Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0026986 (myelodysplastic syndrome)
 14,926 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Initially, immune (idiopathic) thrombocytopenic purpura (ITP) was considered to be a disease of increased platelet destruction. Consequently, treatments for ITP patients were focused on reducing the destruction of platelets. However, recent research on the pathogenesis of ITP points to a role of suboptimal platelet production, and this has led to the development of new treatment options which increase platelet production such as the novel thrombopoiesis-stimulating agent, romiplostim. In two, multicentre, randomized, placebo-controlled, double-blinded, phase III trials, romiplostim was able to increase and sustain platelet counts in both splenectomized and non-splenectomized patients. Eighty-three per cent (69/83) of the romiplostim-treated patients achieved an overall platelet response compared with 7% (3/42) of patients receiving placebo (P < 0.0001; Cochran-Mantel-Haenszel test controlled for splenectomy and baseline concurrent ITP therapy). Patients from the romiplostim studies, with platelet counts below 50 x 10(9)/L, were able to enter a long-term, open-label, extension study. The results of the long-term study showed that platelet counts above 50 x 10(9)/L were maintained for > or =10, > or =25 and > or =52 consecutive weeks by 78% (102/131), 54% (66/122) and 35% (29/84) of patients, respectively. Romiplostim appears to be generally well tolerated and several patients have now been treated for more than 3 yrs. Most adverse events tend to be mild to moderate in nature. Romiplostim provides a valid treatment option that may bring about a change in the way that patients with ITP are treated in the future. Further studies are now being undertaken in paediatric patients with ITP, patients with myelodysplastic syndrome and patients with chemotherapy-induced thrombocytopenia.
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PMID:Romiplostim: a breakthrough treatment for the management of immune thrombocytopenic purpura. 1920 Mar 4

Platelets play a pivotal role in maintaining hemostatic competence. Thrombocytopenia, irrespective of its etiology, is associated with a risk for bleeding. Treatment modalities for chronic idiopathic thrombocytopenic purpura (ITP) are numerous, but the response is variable, often disappointing and associated with high risks. Better understanding of the pathophysiology of chronic ITP, indicating impaired platelet production rather than simply increased turnover, led to clinical trials aimed at increasing platelet production with thrombopoietin receptor agonists. To date, two compounds have been investigated extensively, romiplostim (AMG-531, Nplate) and eltrombopag (SB-497115, Promacta, Revolade). The success of this treatment further paved the way for evaluating its efficacy in raising platelet counts in hepatitis C virus (HCV)-related infection and myelodysplastic syndrome. Although there is less experience in hepatitis C than in chronic ITP, preliminary data are highly promising. This review will focus on the experience gained with eltrombopag in chronic ITP and HCV-related thrombocytopenia.
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PMID:Eltrombopag in chronic idiopathic thrombocytopenic purpura and HCV-related thrombocytopenia. 1934 29

Thrombocytopenia is a condition of unusually low level of platelets in blood, resulting from an imbalance between the production and destruction of platelets, and is associated with aplastic anemia, myelodysplasia, and idiopathic thrombocytopenic purpura (ITP). Thrombocytopenia can also be associated with severe chronic liver disease as a result of several factors that may act in concert, including reduced production of the endogenous thrombopoietic growth factor, thrombopoietin (TPO). This article examines the nature of thrombocytopenia, ITP, and TPO.
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PMID:Thrombopoietin agonists for the treatment of thrombocytopenia in liver disease and hepatitis C. 1962 64

A boy 3 years 7 months old with thrombocytopenia and history of intracranial hemorrhage who underwent bone marrow transplantation is presented. He was refractory to steroids, immunoglobulin G, vincristine, azathioprine, cyclosporine A, interleukin-11, chemotherapy, and splenectomy. Idiopathic thrombocytopenic purpura was excluded by light /electron microscopic and flow cytometric findings; the diagnosis of refractory cytopenia, a subgroup of pediatric myelodysplastic syndrome, was made. Naked megakaryocyte nuclei were 55.38 +/- 28.2% vs. 31.67 +/- 23.22% of all megakaryocytes in the patient and the control group of 9 patients with idiopathic thrombocytopenic purpura, respectively (p = .016). The posttransplatation course was complicated by delayed platelet engraftment, bronchiolitis obliterans associated with pneumocystis carinii pneumonia, which resolved completely.
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PMID:Excessive naked megakaryocyte nuclei in myelodysplastic syndrome mimicking idiopathic thrombocytopenic purpura: a complicated pre- and post-transplantation course. 1965 88

