Chronic Idiopathic Thrombocytopenic Purpura Research Articles

Important Recommendations Regarding the Test-and-Treat Strategy for Helicobacter pylori Infection in Children.

Helicobacter pylori is a commonly encountered pathogen in medical practice. It causes chronic gastritis in patients of different ages. Many published papers have provided different opinions on whether the test-and-treat strategy for H. pylori infection should be implemented in children. It is critical that the opinion in favor of this strategy was published in Europe, where ESPGHAN/NASPGHAN guidelines have not recommended the use of test-and-treat strategy for H. pylori in children. Herein, I propose my opinion regarding this debate using 4 main points. First, this strategy should be implemented in areas where its benefits outweigh the associated risks. Thus, if it is not tailored to the locality, the results of the test-and-treat strategy for H. pylori in children may be erroneous. Second, the association between H. pylori infection and other diseases such as asthma and other allergic diseases should not be factored in when considering the test-and-treat strategy. This is because these diseases are associated with H. pylori noninfection and not with its posteradication status. Third, there is evidence that H. pylori infection can significantly alter children's intestinal microbiota. Finally, gastroscopy should not be performed in all H. pylori-positive children, particularly if the drug susceptibility test is not available. In the near future, it will be possible to easily conduct drug susceptibility tests for H. pylori using fecal samples. I believe that this report may expand the test-and-treat strategy for children infected with asymptomatic H. pylori outside of Japan and prevent not only gastric cancer but also minor diseases such as iron deficiency anemia, chronic idiopathic thrombocytopenic purpura, and failure to thrive. Pediatricians are responsible for keeping children healthy not only during childhood but also in adulthood. Thus, even if there are only a few H. pylori-related diseases and no severe cases in children, it is necessary to take early measures to prevent problems (eg, incidence of gastric cancer) in adulthood.

Development and Validation of a UV Spectroscopic Method to Estimate Eltrombopag Olamine along with Bulk and In-house Formulation

The current UV Spectroscopic method developed involving ethanol as a solvent is simple, fast, specific, precise, and sensitive for the estimation of Eltrombopag Olamine in bulk in day-to-day analysis. As per the ICH Q2 (R1) guideline, the method was validated. Eltrombopag Olamine is a drug used to treat thrombocytopenia (a low blood platelet count) in adults and youngsters with chronic immune idiopathic thrombocytopenic purpura that didn't get well with different treatments. Eltrombopag Olamine is additionally accustomed to treating severe aplastic anemia. It’s conjointly being studied within the treatment of different conditions and kinds of cancer. Eltrombopag Olamine binds to the thrombopoietin receptor, which causes the bone marrow to create more platelets. It’s class of thrombopoietin receptor agonists, also known as Promacta. Eltrombopag is also recently approved (2012) for the treatment of thrombocytopenia in a patient with chronic hepatitis C to start and sustain interferon-based therapy. The solvent used in the entire method development and validation was ethanol. The maximum wavelength of absorption was found to be 423nm. Beer’s law was obeyed in the concentration range of 5 to 30ug/ml with a correlation coefficient of 0.9966. The method was precise with an RSD of less than 2%, the LOD, and LOQ were found to be 6.18ug/ml and 18.7ug/ml respectively, % recovery of the drug is 98 to 100%. The method was validated for linearity, precision, accuracy, and robustness and all parameters were found to be satisfactory which proves that this method can be used for routine analysis of Eltrombopag Olamine.

<i>Helicobacter pylori</i> infection in children with immune thrombocytopenia

To detect the association between Helicobacter pylori (H. pylori) infection and immune thrombocytopenia in children and adolescents. Immune thrombocytopenia (ITP) is a common bleeding disorder in childhood. H. pylori is a widespread organism that is present in about 50% of the global population. There is an obvious relation between helicobacter pylori infection and chronic idiopathic thrombocytopenic purpura. A cross-sectional study was conducted in 95 patients with ITP who were recruited from the Hematology Unit, Department of Pediatrics, Menoufia University Hospital in the period from June 2021 to June 2022. The age of the patients ranged between 3.5 and 7.5 years. Fifty-five of them were males and 40 were females. The study was approved by the Ethical Committee of the Faculty of Medicine, Menoufia University. Out of the studied ITP children, 62 (65.3%) were positive for H. pylori antigen in stool, and 33 (34.7%) were negative. There was a significant difference between H. pylori-positive and H. pylori-negative patients regarding the grade of bleeding at presentation; 51 (82.3%) H. pylori-positive patients presented with grade 3 bleeding, 35 (56.5%) of them presented with skin and gum bleeding, 16 (25.8%) presented with skin bleeding and epistaxis. There was a statistically significant difference in the rate of recovery between H. pylorinegative patients (78.8%) and H. pylori-positive patients (22.6%). There was a significant rise in the platelet count in H. pylori-positive patients after the treatment of H. pylori. The prevalence of H. pylori infection in ITP pediatric patients was 65.3%. There was a significant rise in the platelet count in H. pylori-positive ITP children after the treatment of H. pylori.

