Peculiar Elongated and Sickle-Shaped Red Blood Corpuscles in a Case of Severe Anemia

Herrick, James B.

doi:10.1001/archinte.1910.00050330050003

Cited by 708 publications

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“…Kidney involvement in SCD has been observed since the first official case of the disease reported in literature, which described the presence of increased diuresis and urine of low specific gravity [9]. …”

Section: Discussionmentioning

confidence: 99%

Renal Tubular Dysfunction in Sickle Cell Disease

Silva

Vieira

Couto

et al. 2013

Kidney Blood Press Res

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Background/Aims: Kidney abnormalities are one of the main chronic complications of sickle cell disease (SCD). The aim of this study is to investigate the occurrence of renal tubular abnormalities among patients with SCD. Methods: This is a prospective study with 26 SCD adult patients in Brazil. Urinary acidification and concentration tests were performed using calcium chloride (CaCl₂), after a 12h period of water and food deprivation. Fractional excretion of sodium (FE_Na), transtubular potassium gradient (TTKG) and solute free water reabsorption (TcH₂O) were calculated. The SCD group was compared to a group of 15 healthy volunteers (control group). Results: Patient`s average age and gender were similar to controls. Urinary acidification deficit was found in 10 SCD patients (38.4%), who presented urinary pH >5.3 after CaCl₂ test. Urinary osmolality was significantly lower in SCD patients (355±60 vs. 818±202mOsm/kg, p=0.0001, after 12h period water deprivation). Urinary concentration deficit was found in all SCD patients (100%). FE_Na was higher among SCD patients (0.75±0.3 vs. 0.55±0.2%, p=0.02). The TTKG was higher in SCD patients (5.5±2.5 vs. 3.0±1.5, p=0.001), and TcH₂O was lower (0.22±0.3 vs. 1.1±0.3L/day, p=0.0001). Conclusions: SCD is associated with important kidney dysfunction. The main abnormalities found were urinary concentrating and incomplete distal acidification defect. There was also an increase in the potassium transport and decrease in water reabsorption, evidencing the occurrence of distal tubular dysfunction.

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Section: Discussionmentioning

confidence: 99%

Renal Tubular Dysfunction in Sickle Cell Disease

Silva

Vieira

Couto

et al. 2013

Kidney Blood Press Res

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“…Sickle cell disease was so named because of the abnormal morphology of red blood cells (RBCs) observed by microscopic examination offixed and stained blood smears obtained from affected patients (1). Subsequently, relationships were found between oxygen and RBC sickling (2) and between intracellular polymerization of abnormal hemoglobin and cell deformation (3)(4)(5).…”

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confidence: 99%

Partially oxygenated sickled cells: sickle-shaped red cells found in circulating blood of patients with sickle cell disease.

Asakura

Mattiello

Obata

et al. 1994

Proc. Natl. Acad. Sci. U.S.A.

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A previously uncharacterized type of sickled cell was found in venous blood ofpatients with sickle cell disease when blood was collected without exposure to air and fixed immediately with 1% glutaraldehyde solution equilibrated with 5% oxygen. These cells were either elongated, resembling irreversibly sickled cells (ISCs), or nonelongated, with a raisinlike shape. Both types assumed a normal discoidal shape upon full oxygenation. Since these cells exist only under partially oxygenated conditions, they are described as partially oxygenated sickled cells (POSCs). POSCs are morphologically distinct from partially deoxygenated sickled cells formed during deoxygenation by having rounded edges, while the latter have sharp edges. Transmission electron microscopy of POSCs revealed various amounts of misaligned Hb S polymers. Investigations in vitro demonstrated the formation of POSC-like cells by partial oxygenation of deoxygenated cells. Since POSCs contain intracellular fibers and sickle readily upon deoxygenation, they may have clinical and pathological significance.Sickle cell disease was so named because of the abnormal morphology of red blood cells (RBCs) observed by microscopic examination offixed and stained blood smears obtained from affected patients (1). Subsequently, relationships were found between oxygen and RBC sickling (2) and between intracellular polymerization of abnormal hemoglobin and cell deformation (3-5). Demonstration of sickling of RBCs from patients with sickle cell disease (SS cells) in vitro is highly dependent upon the method of deoxygenation. For example, classic sickle-or crescent-shaped cells are formed after slow deoxygenation (6-9), whereas SS cells with a granular or mosaic appearance result from rapid deoxygenation with nitrogen (6) or sodium dithionite (7). These differences may be explained by the number and size of domains of polymerized Hb S formed in the cells (10). During morphologic studies of SS cells, we noticed that the number and shape of sickled cells in venous blood were altered by the oxygenation of blood during and after blood collection. To avoid postcollection artifacts, we developed a method to collect blood under venous oxygen pressure without exposure to air. This enabled us to discover two additional types of reversibly sickled cells, elongated sickled cells with a shape like irreversibly sickled cells (ISCs) and shrunken cells with a raisin-like appearance. Since these cells exist only under partially oxygenated conditions, they are described as partially oxygenated sickled cells (POSCs) (11). We report our investigation of the morphologic properties and analysis by electron microscopy ofintracellular polymers of POSCs found in venous blood of patients with sickle cell disease. MATERIALS AND METHODSPreparation of Blood Samples. To minimize sickling during blood drawing (12), blood was drawn from the antecubital vein after release of the tourniquet. A conventional 5-ml plastic disposable syringe was used by the technique similar to that used for collectio...

