1/37. Hereditary stomatocytosis: membrane and metabolism studies.A defect in the protein kinase-mediated phosphorylation of erythrocyte membrane proteins, previously unrecognized in stomatocytosis, was discovered in a boy with hereditary stomatocytosis and severe hemolytic anemia. The high-sodium, low-potassium erythrocytes of this patient were remarkably permeable to both sodium and potassium. The rate of ouabain-inhibitable active cation transport was more than ten times normal and was sustained by an increase of similar magnitude in glycolysis. The deformability in vitro of fresh stomatocytes was reduced and deteriorated further after a brief period of incubation with glucose. Ferrokinetic studies showed that these rigid cells were sequestered by the spleen. When stomatocytes were deprived of glucose in vitro, ATP depletion and ATPase cation pump failure rapidly ensued. Because of their permeability defect, such depleted cells rapidly became swollen and lysed. Prolonged entrapment in acidic, hypoglycemic regions of the spleen would recapitulate these unfavorable events in vivo. In this regard, splenectomy was followed by an improvement in erythrocyte survival, although evidence of continuing hemolysis was obtained.- - - - - - - - - - ranking = 1keywords = membrane (Clic here for more details about this article) |
2/37. Red cell calcium leak in congenital hemolytic anemia with extreme microcytosis.A child with congenital hemolytic anemia, extreme microcytosis and bizarre red cell morphology has been studied. splenectomy at the age of 21 mo greatly improved the hemolytic anemia, although red cell morphology was unchanged. Aniso- and poikilocytosis were marked on a stained smear, and there were many small hyperchromatic cells of irregular shape. The MCV of 25 cu mu was very low and the MCHC was normal. osmotic fragility of fresh blood was increased, and postsplenectomy blood showed a fraction of extremely fragile cells. Concentration and fluxes of Na and K were normal, except K efflux, which was stimulated by external Ca2 . Inward Ca2 movement into the patient's red cells was elevated three- to fourfold above red cells of the same mean age. Red cell Ca2 concentration was raised 2.5 times normal and most of the Ca2 was localized in the stroma. Red cell lipid, sialic acid, and ouabain-binding sites, all per milliliter of cells, were increased by 16%-23%, and, since these substances estimate the amount of membrane, it was likely that Ca2 content per unit of membrane area was at least twice normal. Deformability of the cells, as judged by their filterability was markedly impaired. It was concluded that the red cell membrane was defective, and an increased membrane Ca2 content was associated with reduced deformability, hemolysis, and distorted red cell morphology in this syndrome.- - - - - - - - - - ranking = 0.8keywords = membrane (Clic here for more details about this article) |
3/37. Altered erythrocyte endothelial adherence and membrane phospholipid asymmetry in hereditary hydrocytosis.The risk for thrombosis is increased in patients with hereditary hydrocytosis, an uncommon variant of hereditary stomatocytosis. erythrocytes from 2 patients with hydrocytosis were studied to gain insight into the mechanism of thrombosis in this disorder. erythrocytes demonstrated abnormal osmotic scan ektacytometry and decreased erythrocyte filtration rates. There was also a mild increase in adherence of erythrocytes to endothelial monolayers in a micropipette assay. Adhesion of erythrocytes to the subendothelial matrix proteins thrombospondin and laminin, however, was not significantly increased. Percentages of hydrocytosis erythrocytes and reticulocytes with phosphatidylserine exposed on the outer surfaces were increased in both patients compared with healthy controls, indicating altered membrane phospholipid asymmetry. Increased phosphatidylserine exposure accelerating thrombin-forming processes has been proposed as a mechanism for thrombosis in sickle cell disease and beta-thalassemia and may play a similar role in hereditary hydrocytosis.- - - - - - - - - - ranking = 1keywords = membrane (Clic here for more details about this article) |
