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We report the case of a 16-month-old patient with chronic immune thrombocytopenia (ITP) patient who experienced delayed treatment-free response (TFR) after romiplostim treatment. He received intravenous immunoglobulin every month to maintain a platelet count above 20,000/μL for 2 years. Thereafter, he received rituximab and cyclosporine as second-line therapy, with no response, followed by romiplostim. After 4 weeks of treatment, the platelet count was maintained above 50,000/μL. Following 7 months of treatment, he discontinued romiplostim, and the platelet count decreased. His platelet counts remained above 50,000/μL, without any bleeding symptoms, 2 years after romiplostim discontinuation. This is the first report of TFR after romiplostim treatment in pediatric chronic ITP.

Idiopathic thrombocytopenic purpura (ITP), or primary immune thrombocytopenia, is an orphan disease associated with thrombocytopenia. One of the most recent and promising approaches to ITP treatment is the use of thrombopoietin receptor agonists (TPO-RAs). The scope of TPO-RA use is expanding rapidly, which stimulates the development of both innovator and generic (or biosimilar) medicines. The aim of the paper was to assess TPO-RA role in ITP treatment, methodological approaches to TPO-RA development, and feasibility of using the platelet count as a pharmacodynamic marker in bioequivalence studies of peptide TPO-RAs in healthy volunteers. Clinical development of new medicines for the treatment of thrombocytopenia includes comparative, parallel-group trials lasting about a year. The standard approach to bioequivalence studies, which is based on the results of comparative pharmacokinetic studies, can be used in marketing authorisation applications for generic non-peptide TPO agonists, while peptide TPO agonists have to comply with specific requirements for biosimilar products. The orphan status of ITP does not affect the development strategy and study design, but it limits the number of patients that could be included into the study. In the absence of valid surrogate biomarkers of efficacy, demonstration of comparable clinical efficacy of the biosimilar and reference drug is usually required in a randomised, parallel, preferably double-blind comparative study. On the other hand, clinical comparability of the biosimilar and reference drug can also be demonstrated in comparative pharmacodynamic studies, if the selected biomarker is a well-established and valid surrogate marker which correlates with patient clinical outcome. Platelet count is a key parameter in both diagnosis of diseases associated with low platelet levels and assessment of treatment efficacy. Therefore, it can be used as a pharmacodynamic marker in bioequivalence studies of biosimilar peptide TPO-RAs. It was concluded that such studies could be performed in healthy volunteers, and not in patients, whose participation in clinical trials is limited due to the orphan status of ITP.

While the prognosis of idiopathic pulmonary arterial hypertension has improved significantly due to newer medications, lung transplantation remains a critical therapeutic option for severe pulmonary arterial hypertension. Hence, it is essential for patients awaiting lung transplantation to avoid complications, including thrombocytopenia, which may affect their surgical outcomes. Herein we present the case of a 21-year-old woman diagnosed with idiopathic pulmonary arterial hypertension at the age of 15. She developed thrombocytopenia while awaiting lung transplantation. Her medication was switched from epoprostenol to treprostinil, suspecting possible drug-induced thrombocytopenia. Furthermore, she was administered thrombopoietin receptor agonists in view of the possibility of idiopathic thrombocytopenic purpura, along with maximum support for right heart failure. Subsequently, her platelet count increased to >70,000/µL, enabling her to successfully undergo bilateral lung transplantation. Post-bilateral lung transplantation, pulmonary arterial hypertension as well as thrombocytopenia appeared to have resolved. In this case, we suspected that thrombocytopenia could have resulted owing to a combination of pulmonary arterial hypertension, right heart failure, drug interactions, and idiopathic thrombocytopenic purpura. Thrombocytopenia is a very critical condition in patients with pulmonary arterial hypertension, especially those awaiting lung transplantation. Several approaches are known to improve intractable thrombocytopenia in patients with pulmonary arterial hypertension.

The adoptive transfer of CAR-T cells, which are modified T cells expressing chimeric antigen receptors (CARs), to target B cell maturation antigen (BCMA) has demonstrated impressive results in treating relapsed/refractory multiple myeloma. Although BCMA CAR-T therapy induces certain complications in some patients, idiopathic thrombocytopenic purpura (ITP) has not been reported as one of them. To the best of our knowledge, this is the first report of the successful treatment of ITP that arose in a relapsed/refractory multiple myeloma patient following anti-BCMA CAR-T cell infusion. Herein, we describe this relatively uncommon complication and provide guidance on its treatment.

Background: A satisfactory therapeutic response is achieved with splenectomy in 60–80% of the patients diagnosed with immune thrombocytopenic purpura (ITP). There is an ongoing consensus on the short-term efficacy of splenectomy, however, its long-term efficacy remains controversial. Our aim was to establish the frequency of resistance and relapse after splenectomy, the occurrence of complications, the therapeutic strategies and the drug efficacy in splenectomy-resistant ITP. Methods: We retrospectively analyzed 138 adult ITP patients who had been previously diagnosed and treated at the Clinic of Hematology, Clinical Center of Serbia, and who underwent splenectomy between 1987 and 2018. Results: Of the 138 ITP patients, 20.3% (n=28/138) were refractory to splenectomy, 11.6% (n=16/138) relapsed and 8.7% (n=12/138) were primarily resistant. The average post-splenectomy follow-up period was 117 months (range 3-474). The average follow-up period of the patients resistant to splenectomy was 147 months (range 23-474). Of the patients refractory to splenectomy, 67.8% (n=19/28) showed a good therapeutic response: 49% (n=14/28) complete remission and 18.8% (n=5/28) partial remission. The response was usually achieved using the following drugs: romiplostim (100%), eltrombopag (75%), cyclosporine (66.67%), mycophenolate mofetil (50%), danazol (50%) and corticosteroids (40.9%). Hemorrhagic and non-hemorrhagic complications occurred in 78.6% (n=22/28) and 28.6% (n=8/28) of the patients, respectively. Conclusion: Splenectomy remains a very efficient therapeutic modality for the treatment of ITP patients with a high percentage of splenectomy-resistant patients achieving remission. Thrombopoietin receptor agonists have shown exceptional results so far in the treatment of refractory ITP patients.

Langerhans cell histiocytosis is a rare haematological disorder with variable clinical findings and a high mortality rate. On the other hand, Kasabach-Merritt syndrome is of rare onset at adult age, requiring the simultaneous presentation of vascular lesion, thrombocytopenia, and consumptive coagulopathy. We present the first reported case of both diseases in a single patient and highlight the difficulties of diagnostic. A 69-year-old woman with immune thrombocytopenic purpura underwent surgery for the removal of giant skin haemangiomas. During post-operative care, intravascular disseminated coagulopathy developed. After weeks of corticosteroids and immunosuppressive therapy with no clinical improvement, pulmonary tuberculosis was diagnosed and appropriate treatment initiated. Despite all the efforts, the patient's clinical condition kept worsening and she eventually died. An autopsy revealed bone marrow Langerhans cell histiocytosis. In this case, the patient's autoimmune background together with tuberculosis and intravascular disseminated coagulopathy masked the presentation and made the diagnosis of a rapidly progressive fatal disease very difficult. info:eu-repo/semantics/publishedVersion

