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Ihtesham A, Maqbool S, Nadeem M, Bilawal Abbas Janjua M, Sundus O, Bakht Naqqash A, Inayat Mohamed W, Turab Haider S, Ahmad M, Ahmad Talha Mustafa M, Osama Mehboob H. Helicobacter pylori induced Immune Thrombocytopenic Purpura and perspective role of Helicobacter pylori eradication therapy for treating Immune Thrombocytopenic Purpura. AIMS Microbiol 2021; 7:284-303. [PMID: 34708173 PMCID: PMC8500795 DOI: 10.3934/microbiol.2021018] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2021] [Accepted: 08/30/2021] [Indexed: 12/12/2022] Open
Abstract
Immune thrombocytopenic purpura (ITP) is an autoimmune disease characterised by production of autoantibodies against platelet surface antigens. Recent studies have demonstrated a paramount association of ITP and Helicobacter pylori (H-pylori) infection with significant rise in platelet count following H-pylori eradication therapy. The H-pylori infection induced ITP is validated by many proposed mechanisms such as molecular mimicry due to production of autoantibodies against H-pylori surface virulent factors (CagA) and cross reactivity of these antibodies with platelet surface antigens (GP IIb/IIIa, GP Ib/IX, and GP Ia/IIa), phagocytic perturbation due to enhanced phagocytic activity of monocytes, enhanced dendritic cell numbers and response, platelets aggregation due to presence of anti- H-pylori IgG and von Willebrand factor (vWf) and finally host immune response against H-pylori virulent factors CagA and VacA leading to ITP. The effectiveness of H-pylori eradication therapy has also been demonstrated with platelet count being used as a predictive factor for assessment of treatment efficacy. Out of 201 patients 118 were responding to the triple therapy and remaining 83 patients were non-responders, showing the response rate of 58.7%. Out of 118 responders 69 patients were showing complete response (CR) and 49 were showing partial response (PR) to the H-pylori eradication therapy. However, more studies are required to elucidate this association and treatment efficacy.
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Affiliation(s)
| | | | | | | | - Omaima Sundus
- House officers Rawalpindi Medical University, Pakistan
| | | | | | | | - Muhmmad Ahmad
- House officers Services Institute of Medical Sciences, Pakistan
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Impact of Helicobacter pylori Eradication in Children with Acute Immune Thrombocytopenia: A Randomized Controlled Study. ARCHIVES OF PEDIATRIC INFECTIOUS DISEASES 2019. [DOI: 10.5812/pedinfect.90522] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
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Pan JQ, Wang W, Wang ML, Li XY, Wang JH, Zhao WW, Tian YY, Dong XS, Jiang YF. Recognition of the human antibody-mediated platelet destruction in adult ITP patients by C-reactive protein. INTERNATIONAL JOURNAL OF CLINICAL AND EXPERIMENTAL PATHOLOGY 2017; 10:10176-10185. [PMID: 31966351 PMCID: PMC6965790] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Received: 05/26/2017] [Accepted: 08/02/2017] [Indexed: 06/10/2023]
Abstract
Immune thrombocytopenia purpura (ITP) is characterized by destruction of circulating platelets and the presence of antiplatelet IgG antibodies, which opsonize platelets for splenic clearance resulting in low levels of circulating platelets, and the disease severity can be predicted neither by antibody isotype nor by titer, indicating that other factors also play a role. Although the main cause of ITP remains unclear, but its relationship with some infection was demonstrated, including viral or bacterial infections. C-reactive protein (CRP), a member of the pentraxin family, is a major acute-phase protein in humans and is a clinical marker of infection. We aimed to investigate the correlation between the levels of CRP and the presence of antiplatelet IgG antibodies in adults with newly diagnosed ITP. CRP levels and platelet counts were measured in the blood samples from a 60 ITP patient (with confirmed anti-GPIIb/IIIa antibodies), 60 infection patients (all without anti-GPIIb/IIIa antibodies) and 60 normal individuals. The bleeding score, recover time of intravenous immune globulin (IVIg) therapy and the number of megakaryocytes in bone marrow were recorded in ITP patients. The platelet count, bleeding score, recover time of intravenous immune globulin (IVIG) therapy and the number of megakaryocytes in bone marrow and CRP concentrations were compared in ITP group using Spearman's correlation coefficient. We examined the influence of intraperioneal CRP administration on antibody-mediated platelet destruction in mice. There were no statistical differences in gender, age and body mass index among the three groups (P>0.05). Though CRP levels are significantly elevated in ITP patients and infection patients (P<0.05), the platelet count was markedly lower only in ITP patients. We found that CRP was inert toward platelets without antiplatelet antibodies in this study. There are a significant correlation between CRP levels and platelet counts, bleeding severity and the number of megakaryocytes in bone marrow aspiration (r=-0.5079, r=0.5498, r=0.4172, P<0.001, respectively). Moreover, a significant correlation was observed between the recovery time of platelet count and CRP levels (r=-0.5569, P<0.001). In mice, platelet count was lower in Anti-CD41 (0.75 μg)+, CRP (200 μg) group as compared with Anti-CD41 (0.75 μg)+, CRP(-) group and Anti-CD41 (0.75 μg)-, CRP (200 μg) group (P<0.05). In summary, this study indicated that CRP levels are significantly elevated in ITP patients all with confirmed anti-GPIIb/IIIa antibodies, which is able to predict the clinical bleeding severity of ITP patients. The slower CRP levels reduction after IVIg treatment predicted slower platelet count recovery in ITP.