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“…The substitution of a hydrophobic side chain for a hydrophilic one on the exterior ofthe protein (3) promotes the aggregation of deoxygenated hemoglobin (Hb) tetramers (4,5) that eventually distort the erythrocyte into a sickled form in the venous circulation (6). One approach toward treatment of sickle cell anemia focuses on the HbS molecule itself by reacting it with chemical modifiers that directly alter the functional properties of the protein and indirectly reduce aggregation in vitro (7,8).…”

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confidence: 99%

Recombinant human sickle hemoglobin expressed in yeast.

Llano

Schneewind

Stetler

et al. 1993

Proc. Natl. Acad. Sci. U.S.A.

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Sickle hemoglobin has been expressed in the yeast Saceharomyces cerevwisa after site-diected mutagenesis of a plasmid conti normal human a-and I3-globin genes.Cassette mutagenesis of this plasnid was achieved by inserting a DNA fragment containing the 3-globin gene in the replicative form of M13mpl8 to make a point mutation and then recondfIy the original paid containing the mutated -globin gene. Pure recombinant hemolbin S was shown to be identical to natural sickle hemoglobin in its ultraviolet and visible absorption bands and by gel dectrophoresi, iboectric focusing, amino acid analysis, mass spectrometry, partial N-terminal sequencing, and finctional properties (Pso, cooperativity, and response to 2,3-bisphosphoglycerate). In yeast and in mammalian cells, cotranlational processing yields the same N-terminal valine residues of hemoglobin a-and a-chains, but in bacterial expression systems the N terminus Is extended by an additional amino acid because the initiator methionine residue is retained. Since the N-terminal valine residues of both chains of hemoglobin S participate in important physiological hunctions, such as oxygen affinity, interaction with anions, and the Bohr coefficient, the yeast expression system is preferable to the bacterial system for recombinant DNA studies. Hence, mutagenesis employing this expression system should permit definitive as ets of the role of any amino acid side chain in hemoglobin S aggregation and could suggest additional approaches to therapeutic intervention. The engineering ofthis system for the synthesis of sickle hemoglobin and its purification to homogeneity in a single column procedure are described.The genetic mutation underlying sickle cell anemia leads to the replacement of Glu-6 on the (-chain with a valine residue (1, 2). The substitution of a hydrophobic side chain for a hydrophilic one on the exterior ofthe protein (3) promotes the aggregation of deoxygenated hemoglobin (Hb) tetramers (4, 5) that eventually distort the erythrocyte into a sickled form in the venous circulation (6). One approach toward treatment of sickle cell anemia focuses on the HbS molecule itself by reacting it with chemical modifiers that directly alter the functional properties of the protein and indirectly reduce aggregation in vitro (7,8). The number and nature of such susceptible sites has been limited to those hydrophilic side chains with enhanced reactivity because of their location in the protein (8, 9). The availability of recombinant DNA technology now permits studies at any site on the HbS tetramer, such as hydrophobic amino acid side chains heretofore not possible to modify by other methods. For sickle cell HbS, the ability to alter hydrophobic sites is especially important since the initial and some of the subsequent stages of aggregation involve hydrophobic interactions. Although the identity of some of these contact sites in the aggregate is known (3)(4)(5)10), there is a lack of information on other contact sites and their contribution to the overall strength of the ...

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Peculiar Elongated and Sickle-Shaped Red Blood Corpuscles in a Case of Severe Anemia

Cited by 708 publications

References 0 publications

Renal Tubular Dysfunction in Sickle Cell Disease

Renal Tubular Dysfunction in Sickle Cell Disease

Partially oxygenated sickled cells: sickle-shaped red cells found in circulating blood of patients with sickle cell disease.

Recombinant human sickle hemoglobin expressed in yeast.

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