Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0002874 (aplastic anemia)
 5,905 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A high negative correlation (coefficient similar to 0.9) between increased 59Fe absorption from a diagnostic 0.56 mg 59Fe2+ dose and the depletion of available storage iron was observed in menstruating and pregnant women, fullterm and premature infants, blood donors, patients with infections, inflammations, tumors, hepatic cirrhosis, gastric surgery, increased urogenital or gastrointestinal blood loss. The increased diagnostic 59Fe2+ absorption is a reliable and sensitive indicator of at least depleted iron stores or prelatent iron deficiency as caused by iron malnutrition or maldigestion, increased iron requirement in pregnancy, infancy, urogenital or gastrointestinal blood loss. Although the messenger system which signalyzes the depletion of iron stores to the iron absorbing enterocytes of the duodenal and jejunal mucosa is not yet known available storage iron seems to control intestinal iron absorption under normal and the great majority o pathological condition in humans. Anemia per se or high erythropoietin levels in blood do not influence iron absorption since patients with even severe erythroblastic hypoplasia, aplastic anemia and megaloblastic anemia due to vitamin B12 deficiency absorb iron according to their iron stores. An only mild hyperplasia of the erythropoietic system in the bone marrow does also not effect iron absorption which was still under the control of available storage iron in patients with hereditary spherocytosis, nonspherocytic congenital hemolytic anemia due to glucose-6-phosphate dehydrogenase deficiency, acquired hemolytic anemia and vitamin B12 deficiency induced megaloblastic anemia..
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PMID:Intestinal iron absorption under the influence of available storage iron and erythroblastic hyperplasia. Comparative studies in children with hereditary spherocytosis, nonspherocytic enzymopenic hemolytic anemia, acquired hemolytic anemia, vitamin B12 deficiency induced megaloblastic anemia, erythroblastic hypoplasia and aplastic anemia. 113 Jan 21

Paroxysmal nocturnal haemoglobinuria is an acquired haemolytic anaemia that may develop into aplastic anaemia or myeloid leukaemia. It has recently been shown that paroxysmal nocturnal haemoglobinuria is due to a defective coupling of specific proteins to glycolipids on the cell surface of haematopoietic cells. One of these proteins is decay-accelerating factor (DAF), and the absence of DAF on the surfaces of blood cells leads to the haemolytic symptoms. The molecular biology of DAF and its relationship to paroxysmal nocturnal haemoglobinuria symptoms is described in this brief review. The molecular defect of paroxysmal nocturnal haemoglobinuria is illustrated in a case report.
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PMID:[Paroxysmal nocturnal hemoglobinuria, a cell surface molecular defect]. 170 Feb 42

The case of a 14 year-old adolescent girl presenting with paroxysmal nocturnal hemoglobinuria (PNH) associated with aplastic anemia is reported. This disease, rare in children, is characterized by an acquired hemolytic anemia, with abnormal sensitivity to complement: PNH actually affects the bone marrow stem cell. This explains its possible association with any type of malignant blood disease and with aplastic anemia. When aplastic anemia is the first sign of the disease, diagnosis is delayed, due to the possible negative response of the specific Ham's test. Therefore, the proper complications of PNH, especially thromboses, may be misappreciated and poorly managed.
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PMID:[Paroxysmal nocturnal hemoglobinuria and aplastic anemia]. 674 73

Paroxysmal nocturnal haemoglobinuria (PNH) is an acquired haemolytic anaemia, clonal in nature, due to somatic mutation. PNH may evolve to aplastic anaemia; more rarely to a myelodysplastic syndrome (MDS) or to acute myeloid leukaemia (AML). We have studied a patient who suffered from PNH and later developed refractory anaemia with ringed sideroblasts (RARS) associated with trisomy 8. By testing peripheral blood cells with appropriate antibodies we have shown that all of the red cells, neutrophils and monocytes, as well as 20% of the lymphocytes, belonged to the PNH clone; in contrast, only 43% of neutrophils and 22% of monocytes belonged to the MDS clone. We infer that the MDS must have arisen from within the PNS clone.
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PMID:Myelodysplasia in a patient with pre-existing paroxysmal nocturnal haemoglobinuria: a clonal disease originating from within a clonal disease. 794 86

Although glucocorticosteroids are widely used, many indications for their use are controversial, and we have an incomplete understanding of their mechanismus of action. Glucocorticosteroids are commonly employed as primary cytotoxic drugs in the treatment of hematopoietic disease with alone and combination chemotherapy such as leukemias, lymphomas, myeloma, acquired hemolytic anemia, aplastic anemia, granulocytopenia, idiopatic thrombocytopenic purpura, nonthrombopenic purpura, thrombotic thrombocytopenic purpura.
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PMID:[In the treatment of hematopoietic disease with glucocorticosteroids]. 816 72

