The Experts below are selected from a list of 144 Experts worldwide ranked by ideXlab platform
Narla Mohandas - One of the best experts on this subject based on the ideXlab platform.
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Red Cell membrane disorders
International Journal of Laboratory Hematology, 2017Co-Authors: J. Narla, Narla MohandasAbstract:Significant advances have been made in our understanding of the structural basis for alteRed Cell function in various inherited Red Cell membrane disorders with Reduced Red Cell survival and resulting hemolytic anemia. The current review summarizes these advances as they relate to defining the molecular and structural basis for disorders involving alteRed membrane structural organization (heReditary spherocytosis [HS] and heReditary elliptocytosis [HE]) and alteRed membrane transport function (heReditary overhydrated stomatocytosis and heReditary xerocytosis). Mutations in genes encoding membrane proteins that account for these distinct Red Cell phenotypes have been identified. These molecular insights have led to improved understanding of the structural basis for alteRed membrane function in these disorders. Weakening of vertical linkage between the lipid bilayer and spectrin-based membrane skeleton leads to membrane loss in HS. In contrast, weakening of lateral linkages among different skeletal proteins leads to membrane fragmentation and decreased surface area in HE. The degrees of membrane loss and resultant increases in Cell sphericity determine the severity of anemia in these two disorders. Splenectomy leads to amelioration of anemia by increasing the circulatory Red Cell life span of spherocytic Red Cells that are normally sequesteRed by the spleen. DisordeRed membrane cation permeability and resultant increase or decrease in Red Cell volume account for alteRed Cellular deformability of heReditary overhydrated stomatocytosis and heReditary xerocytosis, respectively. Importantly, splenectomy is not beneficial in these two membrane transport disorders and in fact contraindicated due to severe postsplenectomy thrombotic complications.
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heReditary spherocytosis elliptocytosis and other Red Cell membrane disorders
Blood Reviews, 2013Co-Authors: Lydie Da Costa, Julie Galimand, Odile Fenneteau, Narla MohandasAbstract:HeReditary spherocytosis and elliptocytosis are the two most common inherited Red Cell membrane disorders resulting from mutations in genes encoding various Red Cell membrane and skeletal proteins. Red Cell membrane, a composite structure composed of lipid bilayer linked to spectrin-based membrane skeleton is responsible for the unique features of flexibility and mechanical stability of the Cell. Defects in various proteins involved in linking the lipid bilayer to membrane skeleton result in loss in membrane cohesion leading to surface area loss and heReditary spherocytosis while defects in proteins involved in lateral interactions of the spectrin-based skeleton lead to decreased mechanical stability, membrane fragmentation and heReditary elliptocytosis. The disease severity is primarily dependent on the extent of membrane surface area loss. Both these diseases can be readily diagnosed by various laboratory approaches that include Red blood Cell cytology, flow cytometry, ektacytometry, electrophoresis of the Red Cell membrane proteins, and mutational analysis of gene encoding Red Cell membrane proteins.
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Red Cell membrane past present and future
Blood, 2008Co-Authors: Narla Mohandas, Patrick G GallagherAbstract:As a result of natural selection driven by severe forms of malaria, 1 in 6 humans in the world, more than 1 billion people, are affected by Red Cell abnormalities, making them the most common of the inherited disorders. The non-nucleated Red Cell is unique among human Cell type in that the plasma membrane, its only structural component, accounts for all of its diverse antigenic, transport, and mechanical characteristics. Our current concept of the Red Cell membrane envisions it as a composite structure in which a membrane envelope composed of cholesterol and phospholipids is secuRed to an elastic network of skeletal proteins via transmembrane proteins. Structural and functional characterization of the many constituents of the Red Cell membrane, in conjunction with biophysical and physiologic studies, has led to detailed description of the way in which the remarkable mechanical properties and other important characteristics of the Red Cells arise, and of the manner in which they fail in disease states. Current studies in this very active and exciting field are continuing to produce new and unexpected revelations on the function of the Red Cell membrane and thus of the Cell in health and disease, and shed new light on membrane function in other diverse Cell types.
