scholarly journals Concomitant Alterations of Sodium Flux and Membrane Phospholipid Metabolism in Red Blood Cells: Studies in Hereditary Spherocytosis*

1967 ◽  
Vol 46 (2) ◽  
pp. 173-185 ◽  
Author(s):  
Harry S. Jacob ◽  
Manfred L. Karnovsky
Keyword(s):  
Red Blood Cells ◽  
Blood Cells ◽  
Hereditary Spherocytosis ◽  
Phospholipid Metabolism ◽  
Membrane Phospholipid ◽  
Sodium Flux

Volume-responsive sodium movements in dog red blood cells

1983 ◽  
Vol 244 (5) ◽  
pp. C324-C330 ◽  
Author(s):  
J. C. Parker
Keyword(s):  
Red Blood Cells ◽  
Blood Cells ◽  
Cell Swelling ◽  
Cell Shrinkage ◽  
Ph Change ◽  
Sodium Permeability ◽  
Sodium Gradient ◽  
Sodium Flux ◽  
Sodium Hydrogen Exchanger

As dog red blood cells are shrunken in vitro, their sodium permeability increases progressively. Some new features of this volume-responsive transport process are described. Retardation of sodium movements in shrunken cells occurs when chloride is replaced by the more conductive anions: nitrate or thiocyanate. Micromolar concentrations of amiloride or quinidine inhibit the increment of sodium flux associated with a reduction in cell volume. In the presence of a large outwardly directed sodium gradient, dog red blood cells can progressively alkalinize the medium in which they are suspended. This pH change is stimulated by cell shrinkage, reversed by cell swelling, retarded when chloride is replaced by nitrate or thiocyanate, and inhibited by micromolar concentrations of amiloride or quinidine. The similarities between the shrinkage-associated sodium flux and the alkalinization phenomenon suggest that the mechanism responsible for increased sodium permeability in shrunken cells can be made to operate as a sodium-hydrogen exchanger.

scholarly journals Fine Structure of the Red Pulp of the Spleen in Hereditary Spherocytosis

Blood ◽  
1972 ◽  
Vol 39 (1) ◽  
pp. 81-98 ◽  
Author(s):  
ZELMA MOLNAR ◽  
HENRY RAPPAPORT
Keyword(s):  
Endothelial Cells ◽  
Red Blood Cells ◽  
Blood Cells ◽  
Hereditary Spherocytosis ◽  
Probable Mechanism ◽  
Hemoglobin Content ◽  
Sinus Endothelial Cells ◽  
In Transit ◽  
Conventional Light Microscopy ◽  
Red Pulp

Abstract The spleens from two children and one adult with hereditary spherocytosis were studied in the electron microscope. Stagnation of the erythrocytes within the splenic cords is attributable to their lack of plasticity as evidenced by the absence of bilobed, tailed, or squeezed forms in transit through the walls of the sinuses. In contrast to the sections studied by conventional light microscopy, the splenic sinuses in hereditary spherocytosis were not "empty," but contained red blood cells, the majority of which had lost their hemoglobin content. Cordal macrophages were increased in all three cases and were abundant in the splenic cords of the adult patient, causing a further impediment to the rapid passage of erythrocytes. Macrophages, and, to a lesser degree, sinus endothelial cells contained the products of hemoglobin breakdown. The macrophages showed active erythrophagocytosis. Sinus endothelial cells rarely contained intact red blood cells, but showed pronounced pinocytotic activity, a probable mechanism of hemoglobin incorporation. Platelets within the endothelial cells of the sinuses were much more frequently seen in the three cases of hereditary spherocytosis than in control spleens. The presence of ferritin in platelets suggests that they too may play a role in clearing the end products of hemolysis from the spleen.

scholarly journals Human red cell membrane adenylate cyclase in normal subjects and patients with hereditary spherocytosis, sickle cell disease and unidentified hemolytic anemias

Blood ◽  
1980 ◽  
Vol 56 (6) ◽  
pp. 963-968 ◽  
Author(s):  
JP Piau ◽  
J Delaunay ◽  
S Fischer ◽  
M Tortolero ◽  
G Schapira
Keyword(s):  
Sickle Cell Disease ◽  
Adenylate Cyclase ◽  
Red Blood Cells ◽  
Sickle Cell ◽  
Blood Cells ◽  
Hereditary Spherocytosis ◽  
Reticulocyte Count ◽  
Cyclase Activity ◽  
Adenylate Cyclase Activity ◽  
Cell Disease