Catch-up vaccination and enhanced immunization against hepatitis B, hepatitis A, measles, mumps, rubella and varicella in children with idiopathic thrombocytopenic purpura.

Limited data exist about the vaccination of children with idiopathic thrombocytopenic purpura (ITP) against vaccine preventable diseases. This study identified the vaccination status of children with ITP against hepatitis A, hepatitis B, measles, mumps, rubella and varicella, completed the immunization of children with inadequate immunization, re-evaluated post-vaccination antibody titers and identified probable vaccination-related complications. All of 46 children had chronic ITP were included. Seroconversion of hepatitis A, hepatitis B, varicella, measles, rubella and mumps vaccines was screened. All children with seronegative antibodies against vaccine preventable disease were given a vaccination appointment. Antibody levels were re-measured during a period ranging from 1 to 6 months. Potential complications were detected. There were 46 children with a mean age of 12.25 years. All children had chronic ITP and received intravenous immunoglobulin at least once previously. Considering the vaccination status, 50% (23 children) had vaccinations appropriate for their age, 47.8% (22 children) did not know their vaccination status and 2.2% (1 patient) did not have vaccinations. Seven children (15.2%) were seropositive for all antibody types and the remaining 39 children were scheduled for vaccination. Post-vaccination antibody titers confirmed that all children became seropositive for each disease. There was no complication in any patient. Immunization against hepatitis B, hepatitis A, measles, mumps, rubella and varicella is insufficient in a considerable number of children with ITP, Hepatitis B Virus (HBV) and Hepatitis A Virus (HAV) immunization being the most frequently inadequate. After immunization, adequate seroconversion levels were achievable without complications.

Variations of Redox Balance in Different Stages of Childhood Immune Thrombocytopenic Purpura.

Few previous studies indicated the role of oxidative stress in the pathogenesis of childhood idiopathic thrombocytopenic purpura (ITP), but there are little data regarding changes in redox balance in different forms of the disease, and changes after therapeutic procedures. We aimed to investigate the values of pro-oxidants and antioxidative capacity in various forms of ITP before and after the applying therapy. The research included 102 children, classified into the following groups: (1) newly diagnosed ITP (ndITP), (2) persistent ITP, (3) chronic ITP (chITP), and (4) control groups: (A) healthy control and (B) previously experienced ITP-healthy children who had been suffering from ITP earlier. During the clinical assessment, a blood sample was taken from the patients, from which the value of pro-oxidants (index of lipid peroxidation measured as TBARS, nitrites [NO2 -], as measurement of nitric oxide [NO] production, superoxide anion radical [O2 -], and hydrogen peroxide [H2O2]) and the capacity of antioxidant protection (activity of superoxide dismutase and catalase, and quantity of reduced glutathione) were determined spectrophotometrically. Our results demonstrated that values of pro-oxidants, especially reflected through the TBARS and O2 -, were the highest in the ndITP and exacerbated chITP groups. Also, the activity of the endogenous antioxidative defense system was the lowest in these groups. Intravenous immunoglobulin therapy in the ndITP group exerted the most prominent effect on the redox balance. It can be concluded that severity and exacerbation of the ITP are closely related to the redox status.

Prognosis and risk factors of chronicity in childhood idiopathic thrombocytopenic purpura: a single-center experience

Objective: In previous studies, chronicity risk factors for idiopathic thrombocytopenic purpura (ITP) are unclear. This study aimed to evaluate the outcome of children with ITP and determine the chronicity risk factors.
 
 Methods: This study retrospectively examined the demographics, laboratories, outcome, and chronicity risk factors among sixty children with ITP and obtained the data from the computer system. We analyzed demographics, treatment, and laboratory risk factors for chronic ITP by IBM SPSS and used binary logistic regression analysis.
 