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Kim TH, Cheung DY. Helicobacter pylori Eradication, a Gordian Knot for Idiopathic Thrombocytopenic Purpura? Gut Liver 2017; 10:323-4. [PMID: 27114429 PMCID: PMC4849680 DOI: 10.5009/gnl16095] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/21/2023] Open
Affiliation(s)
- Tae Ho Kim
- Department of Internal Medicine, The Catholic University of Korea College of Medicine, Seoul, Korea
| | - Dae Young Cheung
- Department of Internal Medicine, The Catholic University of Korea College of Medicine, Seoul, Korea
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Frydman GH, Davis N, Beck PL, Fox JG. Helicobacter pylori Eradication in Patients with Immune Thrombocytopenic Purpura: A Review and the Role of Biogeography. Helicobacter 2015; 20:239-51. [PMID: 25728540 PMCID: PMC4506733 DOI: 10.1111/hel.12200] [Citation(s) in RCA: 41] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Idiopathic thrombocytopenic purpura (ITP) is typically a diagnosis of exclusion, assigned by clinicians after ruling out other identifiable etiologies. Since a report by Gasbarrini et al. in 1998, an accumulating body of evidence has proposed a pathophysiological link between ITP and chronic Helicobacter pylori (H. pylori) infection. Clinical reports have described a spontaneous resolution of ITP symptoms in about 50% of chronic ITP patients following empirical treatment of H. pylori infection, but response appears to be geography dependent. Studies have also documented that ITP patients in East Asian countries are more likely to express positive antibody titers against H. pylori-specific cytotoxic-associated gene A (CagA), a virulence factor that is associated with an increased risk for gastric diseases including carcinoma. While a definitive mechanism by which H. pylori may induce thrombocytopenia remains elusive, proposed pathways include molecular mimicry of CagA by host autoantibodies against platelet surface glycoproteins, as well as perturbations in the phagocytic activity of monocytes. Traditional treatments of ITP have been largely empirical, involving the use of immunosuppressive agents and immunoglobulin therapy. However, based on the findings of clinical reports emerging over the past 20 years, health organizations around the world increasingly suggest the detection and eradication of H. pylori as a treatment for ITP. Elucidating the exact molecular mechanisms of platelet activation in H. pylori-positive ITP patients, while considering biogeographical differences in response rates, could offer insight into how best to use clinical H. pylori eradication to treat ITP, but will require well-designed studies to confirm the suggested causative relationship between bacterial infection and an autoimmune disease state.