Background: LPS-responsive beige -like anchor protein (LRBA) deficiency is a primary immunodeficiency disease caused by loss of LRBA protein expression, due to biallelic mutations in LRBA gene. LRBA deficiency patients exhibit a clinically heterogeneous syndrome. The main clinical complication of LRBA deficiency is immune dysregulation. Furthermore, hypogammaglobulinemia is found in more than half of patients with LRBA-deficiency. To date, no patients with this condition have been reported in Colombia Objective: To evaluate the expression of the LRBA protein in patients from Colombia with clinical phenotype associated to LRBA-deficiency. Methods: In the present study the LRBA-expression in patients from Colombia with clinical phenotype associated to LRBA-deficiency was evaluated. After then, the clinical, the immunological characteristics and the possible genetic variants in LRBA or other genes associated with the immune system in patients that exhibit decrease protein expression was evaluated. Results: In total, 112 patients with different clinical manifestations associated to the clinical LRBA phenotype were evaluated. The LRBA expression varies greatly between different healthy donors and patients. Despite the great variability in the LRBA expression, six patients with a decrease in LRBA protein expression were observed. However, no pathogenic or possible pathogenic biallelic variants in LRBA, or in genes related with the immune system were found. Conclusion: LRBA expression varies greatly between different healthy donors and patients. Reduction LRBA-expression in 6 patients without homozygous mutations in LRBA or in associated genes with the immune system was observed. These results suggest the other genetic, epigenetic or environmental mechanisms, that might be regulated the LRBA-expression. Resumen Antecedentes: la deficiencia de LRBA (del inglés, LPS-responsive beige -like anchor protein) es una inmunodeficiencia primaria causada por la pérdida de la expresión de la proteína LRBA, debido a mutaciones bialélicas en el gen LRBA. Los pacientes con deficiencia de LRBA exhiben un síndrome clínicamente heterogéneo. La principal complicación clínica de la deficiencia de LRBA es la desregulación inmune. Además, la hipogammaglobulinemia se encuentra en más de la mitad de los pacientes con deficiencia de LRBA. Hasta la fecha, no se han reportado pacientes con esta afección en Colombia Objetivo: Evaluar la expresión de la proteína LRBA en pacientes de Colombia con fenotipo clínico asociado a deficiencia de LRBA Métodos: En el presente estudio se evaluó la expresión de LRBA en pacientes de Colombia con fenotipo clínico asociado a deficiencia de LRBA. Después de eso, se evaluaron las características clínicas, inmunológicas y las posibles variantes genéticas en LRBA o en otros genes asociadados con el sistema inmune en pacientes que exhiben una disminución de la expresión de la proteína. Resultados: En total, se evaluaron 112 pacientes con diferentes manifestaciones clínicas asociadas al fenotipo clínico LRBA. La expresión de LRBA varía mucho entre diferentes donantes sanos y pacientes. A pesar de la gran variabilidad en la expresión de LRBA, se observaron seis pacientes con una disminución en la expresión de la proteína LRBA. Sin embargo, no se encontraron variantes bialélicas patógenas o posibles patógenas en LRBA, o en genes relacionados con el sistema inmune. Conclusión: La expresión de LRBA varía mucho entre diferentes donantes sanos y pacientes. Se observó reducción de la expresión de LRBA en 6 pacientes sin mutaciones homocigotas en LRBA o en genes asociados. Estos resultados sugieren los otros mecanismos genéticos, por ejemplo epigenéticos o ambientales, que podrían estar regulados por la expresión de LRBA

In otherwise healthy children or adults, immune thrombocytopenic purpura (ITP) has a low platelet count, usually less than 100,000, in the presence of common petechiae, bruises, or bleeding. It is explained that there is. ITP is most commonly found in children of all ages, not just adults. This activity describes the role of an inter-expert team in the evaluation and treatment of patients with immune thrombocytopenic purpura (ITP). The aim of this review article is to determine the etiology of immune thrombocytopenic purpura, formulate the patient's unique presentation with ITP, interpret general physical exam findings associated with ITP, and improve coordination of care among international team members. Outcomes will be discussed for patients with ITP.

A púrpura trombocitopênica idiopática (PTI) é uma doença autoimune caracterizada pelo baixo número de plaquetas, as células que desempenham um papel no processo de coagulação do sangue, e atingi principalmente pessoas na faixa dos 18 a 24 anos e manifestar-se através de pequenos sangramentos e machas roxas na pele. Esse estudo tem como como objetivo ajudar a ampliar o conhecimento dos leitores focando no diagnóstico da PTI com base no compilado de materiais bibliográficos adquiridos através de buscas nas plataformas Scientific Electronic Lirary Online - SCIELO, Google Acadêmico, Ministério da saúde (MS), biblioteca Virtual em Saúde, que após passar por critérios de exclusão e inclusão, resultaram em 25 citações, entre artigos e protocolos. Os resultados obtidos mostram que em casos de suspeita de PTI o diagnóstico é feito por processo de exclusão, após a realização da anamsese, hemograma completo e do esfregaço e for confirmado a presença de trombocitopenia, serão realizados exames para excluir outras doenças que também causam trombocitopenia, constatando a ausência de outras condições clínicas será confirmado o diagnóstico de PTI. Idiopathic thrombocytopenic purpura (ITP) is an autoimmune disease characterized by a low number of platelets, the cells that play a role in the blood clotting process, and affects mainly people between the ages of 18 and 24 and is manifested through minor bleeding and purple spots on the skin. This study aims to help expand readers' knowledge by focusing on the diagnosis of ITP based on the compilation of bibliographic materials acquired through searches on the Scientific Electronic Lirary Online platforms - SCIELO, Google Scholar, Ministry of Health (MS), Virtual Library in Health, which after going through exclusion and inclusion criteria, resulted in 25 citations, among articles and protocols. The results obtained show that in cases of suspected ITP, the diagnosis is made by exclusion process, after performing the anamsis, complete blood count and smear and confirming the presence of thrombocytopenia, tests will be performed to exclude other diseases that also cause thrombocytopenia noting the absence of other clinical conditions, the diagnosis of ITP will be confirmed. La púrpura trombocitopénica idiopática (PTI) es una enfermedad autoinmune caracterizada por un bajo número de plaquetas, las células que desempeñan un papel en el proceso de coagulación de la sangre, y afecta principalmente a personas de 18 a 24 años y se manifiesta a través de sangrado leve y manchas moradas en la piel. piel. Este estudio tiene como objetivo ayudar a ampliar el conocimiento de los lectores al enfocarse en el diagnóstico de la ITP a partir de la recopilación de materiales bibliográficos adquiridos a través de búsquedas en las plataformas Scientific Electronic Lirary Online - SCIELO, Google Scholar, Ministerio de Salud (MS), Biblioteca Virtual en Salud , que luego de pasar por criterios de exclusión e inclusión, resultó en 25 citas, entre artículos y protocolos. Los resultados obtenidos muestran que en los casos de sospecha de PTI, el diagnóstico se realiza por proceso de exclusión, luego de realizar la anamsis, hemograma completo y frotis y confirmar la presencia de trombocitopenia, se realizarán exámenes para descartar otras enfermedades que también provoquen trombocitopenia notando la ausencia de otras condiciones clínicas, se confirmará el diagnóstico de PTI.

Aim To evaluate thrombocytopenic pregnancies including gestational thrombocytopenia (GT), idiopathic thrombocytopenic purpura (ITP), and hypertensive disorders of pregnancy (HDP). Materials and Methods We evaluated the pregnancy outcomes and laboratory findings of 385 patients diagnosed with GT, ITP, or HDP whose thrombocyte levels were Results GT, ITP, and HDP were the final diagnoses in 315 (81.8%), 35 (9.1%), and 35 (9.1%) cases, respectively. Patients diagnosed during the 1st trimester and diagnosed with ITP had significantly lower minimal platelet counts during the antenatal period and prior to delivery (p Conclusion Thrombocytopenic pregnancies must be carefully evaluated with regard to the severity of thrombocytopenia, gestational period at initial diagnosis, and etiology. In particular, patients with ITP must be evaluated carefully as these patients are more likely to require transfusions and have platelet counts

Overt polyautoimmunity (PolyA) corresponds to the presence of more than one well-defined autoimmune disease (AD) manifested clinically in a single patient. The current study aimed to describe the main characteristics of juvenile PolyA in a pediatric rheumatology setting and analyze the chronological aspects, index cases, familial autoimmunity, and clustering pattern. This was a cross-sectional and multicenter study in which 313 children with overt PolyA were included. Patients were systematically interviewed and their medical records reviewed using a questionnaire that sought information about demographic, clinical, immunological, and familial characteristics. A hierarchical cluster analysis was done to determine similarities between autoimmune diseases based on PolyA. PolyA occurred simultaneously in 138 (44%) patients. Multiple autoimmune syndrome was observed in 62 (19.8%) patients. There were 25 index diseases of which, systemic lupus erythematosus (SLE, n = 134, 42.8%), juvenile idiopathic arthritis (JIA, n = 40, 12.7%), Hashimoto's thyroiditis (HT, n = 24, 7.66%), immune thrombocytopenic purpura (ITP n = 20, 6.39%), antiphospholipid syndrome (APS, n = 15, 4.79%), and vitiligo (VIT, n = 15, 4.79%) were the most frequent and represented 79.23% of the total number of patients. Familial autoimmunity influenced PolyA. A high aggregation of autoimmunity was observed (λr = 3.5). Three main clusters were identified, of which SLE and APS were the most similar pair of diseases (based on the Jaccard index) followed by HT and JIA, which were related to ITP and Sjogren's syndrome. The third cluster was composed of localized scleroderma and VIT. Our findings may assist physicians to make an early diagnosis of this frequent condition. Pediatric patients with ADs should be systematically assessed for PolyA.