When corticosteroid therapy, immunoglobulin and splenectomy fail to control chronic idiopathic thrombocytopenic purpura and the risk of bleeding remains high, romiplostim is an acceptable option but close monitoring is needed to evaluate long-term risks. Eltrombopag (Revolade, GlaxoSmithKline) is a synthetic non-peptide agonist of endogenous receptors for thrombopoietin, a platelet growth factor. Clinical evaluation of eltrombopag in this setting is mainly based on a double-blind placebo-controlled trial in a heterogeneous group of 114 patients. The platelet count rose to at least 50,000/mm3 for five weeks in about one-quarter of patients receiving oral eltrombopag 50 mg/day. An indirect comparison providing weak evidence suggests that romiplostim is more effective. Clinical trials did not provide evidence that either drug reduced the frequency of bleeding. The haematological risks associated with eltrombopag are poorly evaluated, and mainly include: thrombosis, bone marrow disorders, and aggravation of thrombocytopenia after drug withdrawal. Aggravation of myelodysplastic syndrome cannot be ruled out in the long term. Hepatic disorders such as photosensitisation are frequent. The risk of cataract formation and renal impairment requires further study. There appears to be a high risk of pharmacokinetic interactions through a variety of mechanisms, including enzyme competition and cation binding, but this risk is not well documented. Eltrombopag is administered orally, making it more convenient than romiplostim, which necessitates weekly subcutaneous injections. In practice, when standard treatments fail in patients with chronic idiopathic thrombocytopenic purpura and a high risk of bleeding, it is better to use romiplostim, which appears to be somewhat more effective than eltrombopag. Eltrombopag also seems to carry a higher risk of non-haematological adverse effects and drug interactions.
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PMID:Eltrombopag. Idiopathic thrombocytopenic purpura after treatment failure: romiplostim is a better option. 2045 33

Thrombocytopenia, common in leukemias and myelodysplastic syndromes (MDS), is responsible for increased risk of bleeding and delay of therapy. Platelet transfusions, although effective in increasing platelet counts, are limited by supply, are associated with risks, and result in limited and transient benefits. Successful development of an alternative treatment approach with thrombopoietin agonists was nearly thwarted when early formulations of recombinant thrombopoietin agonists elicited antibodies that cross-reacted with and neutralized endogenous thrombopoietin. The effectiveness of these recombinant agents led to the development of second-generation thrombopoietin receptor agonists that do not induce cross-reacting neutralizing antibodies against thrombopoietin. Two of the novel thrombopoietin receptor agonists, romiplostim and eltrombopag, have established clinical activity in chronic immune (idiopathic) thrombocytopenic purpura (ITP), and are being explored for the treatment of thrombocytopenia in MDS.
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PMID:Thrombocytopenia in patients with myelodysplastic syndromes. 2062 Apr 39

The current concepts and the management of ITP have significantly changed in the past decade. Decreased use of cytotoxic therapy and the introduction of new selective modalities of drug such as TPO-r mimetics are the landmarks of this change. Discovered in the middle of last decade, followed by experiments in mice and then approved in humans, Eltrombopag is the first TPO-r mimetic available. It has been used and validated in several clinical studies in different etiologies of thrombocytopenia, including primary ITP (chronic Immune ThrombocytoPenia) and secondary ITP, due to hepatitis C and more recently in bone marrow failure as myelodysplastic syndromes. Good tolerability and low side effects are the strengths of this drug, contrasted with issues regarding administration (it must be taken every day apart from specific meals containing high levels of calcium, which leads to problems with compliance). We review the first clinical studies with this agent, emphasizing the significant findings.
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PMID:Eltrombopag. 2105 63