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Affiliation(s)
- Galit H. Frydman
- Department of Biological Engineering, Division of Comparative Medicine, Massachusetts Institute of Technology, Cambridge, MA, USA
| | - Nick Davis
- Department of Biological Engineering, Division of Comparative Medicine, Massachusetts Institute of Technology, Cambridge, MA, USA
| | - Paul L. Beck
- The Gastrointestinal Research Group, Division of Gastroenterology, University of Calgary, Calgary, AB, Canada
| | - James G. Fox
- Department of Biological Engineering, Division of Comparative Medicine, Massachusetts Institute of Technology, Cambridge, MA, USA
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Campuzano-Maya G. Hematologic manifestations of Helicobacter pylori infection. World J Gastroenterol 2014; 20:12818-12838. [PMID: 25278680 PMCID: PMC4177465 DOI: 10.3748/wjg.v20.i36.12818] [Citation(s) in RCA: 39] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/03/2014] [Revised: 06/10/2014] [Accepted: 07/16/2014] [Indexed: 02/06/2023] Open
Abstract
Helicobacter pylori (H. pylori) is the most common infection in humans, with a marked disparity between developed and developing countries. Although H. pylori infections are asymptomatic in most infected individuals, they are intimately related to malignant gastric conditions such as gastric cancer and gastric mucosa-associated lymphoid tissue (MALT) lymphoma and to benign diseases such as gastritis and duodenal and gastric peptic ulcers. Since it was learned that bacteria could colonize the gastric mucosa, there have been reports in the medical literature of over 50 extragastric manifestations involving a variety medical areas of specialization. These areas include cardiology, dermatology, endocrinology, gynecology and obstetrics, hematology, pneumology, odontology, ophthalmology, otorhinolaryngology and pediatrics, and they encompass conditions with a range of clear evidence between the H. pylori infection and development of the disease. This literature review covers extragastric manifestations of H. pylori infection in the hematology field. It focuses on conditions that are included in international consensus and management guides for H. pylori infection, specifically iron deficiency, vitamin B12 (cobalamin) deficiency, immune thrombocytopenia, and MALT lymphoma. In addition, there is discussion of other conditions that are not included in international consensus and management guides on H. pylori, including auto-immune neutropenia, antiphospholipid syndrome, plasma cell dyscrasias, and other hematologic diseases.
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Shim YJ, Kim UH, Suh JK, Lee KS. Natural course of childhood chronic immune thrombocytopenia using the revised terminology and definitions of the international working group: a single center experience. Blood Res 2014; 49:187-91. [PMID: 25325039 PMCID: PMC4188785 DOI: 10.5045/br.2014.49.3.187] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2014] [Revised: 08/26/2014] [Accepted: 08/26/2014] [Indexed: 11/17/2022] Open
Abstract
BACKGROUND The immune thrombocytopenia (ITP) criteria were newly standardized by the International Working Group. Thus, we analyzed the natural course of childhood chronic ITP to predict the prognosis based on the revised criteria. METHODS The medical records of children with chronic ITP from May 2000 to February 2013 in our institute were reviewed. RESULTS Forty-seven children with chronic ITP who were not undergoing corticosteroid therapy were included. Their initial platelet count was 23±25×10(9)/L, and age at diagnosis was 6.3±4.1 years. The follow-up period was 5.4±3.7 years. Among them, 44.7% (21/47) showed spontaneous remission and maintained a platelet count ≥100×10(9)/L. And 66.0% (31/47) maintained a platelet count ≥50×10(9)/L until the last follow-up date. The time periods required for the platelet count to be maintained ≥50×10(9)/L and ≥100 ×10(9)/L were 3.1±2.7 and 3.6±2.7 years. Age at diagnosis in the ≥50×10(9)/L group (5.7±4.4 years) was significantly lower than the age at diagnosis in the <50×10(9)/L group (7.4±3.3 years) (P=0.040). And follow-up period was the factor influencing prognosis between the ≥100×10(9)/L group and <50×10(9)/L group (P=0.022). CONCLUSION Approximately 45% of children with chronic ITP recovered spontaneously about 3-4 years after the diagnosis and 2/3 of patients maintained a platelet count ≥50×10(9)/L, relatively safe state. Age at diagnosis of ITP and follow-up period were the factors influencing prognosis in this study.
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Affiliation(s)
| | - Uk Hyun Kim
- Incheon Medical Center Beakryung Hospital, Beakryung-do, Korea
| | - Jin Kyung Suh
- Division of Pediatric Hematology/Oncology, Asan Medical Center Children's Hospital, Department of Pediatrics, University of Ulsan College of Medicine, Seoul, Korea
| | - Kun Soo Lee
- Department of Pediatrics, Kyungpook National University Hospital and Kyungpook National University School of Medicine, Daegu, Korea
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Hill LJN, Tung EE. From prednisone to pylori: a case of Helicobacter pylori-induced chronic immune thrombocytopenia. BMJ Case Rep 2014; 2014:bcr-2014-205786. [PMID: 25035453 DOI: 10.1136/bcr-2014-205786] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022] Open
Abstract
A 54-year-old woman was seen by her primary care internist for a general health maintenance visit. Her major chronic illness was immune thrombocytopenic purpura (ITP) for which she had been treated with prednisone therapy for the past 15 years. Recent review of possible aetiologies of her chronic thrombocytopenia revealed infection with Helicobacter pylori. Successful eradication resulted in complete resolution of her thrombocytopenia within 2 months. She was weaned from steroid therapy and at 1-year follow-up, her platelet counts remained in the normal range. This case report summarises what is known about the association of H. pylori infection and ITP.