4/37. An extreme consequence of splenectomy in dehydrated hereditary stomatocytosis: gradual thrombo-embolic pulmonary hypertension and lung-heart transplantation.Dehydrated hereditary stomatocytosis (DHS) belongs to the heterogeneous class of hemolytic anemias with leaky red cell membranes. splenectomy is a highly deleterious treatment, because it favors, with virtually no exception, the occurrence of thromboembolic disease. We describe here the extreme case of a patient with DHS and an associated sickle cell trait. splenectomy was carried out due to a splenic infarction that occurred during an airplane journey. About 12 years later, the patient noticed an exertional dyspnea, which gradually worsened to such a degree that she became severely incapacitated within 5 years. Eventually, the patient developed a cor pulmonale associated with chronic thromboembolic pulmonary hypertension (CTEPH) and successfully underwent a heart-lung transplant operation. This case ranks as one of the most severe examples ever recorded of the effect that splenectomy may have in DHS patients. Nonetheless, it represents the first case to receive a heart-lung transplant.- - - - - - - - - - ranking = 0.2keywords = membrane (Clic here for more details about this article) |
5/37. Dehydrated hereditary stomatocytosis is associated with neonatal hepatitis.Dehydrated hereditary stomatocytosis (DHSt) is an inherited haemolytic anaemia associated with increased red cell membrane permeability to Na( ) and K( ). It is increasingly recognized that a syndrome of self-limiting perinatal ascites can accompany the haemolysis. The cause of the perinatal ascites is unknown, and it has been argued that this could be due to cardiovascular, hepatic or lymphatic problems. We describe the case of a 16-year-old girl who presented neonatally with abnormal liver function tests and ascites. She was extensively investigated at that time. A liver biopsy showed hepatitis and fatty changes. Her ascites resolved within 6 months. At the age of 15 years, she developed an episode of acute haemolysis and was re-investigated. A diagnosis of DHSt was made. Pseudohyperkalaemia, due to ex vivo loss of K( ) from red cells, was present. This study confirms the previously noted association of DHSt, pseudohyperkalaemia and perinatal ascites, and suggests that the latter is of predominantly hepatic origin.- - - - - - - - - - ranking = 0.2keywords = membrane (Clic here for more details about this article) |
6/37. Coexistence of congenital red cell pyruvate kinase and band 3 deficiency.The authors report the case of a 9-year-old Caucasian girl, born in northern portugal, with chronic nonspherocytic haemolytic anaemia and without family history of anaemia. The aethiological study of this anaemia revealed pyruvate kinase deficiency (PKD), because of two previously described mutations (426Arg-->Trp and 510Arg-->Gln). Since the blood smear revealed features not fully compatible with PKD diagnosis, additional tests were performed for the propositus and her parents, namely red blood cell membrane protein analysis. A decrease in proteins band 3 (15%) and 4.2 (18%) was found in the propositus. Her father presented only a decrease in band 3 (11%). Coexistence of PKD and erythrocyte membrane proteins deficiency in the same patient is very uncommon. Our findings suggest that a careful blood smear observation may lead to the identification of a combined deficiency in erythrocyte membrane proteins and enzymopathies.- - - - - - - - - - ranking = 0.6keywords = membrane (Clic here for more details about this article) |
7/37. Nonimmune hydrops fetalis due to congenital xerocytosis.Hereditary xerocytosis is a rare hemolytic anemia in which erythrocytes are dehydrated due to a loss of potassium and water through their cell wall membrane. In adults, this condition leads to a mild-to-moderate hemolysis. We report a case of hydrops fetalis secondary to hereditary xerocytosis. Management with intrauterine erythrocyte and albumin transfusions resulted in a favorable postnatal course.- - - - - - - - - - ranking = 0.2keywords = membrane (Clic here for more details about this article) |