 Results: Of 60 children with ITP, 32 (53.3%) had acute, 25 (41.7%) had chronic, and 3 (5%) had persistent ITP. Demographics, laboratories (age

Suspected ALPS with clinical and laboratory findings: Three patients—three different diagnoses

<abstract> <p>Autoimmune lymphoproliferative syndrome is a rare genetic disorder characterized by dysregulation of the immune system due to defective Fas mediated lymphocyte apoptosis. The clinical spectrum includes lymphoproliferative disease with lymphadenopathy, hepatomegaly, splenomegaly and an increased risk of lymphoma, as well as autoimmune disease typically involving blood cells. Definitive diagnosis is made by demonstrating infectious/non-malignant chronic lymphoproliferation for more than six months, high CD3+CD4−CD8− T Cell and defective lymphocyte apoptosis or one of the <italic>FAS, FASL, CASP10</italic> mutations. Since clinical and laboratory findings may overlap with other immune dysregulation or autoimmune diseases, differential diagnosis of autoimmune lymphoproliferative syndrome remains essential. Here, we present three cases of suspected autoimmune lymphoproliferative syndrome with clinical and laboratory findings, which resulted in three different diagnoses (chronic idiopathic thrombocytopenic purpura, ALPS-like and ALPS) after diagnostic evaluations. For all three cases, next-generation sequencing, flow cytometric analysis, protein expression and Fas mediated lymphocyte apoptosis with functional assays were performed.</p> </abstract>

Leukocytoclastic Vasculitis Masquerading as Chronic Idiopathic Thrombocytopenic Purpura.

Idiopathic thrombocytopenic purpura and leukocytoclastic vasculitis can present in a similar fashion and can be very hard to differentiate clinically without a biopsy. This can cause diagnostic dilemma and delay in management. A thorough evaluation is recommended to determine etiology, although about half are idiopathic. A patient aged 79 years with longstanding thrombocytopenia secondary to chronic idiopathic thrombocytopenic purpura presented with a rash. Although it was thought to be secondary to idiopathic thrombocytopenic purpura, a biopsy revealed presence of leukocytoclastic vasculitis. Although most leukocytoclastic vasculitis cases are mild and resolve without intervention, many go undiagnosed due to biopsy delays. Health care professionals should determine and treat the underlying cause.

Correlates with Vaccine Protective Capacity and COVID-19 Disease Symptoms Identified by Serum Proteomics in Vaccinated Individuals.

In the last two years, the coronavirus disease 19 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been a scientific and social challenge worldwide. Vaccines have been the most effective intervention for reducing virus transmission and disease severity. However, genetic virus variants are still circulating among vaccinated individuals with different disease symptomatology. Understanding the protective- or disease-associated mechanisms in vaccinated individuals is relevant to advances in vaccine development and implementation. To address this objective, serum-protein profiles were characterized by quantitative proteomics and data-analysis algorithms in four cohorts of uninfected and SARS-CoV-2-infected vaccinated individuals with asymptomatic, non-severe, and severe disease symptomatology. The results show that immunoglobulins were the most overrepresented proteins in infected cohorts when compared to PCR-negative individuals. The immunoglobulin profile varied between different infected cohorts and correlated with protective- or disease-associated capacity. Overrepresented immunoglobulins in PCR-positive individuals correlated with protective response against SARS-CoV-2, other viruses, and thrombosis in asymptomatic cases. In non-severe cases, correlates of protection against SARS-CoV-2 and HBV together with risk of myasthenia gravis and allergy and autoantibodies were observed. Patients with severe symptoms presented risk for allergy, chronic idiopathic thrombocytopenic purpura, and autoantibodies. The analysis of underrepresented immunoglobulins in PCR-positive compared to PCR-negative individuals identified vaccine-induced protective epitopes in various coronavirus proteins, including the spike receptor-binding domain RBD. Non-immunoglobulin proteins were associated with COVID-19 symptoms and biological processes. These results evidence host-associated differences in response to vaccination and the possibility of improving vaccine efficacy against SARS-CoV-2.

Endothelial nitric oxide synthase Glu298Asp gene polymorphism in the cases of idiopathic thrombocytopenic purpura.

