30 years of age. In the present study median age of H. pylori positive and H. pylori negative patients was 30 years.

Similar to other studies, no significant difference was demonstrated in the prevalence of H. pylori infected males and females. Duration of ITP is important in monitoring response to treatment of H. pylori. Shorter the duration better is the response. The median duration of H. pylori positive patients was 20 months and H. pylori negative patients was 17 months.

Significant association between H. pylori positivity and dyspepsia was reported by Patel P et al [17], but not by Stasi et al [l8]. In the present study there was no significant association between H. pylori and dyspepsia (P<0.38). No studies showed any significant association between the initial platelet count and H. pylori positivity [19] but most of the H. pylori infected ITP patients presented with severe form of ITP at the time of diagnosis. In the present study 14 of 18 (77.77%) H. pylori ITP patients presented with severe ITP at the time of diagnosis and their platelet counts were < 30000 cells/cmm and it is statistically significant, P value < 0.003.

H.pylori has been implicated in a number of autoimmune diseases like ITP [20]. The first association was proved in 1998 by Gasberrini et al [21]. Small study by Emilia et al (13 positive of 30) also proved significant association [22]. In the present study 18 (36%) were positive out 50 ITP patients. Similar to other studies, the presnt study also proves significant association between H. pylori and ITP.

Most of the studies had found a high frequency of H. pylori infection in patients with ITP and it was observed that in most of them after the eradication of H. pylori there was a significant increase in platelet count [23-25]. Worldwide analysis had found that 65.7% of ITP patients are infected with H. pylori. In contrast some studies from USA [26] and France [27] have reported only a low frequency of H. pylori infection. The possible explanation for this could be the low prevalence of H. pylori infection in this population. The reason for such discordant reports in uncertain but it might reflect the results of studying diverse patient groups, failure to stop concomitant treatment and the genetic diversity of H. pylori.

The frequency of H. pylori association with ITP reflected the prevalence of H. pylori in that geographical area. H. pylori positivity was propionate to the general population. This explains why most of the reports are from Japan and Italy. Successful H. pylori eradication led to good platelet response in areas where H. pylori infection rate in ITP patients was higher than in those where no association was found.

Conclusion

The present study confirms the existence of association between H. pylori and ITP.

International Journal of Medical Research and Review 2019;7(6)523
Antony A. et al: Prevalence of H. pylori in Immune Thrombocytopenic

A significant association between the platelet counts at presentation in H. pylori positive ITP patients was observed.

What the study adds to the existing knowledge?

There was no significant association with other parameters like sex, age, residence, socioeconomic status, bleeding, dyspepsia and endoscopy findings. Considering the low costs and non - invasiveness of the diagnostic test and the favorable toxicity profile of eradication compared to the standard treatment for ITP the detection and eradication of H. pylori should be considered in high prevalent areas. The British society of Hematology also recommends H. pylori eradication and screening as a treatment in ITP.

Author’s contribution

Dr. K Chenthil: Study design. Dr. Anny Antony: Sample collection. Dr. Margaret C.: Data collection. Dr. R. Karthikeyan: Data analysis. Dr. Anny Antony: Manuscript writing. Dr. Muhammed Ali: Revision of manuscript.