Iain C. Macdougall - One of the best experts on this subject based on the ideXlab platform.
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Pure Red Cell Aplasia Induced by Erythropoiesis-Stimulating Agents
Clinical Journal of The American Society of Nephrology, 2008Co-Authors: Carol A. Pollock, David W. Johnson, Walter H. Hörl, Jerome Rossert, Nicole Casadevall, Huub Schellekens, Robert Delage, Angel L.m. De Francisco, Iain C. Macdougall, Robin ThorpeAbstract:Pure Red Cell aplasia in patients who are treated for anemia of chronic kidney disease with erythropoiesis-stimulating agents such as epoetin was first reported in 1998. Although the incidence of pure Red Cell aplasia peaked in 2002, it remains important for nephrologists to know how to investigate a suspected case of pure Red Cell aplasia and how to identify other causes of hyporesponsiveness to erythropoiesis-stimulating agents, which account for the vast majority of such cases. The authors reviewed the current status of information in the literature and drew on their personal experiences with patients regarding the diagnosis and management of epoetin-induced pure Red Cell aplasia. The mechanism for development of epoetin-induced pure Red Cell aplasia remains unconfirmed. It generally occurs after the production of neutralizing anti-erythropoietin antibodies. Elucidation of a suspected pure Red Cell aplasia case requires a systematic approach, beginning with simple measurements such as blood Cell counts, because most cases of erythropoiesis-stimulating agent hyporesponsiveness are attributable to other causes. If these criteria indicate that the patient9s response to erythropoiesis-stimulating agent therapy is very poor, then bone marrow examination and measurement of anti-erythropoietin antibodies is justified. If pure Red Cell aplasia is confirmed, then cessation of erythropoiesis-stimulating agent therapy and initiation of immunosuppressive therapy are recommended. Continued study of epoetin-induced pure Red Cell aplasia is needed to help nephrologists prevent or manage future cases and will have implications for the use of other protein-based therapeutic agents.
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treatment of erythropoietin induced pure Red Cell aplasia a retrospective study
The Lancet, 2004Co-Authors: David Verhelst, Jerome Rossert, Nicole Casadevall, Anne Kruger, Kaiuwe Eckardt, Iain C. MacdougallAbstract:Summary Background Recombinant human erythropoietin is the standard treatment for anaemia related to chronic kidney disease, and its widespread use has been favouRed by a very high therapeutic index. However, since 1998, more than 200 patients worldwide with chronic kidney disease treated in this way have developed neutralising antibodies to erythropoietin, causing pure Red Cell aplasia. We aimed to collate clinical and pathological features in patients unequivocally shown to have erythropoietin-induced pure Red Cell aplasia. Methods We retrospectively obtained data from the files of 47 patients with pure Red Cell aplasia. We assessed treatment and outcome of patients and defined recovery from pure Red Cell aplasia as an increase in reticulocyte counts to more than 20 000 per μL in patients who were no longer transfusion-dependent. Findings When patients developed pure Red Cell aplasia, all were receiving erythropoietin subcutaneously, and the product most typically prescribed was epoetin alfa (Eprex, Ortho Biotech). The median delay between start of erythropoietin treatment and occurrence of pure Red Cell aplasia was 11 months (IQR 7·5–14). Nine patients received no immunosuppressive treatment, and none of these recoveRed. Of 37 patients who received immunosuppressive therapy, 29 (78%) recoveRed. All six patients who received a kidney transplant recoveRed within 1 month, and recovery rates were between 56% and 88% in patients treated with corticosteroids, corticosteroids plus cyclophosphamide, or ciclosporin. No relapse of pure Red Cell aplasia happened after stopping immunosuppressive treatment, but no patient was rechallenged with erythropoietin. Interpretation Immunosuppressive treatment accelerates recovery from erythropoietin-induced pure Red Cell aplasia.
Dennis W Raisch - One of the best experts on this subject based on the ideXlab platform.
