RED BLOOD CELL INDEXES IN PATIENTS WITH HEREDITARY SPHEROCYTOSIS AND β-THALASSEMIA COMBINATION

2002 ◽  
Vol 19 (8) ◽  
pp. 569-573 ◽  
Author(s):  
Nejat Akar ◽  
Hafize Gökçe
Keyword(s):  
Blood Cell ◽  
Red Blood Cell ◽  
Hereditary Spherocytosis

scholarly journals Combined spectrin and ankyrin deficiency is common in autosomal dominant hereditary spherocytosis

Blood ◽  
1993 ◽  
Vol 82 (10) ◽  
pp. 2953-2960 ◽  
Author(s):  
P Savvides ◽  
O Shalev ◽  
KM John ◽  
SE Lux
Keyword(s):  
Blood Cell ◽  
Red Blood Cell ◽  
Autosomal Dominant ◽  
Hereditary Spherocytosis ◽  
Band 3 ◽  
Normal Range ◽  
Dominant Form ◽  
Autosomal Dominant Form ◽  
The Common ◽  
Ankyrin Deficiency

Abstract The common autosomal dominant form of hereditary spherocytosis (HS) has been genetically linked to defects of the erythroid ankyrin gene in a few families; however, the frequency of ankyrin deficiency and its relationship to red blood cell (RBC) spectrin content are unknown. To test these questions, we measured RBC spectrin and ankyrin by radioimmunoassay in 39 patients from 20 families with dominant HS. Normal RBCs contained 242,000 +/- 20,500 spectrin heterodimers and 124,500 +/- 11,000 ankyrins per cell. In dominant HS, RBC spectrin and ankyrin ranged from about 40% to 100% of normal and were continuously distributed. Measurements in the same patient on different occasions were reproducible (+/- 5% to 10%) and RBCs from affected members of a kindred contained similar amounts of spectrin and ankyrin (+/- 3% to 4%). Spectrin and ankyrin levels were almost always less than the assay controls, but were less than the normal range in only 75% and 80% of kindreds, respectively. Remarkably, the degree of RBC spectrin and ankyrin deficiency was very similar in 19 of 20 HS kindreds. One otherwise typical family differed, with marked ankyrin deficiency (45% of control) and a relatively mild spectrin deficit (81%). We conclude that most patients with dominant HS have combined ankyrin and spectrin deficiency and that the two proteins are usually about equally deficient, suggesting that defects in ankyrin expression, ankyrin stability, or ankyrin band 3 (AE1) interactions may be common in dominant HS.

Red blood cell aquaporin-1 expression is decreased in hereditary spherocytosis

2016 ◽  
Vol 95 (10) ◽  
pp. 1595-1601 ◽  
Author(s):  
Renée L. Crisp ◽  
Romina E. Maltaneri ◽  
Daniela C. Vittori ◽  
Liliana Solari ◽  
Daniel Gammella ◽  
...  
Keyword(s):  
Blood Cell ◽  
Red Blood Cell ◽  
Hereditary Spherocytosis ◽  
Aquaporin 1

Nitric Oxide Scavenging, Abnormal Vasoregulation and Oxidative Damage in sph/sph Mice with Severe Hereditary Spherocytosis: Possible Consequences of Red Blood Cell Hemolysis.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 1660-1660
Author(s):  
Anne C. Schraufnagel ◽  
Barb Piknova ◽  
Kirkwood A. Pritchard ◽  
Neil Hogg ◽  
Nancy J. Wandersee
Keyword(s):  
Nitric Oxide ◽  
Blood Cell ◽  
Oxidative Damage ◽  
Xanthine Oxidase ◽  
Red Blood Cell ◽  
Hereditary Spherocytosis ◽  
Membrane Skeleton ◽  
Oxidative Enzymes ◽  
Endothelial Cell Function ◽  
Scavenging Capacity