Idiopathic Thrombocytopenic Purpura (ITP) is a multifactorial disease with decreased count of platelet that can lead to bruising and bleeding manifestations. This study was intended to identify critical genes associated with chronic ITP. The gene expression profile GSE46922 was downloaded from the Gene Expression Omnibus database to recognize Differentially Expressed Genes (DEGs) by R software. Gene ontology and pathway analyses were performed by DAVID. The biological network was constructed using the Cytoscape. Molecular Complex Detection (MCODE) was applied for detecting module analysis. Transcription factors were identified by the PANTHER classification system database and the gene regulatory network was constructed by Cytoscape. One hundred thirty-two DEGs were screened from comparison newly diagnosed ITP than chronic ITP. Biological process analysis revealed that the DEGs were enriched in terms of positive regulation of autophagy and prohibiting apoptosis in the chronic phase. KEGG pathway analysis showed that the DEGs were enriched in the ErbB signaling pathway, mRNA surveillance pathway, Estrogen signaling pathway, and Notch signaling pathway. Additionally, the biological network was established, and five modules were extracted from the network. ARRB1, VIM, SF1, BUB3, GRK5, and RHOG were detected as hub genes that also belonged to the modules. SF1 also was identified as a hub-TF gene. To sum up, microarray data analysis could perform a panel of genes that provides new clues for diagnosing chronic ITP.

Idiopathic thrombocytopenic purpura (ITP) is a common hematological disease and the abnormal platelet destruction in the spleen is a critical pathological mechanism for ITP. However, the metabolomic change in the spleen caused by ITP is still unclear. In the present study, the metabolomic information of 18 ITP and 20 normal spleen samples were detected by using 1H high-resolution magic angle spinning NMR spectroscopy (1H MAS NMR). Compared with normal spleen, the concentrations of acetate, alanine, glutamine, glycerol, isoleucine, lysine, valine, phenylalanine, leucine, and methanol in ITP spleen tissue were elevated and 3-hydroxybutyric acid, ascorbate, asparagine, ethanol, glycogen, low-density lipoprotein, malonate, myo-inositol, glycerophosphocholine, pyroglutamate, and taurine were decreased. Amino acids metabolic pathways, such as branched-chain amino acids pathway, were identified as the main involved pathways based on enrichment analysis. The decrease in taurine level in the spleen was the most obvious metabolic signature involving ITP with high sensitivity and specificity to distinguish the spleen of ITP from the normal (CI: 0.825–0.982). Notably, the level of taurine in the spleen was negatively correlated with the efficacy of splenectomy (r = 0.622, p = 0.006). Collectively, the data from our study revealed previously unknown ITP-related metabolomic changes in the spleen and found a potential diagnostic and efficacy-predictive biomarker for ITP treatment.

Background: The purpose of this study is to compare the clinical efficacy of laparoscopic splenectomy (LS) and open splenectomy (OS) in the treatment of Idiopathic thrombocytopenic purpura. Methods: We systematically searched PubMed, Web of science, EMBASE, Clinicaltrials.gov, and Cochrane Central Register for studies (study published from July 1992–January 2020). This study analyzed the clinical effect of LS and OS on idiopathic thrombocytopenic purpur. Results: This study showed that compared with OS, the LS's Overall response (OR: 0.60, 95% confidence interval (CI): 0.23–1.59, P = .30), Complication (OR: 0.59, 95% CI: 0.18–1.94, P = .38), Accessory spleen(OR: 1.70, 95% CI: 0.98–2.98, P = .06), Wound infections (OR: 0.65, 95% CI: 0.26–1.59, P = .34), Pancreatic fistula (OR: 0.73, 95% CI: 0.16–3.30, P = .68), was no significant, the Operative time (weighted mean difference (WMD): 49.33, 95% CI: 36.29–62.37, P

We report a case reflecting a suitable use of telemedicine in Oral Medicine. A general dental practitioner, working in a small Patagonian village (more than 1,000 km away from our institution), referred us a case using Instagram and WhatsApp. It was a 7-year-old female with chief complaint of spontaneous gingival bleeding, with no previous medical conditions. publishedVersion Fil: Gilligan, Gerardo Marcelo. Universidad Nacional de Córdoba. Facultad de Odontología. Departamento de Medicina Oral; Argentina. Fil: Piemonte, Eduardo. Universidad Nacional de Córdoba. Facultad de Odontología. Departamento de Medicina Oral; Argentina. Fil: Lazos, Jerónimo. Universidad Nacional de Córdoba. Facultad de Odontología. Departamento de Medicina Oral; Argentina. Fil: Panico, René. Universidad Nacional de Córdoba. Facultad de Odontología. Departamento de Medicina Oral; Argentina.

Introduction: Helicobacter pylori(H. pylori) is a gram-negative microaerophilic bacterium that colonizes the stomachs of over half the human population.Objectives of the study: The main objective of the study was to analyse the helicobacter pylori eradication on platelet counts of adult patients with idiopathic thrombocytopenic purpura.Material and methods: This descriptive study was conducted in University College of Medicine & Dentistry, University of Lahore during March 2019 to November 2019. The study included all adult patients of both sexes, who were diagnosed with ITP. If platelet count and patient status allowed, we diagnosed H.pylori infection was by histological examination of different biopsies obtained from different areas of stomach and duodenum (including the gastric antrum) via esophagogastroduodenoscopy (EGD). IF EGD is not applicable, we diagnosedH. pyloriinfection by the positivity of serum antibodies or urease breath test. We first did serological testing.Results: The median age was 55 years (range: 35-76 years), 18 were men (7 women), and the median platelet count was 78×103/μL (range: 6-96×103/μL). The median follow-up durationof this study was 57.57 months. Twenty-three patients had histologically confirmedH. pyloriinfection from UBT or CLO test. All patients experienced complete bacterial eradication. Of these patients, 2 had received immunosuppressive and anti-RhD immunoglobulin treatment beforeH. pylorieradication therapy.Conclusion: It is concluded that H. pylorieradication in ITP patients Leads to significant Improvement of peripheral blood platelet count in most patients.

Nocardiosis is a life-threatening disease if unrecognized and maltreated. We describe a case of disseminated nocardiosis in a patient with idiopathic thrombocytopenic purpura under steroid therapy. She presented with a 2-week history of progressive symmetrical limb weakness, fatigue, and profuse sweating. Brain MRI revealed ring-enhanced lesions at the cerebellum and left parietal lobe with brain oedema. Chest CT revealed a left upper lobe nodule. Aspirate culture confirmed the diagnosis of nocardiosis. We administered antibiotics and dexamethasone to ameliorate the brain oedema. The patient improved clinically after 2 weeks. Follow-up brain MRI showed improvement. Clinicians should consider nocardiosis in immunocompromised patients with non-specific symptoms.

When faced with a life‐threatening non‐cancerous blood disorder, the term “benign” is a misnomer. Devastating diseases like catastrophic antiphospholipid antibody syndrome, acquired hemophilia, and severe immune thrombocytopenia present a challenge to the hematologist. They are often difficult to treat and lack appropriately powered, unbiased evidence to support management. Moreover, the label “benign” does a disservice as it subconsciously triggers discrepancies in prioritization for the care provider, the system, the patient and his/her family. Despite our progressive advances in non‐malignant hematology, there remain many knowledge and care gaps that can be effectively addressed by more international collaboration, more clinical and research infrastructure and more expertly trained clinicians. To highlight the need, is it time to reconsider the term “benign” hematology?

Although extraintestinal manifestations of inflammatory bowel diseases are not uncommon, few reports have described concurrent idiopathic thrombocytopenic purpura (ITP). Spontaneous pneumomediastinum is also a rare complication of ulcerative colitis (UC). This report describes the case of a 14-year-old boy who experienced recurrent ulcerative colitis 3 months after temporary improvement following treatment with prednisolone (20 mg/day) and granulocyte/monocyte adsorption apheresis. His platelet counts decreased, suggesting ITP. The dosage of prednisolone was increased to 60 mg/day; however, his thrombocytopenia did not improve and he suddenly developed pneumomediastinum. A continuous infusion of cyclosporine increased his platelet counts and improved his ulcerative colitis. Cyclosporine should be considered when steroid-resistant ITP accompanies UC.

