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Query: UMLS:C0039730 (thalassemia)
 10,305 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In human red cells, Ca is mainly bound to the inner side of the plasma membrane. A smaller part may be present within intracellular Ca storing vesicles, while only a few percent of total red cell Ca is in ionized form. In some hemolytic anemias (sickle cell anemia, beta-thalassemia), an increased number of endocytotic vesicles storing Ca is probably responsible for the elevation of total red cell Ca content. Red cell Ca inward transport, which is partially susceptible to inhibition by Ca entry blockers, has been reported to be enhanced by physiological shear stress and enrichment in membrane cholesterol, as well as in some hemolytic anemias. Normal intracellular ionized Ca levels have been assessed in several diseases where elevated Ca inward transport rates or decreased Ca efflux through the Ca pump (hemolytic anemias, cystic fibrosis, essential hypertension) had been observed previously. Thus, red cell Ca homeostasis is apparently capable of keeping ionized Ca levels within the physiological range of 20-60 nM under most pathological conditions investigated so far. Conceptually, changes in red cell Ca homeostasis (or also in other red cell membrane parameters) may be of pathophysiological importance in two respects: 1) A disturbance may be directly responsible for some of the symptoms associated with a disease. This is the case in sickle cell anemia, where red cell dehydration is possibly caused by transient elevations of intracellular ionized calcium, which may activate K efflux through the Ca-activated K channel. The presence of dehydrated red cells will, in turn, lead to microvascular occlusion, a pathophysiologically important phenomenon in sickle cell anemia.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Calcium homeostasis of human erythrocytes and its pathophysiological implications. 164 22

To define how excess unpaired alpha- and beta-globin chains in severe beta-thalassemia and severe alpha-thalassemia interacting with the membrane might alter cellular and membrane properties, we performed a series of biophysical and biochemical analyses on erythrocytes obtained from affected patients. Detailed analysis of cellular and membrane deformability characteristics showed that both forms of thalassemic erythrocytes have excess surface area in relation to cell volume and increased membrane dynamic rigidity. The deformability characteristics of thalassemic erythrocytes in hypertonic media differed significantly from that of normal erythrocytes of identical cell density. These findings suggest that dynamic rigidity of thalassemic erythrocytes is influenced not only by cytoplasmic viscosity determined by cell hemoglobin concentration but also by the extent and type of globin interacting with the membrane. In contrast to the above-noted similarities, major differences were noted in the mechanical stability of the alpha- and beta-thalassemic membranes and in their state of cell hydration. While the mechanical stability of alpha-thalassemic membranes was normal or marginally elevated, the stability of beta-thalassemic membranes was markedly decreased to half the normal value. Cell-density analysis showed that the alpha-thalassemic erythrocytes were uniformly less dense than normal, while beta-thalassemic erythrocytes had a broad-density distribution, with all populations having both lower and higher than normal density values, implying cellular dehydration in beta-thalassemia and not in alpha-thalassemia. Membrane-protein analysis revealed that excess globin chains were bound to the membrane skeletons of both alpha- and beta-thalassemic erythrocytes, with the highest amounts being found in membrane skeletons derived from erythrocytes of splenectomized individuals with beta-thalassemia intermedia. These data demonstrate that interaction of excess alpha- and beta-globin chains with membranes produces different cellular changes and suggest that the observed differences in the pathophysiology of alpha- and beta-thalassemias may be related to different cellular effects induced by the excess in beta- and alpha-globin chains.
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PMID:Cellular and membrane properties of alpha and beta thalassemic erythrocytes are different: implication for differences in clinical manifestations. 280 58

Patients with Hb SC disease were found to have microcytic and hyperchromic red cell indices despite mild reticulocytosis. Iron deficiency anemia was ruled out by the finding of normal serum ferritin levels. In order to determine whether the microcytosis was due to coexistent alpha-thalassemia, restriction endonuclease mapping was performed on genomic DNA extracted from peripheral blood leukocytes. Patients with Hb SC disease had microcytic indices despite the presence of a full complement of four alpha-genes (alpha alpha/alpha alpha), suggesting that the microcytosis may be due to cellular dehydration (or xerocytosis), since the mean corpuscular hemoglobin concentration in Hb SC disease patients was significantly higher than in controls. This possibility was investigated further by the determination of RBC cation content. RBC Na levels were similar in SC and normal red cells. Hb SC RBCs, however, had significantly reduced K levels. These findings show that RBC cation content, and thus cell water, is decreased in Hb SC disease. The decreased RBC K level in the presence of normal cellular Na concentration suggests selective K loss that is not due to inhibition of the Na K pump. Ouabain-insensitive K+ efflux was increased to four times normal in SC cells. Cell dehydration was confirmed by the demonstration of increased high-density RBCs on discontinuous Stractan density gradients and by osmotic gradient ektacytometry. Cellular dehydration and its sequelae were worse in CC erythrocytes and milder in AC cells than in Hb SC red cells. Taken together, these data indicate that in Hb SC disease the RBCs are severely dehydrated and typically microcytic and hyperchromic. Hb SC RBCs seem to be dehydrated due to selective K loss. These findings suggest a functional interrelationship between Hb SC, the red cell membrane, and cation regulation.
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PMID:The xerocytosis of Hb SC disease. 294 42

