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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 -
Indian Journal of Pediatrics Jan 2020Hemolytic anemias are a group of disorders with varied clinical and molecular heterogeneity. They are characterized by decreased levels of circulating erythrocytes in... (Review)
Review
Hemolytic anemias are a group of disorders with varied clinical and molecular heterogeneity. They are characterized by decreased levels of circulating erythrocytes in blood. The pathognomic finding is a reduced red cell life span with severe anemia or, compensated hemolysis accompanied by reticulocytosis. The diagnostic workup or laboratory approach for hemolytic anemias is based on methodical step-wise testing which includes red blood cell morphology, hematological indices with increased reticulocyte count along with clinical features of hemolytic anemias. If conventional laboratory tests are unable to detect the underlying cause of hemolysis, genetic testing is recommended. Sanger sequencing along with conventional testing is the most efficient way to diagnose the underlying genetic causes, especially in thalassemias/hemoglobinopathies, if required. However, hemolytic anemias being highly heterogeneous disorders, next-generation sequencing-based screening is rapidly becoming an efficient way to decipher the etiologies where common causes have been excluded.
Topics: Anemia, Hemolytic; Anemia, Hemolytic, Congenital Nonspherocytic; Clinical Laboratory Techniques; Elliptocytosis, Hereditary; Erythrocytes; Genetic Testing; Glucosephosphate Dehydrogenase Deficiency; Hematologic Tests; Hemoglobinopathies; Hemoglobinuria, Paroxysmal; Hemolysis; High-Throughput Nucleotide Sequencing; Humans; Pyruvate Kinase; Pyruvate Metabolism, Inborn Errors; Reticulocyte Count; Spherocytosis, Hereditary; Thalassemia
PubMed: 31823208
DOI: 10.1007/s12098-019-03119-8 -
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 -
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 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 -
Romanian Journal of Morphology and... 2022Next to A and B antigens, agglutinogen D exhibits the highest immunogenicity. Following the transfusion of D-positive red blood cells (RBCs), almost 80% of D-negative... (Review)
Review
Next to A and B antigens, agglutinogen D exhibits the highest immunogenicity. Following the transfusion of D-positive red blood cells (RBCs), almost 80% of D-negative recipients develop anti-D antibodies (Abs). Subsequently, anti-D immunization further promotes the synthesis of Abs towards other blood group antigens in or outside the Rh system. The D antigen is also involved in 95% of cases of hemolytic disease of the newborn. Transfusions, hemotherapy, grafts, and obstetric history (abortions, ectopic pregnancy, births) are all risk factors for Rh isoimmunization. In the case of ABO compatibility between mother and fetus, Rh-positive fetal RBCs that have reached the maternal bloodstream are not destroyed by group agglutinins, and Rh antigenic sites are not hidden by the maternal immune system. But a Rh-negative mother with a homozygous Rh-positive husband will certainly have a Rh-positive fetus. As it has an irreversible evolution, the Rh isoimmunization once installed cannot be influenced in the sense of decreasing the Ab titer, therefore, injectable globulin has no effect. A particular case was that of a newborn with Rh system incompatibility associated with hereditary spherocytosis The clinical balance at birth reflects the severe jaundice of the female newborn of 3140 g, gestational age 38∕39 weeks, extracted by lower-segment transverse Caesarean section, with a double loop nuchal cord, Apgar score 8. Because the jaundice was severe and atypical (face and upper chest), we considered the possibility of coexistence of hemolytic disease of the newborn by Rh blood group incompatibility associated with hereditary spherocytosis, as it turned out to be true and mentioned. Changes in genes encoding proteins in the structure of the RBC membrane have amplified hemolysis induced by maternal-fetal isoimmunization in the Rh system. Massive hemolysis accentuated by congenital spherocytosis, confirmed later, imposed blood transfusion and dynamic monitoring.