The objective of our study is to present two cases showing the effects of traditional Korean herbal medicines based on traditional Korean medicine (TKM) for the treatment of immune thrombocytopenic purpura (ITP). One patient showed no response to treatment with steroids and an immunosuppressive agent. Moreover, liver toxicity and side effects of steroids were evident. However, after he ceased conventional treatment and started to take an herbal medicine, his liver function normalized and the steroid side effects resolved. Ultimately, he achieved complete remission. Another patient with ITP had sustained remission after steroid therapy in childhood, but extensive uterine bleeding and thrombocytopenia recurred when she was 16 years old. She was managed with steroids again for 2 years, but severe side effects occurred, and eventually she ceased taking steroids. She refused a splenectomy, and was then treated with a herbal medicine for 7 months, ultimately leading to sustained remission again. Many patients with resistance to first-line treatments tend to be reluctant to undergo a splenectomy, considered a standard second-line treatment. In conclusion, herbal medicines, based on TKM, may offer alternative treatments for persistent or chronic ITP that is resistant to existing first-line treatments.

A 22-year-old woman had been diagnosed with idiopathic thrombocytopenic purpura (ITP) 5 years earlier. After undergoing splenectomy, she relapsed frequently following prednisolone tapering. She was complicated with minimal change nephrotic syndrome (MCNS) while taking 20 mg of prednisolone. Despite treatment with prednisolone, cyclosporin and low-density lipoprotein-apheresis, MCNS and ITP did not improve. We added rituximab in 4 weekly infusions of 375 mg/m2. MCNS and ITP were in complete remission. After administering rituximab once, all medicines were discontinued. No relapse had occurred by 50 months following the first rituximab administration. Rituximab affects steroid-resistant MCNS and ITP for a long time without complications.

Background: The ZOE-50 (NCT01165177) and ZOE-70 (NCT01165229) phase 3 clinical trials showed that the adjuvanted recombinant zoster vaccine (RZV) was >= 90% efficacious in preventing herpes zoster in adults. Here we present a comprehensive overview of the safety data from these studies. Methods: Adults aged >= 50 (ZOE-50) and >= 70 (ZOE-70) years were randomly vaccinated with RZV or placebo. Safety analyses were performed on the pooled total vaccinated cohort, consisting of participants receiving at least one dose of RZV or placebo. Solicited and unsolicited adverse events (AEs) were collected for 7 and 30 days after each vaccination, respectively. Serious AEs (SAEs) were collected from the first vaccination until 12 months post-last dose. Fatal AEs, vaccination-related SAEs, and potential immune-mediated diseases (pIMDs) were collected during the entire study period. Results: Safety was evaluated in 14,645 RZV and 14,660 placebo recipients. More RZV than placebo recipients reported unsolicited AEs (50.5% versus 32.0%); the difference was driven by transient injection site and solicited systemic reactions that were generally seen in the first week post-vaccination. The occurrence of overall SAEs (RZV: 10.1%; Placebo: 10.4%), fatal AEs (RZV: 4.3%; Placebo: 4.6%), and pIMDs (RZV: 1.2%; Placebo: 1.4%) was balanced between groups. The occurrence of possible exacerbations of pIMDs was rare and similar between groups. Overall, except for the expected local and systemic symptoms, the safety results were comparable between the RZV and Placebo groups irrespective of participant age, gender, or race. Conclusions: No safety concerns arose, supporting the favorable benefit-risk profile of RZV. (C) 2019 GlaxoSmithKline Biologicals SA. Published by Elsevier Ltd.

Idiopathic Thrombocytopenic Purpura (ITP) is an autoimmune disorder. ITP can occur in children and adults. This disease can be fatal because the platelet count is low due to the destruction of excessive platelets so that it can interfere with vital organs and bleeding occurs. The lack of knowledge of ordinary people about ITP disease, so many people assume that bruises and nosebleeds on the body are caused by fatigue. For that, we need a system that can imitate the expertise of an expert in diagnosing this disease based on the symptoms felt. The method used to support the expert system is the K-Nearest Neighbor and Certainty Factor methods which are a combination of 2 methods, where the classification results from the K-Nearest Neighbor method will be given a certainty value by the Certainty Factor method so as to produce a prediction. The results of combining the two methods can produce certainty in the diagnosis. Based on the test results using 3 test scenarios using parameter values k=3, k=5, k=7 and the results obtained the highest accuracy value with parameter value k=7 obtained an accuracy rate of 90,9%.

The aim of the present study was to evaluate the effectiveness and safety of recombinant human interleukin-11 (IL-11) with glucocorticoids for treatment of adult idiopathic thrombocytopenic purpura (ITP) and the regulatory effect on immune mechanisms. A total of 80 patients with initial diagnosis of ITP admitted to our hospital were selected. Patients were randomly divided into the control group and observation group, with 40 cases each. The control group received glucocorticoids treatment, and the observation group received IL-11 and glucocorticoids. The treatment effects were compared. The total effective rate and effective degree of the observation group was higher than in the control group and the difference was statistically significant (P0.05). In the observation group, onset time was reduced, platelet recovery level increased and platelet antibody positive rate decreased, and the differences were statistically significant (P

We presented the clinical data of one patient with renal cell carcinoma associated with idiopathic thrombocytopenic purpura in this case report. We reported a 56-year-old man who presented with petechiae and ecchymoses. Laboratory studies showed the platelet count of 2 × 109/L and an abdominal computed tomography (CT) scan revealed tumors in the right renal. There were purpura on the legs and cough without abdominal pain and melena at this time. Idiopathic thrombocytopenic purpura was diagnosed according to the clinical symptoms and laboratory test. The patient received radical nephrectomy for renal carcinoma, and his idiopathic thrombocytopenic purpura was cured after the surgery. Pathological biopsy confirmed it was renal clear cell carcinoma. The patient has been followed up for more than 3 months after surgery, and the ecchymoses had not been recurred and the patient’s thrombocytopenia was recovered. Idiopathic thrombocytopenic purpura associated with kidney cancer is rare. The patient in this case report was treated with radical nephrectomy, and the effectiveness of idiopathic thrombocytopenic purpura was satisfactory.

Background: Polyautoimmunity is defined as the presence of more than one autoimmune disorder in a single patient. Lipopolysaccharide (LPS)-responsive beige-like anchor (LRBA) deficiency is one of the monogenic causes of polyautoimmunity. The aim of this study was to report the characteristics of polyautoimmunity in patients with LRBA deficiency. Methods: A total of 14 LRBA deficiency patients with confirmed autoimmunity were enrolled in this study. For those patients with polyautoimmunity, demographic information, clinical records, laboratory, and molecular data were collected. We also compared our results with the currently reported patients with LRBA deficiency associated with polyautoimmunity. Results: In 64.2% (9 out of 14) of patients, autoimmunity presented as polyautoimmunity. In these patients, autoimmune cytopenias were the most frequent complication, observed in seven patients. Three patients presented with four different types of autoimmune conditions. The review of the literature showed that 41 of 72 reported LRBA deficient patients (74.5%) had also polyautoimmunity, with a wide spectrum of autoimmune diseases described. Hematopoietic stem cell transplantation is increasingly used as the treatment for patients with severe polyautoimmunity associated to LRBA deficiency. Conclusions: Mutation in LRBA gene is one of the causes of monogenic polyautoimmunity. Awareness of this association is important in order to make an early diagnosis and prompt treatment. © 2018, © 2018 Taylor and Francis.

IgG4-related disease (IgG4RD) is a multi-organ disorder characterized by an elevated serum IgG4 level and IgG4-positive plasma cell infiltration of the affected organs, accompanied by tissue fibrosis and sclerosis. Although it can affect any organ, to our knowledge, no cases involving concurrent autoimmune neutropenia and thrombocytopenia have been reported. A 62-year-old man visited our hospital and was diagnosed with IgG4RD accompanied by interstitial pneumonitis, lymphadenopathy, and interstitial nephritis. During his clinical course, he developed autoimmune neutropenia and idiopathic thrombocytopenic purpura. Our case, invoving multiple hematological abnormalities, might help deepen our understanding of the pathophysiology of IgG4RD.