Dactylitis commonly occurs in patients with homozygous hemoglobin S disease (sickle cell anemia), sickle cell-hemoglobin C disease or sickle cell-beta-thalassemia. A case is reported of dactylitis associated with sickle cell trait, a very rare occurrence. It may be that in this patient the disorder was secondary to severe diarrhea and dehydration.
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PMID:Dactylitis in a child with sickle cell trait. 397 4

The concurrence of sickle cell anemia and alpha-thalassemia results in less severe hemolytic anemia apparently as a result of reduced intraerythrocytic concentration of hemoglobin S and its retarded polymerization. We have evaluated the effect of alpha-globin gene number on several interrelated properties of sickle erythrocytes (RBC) that are expected to correlate with the hemolytic and rheologic consequences of sickle cell disease. The irreversibly sickled cell number, proportion of very dense sickle RBC, and diminished deformability of sickle RBC each varied directly with alpha-globin gene number. Sickle RBC density was a direct function of the mean corpuscular hemoglobin concentration (MCHC). Even in nonsickle RBC, alpha-globin gene number varied directly with RBC density. Despite differences in alpha-globin gene number, sickle RBC of the same density had the same degree of deformability and dehydration. These data indicate that the fundamental effect of alpha-thalassemia is to inhibit the generation of sickle RBC having high density and MCHC, and that the other beneficial effects of sickle RBC are secondary to this process. The less consistent effect on overall clinical severity reported for subjects with this concurrence may reflect an undefined detrimental effect of alpha-thalassemia, possibly on the whole blood viscosity or on sickle RBC membrane-mediated adherence phenomena.
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PMID:Concurrent sickle cell anemia and alpha-thalassemia. Effect on pathological properties of sickle erythrocytes. 669 Apr 72

Several hemoglobinopathies are associated with abnormalities in the permeability of the red cell membrane, in some cases leading to permanent alterations of the intracellular milieu. Homozygous sickle cell disease is the most thoroughly studied example. Deoxygenation of sickle cells causes a transient increase in the permeability to monovalent cations and Ca; prolonged deoxygenation can lead to a permanent accumulation of Ca and loss of total cations and water. Although the mechanisms for the permeability changes are not yet defined, mechanical stress on the membrane, with subsequent damages by excess Ca or membrane-associated hemoglobin have been suggested to play a role. Loss of cell water and increase in mean cell hemoglobin concentration causes massive reduction of cell deformability in the oxygenated state and makes the hemoglobin more likely to undergo sickling because of the strong concentration dependence of the sickling process. Limited evidence suggests the occurrence of permeability defects in other hemoglobinopathies and the thalassemias. The suggested alterations range from a slight increase in K permeability of incubated thalassemia cells to substantial dehydration of cells from patients with homozygous hemoglobin C disease. Oxidative damage to the membrane, involving an abnormal hemoglobin-membrane association, may underly the permeability changes in these cells.
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PMID:The effect of abnormal hemoglobins on the membrane regulation of cell hydration. 703 77

To ascertain the quantitative effect on the disease beta-thalassemia of a low-magnesium (Mg) diet compared with a high-Mg diet and a standard-Mg diet, we studied the effect these diets had over a 4-week period on beta-thalassemic (beta thal) mice compared with normal C57BL/6 mice used as controls. The low-Mg diet consisted of 6 +/- 2 mg Mg/kg body weight/d, the high-Mg diet 1,000 +/- 20 mg Mg/kg body weight/d, and the standard-Mg diet 400 +/- 20 mg Mg/kg body weight/d. Beta thal mice that were fed the low-Mg diet became more anemic, had reduced serum and erythrocyte Mg, and had decreased erythrocyte K. Their K-Cl cotransport increased, followed by commensurate cell dehydration. The high-Mg group showed a significant improvement of the anemia, increased serum and erythrocyte Mg, increased erythrocyte Mg, increased erythrocyte K, reduced K-Cl cotransport, and diminished cell dehydration. C57BL/6 control mice that received the low-Mg diet experienced anemia with erythrocyte dehydration, whereas the high-Mg diet had little effect on the hematologic parameters. Beta thal and C57BL/6 control mice that were fed a standard diet showed no changes. These results indicate that dietary Mg supplementation corrects hypomagnesemia and improves anemia in murine beta thal and should be assessed in human beta-thalassemia.
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PMID:Dietary magnesium supplementation ameliorates anemia in a mouse model of beta-thalassemia. 924 63

