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The Journal of Clinical Investigation Mar 1987To explain the transient anemia and poikilocytosis seen during infancy in hereditary elliptocytosis (HE), we resealed erythrocyte (RBC) ghosts from affected children or...
To explain the transient anemia and poikilocytosis seen during infancy in hereditary elliptocytosis (HE), we resealed erythrocyte (RBC) ghosts from affected children or their elliptocytic parents with 2,3-diphosphoglycerate (DPG) (0-8 mM), a compound that dissociates membrane skeletons, then measured ghost mechanical stability in the ektacytometer. Without added 2,3-DPG, ghost mechanical stability was subnormal in infantile poikilocytosis (IP) and HE but was even more abnormal in hereditary pyropoikilocytosis (HPP). Addition of 2,3-DPG (2.55 mM) to IP or HE ghosts, decreased their stability to that of HPP ghosts (without 2,3-DPG). Nonphysiological 2,3-DPG levels (6-8 mM) were required to elicit a similar effect in normal ghosts. The data suggest that free 2,3-DPG, present in neonatal RBC as a consequence of diminished binding to HbF, may render HE susceptible to in vivo fragmentation. The developmental switch from fetal to adult hemoglobin, by diminishing available free 2,3-DPG, may explain the abatement of poikilocytosis and hemolytic anemia that accompanies maturation.
Topics: 2,3-Diphosphoglycerate; Diphosphoglyceric Acids; Elliptocytosis, Hereditary; Erythrocyte Deformability; Erythrocyte Membrane; Erythrocytes, Abnormal; Female; Hot Temperature; Humans; Infant, Newborn; Macromolecular Substances; Male; Osmolar Concentration; Spectrin
PubMed: 3818955
DOI: 10.1172/JCI112905 -
The Journal of Clinical Investigation Mar 1987Hemoglobin Mississippi (HbMS: beta 44ser----cys) has anomalous properties that include disulfide linkages with normal beta-, delta-, gamma-, and alpha-chains, and the...
Hemoglobin Mississippi (HbMS: beta 44ser----cys) has anomalous properties that include disulfide linkages with normal beta-, delta-, gamma-, and alpha-chains, and the formation of high molecular weight multimers. While heterozygotes for HbMS are clinically and hematologically normal and carriers of the beta +-thalassemia gene in our family had mild microcytic anemia, the proband with HbMS-beta +-thalassemia had a hemoglobin level of 7 g/dl, mean corpuscular volume (MCV) of 68 fl, reticulocytes of 2-6%, HbF of 18%, marked anisocytosis and poikilocytosis, and splenomegaly, all features of thalassemia intermedia. With oxidant stress, her erythrocytes developed multiple dispersed Heinz bodies, but HbMS was only mildly unstable. HbMS was susceptible to proteolytic degradation in the presence of ATP. The unexpectedly severe clinical findings in HbMS-beta +-thalassemia may result from the proteolytic digestion of HbMS, as well as the excessive alpha-chains characteristic of beta +-thalassemia, which combined provide the increment of cellular damage that results in the phenotype of thalassemia intermedia.
Topics: Child; Erythrocyte Indices; Erythrocytes, Abnormal; Female; Fetal Hemoglobin; Heinz Bodies; Hemoglobins, Abnormal; Heterozygote; Humans; Microscopy, Electron; Pedigree; Peptide Hydrolases; Phenotype; Reticulocytes; Thalassemia
PubMed: 2434529
DOI: 10.1172/JCI112890 -
Blood Jan 1987The In(Lu) phenotype is inherited as an autosomal dominant trait and is characterized by suppression of the Lutheran, P1, i, and Aua erythrocyte blood group antigens. We...
The In(Lu) phenotype is inherited as an autosomal dominant trait and is characterized by suppression of the Lutheran, P1, i, and Aua erythrocyte blood group antigens. We have developed a monoclonal antibody (L21) that strongly agglutinates all erythrocytes except In(Lu), and we have identified eight In(Lu) individuals among 42,000 blood donors tested. Studies of two families confirmed the dominant mode of inheritance and revealed several new features of this phenotype. The erythrocytes of all five affected individuals from the two families exhibited diminished hemagglutination by the lectin concanavalin A, although they reacted normally with several other lectins. The erythrocytes of two affected individuals in one family exhibited marked acanthocytosis. The erythrocytes of the proposita of the other family exhibited a mild degree of poikilocytosis, but the cells of the other two affected individuals in this family had normal morphology. The osmotic fragility of fresh In(Lu) erythrocytes was normal, but after incubation for 24 hours at 37 degrees C in plasma the In(Lu) cells exhibited a marked increase in resistance to osmotic lysis. During the incubation period the erythrocytes lost K+ and their total cation content was diminished. These data indicate that in addition to the suppression of blood group antigens noted previously, the In(Lu) phenotype includes a variety of morphological abnormalities and a defect in electrolyte metabolism. The use of L21 and similar monoclonal antibodies provides a more sensitive means of detecting In(Lu) erythrocytes than typing with human anti-Lub antisera.
