Poor response to prednisolone of idiopathic thrombocytopenia with human T-lymphotropic virus type I infection

We describe the unique clinical characteristics of patients with idiopathic thrombocytopenic purpura (ITP) who are infected by human T-lymphotropic virus type I (HTLV-I). Thirty-seven patients with ITP were examined in the present study: 10 patients had HTLV-I infection, and the remaining 27 did not. The mean age of the group with HTLV-I infection was significantly older than that of the group without infection (57.8 +/- 14.0 and 42.4 +/- 20.1, P = 0.022). The difference in mean platelet counts at diagnosis between the two groups was not significant, 29 x 10(9)/L and 21 x 10(9)/L, respectively. The levels of platelet associated IgG, red blood cell count, white blood cell count, bone marrow cell count, and megakaryocyte count did not show any significant difference. Nine patients in the group with HTLV-I infection were treated with prednisolone (1 mg/kg, daily oral). Only 3 of them responded to the therapy (one complete response [CR] and two partial responses [PR]). However, 17 of 22 patients not infected with HTLV-I were treated with prednisolone successfully: 14 patients achieved CR, and 3 patients achieved PR. There was a significant difference in response to prednisolone between the two groups (P = 0.034). Two patients with the infection and one patient without the infection achieved CR with splenectomy. These results suggest that HTLV-I infection may cause immune thrombocytopenia by a different mechanism than classical ITP; HTLV-I may modify the clinical features of ITP through an unknown immune pathway.     

Purification of Placenta-Eluted Gamma Globulins and Their Strong Effect against Graft-versus-Host Reactions In Vitro and In Vivo

A retrospective study was performed to determine the prevalence of Helicobacter pylori (H pylori) infection, the effect of H pylori eradication on platelet counts, and the characteristic clinical features of chronic immune or idiopathic thrombocytopenic purpura (ITP) with H pylori infection. H pylori infection was found in 300 patients, a group that was significantly older (P < .005) and had more cases of hyperplastic megakaryocytes in the bone marrow (P = .01) than patients without H pylori infection. H pylori eradication therapy was performed in 207 H pylori-positive ITP cases, and the platelet count response was observed in 63% of the successful eradication group and in 33% of the unsuccessful eradication group (P < .005). In the successful group, the complete remission and partial remission rates were 23% and 42%, respectively, 12 months after eradication. In the majority of responders, the platelet count response occurred 1 month after eradication therapy, and the increased platelet count continued without ITP treatment for more than 12 months. H pylori eradication therapy was effective even in refractory cases, which were unresponsive to splenectomy. In conclusion, H pylori infection was involved in most ITP patients older than 40 years in Japan, and eradication therapy should be the first line of treatment in H pylori-positive ITP patients.     

Can Eradication Therapy for Helicobacter pylori Really Improve the Thrombocytopenia in Idiopathic Thrombocytopenic Purpura? Our Experience and a Literature Review

Helicobacter pylori has recently been postulated to play a role in the pathogenesis of autoimmune diseases, including idiopathic thrombocytopenic purpura (ITP). We investigated the prevalence of H pylori infection and the effects of its eradication in 61 patients with ITP. H pylori infection was found in 50 patients (83%), an incidence significantly higher than not only healthy volunteers in Japan (60%) but also subjects in other reported ITP series (approximately 43%-71%). In our study, the mean age of H pylori-positive ITP patients (58.0 years) was significantly higher than that of H pylori-negative ITP patients (40.5 years). Bacterium eradication efforts were performed in 29 infected ITP patients and succeeded in 27 patients (93%). The 29 patients with eradicated H pylori infections showed significant increases in platelet counts compared with patients with uneradicated infections or who were H pylori-negative. During the follow-up period (median, 11.0 months), 16 (55%) of 29 patients achieved a major or a minor response. The patients who achieved a major response had not received previous prednisolone therapy, suggesting a relationship between prednisolone therapy and the response to eradication efforts. The assessment of H pylori infection and its eradication should be attempted in cases of ITP, because this approach may be a good new strategy for treating some ITP patients, especially elderly Japanese patients. Some regional factors have been suggested as causes of H pylori-associated ITP.     