Deposition of free iron is a characteristic feature of beta-thalassemia (beta-thal) red blood cells believed to play an important role in the generation of oxidative injury to the cell membrane. Increased red blood cell KCI cotransport, reduced K content, and cell dehydration are also found in beta-thal red blood cells. It is not known, however, whether deposition of free iron plays a role in these membrane transport changes. To explore this issue, we studied-both in vitro and in vivo-the effect on KCI cotransport of removing red blood cell membrane free iron from beta-thal erythrocytes. Eleven patients with beta-thal major who underwent long-term transfusion and were treated with deferiprone (75 mg/kg/day) for 9 months participated in the study. Deferiprone therapy removed membrane free iron from beta-thal erythrocytes, which was followed by reduced KCI cotransport activity. The reduced KCI cotransport activity was accompanied by an increase in the red blood cell K content. These data suggest that the increased activity of KCI cotransport in beta-thal red blood cells is mediated by the deposition of membrane free iron, a mechanism that may be attenuated by deferiprone therapy.
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PMID:Deferiprone therapy in homozygous human beta-thalassemia removes erythrocyte membrane free iron and reduces KCl cotransport activity. 1038 83

We report three children with tubulointerstitial renal failure following leptospirosis. All had acute nonoliguric renal failure with mild hypocalemia and mild metabolic acidosis. Maximum blood urea nitrogen (BUN) and creatinine were 217 and 7.1 mg/dl, respectively, on the 6th day of disease, and no patient required dialysis. They presented with acute febrile illness and dehydration, and required intravenous fluid supplements. Myalgia, vomiting, and bleeding were found in two children. Abdominal pain, arthralgia, diarrhea, and conjunctival suffusion were found in one child. Only one child, who had an underlying disease of beta-thalassemia/Hb E, had jaundice, hepatosplenomegaly, anemia, and thrombocytopenia. Penicillin treatment was given in one case. All recovered, with normal renal function. The leptospirosis complement fixation test was used to confirm diagnosis. L. batavia was considered the etiologic agent in two of the children.
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PMID:Tubulointerstitial renal failure in childhood leptospirosis. 1053 63

To test the hypothesis that HbOARAB induces an increase in red cell mean corpuscular haemoglobin concentration (MCHC), we studied members of four Tunisian families who were either homo- or heterozygous for HbOARAB or were double heterozygotes for HbS and HbOARAB. The alpha-gene status was also tested. The findings included: (1) Distinctive variation in red cell density (MCHC) as determined by separation of red cells on isopycnic gradients: (a) All red cells from patients homozygous for HbOARAB were denser than normal red cells, as is observed for homozygous HbC patients. (b) In patients heterozygous for HbOARAB, red cell density was strongly influenced by the presence of alpha-thalassaemia. The coexistence of -alpha/alphaalpha resulted in an average red cell density slightly greater than normal (AA) red cells. Patients heterozygous for HbOARAB with a normal complement of four alpha genes had denser red cells similar to sickle cell disease with some cells of normal density but with most cells very dense. (c) Finally, the double heterozygotes for HbS and HbOARAB had significant haemolytic anaemia and red cells denser than normal with some as dense as the densest cells found in sickle cell anaemia. (2) Reticulocytes in patients homozygous for HbOARAB were found in the densest density fraction of whole blood. (3) Cation transport in patients homozygous for HbOARAB was abnormal, with K:Cl cotransport activity similar to that of HbS-Oman and only somewhat lower than in sickle cell anaemia red cells. The activity of the Gardos channel was indistinguishable from that found in HbS, HbC and HbS-Oman cells. We conclude that the erythrocytic pathogenesis of HbOARAB involves the dehydration of red cells due, at least in part, to the K:Cl cotransport system. The similarity of the charge and consequences of the presence of both HbC and HbOARAB, which are the products of mutations at opposite ends of the beta-chain, raises the possibility that this pathology is the result of a charge-dependent interaction of these haemoglobins with the red cell membrane and/or its cytoskeleton and that this abnormality is present early in red cell development.
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PMID:The erythrocyte effects of haemoglobin O(ARAB). 1058 51


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