Topics: Antibodies, Monoclonal; Antigens, Surface; Cations; Erythrocytes; Erythrocytes, Abnormal; Lutheran Blood-Group System; Osmotic Fragility; Pedigree; Receptors, Mitogen
PubMed: 3790728
DOI: No ID Found -
Blood Jun 1986Hemolytic anemia with red cell fragmentation, poikilocytosis, and elliptocytosis was discovered in a 6-week-old black infant. Both parents and a brother of the...
Hemolytic anemia with red cell fragmentation, poikilocytosis, and elliptocytosis was discovered in a 6-week-old black infant. Both parents and a brother of the propositus had compensated mild Hereditary Elliptocytosis (HE). Elliptocytosis was prominent in the proband's father with the presence of numerous rod-shaped cells whereas, in the proband's mother, elliptocytosis was less marked and cells were less elongated than in the father. The proband's red cells fragmented at 45 degrees C instead of 49 degrees C for control cells. Both the parents' and brother's red cells fragmented at 47 degrees C. The deformability of the proband's red cells was markedly reduced when measured with the ektacytometer; the red cells of both the proband's parent and brother exhibited an intermediate decrease in red cell deformability. Spectrin self-association was defective in the propositus as well as in his parents and brother. Limited tryptic digestion of the proband's spectrin, followed by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE), revealed a complete absence of the normal 80,000 dalton alpha I domain and the presence of an abnormal 65,000 dalton peptide. Two-dimensional isoelectric focusing/SDS-PAGE of limited tryptic digests of spectrin from both the proband's parents and brother revealed a decrease in the normal 80,000 alpha I domain and the presence of the 65,000 peptide variant. On the basis of biochemic studies performed on the patients' spectrin, we concluded that the proband had homozygous HE, having inherited the structural defect of spectrin present in a heterozygous state in each of his parents. On a clinical and morphologic level, homozygous HE imitates two other forms of congenital hemolytic anemia associated with a spectrin self-association defect: HE with pycnocytosis in infancy and Hereditary Pyropoikilocytosis. This report emphasizes the importance of confronting clinical and rheological as well as biochemical investigations in studying and discussing different entities.
Topics: Electrophoresis, Polyacrylamide Gel; Elliptocytosis, Hereditary; Erythrocyte Deformability; Female; Homozygote; Hot Temperature; Humans; Infant; Isoelectric Focusing; Male
PubMed: 3708157
DOI: No ID Found -
Journal of the National Medical... Nov 1985Sarcoidosis is a recently identified cause of functional asplenia that can be diagnosed by radionuclide imaging. A 31-year-old woman with a five-year history of...
Sarcoidosis is a recently identified cause of functional asplenia that can be diagnosed by radionuclide imaging. A 31-year-old woman with a five-year history of histologically compatible sarcoidosis was found to have nonvisualization of the spleen on technetium 99m sulfur colloid (radiopharmaceutical) liver-spleen scan. This scintigraphic finding was accompanied by poikilocytosis and Howell-Jolly bodies in the peripheral blood smear. A subsequent gallium 67 citrate scan reflected an abnormal increase in concentration of activity in the spleen, suggesting an active inflammatory process.Based upon this constellation of findings, it was concluded that acquired functional asplenia is the result of reticuloendothelial cell replacement via infiltration of the spleen by epithelioid cell granulomas of active sarcoidosis. This case also illustrates the reversibility of functional asplenia of sarcoidosis following adrenocorticosteroid therapy. Functional asplenia in sarcoidosis is now found to have a recognizable radionuclide imaging pattern.
Topics: Adult; Female; Humans; Sarcoidosis; Spleen; Splenic Diseases; Ultrasonography
PubMed: 3908697
DOI: No ID Found -
Canadian Journal of Comparative... Jul 1985Ninety-eight calves were studied to determine if anemia and poikilocytosis were related to iron or copper status or hemoglobin type. No significant differences were... (Comparative Study)
Comparative Study
Ninety-eight calves were studied to determine if anemia and poikilocytosis were related to iron or copper status or hemoglobin type. No significant differences were found in serum iron, total iron binding capacity, marrow iron, plasma copper or hemoglobin type between affected and normal calves. Poikilocytes were strongly inversely correlated (-0.9177) with age. Calves less than six weeks of age had more poikilocytes, lower serum iron, higher total iron binding capacity, less adult hemoglobin and more neonatal and fetal hemoglobin than calves greater than six weeks of age.
Topics: Anemia; Animals; Cattle; Cattle Diseases; Copper; Erythrocytes, Abnormal; Female; Fetal Hemoglobin; Hematologic Diseases; Hemoglobins; Iron; Male
PubMed: 2412677
DOI: No ID Found -
The Journal of Clinical Investigation Sep 1981Hereditary pyropoikilocytosis (HPP) is a hemolytic anemia characterized by microspherocytosis, poikilocytosis, and an unusual thermal sensitivity of erythrocytes. We...
