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European Journal of Case Reports in... 2021We report the case of a 77-year-old-man with a history of type 2 diabetes mellitus who underwent endoscopic retrograde cholangiopancreatography (ERCP) because of a...
UNLABELLED
We report the case of a 77-year-old-man with a history of type 2 diabetes mellitus who underwent endoscopic retrograde cholangiopancreatography (ERCP) because of a gallstone in the common bile duct. Thirty-six hours after the procedure, the patient developed persistent fever and epigastric pain associated with de novo jaundice. Massive haemolysis (with exuberant spherocytosis) occurred and patient died in 3 hours. was isolated in the blood cultures. Massive haemolysis associated with has a high mortality rate. Management involves a high index of suspicion after gastrointestinal procedures like ERCP, surgical consultation, antibiotic therapy, transfusion of red cell concentrates and, potentially, hyperbaric oxygen therapy.
LEARNING POINTS
Endoscopic retrograde cholangiopancreatography (ERCP) can be complicated by Clostridium perfringens bacteraemia with devastating consequences. infection should be suspected in an icteric, febrile patient with abdominal pain, especially if intravascular haemolysis is present.Management of intravascular haemolysis and inflammation in a patient following ERCP should be multidisciplinary, involving surgery when needed and potentially hyperbaric oxygen therapy; penicillin or penicillin-derived antibiotics associated with clindamycin or metronidazole are the mainstays of antibiotic therapy.
PubMed: 34671578
DOI: 10.12890/2021_002811 -
Journal of Pediatric Hematology/oncology Mar 2022The aim of this study was to evaluate the demographics, clinical, and laboratory findings and treatment responses of patients with hereditary spherocytosis (HS).
OBJECTIVE
The aim of this study was to evaluate the demographics, clinical, and laboratory findings and treatment responses of patients with hereditary spherocytosis (HS).
MATERIALS AND METHODS
Data of children with HS were examined. Diagnosis was based on clinical history, physical examination, family history, presence of spherocytes on peripheral blood smear, and osmotic fragility test.
RESULTS
A total of 101 patients were included. The median (range) age at diagnosis was 38.0 (1 to 188) months. Mild, moderate, and severe forms of HS were present in 29 (28.7%), 15 (14.9%), and 57 (56.4%) patients, respectively. Family history was available in 73 patients and 56 of these (76.7%) had a positive family history for HS. Forty-five (44.5%) patients needed regular transfusions and all of these had severe disease. Although most patients did not require transfusion postsplenectomy, 2 of 45 (4.4%) patients continued to require transfusion. Transfusion dependence was significantly (P<0.001) higher in patients with severe spherocytosis.
CONCLUSIONS
In HS, splenomegaly, pallor, and jaundice are the most common clinical features. Splenectomy dramatically reduces hemolysis in most cases and virtually abolishes further requirement for transfusion.
Topics: Child; Erythrocyte Count; Hematologic Tests; Humans; Spherocytosis, Hereditary; Splenectomy; Splenomegaly
PubMed: 34054043
DOI: 10.1097/MPH.0000000000002211 -
BMC Genomics Jun 2023Hereditary spherocytosis (HS) is a common inherited hemolytic anemia, caused by mutations in five genes that encode erythrocyte membrane skeleton proteins. The red blood...
BACKGROUND
Hereditary spherocytosis (HS) is a common inherited hemolytic anemia, caused by mutations in five genes that encode erythrocyte membrane skeleton proteins. The red blood cell (RBC) lifespan could directly reflect the degree of hemolysis. In the present cohort of 23 patients with HS, we performed next-generation sequencing (NGS) and Levitt's carbon monoxide (CO) breath test to investigate the potential genotype-degree of hemolysis correlation.
