The Experts below are selected from a list of 270 Experts worldwide ranked by ideXlab platform
Hannah Tamary - One of the best experts on this subject based on the ideXlab platform.
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Impact of Next-Generation Sequencing on the Diagnosis and Treatment of Congenital Anemias
Molecular Diagnosis & Therapy, 2020Co-Authors: Orna Steinberg-shemer, Hannah TamaryAbstract:Congenital Anemias are a wide spectrum of diseases including hypoproliferative anemia syndromes, dyserythropoietic Anemias, sideroblastic Anemias, red blood cell membrane and enzymatic defects, hemoglobinopathies, and thalassemia syndromes. The various congenital anemia syndromes may have similar clinical and laboratory presentations, making the diagnosis challenging. The traditional work-up, which includes a complete blood count, blood smears, bone marrow studies, flow cytometry, and the osmotic fragility test, does not always lead to the diagnosis. Specialized tests such as red blood cell enzyme activity and ektacytometry are not widely available. In addition, red blood cell transfusions may mask some of the laboratory characteristics. Therefore, genetic testing is crucial for accurate diagnosis of patients with congenital Anemias. However, gene-by-gene testing is labor intensive because of the large number of genes involved. Thus, targeted next-generation sequencing using custom-made gene panels has been increasingly utilized, with a high success rate of diagnosis. Accurate genetic diagnosis is important for determining specific therapeutic modalities, as well as for avoiding splenectomy when contraindicated. In addition, molecular diagnosis can allow for genetic counseling and prenatal diagnosis in severe cases. We suggest a work-up scheme for patients with congenital Anemias, including early incorporation of targeted next-generation sequencing panels.
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hypocholesterolemia in chronic Anemias with increased erythropoietic activity
American Journal of Hematology, 2007Co-Authors: Hanna Shalev, Joseph Kapelushnik, Asher Moser, Hilla Knobler, Hannah TamaryAbstract:Hypocholesterolemia of unknown etiology has been previously described in various chronic Anemias. Few small studies also suggested that those patients have a lower incidence of atherosclerotic events. The aim of our study was to determine the extent of hypocholesterolemia in various types of Anemias. We studied 59 patients with chronic Anemias associated with high-erythropoietic activity (thalassemia intermedia, congenital dyserythropoietic anemia type I, congenital spherocytosis), 8 patients with low-erythropoietic activity Anemias (acquired aplastic anemia, Fanconi anemia, and Diamond Blackfan anemia), and 20 healthy controls. Mean serum cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, triglycerides, hemoglobin, serum ferritin, soluble transferrin receptor (STR), and serum erythropoietin levels were determined in each patient. All patients with chronic anemia and increased erythropoietic activity had hypocholesterolemia, whereas none of those with low erythropoietic activity was hypocholesterolemic. Mean serum cholesterol, HDL cholesterol, and LDL cholesterol levels were found to be significantly lower in the high-erythropoietic activity group (80+/-19 mg/dl; 31+/-10 mg/dl; 35+/-14 mg/dl, respectively) compared with the control group (P<0.001; 0.001; 0.001, respectively) and the low-erythropoietic activity group (P<0.001; 0.001; 0.01, respectively). Significant inverse correlation (R2=0.507) was observed between serum cholesterol and STR levels, which in the absence of iron deficiency reflect bone marrow activity. Taken together, our results imply that hypocholesterolemia accompanies Anemias with high-erythropoietic activity. We suggest that the high-erythropoitic activity-associated hypocholesterolemia is due to increased cholesterol requirements by the proliferating erythoid cells. Further studies are needed to elucidate the exact mechanism and the possible clinical consequences of this phenomenon.
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Hypocholesterolemia in chronic Anemias with increased erythropoietic activity.
American journal of hematology, 2007Co-Authors: Hanna Shalev, Joseph Kapelushnik, Asher Moser, Hilla Knobler, Hannah TamaryAbstract:Hypocholesterolemia of unknown etiology has been previously described in various chronic Anemias. Few small studies also suggested that those patients have a lower incidence of atherosclerotic events. The aim of our study was to determine the extent of hypocholesterolemia in various types of Anemias. We studied 59 patients with chronic Anemias associated with high-erythropoietic activity (thalassemia intermedia, congenital dyserythropoietic anemia type I, congenital spherocytosis), 8 patients with low-erythropoietic activity Anemias (acquired aplastic anemia, Fanconi anemia, and Diamond Blackfan anemia), and 20 healthy controls. Mean serum cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, triglycerides, hemoglobin, serum ferritin, soluble transferrin receptor (STR), and serum erythropoietin levels were determined in each patient. All patients with chronic anemia and increased erythropoietic activity had hypocholesterolemia, whereas none of those with low erythropoietic activity was hypocholesterolemic. Mean serum cholesterol, HDL cholesterol, and LDL cholesterol levels were found to be significantly lower in the high-erythropoietic activity group (80 ± 19 mg/dl; 31 ± 10 mg/dl; 35 ± 14 mg/dl, respectively) compared with the control group (P < 0.001; 0.001; 0.001, respectively) and the low-erythropoietic activity group (P < 0.001; 0.001; 0.01, respectively). Significant inverse correlation (R2 = 0.507) was observed between serum cholesterol and STR levels, which in the absence of iron deficiency reflect bone marrow activity. Taken together, our results imply that hypocholesterolemia accompanies Anemias with high-erythropoietic activity. We suggest that the high-erythropoitic activity-associated hypocholesterolemia is due to increased cholesterol requirements by the proliferating erythoid cells. Further studies are needed to elucidate the exact mechanism and the possible clinical consequences of this phenomenon. Am. J. Hematol., 2007. © 2006 Wiley-Liss, Inc.