Актуальность. Идиопатическая тромбоцитопеническая пурпура (ИТП) аутоиммунное заболевание, обусловленное выработкой антител к структурам мембраны тромбоцитов и их предшественников мегакариоцитов, что вызывает не только повышенную деструкцию тромбоцитов, но и неадекватный тромбоцитопоэз. Данное заболевание характеризуются значительной потерей трудоспособности, ухудшением качества жизни, смертностью, а также частыми госпитализациями и ростом расходов на здравоохранение. Оценка финансовых затрат государства вследствие лечения ИТП является актуальной задачей. Методология. Были построены две фармакоэкономические модели для проведения анализа минимизации затрат и «влияния на бюджет». Гипотеза моделирования базируется на сопоставимой эффективности и безопасности агонистов рецепторов тромбопоэтина (ТПО), исходя из отсутствия статистически значимых отличий по результатам непрямого сравнения, и эффективность ромиплостима принята равной эффективности элтромбопага. Прямые медицинские затраты рассчитывались исходя из затрат на лекарственные препараты из группы агонистов ТПО-рецепторов, введение лекарственных препаратов, терапию спасения, лечения кровотечений, наблюдение пациентов с ИТП в процессе терапии. Расчёты проводились на основании зарегистрированных предельных отпускных цен препаратов из перечня жизненно необходимых и важнейших лекарственных препаратов (ЖНВЛП), а также нормативов финансовых затрат в системе здравоохранения Российской Федерации в 2018 г. Результаты. Клинико-экономический анализ использования препаратов из группы агонистов рецепторов тромбопоэтина в терапии хронической ИТП у взрослых показал, что применение препарата элтромбопаг по сравнению с препаратом ромиплостим у пациентов с хронической ИТП при неэффективности предшествующей терапии является более целесообразным с экономической точки зрения при сохранении сопоставимой клинической эффективности. Сокращение затрат на одного пациента в год составило 796 967 руб. (33 %). При постепенном увеличении доли элтромбопага в закупках агонистов ТПО-рецепторов можно сократить бюджетные расходы системы здравоохранения Российской Федерации на 1 693 млн руб. (8 %) за 5 лет. Заключение. Применение препарата элтромбопаг при сопоставимой эффективности и безопасности является более экономически целесообразным вариантом лечения хронической ИТП в сравнении с препаратом ромиплостим., Actuallity. Idiopathic thrombocytopenic purpura (ITP) is an autoimmune disease caused by the production of antibodies to the platelet and megakaryocytes membrane structure, which causes to increase the platelet destruction, but also inadequate thrombocytopoiesis. The disease is characterized by a significant loss of ability to work and decreasing quality of life, higher mortality rate, as well as frequent hospitalizations, reflecting to health care resources utilization. Therefore, burden of disease assessment is a point of high interest. Methodology. Two pharmacoeconomic models were developed for the "cost-minimization" and "budget impact" analysis on the basis of Microsoft Excel software. The modeling hypothesis is comparable efficacy and safety of thrombopoietin receptor agonists (TPO), based on the absence of statistically significant differences from the results of an indirect comparison and the efficacy of romiplostim is assumed to be equal to the efficacy of eltrombopag. Direct medical costs were calculated based on the costs of drugs from the TPO receptor agonist group, the administration of drugs, «rescue therapy», bleeding treatment, and follow-up monitoring of patients with ITP during therapy. Calculations were based on registered limit transfer drug prices from the VED List and standards of the financial expenses per medical care volume unit of Russian Federation in 2018. The reduction in costs per patient per year is 796,967 rubles (33 %). Results. Clinical and economic analysis of drugs from the group of thrombopoietin receptor agonists in the therapy of chronic idiopathic thrombocytopenic purpura in adults has shown that eltrombopag in comparison with romiplostim in patients with chronic ITP at the background of previous treatment failure is more economically expedient being not less clinical effective. It is possible to reduce the budget impact of the healthcare system of the Russian Federation by 1,693 million rubles (8 %) for 5 years with the gradual increasing in eltrombopag share in the purchase of TPO receptor agonists. Conclusion. Eltrombopag with comparable efficacy and safety is more economically sound option of chronic ITP treatment as compared to romiplostim.

Background: Idiopathic thrombocytopenic purpura (ITP) is a primary autoimmune disease with a decreased platelet count caused by platelet destruction mediated mainly by platelet antibodies. T follicular helper (TFH) cells have demonstrated important roles in autoimmune diseases. The aim of this study is to explore the might role of TFH cells in the patients of ITP. Methods: Twenty-three ITP patients and 12 healthy controls (HC) were enrolled in this study. The frequency of circulating TFH cells in both the patients and HC was analyzed by flow cytometry. Serum interleukin (IL)-21 and IL-6 levels were measured using ELISA, and platelet antibodies were tested using a solid phase technique. Additionally, IL-21, IL-6, Bcl-6 and c-Maf mRNA expressions in peripheral blood mononuclear cells (PBMCs) were detected using real-time PCR. Results: The percentages of circulating CXCR5+ CD4+TFH cells with ICOShigh or PD-1high expression were significantly higher in the ITP patients than in the HC. Moreover, the frequencies of circulating CXCR5+ CD4+TFH cells with inducible costimulator (ICOS)high or programmed death-1 (PD-1)high expression were notably higher in ITP with platelet-antibody-positive ( ITP (+) ) patients than in ITP with platelet-antibody-negative ( ITP (-) ) patients and HC, as were the serum IL-21 and IL-6 levels (significant). Moreover, a positive correlation was found between the CXCR5+CD4+TFH cells with ICOShigh or PD-1high expression and the serum IL-21 levels of ITP (+) patients. Additionally, the mRNA expression levels of IL-21, IL-6, Bcl-6 and c-Maf were significantly increased in ITP patients, especially in ITP (+) patients. Conclusions: This study demonstrated TFH cells and effector molecules might play an important role in the pathogenesis of ITP, which are possible therapeutic targets in ITP patients.

Background The presentation of clinical leptospirosis has been historically associated with animal workers, slaughterhouse workers and medical veterinarians. This association has shifted to be related to flooding events and outdoor activities; few cases are related to high-risk factors found in immunosuppressed patients. Scarcely a handful of cases have serological evidence of immune response against Leptospira serovar Bratislava representing serogroup Australis, a serovar associated with poor reproductive performance in swine and horses, and recently with cats. Case presentation Herein, we describe a rare clinical presentation of disseminated Leptospira infection in an immunosuppressed 65-year-old woman. She was admitted to the emergency room with fever, bacteraemia, bilateral uveitis and pulmonary involvement. The patient denied outdoor activities; she only had wide exposure to faeces and urine from cats living in her home. Her medical history included idiopathic thrombocytopenic purpura (ITP) diagnosed at the age of 18. She did not respond to medical treatment, and a splenectomy was performed. At age 60, she was diagnosed with Chronic Myeloid Leukemia (CML), and was treated with a tyrosine kinase inhibitor (TKI) –Imatinib. The patient voluntarily discontinued the treatment for the last 6 months. After extensive workup, no microorganisms were identified by the commonly used stains in microbiology. The diagnosis was performed through dark-field microscopy, microagglutination test (MAT), Leptospira genus-specific PCR, the IS1500 PCR for identification of pathogenic species, and 16S based sequencing for the genus identification. Conclusion Immunosuppressed patients may acquire uncommon infections from ubiquitous microorganisms. In this case, serology evidence of exposure to Leptospira serovar Bratislava by MAT and the presence of the Leptospira genus were identified. It should be on mind for the diagnosis in otherwise healthy patients, and thoroughly search on splenectomised patients exposed to animals. Additionally, this report highlights the usefulness of PCR for diagnosis of this potentially life-threatening illness.

Zika virus (ZIKV) infection has been associated with the development of Guillain-Barre syndrome (GBS) and idiopathic thrombocytopenic purpura (ITP). Whether ZIKV infection is related to other autoimmune diseases is unknown. Therefore, an association study to evaluate rheumatic and thyroid autoimmunity in patients with ZIKV disease was conducted through a panel of 14 autoantibodies. In addition, a literature review on ZIKV, and GBS and ITP was performed. Our results disclosed a lack of association of rheumatoid and thyroid autoimmunity with ZIKV disease. A total of 272 cases of GBS related to ZIKV were retrieved from the literature, the majority of them being males (54.8%). Electrophysiological findings indicated acute inflammatory demyelinating polyneuropathy as the most frequent subphenotype (75.7%). Up to date, twenty-four cases of ITP in patients with ZIKV disease have been published. Although a few fatal cases have been observed, most of the reported patients responded well to immunomodulatory treatment. A review of the mechanisms incriminated into the development of autoimmune phenomenon in ZIKV disease indicates molecular mimicry as the most plausible one. Nevertheless, more research aimed at deciphering ZIKV disease pathogenesis and its relationship with autoimmunity is warranted.