BackgroundNitric oxide (NO) can induce apoptosis in megakaryocytes. Stimulatory function of NO on platelet production may be important in the pathophysiology of idiopathic thrombocytopenic purpura (ITP). NO is produced by three isoforms of NO synthase (NOS). The endothelial nitric oxide synthase (eNOS) isoform has been detected in platelets. Polymorphism of the eNOS gene, which supplies NO synthesis, changes the functions of this enzyme. In this study, the role of eNOS Glu298Asp gene polymorphism in etiopathogenesis, its course, and treatment of ITP was investigated.MethodsSixty-six patients [51 newly diagnosed ITP (ND-ITP), 15 chronic ITP (CH-ITP), and 60 healthy controls (HC)] were enrolled in this study.ResultsIn all patients, the frequency of the GT genotype was 48.5%. The frequency of the GG genotype was determined to be 40.9% and the TT genotype was 10.6%. The most common allele in all patients was the G allele. eNOS Glu298Asp gene polymorphism might be a risk factor in the etiopathogenesis of ITP. Patients with the GG genotype were thought to have a high intention for CH-ITP. Patients with the GG genotype responded effectively to medical treatment using IVIG therapy. The presence of the G allele was observed to have a positive effect on the medical treatment of patients with CH-ITP, whereas the T allele exhibited a negative effect.ConclusionIn the present study, a significant correlation was found between ITP and eNOS Glu298Asp gene polymorphism. This correlation suggested that eNOS Glu298Asp gene polymorphism might be a risk factor in the ethiopathogenesis of ITP.

Splenectomy in a patient with chronic idiopathic thrombocytopenic purpura with critical thrombocytopenia, an anesthetic challenge

Immune thrombocytopenic purpura, also termed as idiopathic thrombocytopenic purpura is an acquired disorder in which there is immune mediated destruction of platelets .Here we describe the perioperative management of a case of chronic ITP undergoing splenectomy. Anesthetic management of the patient with ITP includes general anesthesia, avoiding NSAIDs and platelet lowering drugs, transfusing platelets, avoiding airway trauma and watching for hemorrhagic complications.

Chronic Idiopathic Thrombocytopenic Purpura during the Pregnancy: A Case Report

Published on: June 2022Journal of Young Pharmacists, 2022; 14(2):261-262Case Report | doi:10.5530/jyp.2022.14.51 Authors: Kommuri Vyduryam, T Vinay Kumar*, Sreya Kosanam, Shaik Asha Begum, Namala Venkata Yaseswi, Vesapogu Pravalika Department of Pharmacology and Pharmacy Practice, Nirmala College of Pharmacy, Mangalagiri, Andhra Pradesh, INDIA. Abstract: A 37-year-old woman was admitted to the hospital after complaining of a petechiae rash all over her body for three days, generalized weakness, pallor, and gum bleeding in one episode, and a history of similar episodes in the past. The patient has Idiopathic Thrombocytopenic Purpura and has been on medication throughout her pregnancy. Peripheral examination reveals microcytic hypochromic anemia with thrombocytopenia, and bone marrow examination reveals an increase in the number of megakaryocytes. She received corticosteroid and antifibrinolytic treatment. Her symptoms are similar to those caused by steroids after being readmitted to the hospital. Idiopathic Thrombocytopenic Purpura appears to be an immune-mediated disease. Although Idiopathic Thrombocytopenic Purpura is a rare condition, it can be fatal, especially during pregnancy because of fetal intracranial hemorrhage.Key words: Idiopathic Thrombocytopenia, Petechiae, Pregnancy, Megakaryocytes, Antifibrinolytic.

Fitness to Serve in the Armed Forces and Internal Medicine: A Retrospective Study.

