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Query: UMLS:C0002871 (anemia)
 52,094 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

New discoveries in cell biology, molecular biology and genetics have unveiled some of the pathophysiological mysteries of some of the bone marrow failure syndromes. Many of these discoveries have revealed why these syndromes show so much clinical overlap and some hold the potential for influencing the development of new therapies. In children and adults with pancytopenia and hypoplastic bone marrows proper differential diagnosis requires that some attention be directed toward defining molecular and cellular pathogenetic mechanisms because, once identified, some of these mechanisms will clearly suggest rational therapeutic approaches, treatment options that should be avoided, or both. In Section I, Drs. Jeffrey Lipton and Grover Bagby review the approach to diagnosis and management of patients with the inherited bone marrow failure syndromes, Fanconi anemia, dyskeratosis congenita, Diamond-Blackfan anemia, and the Shwachman-Diamond syndrome. Extraordinary progress has been made in identifying the genes bearing pathogenetically relevant mutations in these disorders, but slower progress has been made in defining the precise functions of the proteins these genes encode in normal cells, in part because it is increasingly obvious that the proteins are multifunctional. In practice, it is clear that in patients with dyskeratosis congenita and Fanconi anemia, the diagnosis must be considered not only in children but in adults as well. In Section II, Dr. Elaine Sloand outlines a very practical and evidence-based approach to diagnosis and management of acquired hypoplastic states emphasizing overlap between non-clonal and clonal hematopoiesis is such conditions. The pathogenesis of T lymphocyte-mediated marrow failure is presented as a clear-cut rationale for use of immunosuppressive therapy and stem cell transplantation. Practical management of patients with refractory disease with and without evidence of clonal evolution (either paroxysmal nocturnal hemoglobinuria [PNH] or myelodysplasia [MDS]) is presented. In Section III, the challenge of hypoplastic MDS is reviewed by Dr. Charles Schiffer. After reviewing the most up-to-date classification scheme, therapeutic options are reviewed, focusing largely on agents that have most recently shown some promising activity, including DNA demethylating agents, thalidomide and CC5013, arsenic trioxide, and immunosuppressive therapy. Here are also outlined the rationale and the indications for choosing allogeneic bone marrow transplantation, the only therapy with known curative potential.
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PMID:Marrow failure. 1556 90

A twelve-year-old boy presented with recurrent episodes of anemia. Complete blood counts showed pancytopenia. Bone marrow was hypercellular with erythroid hyperplasia and depleted stores of iron. Positive Ham's test and sucrose lysis test revealed that he had paroxysmal nocturnal hemoglobinuria. There was a delay of nearly two years in the diagnosis in this patient. Paroxysmal nocturnal hemoglobinuria is rare in childhood. It must however be considered in a child who presents with unexplained anemia or bone marrow failure so that an early and accurate diagnosis is reached.
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PMID:Paroxysmal nocturnal hemoglobinuria with onset in childhood: a case report. 1629 81

An eight year old boy presented with severe anemia and bleeding spots. Complete blood count showed pancytopenia. There was mild reticulocytosis. Bone marrow was hypocellular with normoblastic erythroid hyperplasia. Ham's test (acidified serum test) was positive which confirmed the diagnosis of Paroxysmal nocturnal hemoglobinuria (PNH). Although PNH is rare in childhood, it should be considered as a diagnostic possibility in cases of aplastic anemia as the two conditions can coexist. The presence of PNH in association with aplastic anemia can influence the outcome of the latter.
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PMID:Paroxysmal nocturnal hemoglobinuria in childhood: an uncommon presentation. 1650 76