Absence of platelet response after eradication of Helicobacter pylori infection in patients with chronic idiopathic thrombocytopenic purpura

Eradication of Helicobacter pylori infection has been associated with the correction of thrombocytopenia in patients with idiopathic thrombocytopenic purpura (ITP). We have analysed the response to eradication of H. pylori in a series of 56 adult patients with chronic ITP. Forty patients had H. pylori infection (71%) that was eradicated in 23 of 32 evaluable patients (72%). Platelet counts did not significantly vary according to H. pylori treatment outcome. Three of 56 patients (5%) achieved a partial response attributable to H. pylori eradication. Therefore, detection of H. pylori infection should not be routinely included in the initial work-up of ITP.     

Acquired amegakaryocytic thrombocytopenic purpura: review of a not very well-defined disorder

Acquired amegakaryocytic thrombocytopenic purpura (AATP) is a hematological disorder characterized by severe thrombocytopenia, probably due to an immunologically induced absence of megakaryocytes with a marked decrease or total absence of megakaryocytes in the bone marrow. AATP may be differentiated from other causes of peripheral destruction of platelets, such as immune thrombocytopenia (ITP). Currently, there are no standard treatments for AATP. However, immunosuppressive therapy including steroids, androgens, anti-thymocyte globulin (ATG), cyclophosphamide, cyclosporine A, immunoglobulins, splenectomy, and allogenic bone marrow transplantation (BMT) have all been utilized with varying degrees of success. However, a positive response in patients with AATP using steroids alone has rarely been reported in the literature.     

Alternate considerations for current concepts in ITP

Immune thrombocytopenia (ITP) is one of the most common forms of autoimmune disease affecting both adults and children. In recent years, there have been tremendous developments in the understanding of the pathogenesis and treatment of this condition. However, certain concepts related to ITP are worth consideration in view of alternative explanations and evidence available. These include (i) ITP is a disorder where thrombocytopenia is induced by autoantibodies against platelets or megakaryocytes, (ii) the mechanism of action of corticosteroids in ITP is through suppression of these autoantibodies, (iii) splenectomy is effective in ITP since spleen is the site of platelet destruction, and (iv) splenectomized ITP patients are at a major risk of infections.     

Clonally Expanded T-Cells in the Peripheral Blood of Patients with Idiopathic Thrombocytopenic Purpura and Helicobacter pylori Infection

Eradication of Helicobacter pylori leads to platelet recovery in some patients with idiopathic thrombocytopenic purpura (ITP). Therefore, the pathogenesis of a subgroup of ITP is probably associated with H pylori infection (H pylori-related ITP). If H pylori-related ITP is a definite subgroup of ITP, specific oligoclonal T-cells might accumulate in the peripheral blood (PB). To address this issue, we performed single-strand conformation polymorphism analysis of complementarity-determining region 3 (CDR3) of the T-cell receptor beta-chain genes of PB T-cells. Fourteen ITP patients with H pylori infection and 12 ageadjusted healthy volunteers were studied. Of the 14 patients, 8 patients (responders) exhibited a platelet response after successful H pylori eradication therapy, but 6 patients (nonresponders) did not. Vbeta5.2, Vbeta15, and Vbeta19 gene usage by clonally expanded T-cells in PB obtained before H pylori eradication therapy was significantly higher in responders than in nonresponders or healthy volunteers (Vbeta5.2, P = .023; Vbeta15, P = .004; Vbeta19, P = .036). Furthermore, an abrogation of clonally expanded T-cells was observed after therapy in some responders. These findings suggest that specific T-cell clones accumulate in H pylori-related ITP and that such clones may be associated with immune-mediated destruction of platelets.     

