Chronic Idiopathic Thrombocytopenic Purpura Patients Research Articles

Efficacy of Helicobacter pylori eradication on platelet recovery in children with chronic idiopathic thrombocytopenic purpura

Aim: Little is known about the influence of environmental factors on the epidemiology of idiopathic thrombocytopenic purpura (ITP). The role of Helicobacter pylori infection in relation to the development and/or persistence of ITP in infected patients remains controversial. Therapy used for eradicating H. pylori has led to a rise in platelet counts in a significant number of adult patients, but few paediatric studies have been undertaken to evaluate such treatment. The aim of this prospective study was to determine the prevalence of H. pylori and to evaluate whether H. pylori eradication can induce chronic ITP regression in children. Methods: To investigate new, non‐invasive techniques for diagnosis of H. pylori infection, an enzyme immunoassay for H. pylori antigens in faeces (HpSA) was evaluated. Patient eligibility criteria included isolated thrombocytopenia (±50 ± 109 L−1) for more than 6 months without any identifiable cause and either normal or increased marrow megakaryocytes. H. pylori status was monitored before eradication and 4, 12, and 24 mo, after the end of treatment using Premier Platinum HpSA. Results: In this study we evaluated 22 chronic ITP patients, 9 of whom were infected with H. pylori. Using repeated HpSA testing, we demonstrated for eradication of H. pylori after treatment in all infected patients. Five of the nine patients had increased platelet counts that persisted throughout the follow‐up period. Conclusion: These results should stimulate additional research into the involvement of H. pylori infection in chronic ITP in childhood. This approach may offer an accepted algorithm at least for some of these patients.

Oral vaccination with autologous platelets in chronic autoimmune thrombocytopenic purpura

Idiopathic thrombocytopenic purpura (ITP) is a common disease of autoimmune mechanism in which nearly 40% of patients need a third-line treatment after steroids and splenectomy failure. Due to the variable results of the multiple therapeutic modalities in refractory patients it is necessary to develop a more effective treatment. Following previous assays of immunotolerance with the administration of ‘oral vaccines’, we propose a therapeutic protocol in chronic ITP patients with autologous cryopreserved or liophilized platelets administered in enteric capsules. The procedure is theoretically feasible and technically easy and does not need the isolation of the specific antigen target of the autoantibodies in each particular case.

Involvement of Fc gamma receptor polymorphism in the therapeutic response of idiopathic thrombocytopenic purpura.

Clearance of autoantibody-sensitized platelets through Fc gamma receptors on phagocytic cells is one of the main mechanisms of thrombocytopenia in idiopathic thrombocytopenic purpura (ITP). We examined the Fc gamma RIIA-131R/H and Fc gamma RIIIA-158V/F polymorphisms in 104 adult chronic ITP patients, and in 59 healthy control subjects using polymerase chain reaction-based allele-specific restriction analysis. The frequency of Fc gamma RIIA genotypes (131H/H, H/R, R/R) was not significantly different between patients and controls, and did not correlate with the responsiveness to treatment. In contrast, among Fc gamma RIIIA genotypes, frequency of 158F/F homotype was smaller in ITP (P < 0.05). Furthermore, in Fc gamma RIIIA-158V/V homotype, the complete remission (CR) rate with medication (treatment with corticosteroid or other immunosuppressive agents) was significantly higher (60%) than that in 158V/F (10%) or 158V/F plus 158F/F, (P < 0.01, P < 0.05). Conversely, the CR rate after splenectomy in 158F/F and 158V/F types (64.3% and 54.6%) was higher than in 158V/V (25%). Our results indicate that the polymorphism of Fc gamma RIIIA, but not Fc gamma RIIA, influences the response to treatment in ITP.

