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Haematology
Published in Stephan Strobel, Lewis Spitz, Stephen D. Marks, Great Ormond Street Handbook of Paediatrics, 2019
Blood film shows macrocytosis and occasional shrunken, speculated erythrocytes (echinocytes,Fig. 11.76). Direct measurement of the pyruvate kinase (PK) enzyme shows a reduced level and there should be a concomitant high level of 2,3-diphosphoglycerate (2,3DPG). Red cell intermediates of metabolism may be helpful in those patients with a marginally low PK level, or with a dysfunctional enzyme or very high reticulocyte count.
Rheology of the Hemolytic Anemias
Published in Gordon D. O. Lowe, Clinical Blood Rheology, 2019
As erythrocyte ATP concentration falls, Ca2+ can enter the cell and increase the efflux of K+ and water; a dehydrated and less deformable cell results.237 Other factors contributing to loss of deformability include the secondary adsorption of cytoplasmic protein on to the cell membrane, thus increasing membrane density,238 and to the formation of spheroechin-ocytes. Patients with PK deficiency who have undergone splenectomy show numerous (30 to 50%) circulating echinocytes235 which filter slowly through 3 μm diameter pores and are aspirated with difficulty into 2.9 μm diameter micropipettes.239 Such obvious echinocyte formation is not seen in the circulating blood of patients who have not undergone splenectomy and these poorly deformable cells are presumably sequestered by the spleen.
Case 13
Published in Atul B. Mehta, Keith Gomez, Clinical Haematology, 2017
This patient is suffering from renal failure. The blood film shows characteristic echinocytes (Burr cells). The reticulocyte count is usually normal or slightly low, and bone marrow examination shows normoblastic erythropoiesis, often without the erythroid hyperplasia expected for the level of anaemia.
In vitro hematotoxicity of Vernonanthura polyanthes leaf aqueous extract and its fractions
Published in Drug and Chemical Toxicology, 2022
Jamira Dias Rocha, Janaina da Silva Ferreira, Jeniffer Gabrielle Vieira Silva, Amanda Silva Fernandes, Jefferson Hollanda Véras, Luciane Madureira de Almeida, Aristônio Magalhães Teles, Leonardo Luiz Borges, Lee Chen-Chen, Elisa Flávia Luiz Cardoso Bailão
Despite of being distinct in composition, VpLAE and its fractions did not present a substantial difference when hematotoxicity was investigated. Erythrocytes are devoid of internal membrane structures, also they are easy to be isolated and handled which provide a valuable in vitro model to evaluate the cytotoxicity of different natural or synthetic xenobiotics (Farag and Alagawany 2018). We observed that, despite the absence of cytotoxicity, the erythrocytes assumed an echinocytic form. Similar results were observed previously with other plant extracts. Fruits and leaf aqueous extracts of Ribes nigrum did not induce hemolysis, but induced echinocytes (Bonarska-Kujawa et al.2014). Leaf aqueous extracts of Aristotelia chilensis and Amaranthus spinosus also induced an alteration of human erythrocyte morphology from the normal discoid shape to an echinocytic form (Suwalsky et al.2008, Prajitha and Thoppil 2017). According to the bilayer couple hypothesis, echinocytes are formed when anionic agents accumulate in the outer half of the erythrocytes lipid bilayer, expanding this structure to the cytoplasmic half, and thereby inducing the formation of spicules (Sheetz and Singer 1974, Gallagher 2018). In this way, the ability of plant extracts to cause this morphological alteration on the erythrocytes surface could be related to the presence of flavonoids that probably accumulate in the outer monolayer of the erythrocytes membrane (Chaudhuri et al.2007, Suwalsky et al.2008).