Assessment of the medical fitness to serve in the armed forces has two objectives: to prevent the military operations from being jeopardized by a medical issue, and to protect soldiers from the sequelae of diseases that could become complicated in the operational field, especially in overseas operations where soldiers are exposed to a remote setting and a long evacuation time. Little is known about fitness decisions for soldiers with systemic or autoimmune diseases. Therefore, we conducted a single-center retrospective study of internal medicine fitness decisions. All the fitness decisions discussed from September 2019 to December 2020 in our department of internal medicine were reviewed. Gender, age, army or service, rank, garrison and health topic were collected from the medical files. Our Military Hospital local ethics committee, in accordance with the French law, approved this study. There were 41 cases, involving 31 men and 10 women (mean age: 31 years), presenting with autoimmune or systemic diseases, metabolic disorders, thrombophilia, congenital or acquired malformations or organ failure, miscellaneous nephropathies, or hemogram abnormalities. Four patients were taking immunosuppressive agents, 3 biologics, and 4 anticoagulants. Among the 15 civilians requiring medical fitness assessment to enlistment, 6 were declared fit. They presented with a history of juvenile idiopathic arthritis with intermediate uveitis without relapse for 7 years, Mayer-Rokitansky-Küster-Hauser syndrome type II with ectopic kidney, solitary kidney with normal renal function and with hypertension, isolated proteinuria, proteinuria with microscopic hematuria, and muscular fibrolipoma with a history of surgical treatment of a vascular malformation. Among the 26 patients already enlisted in the armed forces, 9 were referred for assessment of medical fitness to serve overseas. Two soldiers were assessed as fit without restrictions; one presented with a history of a single episode of deep vein thrombosis after surgery, and the other had a history of monoclonal gammopathy of renal significance without relapse and without treatment for 8 years. Four soldiers were assessed as fit only for overseas territories with sanitary structures similar to mainland France. They presented with immunoglobulin A (IgA) nephropathy and treatment with angiotensin-converting enzyme inhibitor, mevalonate kinase deficiency and treatment with anakinra, chronic idiopathic thrombocytopenic purpura, and history of unilateral partial renal infarction. The 17 other soldiers were referred for dispensation, long-sickness leave granting, or for specification toward administrative coding of their disease. We have described the first exhaustive study of specialized fitness decisions referred to an internal medicine department. One-third of the referred patients were declared fit to serve in the armed forces. Further studies are needed to confirm these results, as our study was monocentric. Fitness decisions must take into account the disease, the treatment, and the operational field characteristics. Soldiers with systemic diseases controlled by immunosuppressive agents can serve in tropical areas if they can reach adequate sanitary structures in a short time. The knowledge of systemic diseases as well as the skillfulness of the internists, which are regularly projected to the operational fields, allows them to provide pragmatic fitness expertise to myriad complex situations.

Laparoscopic splenectomy in patients with idiopathic thrombocytopenic purpura and very low platelet count.

Background:Chronic idiopathic thrombocytopenic purpura (ITP), is an autoimmune disease associated with a reduction in circulating blood platelets under 150±109g/L which persists longer than 6 months without any specific cause. With the current study, we aimed to evaluate the efficacy and safety of laparoscopic splenectomy in ITP patients with a very low platelet count and normal coagulation status.Methods:From April 2007 to January 2012, laparoscopic splenectomy was performed on 60 patients with chronic ITP who could not achieve a sustained recovery after steroid therapy.Results:Patients consisted of male/female ratio of 24 (40%):36 (60%) with the mean age of 53±15.1 years. All patients had normal coagulation state even with very low platelet count (below 5×103) before laparoscopic splenectomy. The mean operative time was 140.00±15.00 minutes. Blood transfusion was required in 10 (16.7%) and 8 (13.3%) patients before and after the operation, respectively. Preoperative transfusion of PRBC was not statistically significant between groups (P=0.265). Bleeding complications during within or after surgery was rare (5.0%). Convalescence was rapid and the mean hospital stay was 3.58±0.68 days (1-14 days) which shows that there was no significant difference in operative time and after operative hospitalization time among the three groups (P=0.070). The patients made a good uneventful recovery and were followed for at least one week who exhibited no postoperative problems.Conclusion: Laparoscopic splenectomy should be considered initially in the management of ITP. Also, very low platelet count should not be contraindicated for laparoscopic splenectomy in ITP patients and sometimes perioperative platelet transfusion may be unnecessary.

Comparative pharmacoeconomic analysis of romiplostim and eltrombopag for the chronic idiopathic thrombocytopenic purpura in Russian Federation

Comparative pharmacoeconomic analysis of romiplostim and eltrombopag for the chronic idiopathic thrombocytopenic purpura in Russian Federation

Impact of target-mediated drug disposition on hetrombopag pharmacokinetics and pharmacodynamics in Chinese healthy subjects and patients with chronic idiopathic thrombocytopenic purpura.