Paroxysmal nocturnal hemoglobinuria (PNH) has been described in association separately with T cell large granular lymphocyte (LGL) clonal expansions and plasma cell dyscrasias. We describe a patient with anemia related to hemolytic PNH, with concurrent T cell LGL oligoclonal expansion and IgG lambda monoclonal gammopathy of undetermined significance. Peripheral blood flow cytometry revealed decreased expression of CD55 and CD59 on erythrocytes and decreased expression of CD55 and CD66 on neutrophils. An LGL population was present in the peripheral blood and was characterized as oligoclonal by polymerase chain reaction-based analysis of the T cell receptor gamma-chain variable region. Serum protein electrophoresis with immunofixation showed a low level IgG lambda monoclonal protein. We describe the diagnostic evaluation of this patient and provide a brief review of the reported associations among PNH, LGL clonal expansion, and monoclonal gammopathy.
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PMID:A patient with paroxysmal nocturnal hemoglobinuria, T cell large granular lymphocyte clonal expansion, and monoclonal gammopathy of undetermined significance. 1692 42

Paroxysmal nocturnal hemoglobinuria (PNH) is characterized by intravascular hemolysis leading to anemia and other clinical manifestations. Transfusions are often required to support hemoglobin at tolerable levels. A PNH patient with aplastic anemia was treated with the complement inhibitor eculizumab, followed by concurrent treatment with recombinant human erythropoietin (rHuEpo). Eculizumab alone reduced hemolysis, increased PNH red blood cell (RBC) mass, and decreased transfusions. Addition of rHuEpo during eculizumab therapy, enhanced erythropoiesis, further increased PNH RBC mass and hemoglobin levels, and rendered the patient transfusion independent for more than two years. These data show that driving erythropoiesis during eculizumab treatment provided further benefit to a patient with PNH and underlying bone marrow failure.
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PMID:Erythopoietin treatment during complement inhibition with eculizumab in a patient with paroxysmal nocturnal hemoglobinuria. 1740 53

Paroxysmal nocturnal haemoglobinuria (PNH) has been recognised as a discrete disease entity since 1882. Approximately a half of patients will eventually die as a result of having PNH. Many of the symptoms of PNH, including recurrent abdominal pain, dysphagia, severe lethargy and erectile dysfunction, result from intravascular haemolysis with absorption of nitric oxide by free haemoglobin from the plasma. These symptoms, as well as the occurrence of thrombosis and aplasia, significantly affect patients' quality of life; thrombosis is the leading cause of premature mortality. The syndrome of haemolytic-anaemia-associated pulmonary hypertension has been further identified in PNH patients. There is currently an air of excitement surrounding therapies for PNH as recent therapeutic developments, particularly the use of the complement inhibitor eculizumab, promise to radically alter the symptomatology and natural history of haemolytic PNH.
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PMID:Recent developments in the understanding and management of paroxysmal nocturnal haemoglobinuria. 1740 57

Paroxysmal nocturnal hemoglobinuria (PNH) is characterized by complement-mediated hemolysis, venous thrombosis, and bone marrow failure. In May 2003, a 33-year-old man was admitted to a hospital with right hypochondralgia and fever. He had a history of aplastic anemia. The patient's diagnosis of diffuse microvessel thrombosis in the hepatic vein due to an unknown cause was derived from the findings of a contrast-enhanced computed tomography examination of the abdominal region, angiographic evaluation of abdominal vessels, and pathohistologic examination of a liver biopsy sample. The patient was subsequently treated with warfarin. The abdominal pain and fever continued, however, and anemia gradually appeared. In April 2004, the patient was referred to our hospital to examine the cause of the thrombosis. On admission, slight anemia and a low serum haptoglobin level were observed. A flow cytometry evaluation of CD55 and/or CD59, CD59, and CD48 expression in erythrocytes, granulocytes, and monocytes, respectively, showed that the respective proportions of negative populations were 5.6%, 97.1%, and 96.2%. The patient then received a diagnosis of aplastic anemia/PNH syndrome, which had caused the hemolytic anemia and thrombosis, although no hemoglobinuria had been observed during his clinical course. This patient is, to our knowledge, the first reported case of a PNH patient with thrombosis present only in hepatic microvessels and not in hepatic large vessels, in spite of the presence of few hemolytic events.
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PMID:Microvascular thrombosis in the hepatic vein of a patient with paroxysmal nocturnal hemoglobinuria. 1798 86