The role of hydrophobic /hydrophilic balance in the activity of structurally flexible vs. rigid cytolytic polypeptides and analogs developed on their basis
Published in Expert Review of Proteomics, 2018
Peter V. Dubovskii, Roman G. Efremov
Similar to other CPs of the venom origin, both CTX and Ltc induce hemolysis of red blood cells (RBC) [64]. It was shown that this is caused by direct interaction of these peptides with the plasma membrane of erythrocytes [17]. From all Ltc, the highest hemolytic activity is observed for Ltc 2a. Interaction of a fluorescently labeled analog of Ltc 2a with erythrocytes proceeds via several steps [65]. First, the peptides are trapped by sialic acids at the surface of erythrocytes. Then, they diffuse to the external leaflet of the erythrocyte plasma membrane, partition into its outer monolayer and form a α-helical structure. At this stage of echinocyte formation, no membrane permeabilization occurs. If concentration of the bound peptide increases, small transient pores of ~ 2 nm in diameter are formed. Such pores induce osmotic shock of the membrane. At this stage (echinocyte-to-spherocyte transformation), the shape of erythrocytes becomes spherical. From this moment, the peptides gain access to phosphatidylserine (PS), which is normally present only in the internal monolayer of the erythrocyte membrane. Due to formation of stable complexes between Ltc2a and PS, diameter of the pores increases up to ~ 13 nm. Hemoglobin leakage occurs through them and the final stage of erythrocyte ghosts develops. In contrast to Ltc2a, Ltc1 possesses lower hemolytic activity. However, similar steps of the erythrocyte membrane transformations were observed, albeit a longer time was required for that [66]. Analysis of the relationship between the net electric charge of Ltc and their hemolytic ability revealed that the positive charge of the peptides favors the activity [17]. Because the outer monolayer of the erythrocyte membrane is formed of zwitterionic phospholipids, this might indicate a role of sialic acid residues, which are present near the membrane surface. Indeed, for cupiennin-1a, another spider venom peptide, featuring high hemolytic activity, enzymatic degradation of sialic acids from erythrocyte’ surface resulted in reduction of the hemolytic activity [67]. This suggests that, most likely, sialic acids increase concentration of CPs near the membrane surface and thus promote their membrane partitioning.
Investigating the ultrastructural and viscoelastic characteristics of whole blood after exposure to the heavy metals cadmium, lead and chromium, alone and in combination
Published in Ultrastructural Pathology, 2022
L Pretorius, H Taute, M Van Rooy, HM Oberholzer
Scanning electron microscopy analysis showed ultrastructural changes to the erythrocytes and fibrin network after heavy metal exposure. The groups that were exposed to metals showed a higher prevalence of altered erythrocyte morphology compared to the control group. The majority of erythrocytes observed in this study had a typical biconcave shape. The predominant altered erythrocyte shape observed was echinocytes with the occasional leptocyte and knizocyte. Overall, the micrographs seem to depict a trend that different groups at different concentrations all showed an increase in erythrocyte deformation which can occur due to oxidative stress, generated by heavy metal exposure.17 The metal-exposed groups were different from the control and showed an increase in erythrocyte deformation from swelling to bulging to the formation of nodule-like spicules/projections. Erythrocyte deformation seems to increase when blood was exposed to Cr, alone and in combination as compared to singular metals, with Cd + Cr group appearing to cause the highest degree of echinocyte formation. This may be due to Cr being a strong redox agent.17 These results are similar to results found in previous studies where Cd exposure caused increased levels of echinocyte formation in Wistar rats and common carp.18,19 Cadmium had the same effect on human blood, along with increased membrane rigidity.20 Any alteration in erythrocyte morphology will reduce their lifespan (usually 120 days) and result in their removal from the circulatory system via phagocytosis, or destruction in the spleen by hemolysis.21 Red blood cell morphology is not the only component affected by heavy metal exposure. Oxidative stress also plays an important role in platelet activation and thus influences the fibrin fiber morphology.22 Reactive oxygen species have been shown to induce platelet activation, suggesting that these highly reactive molecules can interfere with the thrombotic process at multiple steps.17 Blood clotting is dependent on interactions between fibrinogen and thrombin to ultimately form polymerized fibers that hold the platelet plug together.23 Apart from oxidative stress, other mechanisms like phosphodiester inhibition, enzymatic changes and membrane interference should also be investigated as a possible explanation for the alterations observed in the fibrin networks.