<Emphasis Type="Italic">Helicobacter pylori</Emphasis> Infection and Idiopathic Thrombocytopenic Purpura

A treatment strategy for idiopathic thrombocytopenic purpura (ITP) is considered with the aim of cure or management of the bleeding tendency. In 1998, Gasbarrini et al reported a high prevalence of Helicobacter pylori infection in patients with ITP and showed that platelet recovery occurred after eradication therapy in most cases. Since then, many studies were performed to evaluate eradication therapy. This article discusses the incidence of H pylori infection in ITP, characteristic clinical features in H pylori-positive ITP, the effectiveness of eradication on platelet count increase, and the mechanisms of development of ITP by H pylori infection. Overall, there was a positive association between H pylori infection and ITP, and eradication of bacterium was accompanied by a significant increase in platelet counts in more than 50% of H pylori-positive ITP cases. These findings suggest that H pylori infection is involved in the mechanisms of thrombocytopenia in most cases of ITP in middle-aged and older patients. This approach could be beneficial to some ITP patients, but there were some uncertainties raised. To confirm the effectiveness of eradication therapy in H pylori-positive ITP, prospective studies conducted in several countries with a new treatment protocol are required, with a large number of ITP cases and longer follow-up.     

Helicobacter pylori eradication in the management of patients with idiopathic thrombocytopenic purpura

PURPOSE: To investigate the relation between Helicobacter pylori infection and the clinical features of idiopathic thrombocytopenic purpura (ITP), and to examine the effects of H. pylori eradication on platelet counts. METHODS: A(13)C urea breath test for H. pylori infection was performed in a cohort of 137 consecutive patients with ITP. Patients who tested positive received standard eradication therapy if their platelet count was <50 x 10(9)/L or if they had symptoms of dyspepsia. RESULTS: H. pylori infection was detected in 64 patients (47%), and was not associated with dyspepsia or other clinical or laboratory features. Eradication therapy was successfully administered to 52 patients. Platelet responses were observed in 17 (33%) of these patients, which lasted for more than 1 year in 11 patients. Duration of ITP was shorter among responders than nonresponders. Only one response was observed among patients with severe thrombocytopenia (platelet count <30 x 10(9)/L). CONCLUSION: The prevalence of H. pylori infection in patients with ITP is similar to that found in the general population. Infection is not associated with distinctive features of the disease. H. pylori eradication may improve the platelet counts in adults in whom the ITP is of recent onset and in those with less severe degrees of thrombocytopenia, but was not effective in patients with chronic severe ITP.     

HIV-related thrombocytopenia

Chronic thrombocytopenia is a common hematologic disorder in patients infected with the human immunodeficiency virus (HIV). Although often asymptomatic, the thrombocytopenia may be associated with a variety of bleeding abnormalities. The underlying pathophysiology includes accelerated peripheral platelet destruction and decreased ('ineffective') production of platelets from the infected megakaryocytes. HIV-related thrombocytopenia (HIV-TP) responds to antiretroviral therapy. Most studies have evaluated the use of AZT (zidovudine) and have shown increased platelet production. Combination therapy (HAART) also resulted in sustained platelet increases. When antiretroviral agents fail to improve the platelet count or cannot be used, other therapies, similar to those used in 'classic' immune thrombocytopenia (ITP), can be employed, including steroids, intravenous immunoglobulin (i.v.intravenous anti-D or splenectomy. Anti-D treatment offers advantages for HIV-TP because the duration of effect appears to be significantly longer than the response duration after i.v. therapy (initial results of our open-arm study were confirmed by our randomized trial). Of note, follow-up of heavily treated patients showed no acceleration of CD4 decline and no change in plasma viral load measurements. Splenectomy has been used to treat HIV-positive patients with refractory thrombocytopenia. Although it is effective therapy, there are concerns about infections and selection of appropriate candidates. Other treatment modalities, such as interferon, vincristine, danazol, low-dose splenic irradiation and staphylococcal protein A immunoadsorption have shown limited success in HIV-TP. Alternatively, thrombocytopenia in HIV-infected patients may be treated with pharmacological hyperstimulation of megakaryocytopoiesis (administration of PEG-rHuMGDF or TPO). Latest evidence indicates that the chemokine receptor CXCR4 (coreceptor for the cellular entry of lymphotropic HIV strains) is expressed on megakaryocytes; as a result, the development of chemokine receptor antagonists may modify the course of the disease.     