The terminal complement inhibitor eculizumab was recently shown to be effective and well tolerated in patients with paroxysmal nocturnal hemoglobinuria (PNH). Here, we extended these observations with results from an open-label, non-placebo-controlled, 52-week, phase 3 clinical safety and efficacy study evaluating eculizumab in a broader PNH patient population. Eculizumab was administered by intravenous infusion at 600 mg every 7 +/- 2 days for 4 weeks; 900 mg 7 +/- 2 days later; followed by 900 mg every 14 +/- 2 days for a total treatment period of 52 weeks. Ninety-seven patients at 33 international sites were enrolled. Patients treated with eculizumab responded with an 87% reduction in hemolysis, as measured by lactate dehydrogenase levels (P < .001). Baseline fatigue scores in the FACIT-Fatigue instrument improved by 12.2 +/- 1.1 points (P < .001). Eculizumab treatment led to an improvement in anemia. The increase in hemoglobin level occurred despite a reduction in transfusion requirements from a median of 8.0 units of packed red cells per patient before treatment to 0.0 units per patient during the study (P < .001). Overall, transfusions were reduced 52% from a mean of 12.3 to 5.9 units of packed red cells per patient. Forty-nine patients (51%) achieved transfusion independence for the entire 52-week period. Improvements in hemolysis, fatigue, and transfusion requirements with eculizumab were independent of baseline levels of hemolysis and degree of thrombocytopenia. Quality of life measures were also broadly improved with eculizumab treatment. This study demonstrates that the beneficial effects of eculizumab treatment in patients with PNH are applicable to a broader population of PNH patients than previously studied. This trial is registered at http://clinicaltrials.gov as NCT00130000.
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PMID:Multicenter phase 3 study of the complement inhibitor eculizumab for the treatment of patients with paroxysmal nocturnal hemoglobinuria. 1805 65

THE HEMOLYTIC ANEMIAS OF UNKNOWN CAUSE CAN BE SEPARATED INTO TWO MAIN GROUPS: (1) those produced by a defect in cell structure, which is usually hereditary, and (2) those due to a hemolysin of immune-body type.The hemolytic anemias associated with hypersensitivity to drugs and disease processes such as leukemia are less well understood and need further investigation. Splenectomy is the only effective treatment in congenital hemolytic jaundice and in acquired hemolytic anemia; the operation should be carried out promptly in most cases. Transfusion may be used in all varieties of hemolytic disease and is the only effective form of therapy in sickle-cell anemia and paroxysmal nocturnal hemoglobinuria.
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PMID:Hemolytic anemias recent advances in diagnosis and treatment. 1811 27

Anemia can result from deficient erythropoiesis [aplastic anemia, myelodysplastic syndromes (MDS), iron deficiency anemia, anemia of chronic disease (ACD), thalassemia, megaloblastic anemia, chronic renal failure, hematological malignancies, etc.], excessive RBC destruction [hereditary spherocytosis, inherited enzyme deficiency, hemoglobinopathies, autoimmune hemolytic anemia (AIHA), paroxysmal nocturnal hemoglobinuria (PNH), etc.], and blood loss. Based on the measured red cell size(MCV), anemia is classified as microcytic, normocytic, or macrocytic. Iron parameters (serum iron, serum ferritin, etc.), reticulocyte count, bone marrow examination, Coombs test, serum vitamin B12 level, and Ham test are also useful in the differential diagnosis of anemia. Novel treatment of anemia includes lenalidomide for 5q(-)MDS, azacitidine for high-risk MDS, and eculizumab for PNH. Oral iron chelator(deferasirox) developed for the treatment of transfusional iron overload is also very useful for the management of patients with bone marrow failure syndromes.
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PMID:[Pathophysiology, diagnosis and treatment of anemia]. 1832 12


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