8/37. Occurrence of hereditary leaky red cell syndrome and partial coagulation factor vii deficiency in a Spanish family.A Spanish family was found to have the coexistence of a hereditary haemolytic syndrome associated with excessively leaky RBC membrane to sodium (Na ) and potassium (K ) cations and a partial coagulation factor vii deficiency. Haemolysis was mild in the propositus and the RBC membrane leak included a marked increase in passive permeability to Na and K . This was associated with an increase in active Na ,K( )-pump activity and in the ouabain-resistant fluxes: Na , K( )-cotransport and Na , Li( )-countertransport. factor vii deficiency was of 50% and no clinical expression of the coagulation deficiency was observed. The family study revealed slightly abnormal RBC membrane cationic fluxes only in the father and decreased coagulation factor VII activity of 67% in the mother. Both parents were clinically and haematologically normal. It is suggested that the propositus has inherited the abnormal gene for leaky RBC syndrome from the father and the partial coagulation factor vii deficiency from the mother.- - - - - - - - - - ranking = 0.6keywords = membrane (Clic here for more details about this article) |
9/37. Congenital haemolytic anaemia in a low birth weight infant due to congenital stomatocytosis.A baby girl born at 31 weeks gestation showed severe haemolytic anaemia and hyperbilirubinaemia which led to exchange transfusion within the first 12 hours of life. There was no blood group incompatibility between mother and child but there was a marked stomatocytosis of the baby's red blood cells. family history revealed a congenital stomatocytosis in the mother. Biochemical characterization of the defect was performed. Phospholipid analysis of the erythrocyte membrane of mother and child showed an increase in phosphatidylserine with a compensatory decrease in phosphatidylcholine and phosphatidylethanolamine. SDS-electrophoresis showed multiple modifications of the protein pattern with a decrease in band 6, an increased content of band 4.1b, a slight decrease in band 7 and a clear change in the shape of the protein band 3 pattern. The results suggest that the basis of the observed abnormalities is a common defect in protein posttranslational modification, rather than multiple genetic defects in the synthesis of several proteins. Haematologic, biochemical and clinical course of the disease in this preterm infant are discussed.- - - - - - - - - - ranking = 0.2keywords = membrane (Clic here for more details about this article) |
10/37. Severe recessive poikilocytic anaemia with a new spectrin alpha chain variant.A severe neonatal haemolytic anaemia was observed in a propositus from the west indies. Frequent blood transfusions were required until complete splenectomy was carried out. Blood smears showed predominant poikilocytosis with spherocytes and microcytes as observed in hereditary pyropoikilocytosis. erythrocytes were completely fragmented after incubation at 45 degrees C. The two asymptomatic parents had normal haematological profiles. The erythrocyte membrane electrophoretic patterns of the splenectomized propositus and her parents were normal. The propositus had a moderate defect in the spectrin (Sp) dimer self-association. Limited tryptic digestion of the propositus' Sp under standard conditions (0 degrees C, 20 h, enzyme-substrate ratio of 1/100) revealed an increased sensitivity to tryptic digestion. The major features detected by one- and two-dimensional electrophoresis gels of Sp tryptic digests were the absence of high molecular weight peptides from the Sp alpha II (48 kDa and 35 kDa peptides) and Sp alpha III (52 kDa peptide) domains with increased amounts of the lower molecular weight peptides from the Sp alpha II and Sp alpha III (29 kDa peptide and 47 kDa peptide) domains respectively. Kinetic studies of Sp tryptic digestion (10 min to 36 h) confirmed the increased tryptic susceptibility of Sp. Immunodetection with specific anti-alpha-chain domain antibodies showed that the highest molecular weight peptides from the alpha II and alpha III domains are released early in digestion, but disappear quickly, with an increase in their corresponding smaller peptides. The molecular weights of the peptides corresponding to the 48 kDa and 35 kDa peptides from the alpha II domain are slightly modified. peptides from the alpha I and alpha IV domains showed no significant abnormalities. The Sps of both parents were normal. These results indicate that the patient has a novel Sp alpha chain defect, which is probably located in the region of the alpha II domain which adjoins the alpha III domain.- - - - - - - - - - ranking = 0.2keywords = membrane (Clic here for more details about this article) |
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