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Journal of Clinical Laboratory Analysis Dec 2021Hereditary spherocytosis (HS), a commonly encountered hereditary hemolytic disease, is mostly inherited in an autosomal dominant manner. The clinical manifestations in... (Review)
Review
BACKGROUND
Hereditary spherocytosis (HS), a commonly encountered hereditary hemolytic disease, is mostly inherited in an autosomal dominant manner. The clinical manifestations in patients with HS show obvious heterogeneity. Moreover, the sensitivity or specificity of some HS diagnostic tests are not ideal and may easily result in misdiagnosis or missed diagnosis in some patients. The objective of this study was to propose a simple and practical diagnostic protocol, which can contribute to the diagnosis of HS and its differential diagnosis with different types of hemolytic anemia such as thalassemia (THAL), autoimmune hemolytic anemia (AIHA), and glucose-6-phosphate dehydrogenase (G6PD) deficiency, thus, to provide an alternative simple and reliable method for better clinical diagnosis of HS.
METHODS
Through combing our research with existing experimental technologies and studies, we propose a simple and practical protocol for HS diagnosis, which will help clinicians to improve HS diagnosis.
RESULTS
Compared with the existing HS diagnostic protocols, the HS diagnostic protocol we proposed is simpler. In this new protocol, some experimental tests with ideal diagnostic efficiency are added, such as mean reticulocyte volume (MRV), mean sphered cell volume (MSCV), mean corpuscular volume (MCV), in combination with the observation of clinical manifestations, family investigation, routine tests for hemolytic anemia, genetic testing, and other screening tests.
CONCLUSION
The HS diagnostic protocol we proposed could improve the clinical practice and efficiency of HS diagnosis.
Topics: Anemia, Hemolytic, Autoimmune; Diagnosis, Differential; Diagnostic Errors; Eosine Yellowish-(YS); Erythrocyte Indices; Glucosephosphate Dehydrogenase Deficiency; Humans; Mutation; Practice Guidelines as Topic; Spherocytosis, Hereditary
PubMed: 34689357
DOI: 10.1002/jcla.24034 -
Chirurgia (Bucharest, Romania : 1990) 2017Hereditary spherocytosis (HS) is a disease affecting the red blood cells membrane and belongs to the congenital hemolytic anemias. The clinical spectrum ranges from... (Review)
Review
Hereditary spherocytosis (HS) is a disease affecting the red blood cells membrane and belongs to the congenital hemolytic anemias. The clinical spectrum ranges from asymptomatic patients to severe forms requiring transfusions in early childhood. The diagnosis can be based on the physical examination, complete red blood cell count, reticulocytes count, medical history and specific tests, preferentially the EMA test (eosin-5-maleimide binding) test and AGLT (Acidified Glycerol Lysis Time). Splenectomy is considered the standard surgical treatment in moderate and severe forms of hereditary spherocytosis. Total splenectomy exposes the patient to a life - long risk of potentially lethal infections and thus, its usage was reconsidered. Because of this reason, a feasible alternative is the partial splenectomy. The use of partial splenectomy aims to retain splenic immunologic function, while at the same time to decrease the rate of hemolysis. The long - term outcomes of patients with total or subtotal splenectomy for congenital hemolytic anemia, still remain unclear, but the majority of the studies showed a qualitative resolution of anemia and reduction of transfusion rate. Despite the well known advantages of conservative surgery, the optimal choice of treatment and outcomes should be confirmed with the patient.
Topics: Erythrocyte Count; Erythrocyte Membrane; Evidence-Based Medicine; Hematologic Tests; Hemolysis; Humans; Reticulocytes; Spherocytes; Spherocytosis, Hereditary; Splenectomy; Treatment Outcome
PubMed: 28463670
DOI: 10.21614/chirurgia.112.2.110 -
British Journal of Haematology Jan 2012Guidelines on hereditary spherocytosis (HS) published in 2004 (Bolton-Maggs et al, 2004) are here replaced to reflect changes in current opinion on the surgical...