RESULTS
In the present cohort, we identified 8 ANK1,9 SPTB,5 SLC4A1 and 1 SPTA1 mutations in 23 patients with HS, and the median RBC lifespan was 14(8-48) days. The median RBC lifespan of patients with ANK1, SPTB and SLC4A1 mutations was 13 (8-23), 13 (8-48) and 14 (12-39) days, respectively, with no statistically significant difference (P = 0.618). The median RBC lifespan of patients with missense, splice and nonsense/insertion/deletion mutations was 16.5 (8-48), 14 (11-40) and 13 (8-20) days, respectively, with no significant difference (P = 0.514). Similarly, we found no significant difference in the RBC lifespan of patients with mutations located in the spectrin-binding domain and the nonspectrin-binding domain [14 (8-18) vs. 12.5 (8-48) days, P = 0.959]. In terms of the composition of mutated genes, 25% of patients with mild hemolysis carried ANK1 or SPTA1 mutations, while 75% of patients with mild hemolysis carried SPTB or SLC4A1 mutations. In contrast, 46.7% of patients with severe hemolysis had ANK1 or SPTA1 mutations and 53.3% of patients with severe hemolysis had SPTB or SLC4A1 mutations. However, there was no statistically significant difference in the distribution of mutated genes between the two groups (P = 0.400).
CONCLUSION
The present study is the first to investigate the potential association between genotype and degree of hemolysis in HS. The present findings indicated that there is no significant correlation between genotype and degree of hemolysis in HS.
Topics: Humans; Hemolysis; Ankyrins; Spectrin; Spherocytosis, Hereditary; Cytoskeletal Proteins; Membrane Proteins; Mutation; Genotype
PubMed: 37280519
DOI: 10.1186/s12864-023-09364-8 -
[Rinsho Ketsueki] the Japanese Journal... 2019Congenital hemolytic anemias are classified into three major categories: red cell membrane disorders, hemoglobinopathies, and red cell enzyme disorders. The membrane... (Review)
Review
Congenital hemolytic anemias are classified into three major categories: red cell membrane disorders, hemoglobinopathies, and red cell enzyme disorders. The membrane disorders are caused by abnormalities in erythrocyte membrane proteins and are often associated with disease-specific deformations of red blood cells. Historically, membrane disorders have been classified according to morphology. In recent years, however, comprehensive genetic analysis with next-generation sequencing has been performed in patients with hemolytic anemia for whom making an accurate diagnosis is difficult. These studies have led to the identification of new causative genes, but there have been inconsistent associations in some cases between the diagnosed disease and the patient's clinical manifestations. Thalassemia is a hemoglobinopathy caused by a quantitative abnormality of one or the other of the globin chains in hemoglobin. Most Japanese patients with thalassemia have mild forms of the disease, which is different from reports in other countries. However, with globalization, the proportion of Japanese patients with intermediate or severe anemia is increasing. Therefore, it is incumbent on hematologists in Japan to be knowledgeable regarding prenatal diagnosis of and gene therapy for thalassemia.
Topics: Erythrocyte Membrane; Humans; Thalassemia
PubMed: 31168008
DOI: 10.11406/rinketsu.60.423 -
Frontiers in Physiology 2018Deformability is an essential feature of blood cells (RBCs) that enables them to travel through even the smallest capillaries of the human body. Deformability is a... (Review)
Review
Deformability is an essential feature of blood cells (RBCs) that enables them to travel through even the smallest capillaries of the human body. Deformability is a function of (i) structural elements of cytoskeletal proteins, (ii) processes controlling intracellular ion and water handling and (iii) membrane surface-to-volume ratio. All these factors may be altered in various forms of hereditary hemolytic anemia, such as sickle cell disease, thalassemia, hereditary spherocytosis and hereditary xerocytosis. Although mutations are known as the primary causes of these congenital anemias, little is known about the resulting secondary processes that affect RBC deformability (such as secondary changes in RBC hydration, membrane protein phosphorylation, and RBC vesiculation). These secondary processes could, however, play an important role in the premature removal of the aberrant RBCs by the spleen. Altered RBC deformability could contribute to disease pathophysiology in various disorders of the RBC. Here we review the current knowledge on RBC deformability in different forms of hereditary hemolytic anemia and describe secondary mechanisms involved in RBC deformability.