Abstract The membrane skeleton, a multiprotein complex located just beneath the plasma membrane, provides the red blood cell (RBC) with the mechanical strength and deformability required to withstand high shear forces generated in the microcapillaries. Spectrin, a tetramer composed of a- and b- subunits, is the backbone of the erythroid membrane skeleton. Previously, we have shown that sph/sph mice have severe hereditary spherocytosis (HS) due to a spontaneous single-base deletion in the murine erythroid a-spectrin gene, Spna1. HS mice have severe hemolytic anemia, compensatory reticulocytosis, altered RBC morphology and increased fragility. Vascular dysfunction in sph/sph mice likely plays an important role in the mechanism by which these mice develop a high incidence of cardiac thrombosis and stroke between 6 and 12 weeks of age. We hypothesize that serum free hemoglobin released from intravascular hemolysis of sph/sph RBCs and xanthine oxidase, released from ischemic tissues, impairs endothelial cell function by scavenging nitric oxide (NO) and increasing oxidative damage. To test this hypothesis, we used helium electroparamagnetic resonance (EPR), to quantify plasma free Hb and NO scavenging capacity in the plasma of the mice; immunohistochemistry to determine tissue and vascular levels of xanthine oxidase and 3-nitrotyrosine; and, facialis arteries to measure changes in acetylcholine, endothelium and eNOS-dependent vasodilation. By EPR we found that the plasma free Hb and NO scavenging capacity in the plasma of sph/sph mice is much greater than that of the normal +/+ mice. Immunohistochemistry (IHC) for XO and NTyr revealed XO staining was decreased in livers of sph/sph mice as compared to livers from normal +/+ mice. XO staining was increased in local patches on the endothelium of lungs isolated from sph/sph mice compared to lungs from +/+ mice. NTyr, a marker of peroxynitrite formation was also increased in a focal manner in lungs of sph/sph mice compared to lungs of +/+ mice. Acetylcholine-induced and eNOS-dependent vasodilation in sph/sph mice was significantly impaired compared to vasodilation in normal +/+ mice. Taken together these data suggest the hemoglobin removal system in sph/sph mice is saturated, leading to increased free Hb and nitric oxide scavenging. IHC studies reveal XO is released from liver in sph/sph mice and once released binds the endothelium of lung, quite distal from the original site of injury. Such changes likely contribute to marked increases in NTyr staining and impaired endothelium and eNOS-dependent vasodilation in facialis arteries isolated from sph/sph mice. Taken together, these data indicate that sph/sph mice with severe HS have increased plasma free Hb and NO scavenging capacity as well as increased release of xanthine oxidase and subsequent binding to vascular endothelial cells to locations that are distal the original site of injury. Such plasma and vascular changes in hemoglobin and oxidative enzymes likely play a critical role in the mechanisms contributing to aberrant vasoregulation and initiating the pathways of oxidative damage found in sph/sph mice.

scholarly journals The Fluid Membrane determines Mechanics of Red Blood Cell Extracellular Vesicles and is Softened in Hereditary Spherocytosis

2017 ◽  
Author(s):  
Daan Vorselen ◽  
Susan M. van Dommelen ◽  
Raya Sorkin ◽  
Jürgen Schiller ◽  
Richard van Wijk ◽  
...  
Keyword(s):  
Blood Cell ◽  
Extracellular Vesicles ◽  
Red Blood Cell ◽  
Hereditary Spherocytosis ◽  
Cell Communication ◽  
Lipid Vesicle ◽  
Bending Modulus ◽  
Rbc Membrane ◽  
Blood Disorder ◽  
Healthy Donors

AbstractExtracellular vesicles (EVs) are widely studied regarding their role in cell-to-cell communication and disease, as well as for applications as biomarker or drug delivery vehicle. EVs contain both membrane and intraluminal proteins, affecting their structural properties and thereby likely their functioning. Here, we use atomic force microscopy for the mechanical characterization of red blood cell (RBC) EVs from healthy individuals as well as from a patient with hereditary spherocytosis (HS) due to ankyrin deficiency. We show that the EVs are packed with proteins, yet their response to indentation is similar to that of a fluid lipid vesicle lacking proteins. The bending modulus of RBC EVs of healthy donors is ~15kbT, agreeing well with the bending modulus of the RBC membrane. Surprisingly, whereas RBCs become more rigid in HS, the excreted vesicles of a patient with this blood disorder have a significantly (~50%) lower bending modulus than donor EVs. These results shed new light on the mechanism and effects of EV budding and may underlie the reported increase in vesiculation and stiffening of RBCs in hereditary spherocytosis patients.

scholarly journals Ektacytometry Analysis of Post-splenectomy Red Blood Cell Properties Identifies Cell Membrane Stability Test as a Novel Biomarker of Membrane Health in Hereditary Spherocytosis

2021 ◽  
Vol 12 ◽  
Author(s):  
M. C. Berrevoets ◽  
J. Bos ◽  
R. Huisjes ◽  
T. H. Merkx ◽  
B. A. van Oirschot ◽  
...  
Keyword(s):  
Cell Membrane ◽  
Blood Cell ◽  
Red Blood Cell ◽  
Clinical Benefit ◽  
Hereditary Spherocytosis ◽  
Case Control ◽  
Stability Test ◽  
Control Cohort ◽  
Cell Membrane Stability ◽  
Rbc Membrane

Hereditary spherocytosis (HS) is the most common form of hereditary chronic hemolytic anemia. It is caused by mutations in red blood cell (RBC) membrane and cytoskeletal proteins, which compromise membrane integrity, leading to vesiculation. Eventually, this leads to entrapment of poorly deformable spherocytes in the spleen. Splenectomy is a procedure often performed in HS. The clinical benefit results from removing the primary site of destruction, thereby improving RBC survival. But whether changes in RBC properties contribute to the clinical benefit of splenectomy is unknown. In this study we used ektacytometry to investigate the longitudinal effects of splenectomy on RBC properties in five well-characterized HS patients at four different time points and in a case-control cohort of 26 HS patients. Osmotic gradient ektacytometry showed that splenectomy resulted in improved intracellular viscosity (hydration state) whereas total surface area and surface-to-volume ratio remained essentially unchanged. The cell membrane stability test (CMST), which assesses the in vitro response to shear stress, showed that after splenectomy, HS RBCs had partly regained the ability to shed membrane, a property of healthy RBCs, which was confirmed in the case-control cohort. In particular the CMST holds promise as a novel biomarker in HS that reflects RBC membrane health and may be used to asses treatment response in HS.