Guidelines on hereditary spherocytosis (HS) published in 2004 (Bolton-Maggs et al, 2004) are here replaced to reflect changes in current opinion on the surgical management, (particularly the indications for concomitant splenectomy with cholecystectomy in children with mild HS, and concomitant cholecystectomy with splenectomy in those with asymptomatic gallstones). Further potential long term hazards of splenectomy are now recognised. Advances have been made in our understanding of the biochemistry of the red cell membrane which underpins the choice of tests. Biochemical assays of membranes proteins and genetic analysis may be indicated (rarely) to diagnose atypical cases. The diagnostic value of the eosin-5-maleimide (EMA) binding test has been validated in a number of studies with understanding of its limitations.
Topics: Humans; Spherocytosis, Hereditary
PubMed: 22055020
DOI: 10.1111/j.1365-2141.2011.08921.x -
Acta Haematologica 2018With the widespread use of genetic diagnostic technologies, many novel mutations have been identified in hereditary spherocytosis (HS)-related genes, including SPTA1,... (Review)
Review
With the widespread use of genetic diagnostic technologies, many novel mutations have been identified in hereditary spherocytosis (HS)-related genes, including SPTA1, SPTB, ANK1, SLC4A1, and EPB42. However, mutations in HS-related genes are dispersed and nonspecific in the diagnosis of some HS patients, indicating significant heterogeneity in the molecular deficiency of HS. It is necessary to provide the molecular and genetic characteristics of these 5 genes for clinicians to examine HS. Here, we reviewed the recent proposed molecular genetic mechanisms of HS.
Topics: Biomarkers; Genetic Association Studies; Genetic Predisposition to Disease; Humans; Mutation; Spherocytosis, Hereditary
PubMed: 29402830
DOI: 10.1159/000486229 -
British Journal of Haematology Nov 2020Hereditary spherocytosis (HS) is a common inherited haemolytic anaemia attributed to disturbances in five different red cell membrane proteins. We performed a...
Hereditary spherocytosis (HS) is a common inherited haemolytic anaemia attributed to disturbances in five different red cell membrane proteins. We performed a retrospective study of 166 children with HS and describe the clinical phenotype according to the genotype. In 160/166 (97%) children with HS a disease-causing mutation was identified. Pathogenic variants in ANK1, SPTB, SLC4A1 and SPTA1 were found in 49%, 33%, 13% and 5% of patients. Children with SLC4A1-HS had the mildest phenotype, showing the highest haemoglobin (P < 0·001), lowest reticulocyte counts (P < 0·001) and lowest unconjugated bilirubin levels (P = 0·006), and none required splenectomy in childhood (P < 0·001). Conversely, children with autosomal recessive SPTA1-HS had the most severe clinical phenotype, with almost all patients undergoing splenectomy in early childhood. Patients with ANK1 and SPTB variants showed a similar clinical phenotype. Within each gene, variant type or location did not predict disease severity or likelihood of splenectomy. Among patients with a genetic diagnosis, 47 (29%) underwent splenectomy (23 partial; 24 total) while 57 (36%) underwent cholecystectomy. Total splenectomy led to greater improvements in haemoglobin (P = 0·02). Select use of genetic testing (especially in patients without a family history) may help predict clinical phenotype in childhood and guide family counselling.
Topics: Adolescent; Age Factors; Alleles; Blood Cell Count; Child; Child, Preschool; Combined Modality Therapy; Female; Genetic Association Studies; Genetic Predisposition to Disease; Genetic Testing; Genotype; Humans; Male; Mutation; Phenotype; Retrospective Studies; Spherocytosis, Hereditary
PubMed: 32436265
DOI: 10.1111/bjh.16750 -
Blood Nov 2022
Topics: Mice; Animals; Blood Platelets; Physical Therapy Modalities; Spherocytosis, Hereditary; Hemostasis
PubMed: 36422862
DOI: 10.1182/blood.2022018189 -
Hematology. American Society of... Nov 2018Significant advances have been made in diagnosis and clinical management of inherited red cell membrane disorders that result in hemolytic anemia. Membrane structural... (Review)
Review
Significant advances have been made in diagnosis and clinical management of inherited red cell membrane disorders that result in hemolytic anemia. Membrane structural defects lead to hereditary spherocytosis (HS) and hereditary elliptocytosis (HE), whereas altered membrane transport function accounts for hereditary xerocytosis (HX) and hereditary overhydrated stomatocytosis (OHS). The degrees of membrane loss and resultant increases in cell sphericity determine the severity of anemia in HS and HE, and splenectomy leads to amelioration of anemia by increasing the circulatory red cell life span. Alterations in cell volume as a result of disordered membrane cation permeability account for reduced life span red cells in HX and OHS. Importantly, splenectomy is not beneficial in these 2 membrane transport disorders and is not recommended because it is ineffective and may lead to an increased risk of life-threatening thrombosis. Rational approaches are now available for the diagnosis and management of these inherited red cell disorders, and these will be discussed in this review.