Paroxysmal Nocturnal Hemoglobinuria (PNH) is an acquired hemolytic anemia characterized by chronic hemolysis, deep thrombosis, and hypoplastic marrow, and thought to be a clonal hematopoietic stem cell disorder. Affected blood cells are deficient in glycosylphosphatidylinositol (GPI)-anchored cell surface proteins. Recent investigations revealed that the PIG-A gene, which participates the biosynthesis of the GPI-anchor, was identified and the mutations were detected in the patients with PNH. Here we discuss the following problems related to the PIG-A gene; (1) the inconsistency of the expression of the GPI-anchored proteins and the mutations of the PIG-A gene, (2) the existence of the multiple PNH clones bearing different PIG-A mutations in a single patient, (3) aplastic anemia-PNH syndrome and PIG-A gene.
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PMID:[Paroxysmal nocturnal hemoglobinuria]. 889 May 86

Paroxysmal nocturnal haemoglobinuria (PNH) is unique because it is an acquired haemolytic anaemia, resulting from an intrinsic red cell membrane disorder. The disease has been shown to be due to a somatic mutation of the phosphatidylinositol glycan complementation class A (pig-a) gene at the level of the haemopoietic stem cell. The defect in synthesis of the glycosylphosphatidylinositol (GPI) anchor results in a deficiency of all proteins that are GPI-bound to red cell, leucocyte and platelet membranes. The function of these proteins is extremely varied but a critical role is the protection of the cell from complement and it is the unopposed action of the complement cascade that results in the intravascular haemolysis and venous thrombosis which are hallmarks of the disease. The relationship between PNH and aplastic anaemia remains intriguing. It appears likely that an insult to a haemopoietic progenitor alters it in such a way that it becomes vulnerable to immune-mediated attack by cytotoxic T cells and/or cytokines. This attack requires one or more GPI-anchored molecules to be effective. Thus a GPI-negative clone would be at a relative advantage, and it is the balance between bone marrow impairment and proliferation of the GPI-negative clone(s) that determines the clinical picture. Prospects for molecular therapy continue to improve. Cell-to-cell transfer of GPI-linked proteins has been demonstrated in murine studies and recombinant CD59 has been expressed on GPI-deficient lymphocytes in vitro. Gene therapy remains a tantalising possibility, although a greater understanding of the pathophysiology of PNH is required, as well as advances in gene therapy techniques, before such an approach can be seriously considered.
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PMID:The glycosylphosphatidylinositol anchor and paroxysmal nocturnal haemoglobinuria/aplasia model. 1243 18

Cardiac surgery in patients with paroxysmal nocturnal hemoglobinuria (PNH), which is an acquired hemolytic anemia associated with thrombocytopenia and an abnormal susceptibility to venous thromboses, requires special perioperative measures. PNH is based on a clonal defect of hematopoietic stem cells characterized by deficiency in glycosyl-phosphatidylinositol-anchored surface proteins. The major mechanism of hemolysis consists of unregulated complement activation. In cardiac surgery, PNH-induced granulocytopenia increases the risk of postoperative infection. PNH-induced complement activation is further exaggerated by extracorporeal circulation in cardiac surgery leading to putative hemolytic crisis. Here, we report on a patient who developed PNH after severe aplastic anemia undergoing aortic valve replacement and coronary revascularization using extracorporeal circulation and discuss the special perioperative management and the relevant literature on this issue. Special emphasis should be given to optimal preoperative patient preparation including G-CSF administration and red blood pack transfusions, perioperative platelet substitution, fluid management, and antibiotic prophylaxis.
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PMID:Aortic valve replacement and coronary revascularization in paroxysmal nocturnal hemoglobinuria. 1767 Jan 47

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare disorder, an acquired chronic hemolytic anemia, often associated with recurrent nocturnal exacerbations, recurrent infections, neutropenia, thrombocytopenia, and episodes of venous thrombosis. Its clinical course is highly variable. It frequently arises in association with bone marrow failure, particularly aplastic anemia and myelodysplastic syndrome. It is also an acquired thrombophilia, presenting with a variety of venous thrombosis, mainly manifested with intra-abdominal thrombosis, here the major cause of mortality. The triad of hemolytic anemia, pancytopenia, and thrombosis makes a truly unique clinical syndrome of PNH, which was reclassified from a purely acquired hemolytic anemia to a hematopoietic stem cell mutation defect of the phosphatidyl inositol glycanclass-A gene. This mutation results in an early block in the synthesis of glycosylphosphatidylinositol (GPI) anchors, responsible for binding membrane functional proteins. Among these proteins are the complement inhibitors, especially CD55 and CD59, that play a key role in protecting blood cells from complement cascade attack. Therefore, in PNH occurs an increased susceptibility of red cells to complement, and consequently, hemolysis. We here review PNH physiopathology, clinical course, and treatment options, especially eculizumab, a humanized monoclonal antibody that blocks the activation of terminal complement at C5 and prevents formation of the terminal complement complex, the first effective drug therapy for PNH.
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PMID:[Paroxysmal nocturnal hemoglobinuria: from physiopathology to treatment]. 2049 98