We report the first case of a patient with hepatitis C virus (HCV) infection and idiopathic thrombocytopenic purpura (ITP), who later developed acquired amegakaryocytic thrombocytopenia (AAMT), with autoantibodies to the thrombopoietin (TPO) receptor (c-Mpl). A 64-year-old woman, with chronic hepatitis C, developed severe thrombocytopenia and was diagnosed with ITP. She died of liver failure. Autopsy revealed cirrhosis and liver carcinoma. In the bone marrow, a marked reduction in the number of megakaryocytes was observed, while other cell lineages were preserved. Therefore, she was diagnosed with AAMT. Additionally, autoantibodies to c-Mpl were detected in her serum. Autoantibodies to c-Mpl are one of the causes of AAMT, acting through inhibition of TPO function, megakaryocytic maturation, and platelet formation. HCV infection induces several autoantibodies. HCV infection might also induce autoantibodies to c-Mpl, resulting in the development of AAMT. This mechanism may be one of the causes of thrombocytopenia in patients with HCV infection.

Background: Several studies have demonstrated that platelet counts in Helicobacter pylori-positive patients with chronic idiopathic thrombocytopenic purpura improved significantly after successful eradication of the infection. However, depending of the geographical region of the study the results have been highly divergent. Objective: The purpose of this study was to evaluate the effect of H. pylori eradication therapy on platelet count in a cohort of chronic idiopathic thrombocytopenic purpura patients from northeastern Brazil. Method: H. pylori status was determined in 28 chronic idiopathic thrombocytopenic purpura patients using the rapid urease test and histology. H. pylori-positive patients received standard triple therapy for one week. The effect of the eradication therapy was evaluated using the 13C-urea breath test two to three months after treatment. Results: The prevalence of H. pylori infection was similar to that found in the general population. Twenty-two patients (78.5%) were H. pylori-positive. Fifteen were treated, 13 (86%) of whom successfully. At six months, 4/13 (30%) displayed increased platelet counts, which remained throughout follow-up (12 months). Platelet response was not associated to mean baseline platelet count, duration of chronic idiopathic thrombocytopenic purpura, gender, age, previous use of medication, or splenectomy. Conclusions: H. pylori eradication therapy showed relatively low platelet recovery rates, comparable with previous studies from southeastern Brazil. The effect of H. pylori eradication on platelet counts remained after one year of follow-up suggesting that treating H. pylori infection might be worthwhile in a subset of chronic idiopathic thrombocytopenic purpura patients. Keywords: Helicobacter pylori eradication, Blood platelet, Idiopathic thrombocytopenic purpura

The self-controlled case series (SCCS) method is useful for estimating the relative incidence (RI) of acute events, such as adverse events (AEs) during a specified risk period following an exposure (e.g., 6-week period after vaccinations or 30-day period after infection-related hospitalizations). In practice, the "optimal" risk period is unknown and must be specified. To date, two approaches are available to guide the specification of the risk period. Both methods do not fully utilize the nature of the bias due to misspecification, which to date has not been characterized. Thus, we elucidate the bias of SCCS estimate of the RI when the risk period is misspecified. We then propose a novel method that more effectively estimates the optimal risk period and the associated RI of AEs. The new method incorporates information on the functional form of the bias. Efficacy of the proposed approach is illustrated with substantial reduction in bias and variance in simulation studies. The proposed method is illustrated with two SCCS studies to determine the (1) risk of idiopathic thrombocytopenic purpura after measles-mumps-rubella vaccination in children and (2) risk of cardiovascular events after infection-related hospitalizations in older patients on dialysis.

A 66-year-old woman who was previously diagnosed with idiopathic thrombocytopenic purpura (ITP) presented with mild right-sided hemiparesis and drowsiness. Head computed tomography (CT) imaging demonstrated a massive left chronic subdural hematoma (CSDH) with a midline shift. Because initial laboratory data showed a significantly decreased blood platelet count (0.3 × 104/mm3), medical treatments such as platelet transfusion, intravenous immunoglobulin (IVIG), and high-dose corticosteroid therapy, were initiated. She clinically and radiologically responded well to these treatments without any surgical intervention. In addition to presenting our case, we searched the PubMed and Ichushi Web databases to comprehensively illustrate clinical characteristics and treatment outcomes of similar cases. Including the present case, we found 19 reports and 23 cases of CSDH associated with ITP in the literature, and assessed 17 reports and 21 cases that were written in English and Japanese. None or mild neurological symptom were seen in 13 cases, and severe, such as coma and hemiparesis, were described in the younger 8 cases with significant difference. All except one were first treated with medical therapies. Most cases of the former group responded well to conservative therapy. On the other hand, most in the latter eventually needed surgical treatment in addition except recent two cases including the present case. CSDH associated with ITP is rarely described, and its management remains controversial. However, this report highlights multiple continuous medical treatments under strict observation and general care might be a useful alternative to avoid surgery in cases presenting with severe neurological deficits and extremely low platelet counts.

Background: LPS-responsive beige-like anchor protein (LRBA) deficiency is a primary immunodeficiency and immune dysregulation syndrome caused by biallelic mutations in the LRBA gene. These mutations usually abrogate the protein expression of LRBA, leading to a broad spectrum of clinical phenotypes including autoimmunity, chronic diarrhea, hypogammaglobulinemia, and recurrent infections. Objective: Our aim was to systematically collect all studies reporting on the clinical manifestations, molecular and laboratory findings, and management of patients with LRBA deficiency. Methods: We searched in PubMed, Web of Science, and Scopus without any restrictions on study design and publication time. A total of 109 LRBA-deficient cases were identified from 45 eligible articles. For all patients, demographic information, clinical records, and immunologic and molecular data were collected. Results: Of the patients with LRBA deficiency, 93 had homozygous and 16 had compound heterozygous mutations in LRBA. The most common clinical manifestations were autoimmunity (82%), enteropathy (63%), splenomegaly (57%), and pneumonia (49%). Reduction in numbers of CD4+ T cells and regulatory T cells as well as IgG levels was recorded for 21.6%, 65.6%, and 54.2% of evaluated patients, respectively. B-cell subpopulation analysis revealed low numbers of switched-memory and increased numbers of CD21low B cells in 73.5% and 77.8% of patients, respectively. Eighteen (16%) patients underwent hematopoietic stem cell transplantation due to the severity of complications and the outcomes improved in 13 of them. Conclusions: Autoimmune disorders are the main clinical manifestations of LRBA deficiency. Therefore, LRBA deficiency should be included in the list of monogenic autoimmune diseases, and screening for LRBA mutations should be routinely performed for patients with these conditions. © 2019 American Academy of Allergy, Asthma and Immunology

Only a few studies have addressed long-term results comparing laparoscopic and open splenectomy in idiopathic thrombocytopenic purpura (ITP). We analyzed the 1-year results comparing age, sex, length of preoperative steroid therapy, diagnosis-to-splenectomy interval, and preoperative platelet count in relation to postoperative response after open and laparoscopic splenectomy.Data collected from two groups, treated by laparoscopic and open splenectomy, respectively, of 20 patients each were retrospectively reviewed. Positive response to splenectomies, evaluated according to the International Working Group guidelines reported by the American Society of Hematology, was statistically related through Student's t test and the Pearson correlation test to the above-mentioned factors.Positive response to splenectomy was observed in 80% and 85% of patients, respectively, in the laparoscopic and open groups (P.10). No statistical differences were observed comparing each of the studied factors between laparoscopic and open splenectomy responder patients (P.10). When percentage increase of postoperative platelet count was related to diagnosis-to-splenectomy interval, a positive correlation was found in the laparoscopic group (r = 0.544, P.05). In addition, a significant negative correlation in both groups was observed comparing preoperative platelet count and percentage postoperative platelet increase, with a greater increase of postoperative platelet count in patients with a lower preoperative platelet count (laparoscopic group, r = -0.663; open group, r = -0.656; P.01).In this series long-term results after laparoscopic splenectomy in ITP patients were as effective as after the open approach. Higher postoperative platelet percentage increase was achieved in both groups in patients with a lower preoperative platelet count. Finally, laparoscopic splenectomy in this study seems to be superior to the open approach in patients with a longer diagnosis-to-splenectomy interval.