Topics: Anemia, Hemolytic, Congenital; Elliptocytosis, Hereditary; Erythrocyte Membrane; Humans; Hydrops Fetalis; Risk Factors; Spherocytosis, Hereditary; Thrombosis
PubMed: 30504335
DOI: 10.1182/asheducation-2018.1.377 -
Acta Haematologica 2019
Topics: Ankyrins; Humans; Mutation; Spherocytosis, Hereditary
PubMed: 30602149
DOI: 10.1159/000495339 -
Pediatric Clinics of North America Dec 2013Primary abnormalities of the erythrocyte membrane are characterized by clinical, laboratory, and genetic heterogeneity. Among this group, hereditary spherocytosis... (Review)
Review
Primary abnormalities of the erythrocyte membrane are characterized by clinical, laboratory, and genetic heterogeneity. Among this group, hereditary spherocytosis patients are more likely to experience symptomatic anemia. Treatment of hereditary spherocytosis with splenectomy is curative in most patients. Growing recognition of the long-term risks of splenectomy has led to re-evaluation of the role of splenectomy. Management guidelines acknowledge these considerations and recommend discussion between health care providers, patient, and family. The hereditary elliptocytosis syndromes are the most common primary disorders of erythrocyte membrane proteins. However, most elliptocytosis patients are asymptomatic and do not require therapy.
Topics: Anemia, Hemolytic, Congenital; Elliptocytosis, Hereditary; Erythrocyte Membrane; Erythrocytes; Humans; Spherocytosis, Hereditary; Splenectomy
PubMed: 24237975
DOI: 10.1016/j.pcl.2013.09.001 -
British Journal of Haematology May 2008Studies during the last three decades have enabled the development of detailed molecular insights into the structural basis of altered function in various inherited red... (Review)
Review
Studies during the last three decades have enabled the development of detailed molecular insights into the structural basis of altered function in various inherited red cell membrane disorders. This review highlights our current understanding of molecular and mechanistic insights into various inherited red cell membrane disorders involving either altered membrane structural organization (hereditary spherocytosis, hereditary elliptocytosis and hereditary ovalocytosis) or altered membrane transport function (hereditary stomatocytosis). The molecular basis for the vast majority of cases of hereditary spherocytosis, elliptocytosis and ovalocytosis have been fully defined while little progress has been made in defining the molecular basis for hereditary stomatocytosis. Mutations in a number of distinct genes account for hereditary spherocytosis and elliptocytosis, while a single genetic defect accounts for all cases of hereditary ovalocytosis. Based on these molecular insights, a comprehensive understanding of the structural basis for altered membrane function has been developed. Loss of vertical linkage between membrane skeleton and lipid bilayer leads to membrane loss in hereditary spherocytosis, while weakening of lateral linkages between skeletal proteins leads to membrane fragmentation and surface area loss in hereditary elliptocytosis. Importantly, the severity of anaemia in both these disorders is directly related to extent of membrane surface area loss. Splenectomy results in amelioration of anaemia.
Topics: Anemia, Hemolytic, Congenital; Elliptocytosis, Hereditary; Erythrocyte Membrane; Erythrocytes, Abnormal; Humans; Spherocytosis, Hereditary
PubMed: 18341630
DOI: 10.1111/j.1365-2141.2008.07091.x