Response to high‐dose intravenous immune globulin as a valuable factor predicting the effect of splenectomy in chronic idiopathic thrombocytopenic purpura patients

This study was conducted to verify whether the response to high-dose intravenous immune globulin (IVIG) was related to the effect of splenectomy in chronic idiopathic thrombocytopenic purpura (ITP) patients. A total of 79 patients over 16 years of age were enrolled in this study. The response to the treatment was classified on the basis of the platelet count as no response (NR, <50 × 109/l), incomplete response (IR, (50–150) × 109/l), and complete response (CR, >150 × 109/l). The response was evaluated after the infusion of high-dose IVIG, within 2 weeks after splenectomy (immediate response), and during a follow-up period of more than 6 months after splenectomy (sustained response), respectively. 58 patients (73.4%) showed responses (CR or IR) to high-dose IVIG. After splenectomy, immediate responses were observed in 73 patients (92%). The response to high-dose IVIG had no relationship with the immediate response to splenectomy (P = 0.333). A follow-up evaluation was possible with 58 patients; 6 patients with NR in immediate responses did not show any response during the follow-up period, and 17 patients relapsed within 6 months after immediate responses, so 35 patients (60.3%) had sustained responses. Responders to IVIG had significantly higher sustained response rates to splenectomy than non-responders (62% vs. 38%, P = 0.001). These results indicate that the response to high-dose IVIG could be a valuable factor predicting the sustained response to splenectomy in chronic ITP patients. Am. J. Hematol. 66:197–202, 2001. © 2001 Wiley-Liss, Inc.

A transforming growth factor-beta1-mediated bystander immune suppression could be associated with remission of chronic idiopathic thrombocytopenic purpura.

Bystander immune suppression has been demonstrated in experimental models of oral immune tolerance induction. This phenomenon is associated with expression of transforming growth factor (TGF)-beta1 and T-helper cell (Th) 2 cytokines. We have studied serum levels of Th cytokines and B- and T-lymphocyte subsets in chronic idiopathic thrombocytopenic purpura (ITP), a disorder in which the production of platelet autoantibodies might be caused by a cytokine network dysregulation. Forty-six patients with ITP were separated into three groups depending on the platelet count (pltc): (1) < 50 x 10(9)/l, (2) 50-150 x 10(9)/l and (3) > 150 x 10(9)/l. We found significantly elevated plasma levels of the Th3 cytokine TGF-beta1 in patients with pltc >150x10(9)/l (23.5+/-2.8ng/ml), compared with patients with pltc <50x10(9)/l (2.3+/-0.6 ng/ml; P<0.0001), patients with pltc 50-150x 10(9)/l (7.2+/-1.7 ng/ml; P<0.0001) and healthy volunteers (9.8+/-1.3 ng/ml; P<0.01). The serum levels of the Thl cytokines interleukin (IL)-2 and interferon (IFN)-y were below the detection limits of the assays. Likewise, the Th2 cytokine IL-4 was not detectable or was very low both in patients and controls. The serum levels of IL-10, a Th2 cytokine, were within the assay range and patients with pltc <50 x 10(9)/l had significantly lower levels (0.6+/-0.1 pg/ml) than both patients with pltc 50-150 x 10(9)/l (1.8 +/- 0.1 pg/ml; P<0.005) and healthy volunteers (1.4+/-0.1 pg/ml; P<0.005). Furthermore, patients with pltc <50 x 10(9)/l and splenectomised patients had significantly higher levels of CD4 + CD25 + activated T cells [26.2 +/- 14.8% (P<0.05) and 26.7+/-11.9% (P<0.005), respectively] than healthy controls (16.5+/-4.0%). Also, the number of natural killer (NK) cells among patients with pltc >150 x 10(9)/l were significantly elevated (26.6+/-16.0%; P<0.05) compared with controls (17.4+/-7.6%). In conclusion, our data corroborate previous findings of elevated numbers of activated T cells in chronic ITP patients with active disease, but neither a clear-cut Th1 nor a Th2 serum cytokine profile could be established. However, ITP in remission was associated with elevated TGF-beta1, which might be a part of a bystander immune suppression. We propose that the effect of possible expression of TGF-beta1 by oral immune tolerance induction deserves to be explored in ITP patients with an active disease.