Hereditary pyropoikilocytosis (HPP) is a hemolytic anemia characterized by microspherocytosis, poikilocytosis, and an unusual thermal sensitivity of erythrocytes. We have investigated the contribution of abnormal membrane skeletal assembly to these abnormal HPP erythrocyte properties. Skeletons prepared from fresh HPP ghosts with Triton X-100 were considerably more fragile than skeletons from control erythrocytes. Spectrin, the major skeleton component, extracted at 0 degrees C from normal erythrocytes, was present primarily as tetramers and high molecular weight complexes. In contrast, spectrin extracted from HPP erythrocytes under identical conditions contained a significant amount of dimers with a concomitant decrease of tetramers. Furthermore, spectrin dimers from HPP erythrocytes differed from normal spectrin dimers in their failure to reassociate into tetramers both in solution and in the membrane. Presumptive HPP carriers (asymptomatic mothers of the two patients) exhibited a mild but reproducible increase of spectrin dimers in 0 degrees C extracts and a defective reassociation of spectrin dimers of tetramers both in solution and in the membrane. We conclude that in HPP, self-association of spectrin dimers into tetramers is defective, which accounts for the instability of membrane skeletons.
Topics: Cytoplasm; Erythrocyte Membrane; Erythrocytes, Abnormal; Humans; Kinetics; Macromolecular Substances; Membrane Proteins; Protein Binding; Spectrin; Spherocytosis, Hereditary
PubMed: 7276161
DOI: 10.1172/jci110293 -
The Journal of Clinical Investigation Aug 1981Erythrocytes from three patients with severe hemolytic anemia, marked erythrocyte fragmentation, and elliptocytic poikilocytosis, were studied in terms of both their...
Erythrocytes from three patients with severe hemolytic anemia, marked erythrocyte fragmentation, and elliptocytic poikilocytosis, were studied in terms of both their membrane protein composition and their mechanical characteristics. Erythrocytes from the patients' parents and one minimally affected and one normal sibling were also studied. Morphologic observations implied that the severely affected patients suffered from homozygous hereditary elliptocytosis because erythrocytes of both parents and the one minimally affected sibling showed moderate elliptocytosis on smear, whereas those of an unaffected sibling had normal morphology. The parallel findings of markedly reduced levels of band 4.1 in the erythrocyte membrane proteins of the patients and an intermediate reduction in the cells of the parents and the putative heterozygous sibling, suggest that the elliptocytic shape of the cells was related to the reduced levels of band 4.1. Additional studies showed marked abnormalities in cellular deformability and membrane fragility in the erythrocytes from the homozygous patients. Importantly, these changes were also closely proportional to the reduced levels of band 4.1, suggesting a central role for this protein in the maintenance of normal membrane stability and normal cell shape. It seems likely that this role for band 4.1 is intimately related to its known biochemical connection to the "membrane skeleton" through its linkage with spectrin and actin.
Topics: Actins; Blood Proteins; Cytoskeletal Proteins; Cytoskeleton; Elliptocytosis, Hereditary; Erythrocyte Membrane; Erythrocytes; Humans; Membrane Proteins; Neuropeptides; Pedigree; Protein Binding; Spectrin
PubMed: 6894932
DOI: 10.1172/jci110275 -
Blood Feb 1976A 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...
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.
Topics: Anemia, Hemolytic, Congenital; Calcium; Cations, Monovalent; Cell Membrane; Cell Membrane Permeability; Child, Preschool; Erythrocytes, Abnormal; Filtration; Humans; Lipids; Male; Osmotic Fragility; Potassium; Sialic Acids; Sodium; Time Factors
PubMed: 1244919
DOI: No ID Found -
The Western Journal of Medicine Mar 1975The significance of erythroblastemia must be considered in the context of the clinical setting in which it is found. Interpretation should take into account the number...
The significance of erythroblastemia must be considered in the context of the clinical setting in which it is found. Interpretation should take into account the number and spectrum of maturity of the nucleated red cells; the presence or absence of reticulocytosis and other red cell abnormalities (for example, poikilocytosis); the presence or absence of anemia; the presence or absence of circulating immature granulocytes or bizarre platelets and the presence or absence of the spleen. Circulating nucleated red cells indicate intravascular hemopoiesis or disruption of marrow structure or the inability of the bone marrow's screen mechanism to prevent their passage into circulation. In the latter situations, it usually indicates an unfavorable prognosis.
Topics: Anemia, Hemolytic; Anemia, Hypochromic; Bone Diseases; Bone Marrow; Bone Marrow Cells; Erythroblasts; Graft Rejection; Heart Failure; Hematologic Diseases; Hematopoietic System; Humans; Infections; Kidney Transplantation; Prognosis; Transplantation, Homologous
PubMed: 1096474
DOI: No ID Found