Introduction: Laparoscopic splenectomy (LS) is the preferred treatment of idiopathic thrombocytopenic purpura (ITP) when medical treatment fails. The objective was to evaluate the feasibility and safety of LS according to the preoperative platelet count. Methods: This study is a retrospective analysis of a series of 199 patients who underwent LS for ITP from 1993 to 2015. The patients were divided into 3 groups according to platelet count: group I ( 50 x 10(9)/L). Results: Operative time was significantly lower in Group III compared to Group I and II (100 +/- 53 and 105 +/- 61 min, P

Mature megakaryocytes depend on the function of Bcl-x(L), a member of the Bcl-2 family of prosurvival proteins, to proceed safely through the process of platelet shedding. Despite this, loss of Bcl-x(L) does not prevent the growth and maturation of megakaryocytes, suggesting redundancy with other prosurvival proteins. We therefore generated mice with a megakaryocyte-specific deletion of Mcl-1, which is known to be expressed in megakaryocytes. Megakaryopoiesis, platelet production, and platelet lifespan were unperturbed in Mcl-1(Pf4Δ/Pf4Δ) animals. However, treatment with ABT-737, a BH3 mimetic compound that inhibits the prosurvival proteins Bcl-2, Bcl-x(L), and Bcl-w resulted in the complete ablation of megakaryocytes and platelets. Genetic deletion of both Mcl-1 and Bcl-x(L) in megakaryocytes resulted in preweaning lethality. Megakaryopoiesis in Bcl-x(Pf4Δ/Pf4Δ) Mcl-1(Pf4Δ/Pf4Δ) embryos was severely compromised, and these animals exhibited ectopic bleeding. Our studies indicate that the combination of Bcl-x(L) and Mcl-1 is essential for the viability of the megakaryocyte lineage. Sylvia and Charles Viertel Foundation Leukemia & Lymphoma Society Refereed/Peer-reviewed

Objectives: Splenectomy is performed in order to provide the treatment in the patients with severe idiopathic throm-bocytopenic purpura, refractory to medical treatment. In this study, we aimed to investigate the postoperatif and long-term outcomes in the patients who underwent splenectomy with the diagnosis of idiopathic thrombocytopenic pur-pura. Materials and Methods: Between 2001-2010 at Dicle University Medical Faculty, General Surgery Department, a retrospective review of the 109 patients who had undergone splenectomy for ITP was reviewed. Age, gender, pres-ence of accessory spleens and location, duration of the operation, number of preoperative platelet tranfusion, number of preoperative and postoperative blood transfusion, length of hospital stay, long-term outcomes, morbidity and mor-tality were recorded. Results: The mean age was 37.10 ± 16.62 (16-72), and there were 88 (80.7%) female and 21 (19.3%) male patients. The mean operation time was 44.87 ± 10:32 (30-120) minutes. The average postoperative blood and preoperative platelet transfusion were 1.63 ± 0.85 (0-3) and 2.01 ± 0.71 (1-3) units, respectively. The accessory spleens were en-countered in 20 (18.3%) patients at the ultrasonographic examination. And also the accessory spleens were encoun-tered in 23 (21.1%) patients during operation and confirmed with histopathologic examination. The most common lo-calization of accessory spleens were splenic hilus. The postoperative complications were occurred in 16 patients (14.7%) and the most complication was atelectasia. The mean length of hospital stay was 4:56 ± 2:45 (2-12) days. Patients were followed for an average of 28 (9-48) months. At the follow-up period, 1 (0.9 %) patient had died. Conclusion: Splenectomy can be performed safely in the treatment of the patients with idiopathic thrombocytopenic purpura unresponsive to medical treatment. Long-term good results can be obtained with splenectomy in these pa-tients. The accessory spleens should not be overlooked to prevent recurrences., Amaç: Splenektomi, medikal tedaviye dirençli ve şiddetli seyreden İdiopatik trombositopenik purpuralı hastalarda te-davi sağlamak amacıyla yapılmaktadır. Bu çalışmada İdiopatik trombositopenik purpura tanısıyla splenektomi uygu-lanan hastalarda postoperatif ve uzun dönem sonuçların irdelenmesi amaçlandı. Gereç ve Yöntem: Dicle Üniversitesi Tıp Fakültesi Genel Cerrahi Kliniğinde 2002-2010 tarihleri arasında İdiopatik trombositopenik purpura tanısıyla splenektomi uygulanan 109 hasta retrospektif olarak değerlendirildi. Hastalarda yaş, cinsiyet, aksesuar dalak varlığı ve yerleşimi, operasyon süresi, preoperatif transfüzyone edilen trombosit ünite sayısı, preoperatif ve postoperatif kan transfüzyon ünite sayısı, hastanede yatış süresi, takip süresi ve sonuçları, morbidite ve mortalite kaydedildi. Bulgular: Hastaların 88\'i (%80.7) kadın, 21\'i (%19.3) erkek idi. Yaş ortalamaları 37.10±16.62 (16-72) yıl idi. Ortalama ameliyat süresi 44.87 ± 10.32 (30-120) dakika idi. Ortalama kan transfüzyonu ve trombosit süspansiyonu sırasıyla 1.63±0.85(0-3) ve 2.01±0.71(1-3) ünite idi. Preoperatif USG ile 20 (%18.3) hastada aksesuar dalak tanımlandı. Has-talarda laparotomide 23\'ünde (%21.1) patoloji tarafından doğrulanan aksesuar dalak tespit edildi. İntraoperatif en sık aksesuar dalak yerleşimi dalak hilusunda saptandı. Hastaların 16\'sında (%14.7) postoperatif dönemde komplikasyon gelişti. En sık görülen komplikasyon atelektazi idi. Hastaların ortalama hastanede yatış süresi 4.56±2.45(2-12) gün idi. Hastalar medyan 28 (9-48) ay takip edildi. Hastaların 1\'inde (%0.9) mortalite gelişti. Sonuç: Splenektomi İdiopatik trombositopenik purpura tedavisinde medikal tedaviye yanıtsız olgularda güvenle uygu-lanabilen bir cerrahi girişimdir ve splenektomiyle bu hastalarda uzun süreli yanıt almak mümkündür. Nüksü engelle-mek için aksesuar dalak gözden kaçırılmamalıdır.

Idiopathic thrombocytopenic purpura (ITP) is an autoimmune disorder characterized by a low platelet count and an increased risk of bleeding. At the same time, ITP patients present an increased risk of thrombosis and atherosclerosis related to the high presence of haemostatic factors and chronic steroid therapy. Although relatively rare, the association of ITP and coronary artery disease represents a complex therapeutic challenge. In particular, no recommendations exist regarding the best management approach. We reviewed the literature making a comparison between coronary artery bypass grafting and percutaneous coronary intervention. © 2011 Published by European Association for Cardio-Thoracic Surgery. All rights reserved.

Mucosal-associated invariant T (MAIT) cells help protect against certain infections and are related to some autoimmune diseases. Immune thrombocytopenia (ITP) is a relatively rare hematological autoimmune disease associated with low platelet count. We designed a cross-sectional study wherein we examined peripheral blood samples of patients with ITP for the number of MAIT cells (CD3+TCR-Vα7.2+CD161+IL-18Rα+ lymphocytes) and their CD4/8 subsets (by flow cytometry) and levels of cytokines (by multiplex assays). The study cohort included 18 patients with ITP and 20 healthy controls (HCs). We first compared the number of MAIT cells between HCs and patients with ITP and then performed subgroup analysis in patients with ITP. The number of total MAIT cells in patients with ITP was significantly lower than that in HCs (p < 0.0001), and the CD4−CD8+ subset of MAIT cells showed the same trend. Moreover, patients with ITP refractory to prednisolone exhibited a significantly lower number of total MAIT and CD4−CD8+ MAIT cells than patients sensitive to prednisolone. The number of total MAIT and CD4−CD8+ MAIT cells was not correlated with the response to thrombopoietin receptor agonist treatment or with Helicobacter pylori infection. We found no relation between cytokine levels and response to prednisolone treatment, although the levels of IP-10 and RANTES showed a correlation with the number of total MAIT and CD4−CD8+ MAIT cells. In conclusion, total MAIT and CD4−CD8+ MAIT cells in peripheral blood were decreased in patients with ITP, correlating with their response to prednisolone.