Oral high‐dose methylprednisolone and intravenous immunoglobulin treatments in adult chronic idiopathic thrombocytopenic purpura

Ten adult patient of chronic idiopathic thrombocytopenic purpura (CITP) used oral prednisone and were treated with seven doses of oral high-dose methylprednisolone (30 mg/kg). Nine of ten patients responded after HDMP treatment (plt > 150 × 109/L). Two patients having 8 and 10 years of history achieved long-term remission after first HDMP treatment. One unresponsive and one responsive patients did not accept IVIG treatment as second therapy and lost the follow-up. The remaining six patients received IVIG (0.5 mg/kg for 5 days) as second therapy after 3 months. Platelet count increased above 150 × 109/L in 4 patients and between 60–80 × 109/L in 2 patients. The peak platelet counts of both therapy users were higher under HDMP than IVIG therapy (252 ± 110.4 vs 174.2 ± 83.7 × 109/L), but the difference was not significant. Responses were transient and returned to pretreatment values at 14–30 days, excluding long-term remission of 2 (2/10) patients after HDMP treatment. No side effect was observed. Thus, oral HDMP appears a good initial therapy for continuous remission in a small ratio of patients and a good security for emergency situations and prior to surgery in adult CITP patients. Am. J. Hematol. 56:191–192, 1997. © 1997 Wiley-Liss, Inc.

Simultaneous measurements of megakaryocyte‐associated IgG (MAIgG) and platelet‐associated IgG (PAIgG) in chronic idiopathic thrombocytopenic purpura

We have simultaneously measured platelet-associated IgG (PAIgG) and megakaryocyte-associated IgG (MAIgG) in 30 untreated patients with chronic idiopathic thrombocytopenic purpura (CITP). Megakaryocytes were purified from bone marrow by 35% Percoll gradient centrifugation, followed by negative immunopanning using magnetic immunobeads. The normal range of MAIgG in 30 healthy donors was 15.5 +/- 10.0 ng/10(5) megakaryocytes, whereas MAIgG in the 30 CITP patients was 140 +/- 59.3 ng/10(5) megakaryocytes, although the values were widely distributed. From the PAIgG and MAIgG data, CITP patients were classified into three types; type I (PAIgG < 200 ng/10(7) platelets and MAIgG < 150 ng/10(5) megakaryocytes), type II (PAIgG > 200 ng and MAIgG > 150 ng), and type III (PAIgG < 200 ng and MAIgG > 150 ng). Patients with types I and III had good clinical courses, but, in contrast, patients with type II responded poorly to steroid therapy followed by splenectomy or became refractory to treatment. In splenectomized patients, MAIgG of responder was promptly decreased to normal range and, in contrast, that of non-responder was persistently elevated. These results indicate that anti-platelet autoantibodies are able to bind with megakaryocytes in the bone marrow as well as with platelets in the peripheral blood, and the results also suggest that megakaryopoiesis in CITP is heterogeneous. Simultaneous measurement of PAIgG and MAIgG may predict the clinical outcome of CIPT.

HLA antigens, blood groups and immunoglobulin levels in idiopathic thrombocytopenic purpura.

Thirty-three patients with idiopathic thrombocytopenic purpura (ITP) were tested for HLA-A, B and C antigens, platelet antibodies, immunoglobulin levels and ABO blood groups. With one exception, ITP proved not to be significantly associated with the HLA antigens studied; an increased frequency of HLA-A28 was found in chronic ITP patients (50 vs. 18.7% in the control population). An increased incidence of blood group A was found in ITP patients (64 vs. 37.98% in the control population), especially in those with acute ITP (84.7%). A significant reduction of IgG levels was noted in patients with chronic ITP, while below-normal levels of IgA were found in both chronic and acute ITP patients. There was no difference in levels of IgM. Circulating platelet isoantibodies were demonstrated in 67.6% of the ITP patients. No correlation was demonstrated between the presence of platelet antibodies, immunoglobulin levels of HLA antigens.

Elevation of platelet associated antibody levels in patients with chronic idiopathic thrombocytopenic purpura expressing the B8 and/or DR3 allotypes.

The HLA type DR3 was present in 11 of 26 patients with Chronic Idiopathic Thrombocytopenic Purpura (ITP), a significantly increased frequency (p less than 0.05). Levels of platelet associated immunoglobulin M(PAIgM) were significantly higher in the B8 and/or DR3 positive group of chronic ITP patients than in the B8 DR3 negative patients despite similar clinical outcomes. Other immunologic parameters assessed, including serum immunoglobulin levels, rate of catabolism of transfused IgG, and antibody coated autologous red cell clearances were similar for both groups. These results suggest that there is an immunobiologic abnormality associated with the B8 DR3 allotypes which may result in a predisposition not only to chronic ITP, but also to a significant increase in PAIgM. These results are in accord with studies linking autoantibody with B8 DR3.