The pharmacokinetics (PK) of hetrombopag were found to be nonlinear across evaluated dose ranges. The aim of this study was to develop a mechanism-based population pharmacokinetic/pharmacodynamic (PopPK/PD) model and to provide a reasonable expected therapeutic dose for a future confirmatory clinical study of hetrombopag. Nonlinear mixed-effects modelling was performed using pooled 2168 hetrombopag concentrations and 1526 platelet counts from 72 healthy subjects and 32 chronic idiopathic thrombocytopenic purpura (ITP) patients from two phase I studies and one phase II study. The final model was evaluated via goodness-of-fit plots, visual predictive check and nonparametric bootstrap. Simulations from the validated PopPK/PD model were used to devise an expected therapeutic dose for later confirmatory clinical study. The pharmacokinetic data of hetrombopag were well described by a modified target-mediated drug disposition (TMDD) model with dual sequential first-order absorption. Mean parameter estimates (interindividual variability) were CL/F 7.66 L/h (63.5%), Vc /F 30.0L (77.2%) and Kdeg 0.693/h (87.1%). The pharmacodynamic profile was well described by a five-compartment lifespan model with four-transit and one-platelet compartments. Simulation results suggested that chronic ITP patients following 10mg once-daily hetrombopag would able to achieve an ideal platelet count level (50-200 × 109 /L). TMDD was the primary reason leading to nonlinear PK profile of hetrombopag. Our PK/PD modelling and simulation results support 10mg once-daily as the recommended therapeutic dose for chronic ITP patients in subsequent confirmatory clinical study of hetrombopag.

Preliminary Study on Apoptotic Proteins in Platelet from Adult Patients with Chronic Immune Thrombocytopenic Purpura

Background: Adult chronic idiopathic thrombocytopenic purpura (ITP) is a chronic and usually lifelong hemorrhagic disorder in which enhanced platelet destruction and ­weakened platelet production lead to thrombocytopenia. In this study, the p38 mitogen-activated protein kinase (p38-MAPK), early growth response 1 (EGR-1), p53, Bcl-xL, Bak, Bax, and reactive oxygen species (ROS) in platelets from adult patients with chronic ITP were investigated. Methods: Platelets were isolated from blood samples collected from 20 adult patients with chronic ITP and 20 healthy volunteers. p38-MAPK, EGR-1, p53, Bcl-xL, Bak, Bax, and ROS were determined by flow cytometry, and the results were analyzed by EXPO32 ADC. Results: Flow cytometry showed the expression levels of p38-MAPK (61.66 ± 19.38% vs. 27.52 ± 14.34%), EGR-1 (62.22 ± 20.48% vs. 9.05 ± 5.79%), p53 (56.82 ± 20.07% vs. 4.35 ± 2.04%), Bak (39.86 ± 11.45% vs. 20.82 ± 11.85%), Bax (36.85 ± 15.99% vs. 6.69 ± 5.01%), and ROS (19.98 ± 1.47% vs. 1.29 ± 0.10%) were all elevated (p < 0.05 compared with healthy volunteers). In addition, pro-survival Bcl-xL (5.38 ± 1.52% vs. 21.20 ± 6.04%) was decreased markedly in platelets from adult patients with chronic ITP (p < 0.05 compared with healthy volunteers). Conclusions: Our findings reveal that platelets in adults with chronic ITP display a proapoptotic gene expression phenotype, based on the enhanced expression of p38-MAPK, EGR-1, p53, Bak, Bax, and ROS, and attenuated expression of Bcl-xL, suggesting increased sensitivity toward apoptosis.

Chimeric Anti CD-20 Monoclonal Antibody-Rituximab in Refractory Childhood Idiopathic Thrombocytopenic Purpura: An Indian Experience.