Successful treatment of refractory idiopathic thrombocytopenic purpura by eradication of Helicobacter pylori

A 53-year-old woman was diagnosed as having idiopathic thrombocytopenic purpura (ITP) in 1990, and treated with prednisolone and splenectomy, which did not result in remission. In November 2000, gastrointestinal endoscopy showed superficial gastritis, and Helicobacter pylori infection was revealed by the rapid urease test and histologic examination. After eradication of Helicobacter pylori by amoxicillin, clarithromycin and lansoprazole, the patient's platelet count was increased from 24 x 10(9)/l to 134 x 10(9)/l and platelet-associated IgG (PAIgG) was decreased from 695 ng/10(7) cells to 33 ng/10(7) cells. This case suggests that eradication of Helicobacter pylori may be useful for treating some patients with refractory ITP.     

A case of lung cancer with idiopathic thrombocytopenic purpura effectively treated for Helicobacter pylori]

A 58-year-old man with cough and bloody sputum was admitted because of right lung tumor and thrombocytopenia. Idiopathic thrombocytopenic purpura (ITP) was diagnosed. For treatment of ITP, he was treated with platelet transfusions, intravenous gamma-globulin and oral prednisolone. However, the platelet count did not completely improved. Since a relationship between ITP and Helicobacter pylori (HP) infection has been reported, and result of urease test was positive, the patient was treated by HP eradication therapy. After the eradication therapy, the platelet count improved to the normal range. The diagnosis of squamous cell carcinoma of the lung was confirmed by a cervical lymph node biopsy. As a result of improvement in platelet count, we were able to perform the chemotherapy of lung cancer.     

Platelet activation in Helicobacter pylori-associated idiopathic thrombocytopenic purpura: eradication reduces platelet activation but seldom improves platelet counts

INTRODUCTION: It has been suggested that Helicobacter pylori eradication often increases platelet counts in patients with chronic idiopathic thrombocytopenic purpura (ITP). In addition, H. pylori has been shown to induce platelet activation (CD62p or P-selectin expression) in previous studies. We assessed the response of platelet count and CD62p expression after eradication therapy in patients with ITP and H. pylori infection. METHODS AND RESULTS: We prospectively studied 15 ITP patients diagnosed with H. pylori infection by serology and breath test. A follow-up breath test was used to document eradication. Two out of 15 patients showed improvement in platelet counts after 6 months, 1 of which may have had drug-induced thrombocytopenia. Overall, certain platelet response rate in our series was 6.7% (1/15). We found that platelet CD62p expression by flow cytometry was elevated in 10/15 (66.7%) H. pylori-infected patients, which is a statistically significant difference when compared with 3/33 (9.1%) control ITP patients seronegative for H. pylori (p = 0.002). In addition, eradication therapy decreased CD62p expression (p = 0.04). However, reduction in platelet activation was not associated with an increase in platelet counts (mean 72.4 x 10(9)/l before and 68.7 after therapy; p = 0.4). CONCLUSION: In our series, platelet activation was common in ITP patients with H. pylori, and eradication therapy decreased platelet activation but seldom increased platelet counts. Increased platelet CD62p expression is a putative link between chronic infections and atherosclerosis, but further study is needed to clarify the implications of our observation.     