Many studies have been performed in the last year concerning the potential role of Helicobacter pylori in different extragastric diseases, reinforcing the idea that specific microorganisms may cause diseases even far from the primary site of infection. While the role of H. pylori on idiopathic thrombocytopenic purpura, sideropenic anemia, and vitamin B12 deficiency has been well established, there is a growing interest in other conditions, such as cardiovascular, neurologic, dermatologic, obstetric, immunologic, and metabolic diseases. Concerning neurologic diseases, there is a great interest in cognitive impairment and neurodegeneration. The aim of this review was to summarize the results of the most relevant studies published over the last year on this fascinating topic.

Cyclic thrombocytopenia (CTP) is a rare disorder characterized by periodic decreases and increases in platelet levels. Each cycle usually spans a period of 3-5 weeks. Clinical features are similar to those of idiopathic thrombocytopenic purpura (ITP), so patients are frequently misdiagnosed as having ITP. However, CTP usually does not respond to most treatments used in ITP such as corticosteroids, splenectomy and intravenous immunoglobulin. In this case report, we present a 33-year-old woman with CTP misdiagnosed as ITP.Siklik trombositopeni (ST) trombosit seviyelerinde periyodik düşüş ve yükselmeler ile karakterize olan nadir görülen bir hastalıktır. Bir siklusun uzunluğu genellikle 3-5 hafta arasındadır. Hastalığın klinik özellikleri idiyopatik trombositopenik purpura (İTP) ile benzerlik gösterdiğinden hastalara sık olarak yanlışlıkla İTP tanısı koyulmaktadır. Ancak ST genellikle kortikosteroidler, splenektomi ve intravenöz immünoglobulin gibi İTP tedavilerine yanıt vermez. Bu olgu sunusunda öncesinde İTP tanısı ile takip edilmiş 33 yaşında bir kadın hasta sunuyoruz.

Purpose In absence of direct comparison randomized controlled trials (RCTs), indirect comparison was conducted to evaluate the efficacy and safety of thrombopoietin-receptor agonists (TPO-RAs) in treatment of adult immune thrombocytopenia (ITP). Methods We searched PubMed, Embase and Cochrane Library, Clinical Trials.gov, China National Knowledge Infrastructure, and Chinese Biomedical Literature Database from their earliest records to May 2017. RCTs comparing the TPO-RAs with placebo in adult ITP were included. Primary outcomes were the overall response rate. Secondary outcomes included safety, durable response, overall or clinically significant bleeding, and the proportion of patients receiving rescue medication. Results Nine randomized placebo-controlled trials (786 participants) were included in this systematic review. Overall response [Risk Ratio(RR) = 0.59, 95%Confidence Interval(CI): 0.24–1.45], the incidence of adverse events (RR = 0.98, 95%CI: 0.79–1.21), durable response (RR = 0.47, 95%CI: 0.08–2.81), the incidence of overall bleeding (RR = 1.15, 95%CI: 0.52–2.57) and clinically significant bleeding (RR = 1.09, 95%CI: 0.37–3.24), and the proportion of patients receiving rescue treatment (RR = 0.95, 95%CI: 0.47–1.90) were similar between eltrombopag and romiplostim. Conclusions Eltrombopag and romiplostim might be equivalent in efficacy and safety for adult ITP, however, physicians should still take into account drug cost and comorbidities of the specific patient while making decisions on the treatment of ITP with TPO-RAs. Registration PROSPERO International Prospective Register of Systematic Review (PROSPERO 2017: CRD42017068661).

O objetivo deste trabalho foi determinar a frequência dos quadros clínicos da púrpura trombocitopênica imune e sua associação com contagem de plaquetas, taxa de resposta à esplenectomia e fatores preditivos do desfecho e da evolução para a cronicidade. Realizou-se estudo retrospectivo com 187 crianças diagnosticadas no Hospital das Clínicas da UFMG, entre 04/1988 e 12/2001. Quadros assintomáticos e leves corresponderam a 76% do total. Hemorragias exclusivamente cutâneas ocorreram em 96% dos casos sintomáticos. A gravidade dos sintomas associou-se à intensidade da plaquetopenia. Evolução aguda foi apresentada por 123 pacientes (70,7%) e crônica por 51 (29,3%). A apresentação insidiosa (26,2%) associou-se a um maior número de esplenectomias (p=4x10-7), a uma menor taxa de resposta à corticoterapia (p=0,003) e constituiu-se, juntamente com a ausência de resposta à corticoterapia (p

This report suggests that single-access laparoscopic splenectomy may be an opportunity to further refine minimally invasive approaches for general surgical disease., Background: Laparoscopic splenectomy has been performed in a standard fashion with 4 to 5 trocars since the early 1990s. Single access laparoscopy has recently gained interest, but single access laparoscopic splenectomy has not been reported to date. It has the possible benefits of less pain, faster recovery, better cosmesis, with theoretically similar costs to that of traditional trocars. Methods: A case is presented and the surgical technique of single access laparoscopic splenectomy is detailed. Results: The patient is an otherwise healthy 24-year-old male with medically refractory idiopathic thrombocytopenic purpura and a platelet count of 15 000. A splenectomy was performed using a single incision laparoscopic technique. The patient was placed in a right lateral decubitus position, and a 2.5-cm left upper quadrant incision was made. A multi-instrument flexible single incision port was used that held 3 trocars. A standard splenectomy was performed through this port. A linear stapler was used to transect the splenic hilum. The procedure time was just over 2 hours. The patient did well, was happy with his incision, and was discharged with a platelet count of 108 000. Conclusions: Single access laparoscopic splenectomy is feasible in select patients and may provide a less painful, better cosmetic result.

Mutations in either ABCG5 or ABCG8 cause sitosterolemia, an inborn error of metabolism characterized by high plasma plant sterol concentrations. Recently, macrothrombocytopenia was described in a number of sitosterolemia patients, linking hematological dysfunction to disturbed sterol metabolism. Here, we demonstrate that macrothrombocytopenia is an intrinsic feature of murine sitosterolemia. Abcg5-deficient (Abcg5(-/-)) mice showed a 68% reduction in platelet count, and platelets were enlarged compared with wild-type controls. Macrothrombocytopenia was not due to decreased numbers of megakaryocytes or their progenitors, but defective megakaryocyte development with deterioration of the demarcation membrane system was evident. Lethally irradiated wild-type mice transplanted with bone marrow from Abcg5(-/-) mice displayed normal platelets, whereas Abcg5(-/-) mice transplanted with wild-type bone marrow still showed macrothrombocytopenia. Treatment with the sterol absorption inhibitor ezetimibe rapidly reversed macrothrombocytopenia in Abcg5(-/-) mice concomitant with a strong decrease in plasma plant sterols. Thus, accumulation of plant sterols is responsible for development of macrothrombocytopenia in sitosterolemia, and blocking intestinal plant sterol absorption provides an effective means of treatment.

The underlying problem in idiopathic thrombocytopenic purpura (ITP) has traditionally been recognized as accelerated platelet destruction. However, recent studies have provided evidence that the pathophysiology of ITP is more complex, and impaired platelet production has emerged as one of the mechanisms contributing to the thrombocytopenia. On these grounds, second-generation thrombopoietic agents have been used in clinical trials to stimulate platelet production in ITP patients who are not responsive to standard treatments. These new molecules bear no structural resemblance to thrombopoietin (TPO) but still bind and activate the TPO receptor. Studies have been completed for two TPO receptor agonists: romiplostim (formerly AMG 531) and eltrombopag (formerly SB497115). Romiplostim is a recombinant protein defined as a peptibody. Results of phase I-II trials published recently demonstrated that romiplostim given as a weekly subcutaneous injection for 1-6 weeks results in doubling of platelet counts and an increase to >50 x 10(9)/L in most treated patients with minimal adverse effects. Eltrombopag is an orally available, small organic compound. In a randomized, double-blind, placebo-controlled phase III trial, ITP patients were given daily oral treatment with placebo or eltrombopag 50 mg. Platelet responses were observed in 59% of eltrombopag-treated patients and in 16% of patients in the placebo arm. No significant adverse events were seen. Other thrombopoietic agents in development, such as AKR-501 (formerly YM 477), appear promising in healthy volunteers. Ongoing phase III clinical trials will reveal the potential of these agents in the management of ITP prior to splenectomy and for long-term maintenance therapy, as well as their relative benefit compared with standard of care treatment.