Reference

  1. Payandeh M, Raeisi D, Sohrabi N, et al. Poor platelet Count Response to Helicobacter Pylori Eradication in Patients with Severe Idiopathic Thrombocytopenic Purpura. Int J Hematol Oncol Stem Cell Res. 2013;7(3)9-14.
  2. Shaikh KH, Ahmed S, Ayyub M, Anwar J. Association of Helicobacter Pylori infection with Idiopathic Thrombo-cytopenic Purpura. J Pak Med Assoc. 2009;59(10)660-663.
  3. 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;97(3)812-814.
  4. Mukai M, Kon Y, Notoya A, Kohno M. Helicobacter pylori associated with idiopathic thrombocytopenic purpura. Am J Med. 2002;113(2)169-171.
  1. Michel M, Cooper N, Jean C, Frissora C, Bussel JB. Does Helicobater pylori initiate or perpetuate immune thrombocytopenic purpura?. Blood. 2004;103(3)890-896.
  2. 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.
  3. Graham DY, Adam E, Reddy GT, Agarwal JP, Agarwal R, Evans DJ Jr, et al. Seroepidemiology of Helicobacter pylori infection in India, Comparison of developing and developed countries. Dig Dis Sci. 1991;36(8)1084-1088.
  4. Gill HH, Majmudar P, Shankaran K, Desai HG. Age-related prevalence of Helicobacter pylori antibodies in Indian subjects. Indian J Gastroenterol. 1994;13(3)92-94.
  5. Dore SP, Krupadas S, Borgonha S, Kurpad A. The 13C urea breath test to assess Helicobacter pylori infection in school children. Natl Med J India. 1997;10(2)57-60.
  6. Katelaris PH, Tipett GHK, Norbu P, Lowe DG, Brennan R, Farthing MJG. Prevalence of Helicobacter pylori and peptic ulcer and relation to symptoms in a Tibetan refugee population in Southern India. Gut. 1992;33(11)1462-1466.
  7. Misra V, Misra SP, Dwivedi M, et al. 'Point Prevalence of Peptic Ulcer and Gastric Histology in Healthy Indians with Helicobacter pylori Infection. Am J Gastroenterol. 1997;92(9)1487-1491.
  8. Haruma K, Okamoto S, Kawaguchi H, Gotoh T, Kamada T, Yoshihara M, et al. Reduced incidence of Helicobacter pylori infection in young Japanese persons between the 1970s and the 1990s. J Clinic Gastroenterol. 1997;25(4)583-586.

International Journal of Medical Research and Review 2019;7(6)524
Antony A. et al: Prevalence of H. pylori in Immune Thrombocytopenic
  1. 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;81(2)162-168.
  2. Liebman HA, Stasi R. Secondary immune thrombo-cytopenic purpura. Curr Opin Hematol. 2007;14(5)557-573.
  3. 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;60(2)237-246.
  4. Michel 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(9)1033-1036.
  5. Patel P, Mendall MA, Khulusi S, Northfield TC, Strachan DP. Helicobacter pylori infection in childhood- risk factors and effect on growth. BMJ. 1994;309(6962)1119-1123.
  6. Stasi R, Rossi Z, Stipa E, Amadori S, Newland AC, Provan D. Helicobacter pylori eradication in the management of patients with idiopathic thrombocytopenic purpura. Am J Med. 2005;118(4)414-419.
  7. Veneri D, Bonani A, Franchini M, Fedrizzi A, Pizzolo G. Idiopathic thrombocytopenia and Helicobacter pylori infection- platelet count increase and early eradication therapy. Blood Transfus. 2011;9(3)340-342.
  8. Liebman H. Other immune thrombocytopenias. Semin Hematol. 2007;44(4-5)S24-34.
  1. Gasbarrini A, Franceschi F, Tartaglione R, et al. Regression of autoimmune thrombocytopenia after eradication of Helicobacter pylori. Lancet. 1998;352(9131)878.
  2. 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;110(12)3833-3841.
  3. Takahashi T, Yujiri T, Tanizawa Y. Helicobacter pylori and chronic ITP- the discrepancy in the clinical responses to eradication therapy might be due to differences in the bacterial strains. Blood. 2004;104(2)594.
  4. Kodama M, Kitadai Y, Ito M, Kai H, Masuda H, Tanaka S et al. Immune response to Cag A protein is associated with improved platelet count after Helicobacter pylori eradication in patients with idiopathic thrombocytopenic purpura. Helicobact. 2007;12(1)36-42.
  5. Galit H Frydman, Nick Davis, Paul L Beck, and James G. Fox, Helicobacter pylori Eradication in Patients with Immune Thrombocytopenic Purpura- A Review and the Role of Biogeography. Helicobact. 2015;20(4)239-251.
  6. Everhart JE, Kruszon-Moran D, Perez-Perez GI, Tralka TS, McQuillan G. Seroprevalence and ethnic differences in Helicobacter pylori infection among adults in the United States. J Infect Dis. 2000;181(4)1359-1363.
  7. Mentis A, Lehours P, Mégraud F. Epidemiology and Diagnosis of Helicobacter pylori infection. Helicobact. 2015;20(1)1-7.

International Journal of Medical Research and Review 2019;7(6)525