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Affiliation(s)
| | - Ericka E Tung
- The Division of Primary Care Internal Medicine, Mayo Clinic College of Medicine, Rochester, Minnesota, USA
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Papagiannakis P, Michalopoulos C, Papalexi F, Dalampoura D, Diamantidis MD. The role of Helicobacter pylori infection in hematological disorders. Eur J Intern Med 2013; 24:685-690. [PMID: 23523153 DOI: 10.1016/j.ejim.2013.02.011] [Citation(s) in RCA: 40] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/09/2012] [Revised: 02/13/2013] [Accepted: 02/21/2013] [Indexed: 12/14/2022]
Abstract
Helicobacter pylori (H. pylori) is a Gram-negative spiral bacterium, classified as a carcinogen of class I, according to the World Health Organization (WHO). The infection is a major cause of gastritis, gastric and duodenal ulcer disease and increases the risk of gastric cancer. It has been implicated in the pathogenesis of several gastrointestinal, systemic or hematological diseases. The present review aims in deciphering the role of the bacterium in hematological disorders, increasing the awareness of gastroenterologists, hematologists and internal medicine practitioners, regarding the bacterium-associated hematological diseases. The efficacy of H. pylori eradication in increasing the platelet count in adult patients with primary immune thrombocytopenia (ITP) has been confirmed, linking the infection with the disease. Moreover, as the bacterium causes iron deficiency anemia (IDA) by several mechanisms, recent guidelines indicate H. pylori infection (Hp-I) to be sought in IDA patients if histology is negative and to be eradicated if present. Furthermore, it has been widely recognized that anti-H. pylori treatment causes regression of the low-grade B-cell gastric MALT lymphomas. Despite the well established associations of Hp-I with the aforementioned hematological disorders, we highlight the possible role of the infection to other hematological diseases or conditions such as non-Hodgkin lymphomas of the stomach, monoclonal gammopathy of undetermined significance, megaloblastic anemia and myelodysplastic syndromes. We finally underline the elevated risk of childhood leukemia and of hemorrhage in patients with coagulation disorders, due to the infection.
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MESH Headings
- Anemia, Iron-Deficiency/complications
- Anemia, Iron-Deficiency/microbiology
- Anemia, Megaloblastic/complications
- Anemia, Megaloblastic/microbiology
- Helicobacter Infections/complications
- Helicobacter Infections/drug therapy
- Helicobacter pylori
- Hematologic Diseases/complications
- Hematologic Diseases/microbiology
- Humans
- Lymphoma, B-Cell, Marginal Zone/complications
- Lymphoma, B-Cell, Marginal Zone/microbiology
- Lymphoma, Non-Hodgkin/complications
- Lymphoma, Non-Hodgkin/microbiology
- Monoclonal Gammopathy of Undetermined Significance/complications
- Monoclonal Gammopathy of Undetermined Significance/microbiology
- Myelodysplastic Syndromes/complications
- Myelodysplastic Syndromes/microbiology
- Purpura, Thrombocytopenic, Idiopathic/complications
- Purpura, Thrombocytopenic, Idiopathic/microbiology
- Stomach Neoplasms/complications
- Stomach Neoplasms/microbiology
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Affiliation(s)
- Panagiotis Papagiannakis
- Department of Haematology, Second Department of Internal Medicine, Hippokration General Hospital, Aristotle University of Thessaloniki (AUTH), Faculty of Medicine, Thessaloniki, Greece
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Hu D, Shao J, Wang L, Zheng H, Xu Y, Song G, Liu Q. Prevalence and risk factors ofHelicobacter pyloriinfection in Chinese maritime workers. Ann Hum Biol 2013; 40:472-6. [DOI: 10.3109/03014460.2013.804121] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/25/2023]
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Payandeh M, Raeisi D, Sohrabi N, Zare ME, Kansestani AN, Keshavarz N, Gholami S, Hashemian AH. Poor platelet Count Response to Helicobacter Pylori Eradication in Patients with Severe Idiopathic Thrombocytopenic Purpura. Int J Hematol Oncol Stem Cell Res 2013; 7:9-14. [PMID: 24505529 PMCID: PMC3913150] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2013] [Accepted: 06/02/2013] [Indexed: 11/22/2022] Open
Abstract