Hanna Shalev - One of the best experts on this subject based on the ideXlab platform.
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hypocholesterolemia in chronic Anemias with increased erythropoietic activity
American Journal of Hematology, 2007Co-Authors: Hanna Shalev, Joseph Kapelushnik, Asher Moser, Hilla Knobler, Hannah TamaryAbstract:Hypocholesterolemia of unknown etiology has been previously described in various chronic Anemias. Few small studies also suggested that those patients have a lower incidence of atherosclerotic events. The aim of our study was to determine the extent of hypocholesterolemia in various types of Anemias. We studied 59 patients with chronic Anemias associated with high-erythropoietic activity (thalassemia intermedia, congenital dyserythropoietic anemia type I, congenital spherocytosis), 8 patients with low-erythropoietic activity Anemias (acquired aplastic anemia, Fanconi anemia, and Diamond Blackfan anemia), and 20 healthy controls. Mean serum cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, triglycerides, hemoglobin, serum ferritin, soluble transferrin receptor (STR), and serum erythropoietin levels were determined in each patient. All patients with chronic anemia and increased erythropoietic activity had hypocholesterolemia, whereas none of those with low erythropoietic activity was hypocholesterolemic. Mean serum cholesterol, HDL cholesterol, and LDL cholesterol levels were found to be significantly lower in the high-erythropoietic activity group (80+/-19 mg/dl; 31+/-10 mg/dl; 35+/-14 mg/dl, respectively) compared with the control group (P<0.001; 0.001; 0.001, respectively) and the low-erythropoietic activity group (P<0.001; 0.001; 0.01, respectively). Significant inverse correlation (R2=0.507) was observed between serum cholesterol and STR levels, which in the absence of iron deficiency reflect bone marrow activity. Taken together, our results imply that hypocholesterolemia accompanies Anemias with high-erythropoietic activity. We suggest that the high-erythropoitic activity-associated hypocholesterolemia is due to increased cholesterol requirements by the proliferating erythoid cells. Further studies are needed to elucidate the exact mechanism and the possible clinical consequences of this phenomenon.
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Hypocholesterolemia in chronic Anemias with increased erythropoietic activity.
American journal of hematology, 2007Co-Authors: Hanna Shalev, Joseph Kapelushnik, Asher Moser, Hilla Knobler, Hannah TamaryAbstract:Hypocholesterolemia of unknown etiology has been previously described in various chronic Anemias. Few small studies also suggested that those patients have a lower incidence of atherosclerotic events. The aim of our study was to determine the extent of hypocholesterolemia in various types of Anemias. We studied 59 patients with chronic Anemias associated with high-erythropoietic activity (thalassemia intermedia, congenital dyserythropoietic anemia type I, congenital spherocytosis), 8 patients with low-erythropoietic activity Anemias (acquired aplastic anemia, Fanconi anemia, and Diamond Blackfan anemia), and 20 healthy controls. Mean serum cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, triglycerides, hemoglobin, serum ferritin, soluble transferrin receptor (STR), and serum erythropoietin levels were determined in each patient. All patients with chronic anemia and increased erythropoietic activity had hypocholesterolemia, whereas none of those with low erythropoietic activity was hypocholesterolemic. Mean serum cholesterol, HDL cholesterol, and LDL cholesterol levels were found to be significantly lower in the high-erythropoietic activity group (80 ± 19 mg/dl; 31 ± 10 mg/dl; 35 ± 14 mg/dl, respectively) compared with the control group (P < 0.001; 0.001; 0.001, respectively) and the low-erythropoietic activity group (P < 0.001; 0.001; 0.01, respectively). Significant inverse correlation (R2 = 0.507) was observed between serum cholesterol and STR levels, which in the absence of iron deficiency reflect bone marrow activity. Taken together, our results imply that hypocholesterolemia accompanies Anemias with high-erythropoietic activity. We suggest that the high-erythropoitic activity-associated hypocholesterolemia is due to increased cholesterol requirements by the proliferating erythoid cells. Further studies are needed to elucidate the exact mechanism and the possible clinical consequences of this phenomenon. Am. J. Hematol., 2007. © 2006 Wiley-Liss, Inc.
Roberta Russo - One of the best experts on this subject based on the ideXlab platform.