PubMed: 29910743
DOI: 10.3389/fphys.2018.00656 -
Biometals : An International Journal on... Oct 2015Iron is an essential element for fundamental cell functions and a catalyst for chemical reactions. Three samples extracted from the human spleen were investigated by...
Iron is an essential element for fundamental cell functions and a catalyst for chemical reactions. Three samples extracted from the human spleen were investigated by scanning (SEM) and transmission electron microscopy (TEM), Mössbauer spectrometry (MS), and SQUID magnetometry. The sample with diagnosis of hemosiderosis (H) differs from that referring to hereditary spherocytosis and the reference sample. SEM reveals iron-rich micrometer-sized aggregate of various structures-tiny fibrils in hereditary spherocytosis sample and no fibrils in hemochromatosis. Hematite and magnetite particles from 2 to 6 μm in TEM with diffraction in all samples were shown. The SQUID magnetometry shows different amount of diamagnetic, paramagnetic and ferrimagnetic structures in the tissues. The MS results indicate contribution of ferromagnetically split sextets for all investigated samples. Their occurrence indicates that at least part of the sample is magnetically ordered below the critical temperature. The iron accumulation process is different in hereditary spherocytosis and hemosiderosis. This fact may be the reason of different iron crystallization.
Topics: Autopsy; Crystallization; Ferric Compounds; Ferrosoferric Oxide; Hemosiderosis; Humans; Iron; Microscopy, Electron, Transmission; Spectroscopy, Mossbauer; Spherocytosis, Hereditary; Spleen
PubMed: 26292972
DOI: 10.1007/s10534-015-9876-2 -
Annals of Human Genetics Mar 2022Glucose-6-phosphate dehydrogenase (G6PD) deficiency, hereditary spherocytosis (HS), and alpha thalassemia (α-thal) are frequent erythrocyte pathologies with different...
BACKGROUND
Glucose-6-phosphate dehydrogenase (G6PD) deficiency, hereditary spherocytosis (HS), and alpha thalassemia (α-thal) are frequent erythrocyte pathologies with different geographic distributions worldwide. Our aim is to report hematological and molecular findings of G6PD deficient Mexican patients in coinheritance with suggestive hereditary spherocytosis (sHS) and α-thal.
METHODS
We studied 78 G6PD deficiency patients. Hematological parameters, acidified glycerol lysis test, erythrocyte morphology, electrophoresis, and hemoglobin quantification were obtained. G6PD and HBA2/HBA1 variants were identified using ARMS-PCR, Gap-PCR, or Sanger sequencing.
RESULTS
Nine G6PD variants were identified; A , A , and A as the most frequent. G6PD Santiago de Cuba and Kamiube were detected in Mexicans for first time. Hematological analysis revealed additional erythrocyte pathologies in 52 patients, 32 with positive osmotic fragility test and spherocytes in blood smear (suggestive hereditary spherocytosis, sHS), 12 with microcytosis and 8 with all three defects who had the most severe phenotype, with significantly lower hematological parameters (Hb, PCV, MCV, and MCH). α-thal variants (α α, α α and -α ) were observed in 65% of patients with microcytosis.
CONCLUSION
Additional erythrocyte defects were observed in 69.3% of G6PD deficiency patients. We stress the importance of searching for the presence of additional erythrocyte hereditary diseases in patients with G6PD deficiency.
Topics: Glucosephosphate Dehydrogenase Deficiency; Humans; Mexico; Phenotype; Polymerase Chain Reaction; alpha-Thalassemia
PubMed: 34844289
DOI: 10.1111/ahg.12451 -
British Journal of Haematology Oct 2019Hereditary erythrocyte membrane disorders are caused by mutations in genes encoding various transmembrane or cytoskeletal proteins of red blood cells. The main... (Review)
Review
Hereditary erythrocyte membrane disorders are caused by mutations in genes encoding various transmembrane or cytoskeletal proteins of red blood cells. The main consequences of these genetic alterations are decreased cell deformability and shortened erythrocyte survival. Red blood cell membrane defects encompass a heterogeneous group of haemolytic anaemias caused by either (i) altered membrane structural organisation (hereditary spherocytosis, hereditary elliptocytosis, hereditary pyropoikilocytosis and Southeast Asian ovalocytosis) or (ii) altered membrane transport function (overhydrated hereditary stomatocytosis, dehydrated hereditary stomatocytosis or xerocytosis, familial pseudohyperkalaemia and cryohydrocytosis). Herein we provide a comprehensive review of the recent literature on the molecular genetics of erythrocyte membrane defects and their reported clinical consequences. We also describe the effect of low-expression genetic variants on the high inter- and intra-familial phenotype variability of erythrocyte structural defects.