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pure Red Cell aplasia and epoetin therapy
The New England Journal of Medicine, 2004Co-Authors: Charles L Bennett, Stefano Luminari, Allen R Nissenson, Martin S Tallman, Stephen A Klinge, Norene Mcwilliams, June M Mckoy, Allison E Lyons, Steve Trifilio, Dennis W RaischAbstract:Background Between 1988 and 1998, antibody-associated pure Red-Cell aplasia was reported in three patients who had undergone treatment with recombinant human erythropoietin (epoetin). Between 1998 and 2000, 13 such cases were reported from France — 12 in patients who had received the Eprex formulation of epoetin alfa and 1 in a patient who had received Neorecormon (a formulation of epoetin beta); both are products that are marketed outside the United States. Methods We obtained reports of epoetin-associated pure Red-Cell aplasia from the Food and Drug Administration and from the manufacturers of Eprex, Epogen (another formulation of epoetin alfa), and Neorecormon. The numbers of case reports and estimates of exposure-adjusted incidence were analyzed according to the product, the cause of anemia, the route of administration, the country in which pure Red-Cell aplasia was identified, and the date on which pure Red-Cell aplasia was reported. Results Between January 1998 and April 2004, 175 cases of epoetin-a...
Deepak Singhal - One of the best experts on this subject based on the ideXlab platform.
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Red Cell alloimmunization is associated with development of autoantibodies and increased Red Cell transfusion requirements in myelodysplastic syndrome
Haematologica, 2017Co-Authors: Rakchha Chhetri, Lakshmi Nath, Shriram V Nath, Sophia Hague, Romi Sinha, Monika M Kutyna, Deepak Singhal, Nicholas WickhamAbstract:Up to 90% of patients with a myelodysplastic syndrome require Red blood Cell transfusion; nevertheless, comprehensive data on Red Cell alloimmunization in such patients are limited. This study evaluates the incidence and clinical impact of Red Cell alloimmunization in a large cohort of patients with myelodysplastic syndrome registeRed in the statewide South Australian-MDS registry. The median age of the 817 patients studied was 73 years, and 66% were male. The cumulative incidence of alloimmunization was 11%. Disease-modifying therapy was associated with a lower risk of alloimmunization while alloimmunization was significantly higher in patients with a revised International Prognostic Scoring System classification of Very Low, Low or Intermediate risk compaRed to those with a High or Very High risk (P=0.03). Alloantibodies were most commonly directed against antigens in the Rh (54%) and Kell (24%) systems. Multiple alloantibodies were present in 49% of alloimmunized patients. Although 73% of alloimmunized patients developed alloantibodies during the period in which they received their first 20 Red Cell units, the total number of units transfused was significantly higher in alloimmunized patients than in non-alloimmunized patients (90±100 versus 30±52; P
M. M. Reid - One of the best experts on this subject based on the ideXlab platform.
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A regional experience of Red Cell aplasia
European Journal of Pediatrics, 1993Co-Authors: J. A. Kynaston, N. C. West, M. M. ReidAbstract:The incidence and current management of Red Cell aplasia in children was determined from a retrospective survey of haematologists and paediatricians in the northern health region of England over a 7-year period. Thirty-three children were diagnosed: 4 had Diamond Blacktan anaemia, 22 transient erythroblastopenia of childhood, and 7 parvovirus B19 aplasia, with annual incidences of 1, 5 and 2 per 1,000,000 children respectively. Many were over-investigated. Three with Diamond Blackfan anaemia were steroid responsive. One with transient erythroblastopenia was retrospectively diagnosed because anaemia did not recur after steroids were stopped. Transient erythroblastopenia is the most common single cause of Red Cell aplasia in immunocompetent children. Time, observation and bone marrow examination before steroid therapy are the ways to distinguish transient erythroblastopenia from Diamond Blackfan anaemia or leukaemia. Interpretation of Red Cell indices using age-related percentiles may Reduce the number of inappropriate investigations of the anaemia, but is often unhelpful in distinguishing the various causes of Red Cell aplasia.