Platelet recovery in patients with idiopathic thrombocytopenic purpura after eradication of Helicobacter pylori

The relationship between Helicobacter pylori infection and idiopathic thrombocytopenic purpura (ITP) has been investigated in several studies. We investigated the prevalence of H. pylori infection and the clinical effects of eradication in 22 Japanese patients with chronic ITP. H. pylori infection was found in 14 (63.6%) of the patients by histologic and culture examinations of biopsy samples obtained by gastrointestinal endoscopy. H. pylori was eradicated by proton pump inhibitors and 2 kinds of antibiotics in 13 (92.9%) of the 14 patients in whom the results of treatment could be evaluated. Five (38.4%) of those 13 patients had platelet recovery (platelet count of more than 100 x 10(9)/L and an increase of more than 30 x 10(9)/L with respect to the baseline value) after eradication. The median follow-up period was 15 months. One patient who had a complete response had a partial relapse after cessation of prednisolone treatment without any evidence of H. pylori reinfection. Another patient, in whom H. pylori was not eradicated even after 2 treatment sessions, had a partial response after treatment. A screening examination for H. pylori infection may be necessary for Japanese patients with newly diagnosed ITP. Although the exact mechanism underlying platelet recovery after H. pylori eradication is not clear, the results of this study indicated that H. pylori eradication treatment is a good option for some patients with chronic ITP.     

Helicobacter pylori and Immune Thrombocytopenic Purpura: Unsolved Questions and Controversies

Immune thrombocytopenic purpura (ITP) is an autoimmune disease mediated by anti-platelet autoantibodies. Recent accumulating evidence indicates that eradication of Helicobacter pylori (H pylori) is effective in increasing platelet count in nearly half of ITP patients infected with this bacterium. The H pylori eradication therapy for adult ITP is becoming very popular in Japan and is now chosen as an initial treatment in H pylori-infected patients. The lack of efficacy of the H pylori eradication regimen in H pylori-negative ITP patients clearly indicates that platelet recovery results from the disappearance of H pylori itself. Despite extensive efforts, clinical features characteristic to H pylori-related ITP and factors predicting the response after the H pylori eradication therapy have not been identified. Great variability in the efficacy of the H pylori eradication therapy in ITP patients exists among countries: a higher response rate has been found in Japan and Italy than in the United States and non-Italian European countries. Some children infected with H pylori show the platelet response after successful eradication of H pylori, but the H pylori eradication therapy is ineffective in patients with secondary ITP. The pathogenesis of ITP associated with H pylori remains obscure; the mechanisms are not simple and may involve multiple steps, including cross-reactivity between H pylori antigen and platelets, and suppression of the reticuloendothelial system. Further studies to evaluate the mechanisms responsible for the platelet response in ITP patients after successful eradication of H pylori may be useful in clarifying the pathogenesis of ITP and developing new therapeutic strategies for ITP.     

Immunologic thrombocytopenia followed by thrombotic thrombocytopenic purpura in two HIV1 patients.

Two homosexual HIV1-positive male patients with thrombotic thrombopenic purpura (TTP) were found to have past history of immune thrombocytopenia (ITP). The first patient had ITP 10 months prior to TTP and was successfully treated by splenectomy. The second patient had ITP 32 months before TTP. No specific treatment was given for his asymptomatic ITP. Association of HIV infection to TTP seems to be frequent. These two types of purpura have different pathogenic mechanisms but share a common altered immune response to antigenic challenge. The occurrence of ITP and TTP in HIV-positive patients may lead to errors in diagnosis and therapy.     