Topics: Alleles; Anemia, Hemolytic, Congenital; Elliptocytosis, Hereditary; Erythrocyte Membrane; Erythrocytes, Abnormal; Humans; Membrane Proteins; Spherocytosis, Hereditary
PubMed: 31364155
DOI: 10.1111/bjh.16126 -
Journal of Biosciences 2020Ankyrins are ubiquitously expressed proteins that play a critical role in the integrity of cytoskeleton and cellular signalling. Their presence in metazoans and... (Review)
Review
Ankyrins are ubiquitously expressed proteins that play a critical role in the integrity of cytoskeleton and cellular signalling. Their presence in metazoans and evolutionary conserved protein primary sequence indicates their functional significance. Tissue-specific isoforms and an array of transcript variants make this protein one of the indispensable cellular components. Membrane-binding domains consist of ankyrin repeats that bind with several functional membrane proteins that enable maintaining cellular integrity. Cytosolic ankyrins help in cellular signal transduction. Linkage studies and recent genome-wide association studies uncovered the pathogenic roles of ankyrins (ankyrin-R, ankyrin-B and ankyrin-G) in several diseases, such as hereditary spherocytosis, long QT syndrome, intellectual disability, and CRASH syndrome, among several others. Identification of in celiac disease may potentially explain the link between neuronal health and immunity. It is thus warranted to investigate the role of neuronal factors in immune diseases and vice versa. In this review, we briefly discussed the contribution of ankyrin genes to human diseases.
Topics: Ankyrins; Celiac Disease; Genetic Diseases, X-Linked; Genome-Wide Association Study; Humans; Intellectual Disability; Long QT Syndrome; Signal Transduction; Spastic Paraplegia, Hereditary; Spherocytosis, Hereditary
PubMed: 33410423
DOI: No ID Found -
Advances in Experimental Medicine and... 2018Spectrin-based proteinaceous membrane skeletal network has been found to be implicated in membrane disorders like hereditary spherocytosis (HS). HS greatly affects... (Review)
Review
Spectrin-based proteinaceous membrane skeletal network has been found to be implicated in membrane disorders like hereditary spherocytosis (HS). HS greatly affects eryptosis via loss of membrane asymmetry which is seen to be the case in haemoglobin disorders like thalassemia and sickle cell disease as well. The biological implications of the status of membrane asymmetry are strongly correlated to spectrin interactions with aminophospholipids, e.g. PE and PS. Fluorescence and X-ray reflectivity (XRR) measurements of spectrin interactions with small unilamellar vesicles (SUVs) and cushioned bilayers of phospholipids, respectively, were studied. Both the XRR and fluorescence measurements led to the characterization of spectrin orientation on the surface of lipid bilayer of phosphatidylcholine (PC) and PC/aminophospholipid mixed membrane systems showing formation of a uniform layer of spectrin on top of the mixed phospholipid bilayer. Fluorescence studies show that spectrin interacts with PC and phosphatidylethanolamine (PE)/phosphatidylserine (PS) membranes with binding dissociation constants (K) in the nanomolar range indicating the role of spectrin in the maintenance of the overall membrane asymmetry of erythrocytes.
Topics: Cell Membrane; Eryptosis; Erythrocytes; Humans; Lipid Bilayers; Phospholipids; Spectrin; Spherocytosis, Hereditary
PubMed: 30637686
DOI: 10.1007/978-981-13-3065-0_1