Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0002895 (sickle cell disease)
 11,747 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Erythrocyte deformability was determined in more than 500 clinical samples, and was found to be elevated in conditions in which fetal-like red cells are produced: aplastic anemia (3/3 cases), myelodysplastic syndromes, polycythemias, sickle cell anemia during treatment with hydroxyurea, paroxysmal nocturnal hemoglobinuria, and recovery from B12 deficiency. Elevated deformability was observed in neonatal erythrocytes, and during recovery from transient erythroblastopenia of childhood, when fetal-like red cells are known to be produced. Increased deformability appears to be a feature of fetal and fetal-like red cells. Forty-eight cases of enzymatically verified glucose-6-phosphate (G-6-PD) deficiency were also examined. Thirty out of 32 G-6-PD(A-) individuals, including both heterozygotes and hemizygotes, exhibited increased deformability during the steady state. In contrast, G-6-PD(Med) hemizygotes had normal deformability. Increased deformability was also found in G-6-PD(Huron) (n=3), G-6-PD(Wayne) (n=4), triose phosphate isomerase deficiency (n=2), and pyruvate kinase deficiency (n=2). An elevated osmoscan was found in more than 90% of female G-6-PD heterozygotes, affording a simple screening test for heterozygotes. Deformability remained high during hemolytic episodes, when older enzyme deficient cells are removed from the circulation. In four cases of G-6-PD deficiency with normal deformability, evidence for co-existing hereditary spherocytosis was found. The combination of conditions with opposing effects on deformability resulted in nearly normal deformability. Because increased red cell deformability is a feature of fetal erythrocytes, these results suggest that the red cells in many cases of glycolytic enzyme deficiency are fetal-like.
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PMID:Increased erythrocyte deformability in fetal erythropoiesis and in erythrocytes deficient in glucose-6-phosphate dehydrogenase and other glycolytic enzymes. 989 Jun 17

Thrombosis is a major complication of human hemolytic anemias such as sickle cell disease, thalassemia, and severe hereditary spherocytosis (HS). Mice with severe HS and severe hereditary elliptocytosis (HE) also suffer from thrombosis, with incidences ranging from 15 and 22% in beta-spectrin- and ankyrin-deficient mice, respectively, to 85 to 100% in alpha-spectrin-deficient and band 3 knockout mice. A contributing factor to thrombosis could be loss of phospholipid asymmetry of the mutant red blood cells (RBCs), with concomitant exposure of the aminophospholipid phosphatidylserine (PS). Increased PS exposure occurs in RBCs from sickle cell and thalassemia patients and in RBCs from band 3-deficient mice. To determine if increased PS exposure correlates with thrombotic risk in HS and HE mice with ankyrin, beta-spectrin, and alpha-spectrin deficiencies, measurements of FITC-labeled annexin V binding to externalized PS on RBCs were performed. PS exposure is elevated in all mice with HS and HE, but the percentage of RBCs with exposed PS does not correlate with thrombotic risk in these mice.
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PMID:Erythroid phosphatidyl serine exposure is not predictive of thrombotic risk in mice with hemolytic anemia. 1077 78

Asplenia in childhood may be congenital (e.g. Ivemark-syndrome) or acquired (functional hyposplenism in sickle cell disease; after splenectomy or bone marrow transplantation). Hereditary spherocytosis is the most common indication for splenectomy in childhood. Virtually every patient without spleen has a significantly increased risk of severe postsplenectomy infection (mostly caused by Streptococcus pneumoniae). Therefore, vaccinations against pneumococci, haemophilus influenzae and, under certain circumstances, meningococci are recommended. In addition a continuous prophylaxis with antibiotics should be performed for at least three years (or even longer depending on the disease) after splenectomy followed by lifelong interventional application of broad spectrum antibiotics in case of any unclear infection or high fever. This prophylaxis must be started as early as four months of age in sickle cell disease. In future the use of penicillin may be hampered by the growing resistance of pneumococci. Due to this fact the indication for splenectomy in childhood should be restricted to patients with hematologic disease (spherocytosis and other hemolytic anemias, chronic ITP etc.) and moderate to severe symptoms. It is unclear whether partial splenectomy for spherocytosis (and other hemolytic anemias) is an alternative regarding both longlasting reduction of hemolysis and prevention of severe infection. After trauma every effort should be undertaken to preserve a splenic remnant.
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PMID:[Antiinfectious prophylaxis in asplenia]. 1157 67