Osmotic gradient ektacytometry: A valuable screening test for hereditary spherocytosis and other red blood cell membrane disorders

2017 ◽  
Vol 40 (1) ◽  
pp. 94-102 ◽  
Author(s):  
E. Llaudet-Planas ◽  
J. L. Vives-Corrons ◽  
V. Rizzuto ◽  
P. Gómez-Ramírez ◽  
J. Sevilla Navarro ◽  
...  
Keyword(s):  
Cell Membrane ◽  
Blood Cell ◽  
Red Blood Cell ◽  
Screening Test ◽  
Hereditary Spherocytosis ◽  
Osmotic Gradient ◽  
Red Blood Cell Membrane

Evaluation of a Flow-Cytometric Osmotic Fragility Test for Hereditary Spherocytosis in Chinese Patients

2015 ◽  
Vol 135 (2) ◽  
pp. 88-93 ◽  
Author(s):  
Yi-Feng Tao ◽  
Zeng-Fu Deng ◽  
Lin Liao ◽  
Yu-Ling Qiu ◽  
Xue-Lian Deng ◽  
...  
Keyword(s):  
Blood Cell ◽  
Red Blood Cells ◽  
Cell Morphology ◽  
Red Blood Cell ◽  
Peripheral Blood ◽  
Blood Cells ◽  
Hereditary Spherocytosis ◽  
Osmotic Fragility ◽  
Flow Cytometric ◽  
Blood Cell Morphology

Background: Osmotic fragility testing based on flow cytometry was recently introduced for the screening of hereditary spherocytosis (HS). This study was undertaken to evaluate the clinical diagnostic value of a flow-cytometric osmotic fragility test for HS. Methods: Peripheral blood was collected from 237 subjects at the First Affiliated Hospital of Guangxi Medical University, including 56 HS patients, 86 thalassemia patients and 95 healthy controls. The samples were examined by flow-cytometric osmotic fragility test and the percentage of residual red blood cells was used to determine HS. Peripheral blood smears were performed to examine the red blood cell morphology. Results: With clinical diagnosis of HS as the gold standard and the percentage of residual red blood cells <23.6% as the diagnostic threshold in the flow-cytometric osmotic fragility test, the sensitivity of the flow-cytometric osmotic fragility test for HS was 85.71% and the specificity was 97.24%. Conclusion: The flow-cytometric osmotic fragility test combined with a red blood cell morphology test by peripheral blood smear could be a simple, practical and accurate laboratory screening method for HS.

scholarly journals Complex Modes of Inheritance in Hereditary Red Blood Cell Disorders: A Case Series Study of 155 Patients

Genes ◽  
2021 ◽  
Vol 12 (7) ◽  
pp. 958
Author(s):  
Immacolata Andolfo ◽  
Stefania Martone ◽  
Barbara Eleni Rosato ◽  
Roberta Marra ◽  
Antonella Gambale ◽  
...  
Keyword(s):  
Blood Cell ◽  
Red Blood Cell ◽  
Hereditary Spherocytosis ◽  
Diagnostic Yield ◽  
Case Series ◽  
Targeted Next Generation Sequencing ◽  
Complex Modes ◽  
Case Series Study ◽  
Molecular Bases ◽  
Dual Inheritance

Hereditary erythrocytes disorders include a large group of conditions with heterogeneous molecular bases and phenotypes. We analyzed here a case series of 155 consecutive patients with clinical suspicion of hereditary erythrocyte defects referred to the Medical Genetics Unit from 2018 to 2020. All of the cases followed a diagnostic workflow based on a targeted next-generation sequencing panel of 86 genes causative of hereditary red blood cell defects. We obtained an overall diagnostic yield of 84% of the tested patients. Monogenic inheritance was seen for 69% (107/155), and multi-locus inheritance for 15% (23/155). PIEZO1 and SPTA1 were the most mutated loci. Accordingly, 16/23 patients with multi-locus inheritance showed dual molecular diagnosis of dehydrated hereditary stomatocytosis/xerocytosis and hereditary spherocytosis. These dual inheritance cases were fully characterized and were clinically indistinguishable from patients with hereditary spherocytosis. Additionally, their ektacytometry curves highlighted alterations of dual inheritance patients compared to both dehydrated hereditary stomatocytosis and hereditary spherocytosis. Our findings expand the genotypic spectrum of red blood cell disorders and indicate that multi-locus inheritance should be considered for analysis and counseling of these patients. Of note, the genetic testing was crucial for diagnosis of patients with a complex mode of inheritance.

Sign in / Sign up

Export Citation Format

Share Document