The treatment of chronic idiopathic thrombocytopenic purpura (ITP) continues to be a challange. A significant proportion of patients continue to be symptomatic despite all available means of therapy. Recently Rituximab, a chimeric anti CD-20 monoclonal antibody has been shown to be an effective mode of therapy in such patients with an overall response rate of appx 50 %.We studied the efficacy and side effects of this therapeutic modality in 10 children (6 girls) with chronic ITP. The patients belonged to pediatric age group (median age: 9 years, range 4–18 years) with 4 children less than 10 years of age. All the patients were screened for systemic illnesses and different secondary causes leading to thrombocytopenia. They all had been treated with standard therapies using conventional and high dose steroids, ciclosporin cyclophosphamide, vincristine, periodic use of high dose IVIG and splenectomy in 6 patients, but had continued to be symptomatic with recurrent mucocutaneous bleeds and markedly low platelet counts (< 20x 109/L). All patients received intravenous Rituximab at a dose of 375 mg/M2 as weekly dose for 4 consecutive weeks. The infusion related side effects were a few (n= 3) and minor. They included urticarial rash (1) and fever(2) that responded to antipyretics. None of these were severe enough to interrupt the treatment. A complete response was defined as a platelet count > 100 x 109/L, partial response (PR) as count > 50x109/L and a minor response as a count < 50x109/L but without the need of continued treatment. Patients showing no significant rise in platelet count were marked as showing no response. Of the 10 evaluable children, 9 (90%) showed overall response; 4 (40%) showed complete response and 4 (40 %) showed partial response. Two (20%) patients showed minor responses. Patients have been under follow up for last 3 years. The patients with CR and PR have been in remission for longer periods (as much as 150 weeks ).The side effects due to the therapy have been few and very mild. Besides infusional reactions in 3 patients (Transient fever in 2 and mild rash in 1) there were no significant toxicities. No correlation could be found between clinical/laboratory parameters with the responsiveness or the duration of response except that patients showing a higher degree of response continued to be in remission for a longer period as compared to the ones with lesser degree of response. The high percentage of response in our patients as compared to the ones in other studies could be due to the fact that our patients belonged to a younger age group. Probably children show a better response.In conclusion, Rituximab offers a safe and convenient modality of treatment in symptomatic children with refractory ITP. Its use is certainly cost effective even in a developing country in view of the good degree of a sustained response in these refractory patients wherein all modalities of treatment have failed.

Apoptosis in platelets from adult patients with chronic idiopathic thrombocytopenic purpura.

Adult chronic idiopathic thrombocytopenic purpura (cITP) is a chronic and usually life-long haemorrhagic disorder in which enhanced platelet destruction and weakened platelet production lead to thrombocytopenia. Platelets were isolated from blood samples collected from 40 adult patients with cITP and 40 healthy volunteers. Mitochondrial membrane potential (ΔΨm) and plasma membrane phosphatidylserine externalization were determined by flow cytometry, and activation of caspase-3 and expressions of Bax, Bak and Bcl-xL were analysed by western blotting. Flow cytometry showed increased mitochondrial depolarization and lower ΔΨm in platelets from adult patients with cITP. In addition, plasma membrane phosphatidylserine externalization was observed on platelets from adult patients with cITP, but rarely from healthy volunteers. Western blot analysis of platelet proteins revealed that, in adult cITP patients, caspase-3 was activated, which cleaved gelsolin and to release a 47-kDa fragment. Moreover, the expressions of Bax and Bak were elevated, and Bcl-xL was decreased markedly in platelets from adult patients with cITP. Our findings reveal, based on loss of mitochondrial membrane potential (Δψm), phosphatidylserine exposure, caspase-3 activation, enhanced expression of Bax and Bak, and attenuated expression of Bcl-xL, that platelet death in the pathogenesis of thrombocytopenia in chronic ITP in adults is apoptotic.

Thiol / disulfide balance and oxidative stress parameters in pediatric patients diagnosed with acute and chronic idiopathic thrombocytopenic purpura.

Changes in oxidative stress and thiol / disulfide balance are thought to play a role in the pathogenesis of idiopathic thrombocytopenic purpura (ITP). Our study investigates total oxidant level (TOS), total antioxidant level (TAS), oxidative stress index (OSI) levels and thiol / disulfide balance in pediatric patients with acute and chronic ITP. Thirty four patients with acute ITP, eighteen patients with chronic ITP and thirty three healthy children (control) were included. TOS, TAS, OSI, thiol / disulfide balance were analyzed. In acute ITP, TAS levels were lower than chronic ITP and control, TOS and OSI levels were higher than control, and native thiol level was lower than chronic ITP (p < 0.05). In acute ITP; disulfide level, disulfide / native thiol and disulfide / total thiol ratios were higher than chronic ITP and control, and native thiol / total thiol ratio was lower than chronic ITP and control group (p = 0.038, p = 0.018, respectively). TOS and OSI levels of the chronic ITP were higher than the control group (p < 0.05). The results of this study have shown that oxidative stress increases in children with acute ITP and chronic ITP, that thiol / disulfide balance is disrupted in favor of disulfide in acute ITP, and that thiol / disulfide balance isn`t disrupted in chronic ITP patients whose platelet count is close to normal and who don`t require treatment.