Hematogones (HGs) are benign immature B cells in bone marrow with a variety of benign and malignant conditions, including idiopathic thrombocytopenic purpura, leukemia, lymphoma, red blood cell aplasia, iron deficiency anemia, amegakaryocytosis, regenerative bone marrow following viral injury, chemotherapy or bone marrow transplantation, copper deficiency, autoimmune cytopenias, neuroblastoma, and acquired immunodeficiency syndrome (AIDS). HGs may cause diagnostic problems because of their morphologic and immunophenotypic similarities to neoplastic lymphoblasts. Herein, two patients with thrombocytopenia and three lineage dysplasias in the bone marrow suggesting myelodysplastic syndrome (MDS) with excess blasts are presented. Light microscopic evaluation of marrow from both patients revealed periodic acid-Schiff (PAS)-negative blasts However, flow cytometric analysis revealed excessive HGs in both patients, implying that the cells that were considered as blasts were actually large HGs. Thus, the patients were diagnosed as immune thrombocytopenic purpura due to the isolated thrombocytopenia, large platelets on blood and bone marrow smears and increased megakaryocytes in the bone marrow. These cases emphasize the importance of distinction of hematogone-rich conditions from leukemia and MDS for accurate diagnosis and treatment, and the reliability of multiparameter flow cytometry for the differential diagnosis.
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PMID:Hematogones in immune thrombocytopenic purpura: diagnostic implication. 2185 65

Myelodysplastic syndromes (MDS) are a group of haematological malignancies categorized by ineffective hematopoiesis that result in dysplasia. Although morphological diagnosis is a traditional and standard technique that is used for the diagnosis of MDS, the heterogeneous blood and bone marrow characteristics of MDS patients can potentially obscure the right diagnosis. Thus, we have utilized flow cytometric immunophenotyping as a supportive mechanism to obtain a more accurate and faster method for detection of abnormal markers in MDS. Flow cytometry was used for analyzing bone marrow samples from newly diagnosed MDS patients to investigate the abnormal antigen expression patterns in granulocytic, monocytic, erythroid, lymphoid lineages and myeloid precursors. The results were compared with those obtained from cases that had Idiopathic Thrombocytopenic Purpura (ITP) as a control. The most common abnormality found in the granulocytic lineage was the decrease of CD10. Low expressions of CD13 were the most frequent abnormality in the monocytic lineage. The erythroid lineage was found to have low expression of CD235A+/CD71+, reduce of CD71 and decreased CD235a. In conclusion, this method is useful for confirming cases in which it is difficult to make a diagnosis by morphology.
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PMID:Qualitative flow cytometric analysis of Malaysian myelodysplastic syndromes (MDS) patients. 2258 53

This study was purposed to establish a new quick and simple diagnostic method with high sensitivity and good specificity for idiopathic thrombocytopenic purpura (ITP) and to evaluate its significance. 240 platelet lysates (from patients with ITP, leukemia, MDS, and healthy adults, each of 60 cases) were randomly assigned to training set (120 cases) or validation set (120 cases), all of them were detected by surface enhanced laser desorption ionization time of flight mass spectrometry (SELDI-TOF-MS), in order to identify the differentially expressed protein, the diagnostic model was established by means of artificial neural network (ANN), and was validated by blind test with SPSS 17.0. The results showed that 5 marked proteins significantly differentially expressed (P < 0.01), m/z of highly expressed proteins were 2234.30, 3476.36, and 7526.29, m/z of low expressed proteins were 4990.02 and 5152.39, respectively. The sensitivity and specificity of diagnostic model were 80.6% and 77.3% respectively. The area under the ROC curve consisting of the output value of artificial neura1 network was 0.837. Efficacy of the model was validated by means of blinded test. It is concluded that the ANN model is useful for clinical diagnosis of ITP on the basis of platelet protein fingerprint spectrum.
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PMID:[Diagnosis model of idiopathic thrombocytopenic purpura based on platelet differential proteome]. 2348 6


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