Effect of Helicobacter pylori eradication on platelet recovery in Japanese patients with chronic idiopathic thrombocytopenic purpura and secondary autoimmune thrombocytopenic purpura

The prevalence of Helicobacter pylori infection and the effect of its eradication on platelet count in 48 Japanese patients with autoimmune thrombocytopenic purpura (AITP), including 40 chronic idiopathic thrombocytopenic purpura (ITP) and eight secondary AITP, were investigated. H. pylori infection was found in 25 ITP patients (62.5%) and in two secondary AITP (25%). H.pylori eradication was obtained in 19 of 19 infected ITP patients (100%), who were not in remission (platelets < 100 x 109/l) at the time of infection assessment. During follow-up (median 14.8 months), 12 of 19 H. pylori-eradicated patients (63.2%) showed a significant increase in platelet count accompanied by a significant decrease of platelet-associated immunoglobulin G (IgG). This response was maintained in all responding patients throughout the follow-up period. However, two infected patients with secondary AITP did not show platelet increase after eradication. The assessment of H. pylori infection and its eradication should be attempted in ITP as this approach could be an effective strategy, at least for some of these patients.     

Does H. Pylori infection play a role in idiopathic thrombocytopenic purpura and in other autoimmune diseases?

Idiopathic thrombocytopenic purpura (ITP), an autoimmune disease caused by sensitization of platelets by autoantibodies leading to platelet destruction, has been associated with some infectious agents, including Helicobacter pylori. The study by Suzuki et al., published in this issue, provides further evidence of the role of H. pylori infection in the pathogenesis of ITP, as confirmed by the increase in the platelet count in patients with ITP, following H. pylori eradication. Interestingly, H. pylori infection has also been shown to play a role in other diseases in which autoimmune mechanisms may be predominant, such as acne rosacea, idiopathic chronic urticaria, and atherosclerosis. While H. pylori eradication is usually recommended in patients with gastric diseases, there are no specific indications for extraalimentary diseases. In the light of the recent findings, a revision of the current guidelines for the management of H. pylori infection may be needed.     

The long-term efficacy of Helicobacter pylori eradication therapy in patients with idiopathic thrombocytopenic purpura

BACKGROUND AND AIM: A beneficial effect of Helicobacter pylori (H. pylori) eradication in patients with H. pylori-positive idiopathic thrombocytopenic purpura (ITP) has been reported by several investigators; however, it was not clear whether the recovered platelet count after H. pylori eradication was maintained for a long period. METHOD: Thirty-eight ITP patients who were examined for H. pylori infection were assessed. H. pylori-positive patients received a standard antibiotic therapy for H. pylori eradication. We investigated the long-term effect of H. pylori eradication on platelet recovery in patients with H. pylori-positive ITP. RESULTS: Of the 38 ITP patients, 26 (68.4%) were positive for H. pylori. The response rate of platelet recovery was 56.5% (13/23 patients). Twelve patients showed complete response (CR) and one showed partial response (PR). The mean platelet counts 6 months after eradication significantly increased from 31 x 10(9)/L to 129 x 10(9)/L in 23 H. pylori-eradicated patients (P < 0.001). The median platelet counts of responders 1, 2, 3, and 4 years after eradication were 168 x 10(9)/L (n = 10), 193 x 10(9)/L (n = 9), 168 x 10(9)/L (n = 7), and 243 x 10(9)/L (n = 4) after a mean follow-up of 25.8 months. CONCLUSION: Eradication therapy for H. pylori-positive patients with ITP was effective and a favorable effect was maintained for long periods.     

Helicobacter pylori eradication can induce platelet recovery in idiopathic thrombocytopenic purpura

Recent reports have suggested an association between Helicobacter pylori infection and idiopathic thrombocytopenic purpura (ITP). The prevalence of H pylori infection and the effect of its eradication in a series of 30 ITP patients were investigated. H pylori infection has been documented in 13 patients (43.33%) by 13C urea breath test and confirmed by histologic examination. Bacterium eradication with antibiotics, obtained in 12 of 13 infected patients (92.3%), led to a complete response in 4 (33.33%) and to a partial response (platelets 90 x 10(9)/L-120 x 10(9)/L) in 2 (16.66%). The response was maintained for a median of 8.33 months, but 1 patient relapsed 7 months after eradication. Search for H pylori infection seems appropriate in ITP patients at diagnosis. Bacterium eradication provides a new good option for a nonimmunosuppressive treatment in some ITP patients.