Splenectomy is frequently required in children with various hematologic disorders. The reported advantages of laparoscopic splenectomy (LS) include less pain, shorter hospital stay, and improved cosmesis. This report evaluates the outcome of children undergoing LS at a single children's facility. One hundred twelve children underwent LS by the lateral approach between August 1995 and February 2001. Indications for LS were hereditary spherocytosis in 58, idiopathic thrombocytopenic purpura in 21, sickle cell disease in 19, and other conditions in 14. LS alone was completed in 89 children and LS and cholecystectomy (LSC) in 20. Three required conversion to open splenectomy. Accessory spleens were identified in 19. Complications included ileus (four), acute chest syndrome (four), bleeding (two), pneumonia (one), and diaphragm perforation (one). There was no mortality. An accessory spleen was missed in one child with recurrent anemia. Average operative time for LS was 106 minutes and for LSC 135 minutes. Operative time for LS decreased with experience but the difference was not significant. Average length of stay was 1.51 days (range 1-11) and was longer in sickle cell disease (2.47 days) versus hereditary spherocytosis (1.29 days) and idiopathic thrombocytopenic purpura (1.16 days). We conclude that LS is safe and effective in children with hematologic disorders and is associated with minimal morbidity, zero mortality, and a short length of stay.
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PMID:Laparoscopic splenectomy has become the gold standard in children. 1189 57

The incidence of gall stones in thalassaemia is less than that in sickle cell anaemia or hereditary spherocytosis. With adequate blood transfusions, the incidence is as low as 2%. There are not many reports on cholelithiasis in thalassaemia. A case of 24-year-old female with thalassaemia major and gall stone is reported here.
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PMID:Cholelithiasis in thalassaemia major. 1240 42

Many types of hemolytic anemia may be associated with liver disease. Liver injury can be caused by the adherence of deformed or hemolyzed erythrocyses to hepatic vascular endothelium. Adhesion of large numbers of hemolyzed red blood cells to hepatic macrophages, or occlusion of hepatic sinusoids by fragmented red cells, can also result in injury of the liver. Thrombosis of the hepatic or portal vein is associated with some types of hemolytic anemia, and can cause severe liner injury. These are some examples of hepatic injury that can be caused by hemolytic anemias. This article discusses some aspects of liver disease that is associated with sickle cell anemia, paroxysmal nocturnal hemoglobinuria, glucose-6-phosphate dehydrogenase deficiency, hereditary spherocytosis, and HELLP syndrome.
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PMID:Anemia and the liver. Hepatobiliary manifestations of anemia. 1251 98

The diagnosis of hereditary spherocytosis (HS) is based on red cell morphology and other conventional tests such as osmotic fragility, autohemolysis and acidified glycerol lysis. However, milder cases are at times difficult to diagnose. Confirmation by red blood cell (RBC) membrane protein analysis is not possible in most laboratories. Recently, a flow cytometric method has been described for quantitating the fluorescence intensity of intact red cells after incubation with the dye eosin-5'-maleimide (EMA), which binds specifically to the anion transport protein (band-3) at lysine-430. This has been shown to be an effective screening test for red cell membrane disorders. We evaluated the usefulness of this approach for screening membrane protein disorders such as HS and hereditary elliptocytosis (HE) and its value in discriminating this group from other hemolytic anemias, such as glucose-6-phosphate dehydrogenase (G6PD) deficiency, beta-thalassemia trait, sickle cell anemia and autoimmune hemolytic anemia. Fluorescence intensity, expressed in mean channel fluorescence (MCF) units, was determined using a Becton Dickinson FACS Caliber flow cytometer. Membrane protein analysis was carried out by sodium dodecyl sulfate-polyacrylamide gel eletrophoresis (SDS-PAGE). RBCs from patients with HS and HE gave significantly lower MCF values (P < 0.001) than the normal control group and other patient groups. The diagnosis of HS in four cases was confirmed by RBC membrane protein electrophoresis and all showed a deficiency of spectrin. The advantage of the EMA dye method are its specificity for membrane disorders, as well as being a simple, user-friendly and rapid method which is inexpensive, provided a flow cytometer is available.
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PMID:Experience with eosin-5'-maleimide as a diagnostic tool for red cell membrane cytoskeleton disorders. 1464 Nov 41