INTRODUCTION ITP is an autoimmune blood disorder in which platelet destruction is mediated by anti-platelet antibodies. The mechanisms of anti-platelet antibodies development are still a little known. The rate of some bacterial or viral agents in cause of ITP is well known. Recently, some study proposed that H pylori infection may be associated with ITP and H pylori eradication can improves platelet counts in infected ITP patients. MATERIALS AND METHOD A baseline platelet count <50×10(3) µL for 4 weeks prior to study entry were required. These patients were tested for H. pylori infection by urea breath. All positive H pylori patients received triple therapy for 7 or 14 days to eradicate H pylori infection. These patients followed for six months. RESULTS Of 92 patients with ITP, H pylori infection was found in 59.7% (55/92). After excluding patients with confounding factors, 41 patients were remained. After H pylori eradication, CR wasn't obtained in any patients. Partial response were obtained only in 3 (7.3%) of the 41 patients and no response in 38 (92.6%) patients. There is a significant difference between the platelet counts of PR and NR groups (P < 0.001). CONCLUSION The results of this study and our previously study showed H pylori eradication therapy has beneficial effect for patients with mild thrombocytopenia but the chance of obtaining a response by H pylori treatment is lower in patients with severe thrombocytopenia.
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Affiliation(s)
- Mehrdad Payandeh
- Medical Biology Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Dariyush Raeisi
- Medical Biology Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Nasrollah Sohrabi
- Department of Medical Laboratory Sciences, Para medicine Faculty, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Mohammad Erfan Zare
- Medical Biology Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran,Student Research Committee, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Atefeh Nasir Kansestani
- Medical Biology Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran,Student Research Committee, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Nazanin Keshavarz
- Student research committee, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Samira Gholami
- Student Research Committee, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Amir Hossein Hashemian
- Department of Biostatistics, Faculty of Public Health, Kermanshah University of Medical Sciences, Kermanshah, Iran,Corresponding Author: Amir Hossein Hashemian, Assisstant professor of biostatistics, Department of Biostatistics, Faculty of Public Health, Kermanshah University of Medical Sciences, Kermanshah, Iran. Tel: +98 831 8281993, Fax: +98 831 8263048. E-mail:
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Platelet Count Response to Helicobacter pylori Eradication in Iranian Patients with Idiopathic Thrombocytopenic Purpura. Mediterr J Hematol Infect Dis 2012; 4:e2012056. [PMID: 22973500 PMCID: PMC3435127 DOI: 10.4084/mjhid.2012.056] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2012] [Accepted: 07/24/2012] [Indexed: 12/11/2022] Open
Abstract
Idiopathic thrombocytopenic purpura (ITP) is an autoimmune hematological disorder characterized by auto antibody-mediated platelet destruction. Although the main cause of ITP remains unclear, but its relationship with some infection was demonstrated. In recent years, many studies have demonstrated improvement of platelet counts in ITP patients after treating Helicobacter pylori infection. The aim of this study was to investigate the effects of H. pylori eradication on platelet count response in Iranian ITP patients. A total of 26 patients diagnosed with both ITP and H. pylori infection. ITP were diagnosed whose platelet counts were less than 100×103/μL. These patients were tested for H. pylori infection by Urea Breath Test and serum H. pylori antibody. All patients received triple therapy for 7 or 14 days to eradicate H. pylori infection. These patients followed for six months. Prevalence of H. pylori was 67.3%. H. pylori eradication achieved in 89.5% (26/29). Of the 26 patients, 15 (57.7%) exhibited a complete response (CR) and 11 (42.3%) were unresponsive. We did not find partial responders. There was a significant difference in the baseline platelet count of responders and non-responders patients (p<0.001). All responders had platelet count ≥50×103/μL and all non-responders had platelet count <50×103/μL. Results of this study revealed that eradication therapy of H. pylori infection can improve platelet counts in ITP patients especially with mild thrombocytopenia and support routine detection and treatment of H. pylori infection in ITP patients in populations with a high prevalence of this infection.
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