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multi gene panel testing improves diagnosis and management of patients with hereditary Anemias
American Journal of Hematology, 2018Co-Authors: Roberta Russo, Immacolata Andolfo, Francesco Manna, Antonella Gambale, Roberta Marra, Barbara Eleni Rosato, Paola Caforio, Valeria Pinto, Piero Pignataro, Kottayam RadhakrishnanAbstract:Mutations in more than 70 genes cause hereditary Anemias (HA), a highly heterogeneous group of rare/low frequency disorders in which we included: hyporegenerative Anemias, as congenital dyserythropoietic anemia (CDA) and Diamond-Blackfan anemia; hemolytic Anemias due to erythrocyte membrane defects, as hereditary spherocytosis and stomatocytosis; hemolytic Anemias due to enzymatic defects. The study describes the diagnostic workflow for HA, based on the development of two consecutive versions of a targeted-NGS panel, including 34 and 71 genes, respectively. Seventy-four probands from 62 unrelated families were investigated. Our study includes the most comprehensive gene set for these Anemias and the largest cohort of patients described so far. We obtained an overall diagnostic yield of 64.9%. Despite 54.2% of cases showed conclusive diagnosis fitting well to the clinical suspicion, the multi-gene analysis modified the original clinical diagnosis in 45.8% of patients (nonmatched phenotype-genotype). Of note, 81.8% of nonmatched patients were clinically suspected to suffer from CDA. Particularly, 45.5% of the probands originally classified as CDA exhibited a conclusive diagnosis of chronic anemia due to enzymatic defects, mainly due to mutations in PKLR gene. Interestingly, we also identified a syndromic CDA patient with mild anemia and epilepsy, showing a homozygous mutation in CAD gene, recently associated to early infantile epileptic encephalopathy-50 and CDA-like anemia. Finally, we described a patient showing marked iron overload due to the coinheritance of PIEZO1 and SEC23B mutations, demonstrating that the multi-gene approach is valuable not only for achieving a correct and definitive diagnosis, but also for guiding treatment.
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clinical aspects and pathogenesis of congenital dyserythropoietic Anemias from morphology to molecular approach
Haematologica, 2012Co-Authors: Achille Iolascon, Maria Rosaria Esposito, Roberta RussoAbstract:Congenital dyserythropoietic Anemias belong to a group of inherited conditions characterized by a maturation arrest during erythropoiesis with a reduced reticulocyte production in contrast with erythroid hyperplasia in bone marrow. The latter shows specific morphological abnormalities that allowed for a morphological classification of these conditions mainly represented by congenital dyserythropoietic Anemias types I and II. The identification of their causative genes provided evidence that these conditions have different molecular mechanisms that induce abnormal cell maturation and division. Some altered proteins seem to be involved in the chromatin assembly, such as codanin-1 in congenital dyserythropoietic anemia I. The gene involved in congenital dyserythropoietic anemia II, the most frequent form, is SEC23B. This condition seems to belong to a group of diseases attributable to defects in the transport of newly synthesized proteins from endoplasmic reticulum to the Golgi. This review will analyze recent insights in congenital dyserythropoietic Anemias types I and II. It will also attempt to clarify the relationship between mutations in causative genes and the clinical phenotype of these conditions.
Patricia A Arndt - One of the best experts on this subject based on the ideXlab platform.
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practical aspects of investigating drug induced immune hemolytic anemia due to cefotetan or ceftriaxone a case study approach
Immunohematology American Red Cross, 2002Co-Authors: Patricia A ArndtAbstract:: In the 1970s, the most common causes of drug-induced immune hemolytic anemia were methyldopa and penicillin. Since 1990, the most common causes of drug-induced immune hemolytic anemia have been the second- and third-generation cephalosporins, cefotetan and ceftriaxone. Three case histories illustrate the common findings in the serologic investigation of immune hemolytic Anemias due to these two drugs.
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severe immune hemolytic anemia associated with prophylactic use of cefotetan in obstetric and gynecologic procedures
American Journal of Obstetrics and Gynecology, 1999Co-Authors: George Garratty, Regina M. Leger, Patricia A ArndtAbstract:Abstract Second- and third-generation cephalosporins, especially cefotetan, are increasingly associated with severe, sometimes fatal immune hemolytic anemia. We noticed that 10 of our 35 cases of cefotetan-induced hemolytic Anemias were in patients who had received cefotetan prophylactically for obstetric and gynecologic procedures. Eight of these cases of severe immune hemolytic anemia are described. (Am J Obstet Gynecol 1999;181:103-4.)
Kristina M. Haley - One of the best experts on this subject based on the ideXlab platform.
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Congenital Hemolytic Anemia
The Medical clinics of North America, 2016Co-Authors: Kristina M. HaleyAbstract:Red blood cell (RBC) destruction can be secondary to intrinsic disorders of the RBC or to extrinsic causes. In the congenital hemolytic Anemias, intrinsic RBC enzyme, RBC membrane, and hemoglobin disorders result in hemolysis. The typical clinical presentation is a patient with pallor, anemia, jaundice, and often splenomegaly. The laboratory features include anemia, hyperbilirubinemia, and reticulocytosis. For some congenital hemolytic Anemias, splenectomy is curative. However, in other diseases, avoidance of drugs and toxins is the best therapy. Supportive care with transfusions are also mainstays of therapy. Chronic hemolysis often results in the formation of gallstones, and cholecystectomy is often indicated.