Topics: Blood Group Incompatibility; Cesarean Section; Female; Hemolysis; Humans; Infant; Infant, Newborn; Jaundice; Pregnancy; Pregnancy Complications; Rh Isoimmunization
PubMed: 36074689
DOI: 10.47162/RJME.63.1.26 -
Blood Nov 2022
Topics: Mice; Animals; Blood Platelets; Physical Therapy Modalities; Spherocytosis, Hereditary; Hemostasis
PubMed: 36422862
DOI: 10.1182/blood.2022018189 -
Current Neurology and Neuroscience... Sep 2021Anemia has been called the fifth cardiovascular risk factor. It is one of the most prevalent pathologies worldwide. In this article, we aimed to perform a narrative... (Review)
Review
PURPOSE OF THE REVIEW
Anemia has been called the fifth cardiovascular risk factor. It is one of the most prevalent pathologies worldwide. In this article, we aimed to perform a narrative review of the main cerebrovascular complications of anemia and its influence on stroke prognosis.
RECENT FINDINGS
Both hypoproliferative anemia (thalassemia, iron deficiency anemia, etc.) and hyperproliferative anemia (sickle cell disease, paroxysmal nocturnal hemoglobinuria, hereditary spherocytosis, etc.) are associated to cerebrovascular disease ranging from transient ischemic attack to ischemic stroke and hemorrhagic stroke with both intraparenchymal hemorrhage and subarachnoid hemorrhage or cerebral venous thrombosis. Anemia is associated to a worse prognosis in patients with cerebrovascular disease In some cases, like sickle cell disease, pathophysiological mechanisms and therapeutic guidelines are well established, while in others, due to their rarity, there are still lack of robust data. More studies are needed to clarify how the prognosis of stroke patients with anemia could be improved.
Topics: Anemia, Sickle Cell; Cerebrovascular Disorders; Hemoglobinuria, Paroxysmal; Humans; Intracranial Thrombosis; Stroke
PubMed: 34480226
DOI: 10.1007/s11910-021-01141-y -
International Journal of Laboratory... May 2017Significant advances have been made in our understanding of the structural basis for altered cell function in various inherited red cell membrane disorders with reduced... (Review)
Review
Significant advances have been made in our understanding of the structural basis for altered cell function in various inherited red cell membrane disorders with reduced red cell survival and resulting hemolytic anemia. The current review summarizes these advances as they relate to defining the molecular and structural basis for disorders involving altered membrane structural organization (hereditary spherocytosis [HS] and hereditary elliptocytosis [HE]) and altered membrane transport function (hereditary overhydrated stomatocytosis and hereditary xerocytosis). Mutations in genes encoding membrane proteins that account for these distinct red cell phenotypes have been identified. These molecular insights have led to improved understanding of the structural basis for altered membrane function in these disorders. Weakening of vertical linkage between the lipid bilayer and spectrin-based membrane skeleton leads to membrane loss in HS. In contrast, weakening of lateral linkages among different skeletal proteins leads to membrane fragmentation and decreased surface area in HE. The degrees of membrane loss and resultant increases in cell sphericity determine the severity of anemia in these two disorders. Splenectomy leads to amelioration of anemia by increasing the circulatory red cell life span of spherocytic red cells that are normally sequestered by the spleen. Disordered membrane cation permeability and resultant increase or decrease in red cell volume account for altered cellular deformability of hereditary overhydrated stomatocytosis and hereditary xerocytosis, respectively. Importantly, splenectomy is not beneficial in these two membrane transport disorders and in fact contraindicated due to severe postsplenectomy thrombotic complications.
Topics: Acid-Base Imbalance; Anemia, Hemolytic, Congenital; Elliptocytosis, Hereditary; Erythrocyte Membrane; Erythrocytes, Abnormal; Humans; Hydrops Fetalis; Metabolism, Inborn Errors; Mutation; Spectrin; Spherocytosis, Hereditary
PubMed: 28447420
DOI: 10.1111/ijlh.12657