Hamartomas of the spleen or splenomas, are uncommon benign tumorous growths in this organ which have not been well characterized in children. We report four patients, 4 to 11 years old, who had splenomegaly and splenic "hamartomas" associated with different hematologic conditions (refractory microcytic anemia, sickle cell anemia, hereditary spherocytosis, and dyserythropoietic hemolytic anemia). All patients had total splenectomy as a primary therapeutic approach or to lessen their transfusion requirements. In only one patient was a focal splenic mass identified preoperatively with contrasted computed tomography (CT) scans and magnetic resonance imaging (MRI). None of the patients showed a mass by ultrasonography. Gross examination showed enlarged spleens (315-724 g) which on cut surface revealed a single nodule in one and multiple bulging nodules in three specimens. The nodules varied from 1.3 to 7 cm and were indistinct from the surrounding nonlymphoid splenic (i.e., red pulp) parenchyma. Histology of the nodules showed red splenic pulp with variable histiocytic proliferation, focal extramedullary hematopoiesis, lympho-plasmacytosis, fibrosis, and siderotic-calcific deposits. Intranodular small T- and B-cell lymphoid aggregates but no organized secondary follicles or periarteriolar sheaths were seen. Proliferation antigen Ki-67 (Mib-1) immunostains showed a low (< 5%) proliferation index in the nodules and surrounding tissue. Reticulin stains did not show a capsule or border between the normal spleen and the nodules. The critical histologic differential diagnosis for these lesions is with benign vascular tumors. These can be identified by their more disorderly pattern, by immunohistochemistry and by their higher proliferation index. It is our contention that these splenic nodules are not true hamartomas, as they seem to result from remote ischemic or infectious/inflammatory insults, leading to the fibro-inflammatory reaction and deposition of calcium and hemosiderin that is better designated with the descriptive term of splenoma. Review of the literature and our own experience indicates that most children with splenic hamartomas or splenomas as we prefer to call them, have an underlying hematologic disorder likely made worse by a state of hypersplenism that explains the consistent improvement in the blood values after splenectomy.
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PMID:"Hamartoma" of the spleen (splenoma) in children. 1503 46

Band 3 proteins, members of the anion exchange family of proteins (AE 0-3), are involved in a number of physiological activities such as cell volume and osmotic homeostasis, HCO3-/Cl- exchange, red cell aging, IgG binding and cellular removal, and the maintenance of the structural integrity of cells. They are present in the membranes of all cells and cellular organelles examined including Golgi, mitochondria and nuclei. The first polymorphisms of band 3 discovered were the asymptomatic band 3 Memphis variants carrying the Lys --> Gly substitution at position 56 in the cytoplasmic tail, and band 3 Texas (high transport band 3 Texas) with a mutation in the critical transmembrane, anion transport domain (Pro --> Leu substitution at position 868). The rate at which band 3 mutations were discovered accelerated in the mid 1990s and there are now over 50 known. The most common polymorphisms of band 3 are the Diego blood group antigens which reside on extracellular loops of the protein. Southeast Asia ovalocytosis (SAO; a nine amino acid deletion of residues 400-408) is a band 3 mutation known only in the heterozygous state in which it does not cause disease. It is thought to confer resistance to malaria by altering red cell deformability. Band 3 mutations are responsible for a subset of the heterogeneous group of disorders known as hereditary spherocytosis (HS). HS is a relatively common congenital or inherited group of anemias characterized by chronic hemolysis and abnormal red cell morphology. Red cells in the subset of HS with band 3 mutations behave like they are band 3 deficient either because the mutant protein is not incorporated into the membrane or because it is not functional. HS can be caused by mutations in any of at least 5 proteins involved in membrane stability. Band 3 mutations are associated with diseases in cells besides erythrocytes. For example, 2 types of distal renal tubular acidosis are the result of band 3 mutations either alone or combined with SAO. Band 3 alterations are implicated in neurological diseases such as familial paroxysmal dyskinesia, idiopathic generalized epilepsies, and neuro- or choreoacanthocytosis although they have not been demonstrated to be causative. Mutations in other genes can cause changes in band 3. An example is sickle cell anemia where the increased oxidation causes accelerated aging of band 3 and increased IgG binding and cellular removal.
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PMID:Band 3 and its alterations in health and disease. 1509 83

Hemolysis presents as acute or chronic anemia, reticulocytosis, or jaundice. The diagnosis is established by reticulocytosis, increased unconjugated bilirubin and lactate dehydrogenase, decreased haptoglobin, and peripheral blood smear findings. Premature destruction of erythrocytes occurs intravascularly or extravascularly. The etiologies of hemolysis often are categorized as acquired or hereditary. Common acquired causes of hemolytic anemia are autoimmunity, microangiopathy, and infection. Immune-mediated hemolysis, caused by antierythrocyte antibodies, can be secondary to malignancies, autoimmune disorders, drugs, and transfusion reactions. Microangiopathic hemolytic anemia occurs when the red cell membrane is damaged in circulation, leading to intravascular hemolysis and the appearance of schistocytes. Infectious agents such as malaria and babesiosis invade red blood cells. Disorders of red blood cell enzymes, membranes, and hemoglobin cause hereditary hemolytic anemias. Glucose-6-phosphate dehydrogenase deficiency leads to hemolysis in the presence of oxidative stress. Hereditary spherocytosis is characterized by spherocytes, a family history, and a negative direct antiglobulin test. Sickle cell anemia and thalassemia are hemoglobinopathies characterized by chronic hemolysis.
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PMID:Hemolytic anemia. 1520 94


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