We have investigated adenylate cyclase in ghosts from normal and pathologic human red blood cells. Basic parameters such as specific activity, apparent Michaelis constant (KMapp), and response to effectors: sodium fluoride (NaF), 5′-guanylyl imidodiphosphate (Gpp (NH)p), isoproterenol, and PGE1 were investigated. Basal and NaF- stimulated activities were measured in ghosts from patients with hereditary spherocytosis, sickle cell disease, and various unidentified hemolytic anemias. Both activities were increased in any of these pathologic conditions as compared with those of normal red blood cells. Normal values were found in patients with hereditary spherocytosis after splenectomy and in patients with heterozygous sickle cell disease. There was a good correlation between the reticulocyte count and adenylate cyclase activity in hereditary spherocytosis and in sickle cell disease with reticulocyte count lower than 10%. The enzyme activity of the first group was about three times that of the second group. There was no correlation at all in sickle cell disease with higher reticulocytosis and in the group of unidentified hemolytic anemias. These results suggest that increased adenylate cyclase activities are not specific of any of these diseases. In the patients with hereditary spherocytosis, the adenylate cyclase activity seems to be essentially related to younger mean age of red blood cell population while in the patients with sickle cell disease and in others with unidentified hemolytic anemias some additional factors might interfere directly with the enzyme and alter its activity.

scholarly journals Non-Immune Hemolytic Anemia of Pregnancy: Heterozygous RBC Variants Elude Diagnosis

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 10-11
Author(s):  
Julie Huang ◽  
Mina Gendy ◽  
Marta Wronska ◽  
Crystal Antoine-Pepeljugoski ◽  
Duc Vo ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Red Blood Cells ◽  
Hemolytic Anemia ◽  
Blood Cells ◽  
Hereditary Spherocytosis ◽  
Conflicts Of Interest ◽  
Case Reports ◽  
Unknown Etiology ◽  
Molecular Testing ◽  
Immune Hemolytic Anemia

A 25 year old G3P2002 El Salvadorean female, with a prior history of pregnancy related anemia of unknown etiology, presented at 24 weeks gestation with symptomatic anemia (hemoglobin 2.9 g/dL) including dizziness, weakness and fatigue and no active signs of bleeding. Blood work included normal range results for LDH, haptoglobin, indirect and direct Coombs indicating no intravascular or immune driven hemolysis. Peripheral smear showed spherocytosis and stomatocytosis, concerning for an intrinsic RBC defect. Other workup included hemoglobin electrophoresis with slight increase in Hb A2 of 3.3%, flow cytometry negative for a lymphoproliferative disorder or paroxysmal nocturnal hemoglobinuria, no evidence of G6PD deficiency, and a bone marrow biopsy negative for marrow dysplasia, aplasia or HLH. Abdominal ultrasound revealed hypersplenism. The anemia was attributed to a non-immune hemolytic anemia with extra corpuscular RBC destruction in the spleen but without evidence of RBC destruction in the bone marrow or peripheral blood. After a prolonged 10-week hospitalization, the patient received a trial of steroids, 8 IV immunoglobulin infusions with minimal benefit, and total of 22 units of packed red blood cells. She underwent an elective induction and delivery at 34 weeks of pregnancy. During the postpartum period, she continued to have persistent anemia. A partial splenic embolization was attempted, complicated by splenic abscesses resulting in a splenectomy. Post splenectomy, the patient's hemoglobin and hematocrit stabilized to 11.7/37.8 at her three week outpatient visit. Molecular testing for Next Generation Sequencing (NGS) with Laboratory Hereditary Hemolytic Anemia Comprehensive Panel was also performed, revealing four different heterozygous variants. While these mutations individually have not been proven to cause hemolysis, the four alterations together, with the stressor of pregnancy, likely induced a non-immune hemolytic anemia. Non-immune hemolytic anemia is caused by intracorpuscular defects within the red blood cells or extracorpscular by environmental factors. The patient was found with four heterozygous variants in HK1, RPS19, SPTA1 and HBB, implicated in intracorpuscular defects. The HK1 gene, expressed in erythrocytes, encodes hexokinase, and provides red blood cells ATP. HK deficiency is a rare hereditary disorder associated with mild to severe non-spherocytic hemolytic anemia. The RPS19 gene encodes for a ribosomal protein involved in erythropoiesis. Clinically significant mutations in this gene cause Diamond Blackfan anemia. The SPTA1 gene encodes alpha spectrin subunits, which are a part of red cell membrane cytoskeleton and maintains its shape. Mutations in this gene have been implicated in hereditary spherocytosis. One case report described severe non-immune hemolytic anemia in a neonate with hereditary spherocytosis secondary a heterozygous mutation of the SPTA1 gene. Lastly, the HBB gene encodes for hemoglobin beta globin chains where alterations have been associated with hemolytic anemia, sickle cell anemia, and beta thalassemia. Several case reports described heterozygous variants of HBB and association with hemoglobin instability and extravascular hemolysis. Heterozygous mutations in the above genes have been rarely reported in literature to cause non-immune hemolytic anemia. Although unclear, pregnancy appeared to be the inciting factor in our patient with these mutational variants that have a potential role in extravascular hemolysis. While there have been few case reports describing autoimmune hemolytic anemia caused by pregnancy, a non-immune hemolytic anemia from 4 heterozygous variants in RBC genes, as seen in our patient, has not been previously described. Disclosures No relevant conflicts of interest to declare.

Hereditary Spherocytosis and Elliptocytosis Erythrocytes Show a Normal Transbilayer Phospholipid Distribution

Blood ◽  
1999 ◽  
Vol 94 (1) ◽  
pp. 319-325 ◽  
Author(s):  
Kitty de Jong ◽  
Sandra K. Larkin ◽  
Stefan Eber ◽  
Paul F.H. Franck ◽  
Ben Roelofsen ◽  
...  
Keyword(s):  
Red Blood Cells ◽  
Intracellular Calcium ◽  
Blood Cells ◽  
Hereditary Spherocytosis ◽  
Annexin V ◽  
Membrane Skeleton ◽  
Atp Depletion ◽  
Phospholipid Bilayer ◽  
Asymmetric Distribution ◽  
Phospholipid Distribution

Phosphatidylserine (PS) asymmetry was determined in red blood cells from patients with hereditary spherocytosis and elliptocytosis. No PS-exposing subpopulations were detected using the very sensitive method with fluorescently labeled annexin V. Treatment withN-ethylmaleimide or adenosine triphosphate (ATP) depletion to inactivate the flipase did not lead to formation of PS-exposing subpopulations in these cells, but elevated intracellular calcium levels did lead to extensive scrambling of the PS asymmetry. Although interactions of the membrane skeleton with the phospholipid bilayer have been suggested to stabilize the asymmetric distribution of PS across the bilayer, our data show that red blood cells with a severely damaged membrane skeleton are able to preserve asymmetry, even under conditions in which restoration of the asymmetric distribution is excluded. Moreover, the loss of membrane asymmetry in these cells requires active scrambling involving high levels of intracellular calcium as in normal cells. Our data show that the severe disorder of the membrane skeleton found in these cells does not affect the activity of flipase or scramblase, indicating that these proteins are not regulated by, nor coupled to the membrane skeleton assembly, and that possible thrombotic events in spherocytosis patients are not likely associated with altered PS topology of the red blood cells.

scholarly journals Analysis of Hereditary Elliptocytosis with Decreased Binding of Eosin-5-maleimide to Red Blood Cells

2015 ◽  
Vol 2015 ◽  
pp. 1-6 ◽  
Author(s):  
Shin-ichiro Suemori ◽  
Hideho Wada ◽  
Hidekazu Nakanishi ◽  
Takayuki Tsujioka ◽  
Takashi Sugihara ◽  
...  
Keyword(s):  
Red Blood Cells ◽  
Blood Cells ◽  
Hereditary Spherocytosis ◽  
Southeast Asian ◽  
Specific Method ◽  
Hereditary Elliptocytosis ◽  
Control Subjects ◽  
Flow Cytometric ◽  
Healthy Control

Flow cytometric test for analyzing the eosin-5-maleimide (EMA) binding to red blood cells has been believed to be a specific method for diagnosing hereditary spherocytosis (HS). However, it has been reported that diseases other than HS, such as hereditary pyropoikilocytosis (HPP) and Southeast Asian ovalocytosis (SAO), which are forms in the category of hereditary elliptocytosis (HE), show decreased EMA binding to red blood cells. We analyzed EMA binding to red blood cells in 101 healthy control subjects and 42 HS patients and obtained a mean channel fluorescence (MCF) cut-off value of 36.4 (sensitivity 0.97, specificity 0.95). Using this method, we also analyzed 12 HE patients. Among them, four HE patients showed the MCF at or below the cut-off value. It indicates that some HE patients have decreased EMA binding to red blood cells. Two of these four HE patients were classified as common HE, and two were spherocytic HE with reduced spectrin. This study demonstrates that, in addition to patients with HPP or SAO, some HE patients have decreased EMA binding to red blood cells.

Sign in / Sign up

Export Citation Format

Share Document