Epidemiological Study of Hereditary Hemolytic Anemia in the Korean Pediatric Population during 1997-2016: a Nationwide Retrospective Cohort Study.

BACKGROUND: Hereditary hemolytic anemia (HHA) is a rare disease characterized by premature red blood cell (RBC) destruction due to intrinsic RBC defects. The RBC Disorder Working Party of the Korean Society of Hematology established and updated the standard operating procedure for making an accurate diagnosis of HHA since 2007. The aim of this study was to investigate a nationwide epidemiology of Korean HHA. METHODS: We collected the data of a newly diagnosed pediatric HHA cohort (2007-2016) and compared this cohort's characteristics with those of a previously surveyed pediatric HHA cohort (1997-2006) in Korea. Each participant's information was retrospectively collected by a questionnaire survey. RESULTS: A total of 369 children with HHA from 38 hospitals distributed in 16 of 17 districts of Korea were investigated. RBC membranopathies, hemoglobinopathies, RBC enzymopathies, and unknown etiologies accounted for 263 (71.3%), 59 (16.0%), 23 (6.2%), and 24 (6.5%) of the cases, respectively. Compared to the cohort from the previous decade, the proportions of hemoglobinopathies and RBC enzymopathies significantly increased (P < 0.001 and P = 0.008, respectively). Twenty-three of the 59 hemoglobinopathy patients had immigrant mothers, mostly from South-East Asia. CONCLUSION: In Korea, thalassemia traits have increased over the past 10 years, reflecting both increased awareness of this disease and increased international marriages. The enhanced recognition of RBC enzymopathies is due to advances in diagnostic technique; however, 6.5% of HHA patients still do not have a clear diagnosis. It is necessary to improve accessibility of diagnosing HHA.

Esplenectomía parcial en niños con anemias hemolíticas congénitas en el Hospital Pediátrico Docente de Matanzas Eliseo Noel Caamaño / Partial splenectomy in children with congenital hemolytic anemia in the Pediatric Hospital Eliseo Noel Caamaño of Matanzas

Introducción: las anemias hemolíticas se caracterizan por una destrucción precoz de los hematíes, con un acortamiento de su vida media. Estos pacientes pueden requerir para el control de la enfermedad o por el desarrollo de complicaciones esplénicas, la necesidad de ser sometidos a una esplenectomía. Por la morbilidad y posibles complicaciones letales como la sepsis post-esplenectomía de la esplenectomía total en niños, se ha empleado la esplenectomía parcial como opción de tratamiento quirúrgico. Objetivo: evaluar los resultados de la esplenectomía parcial en los pacientes con anemias hemolíticas congénitas. Materiales y Métodos: se realizó un estudio prospectivo, descriptivo longitudinal, del universo de los 15 pacientes con anemias hemolíticas congénitas a los que se les realizó esplenectomía parcial. Resultados: se encontró que la drepanocitosis y la esferocitosis hereditaria fueron los diagnósticos más frecuentes dentro de los casos operados. Las principales indicaciones de la esplenectomía parcial fueron la crisis de secuestro esplénico y la necesidad de transfusiones de sangre respectivamente. Las variables hematológicas analizadas en el período postoperatorio mostraron una respuesta favorable al tratamiento quirúrgico. Conclusiones: la esplenectomía parcial llevó a un mejoramiento clínico y hematológico en los pacientes con anemias hemolíticas congénitas, tributarios de tratamiento quirúrgico, sin complicaciones significativas en un período de seguimiento de 5 años (AU).

Introduction: congenital hemolytic anemia are characterized by an early destruction of red blood cells, with a shortening of their average life. For the control of the disease or due to the development of splenic complications, these patients may require to undergo splenectomy. Due to the morbidity and possible lethal complications such as post-splenectomy sepsis of total splenectomy in children, partial splenectomy has been used as a surgical treatment option. Objective: to evaluate the results of partial splenectomy in patients with congenital hemolytic anemia. Materials and Methods: a longitudinal prospective, descriptive study was performed in 15 patients with congenital hemolytic anemia who underwent partial splenectomy. Results: sickle cell disease and hereditary spherocytosis were the most frequent diagnoses in the group of operated cases. The main indications of partial splenectomy were splenic sequester crises and the necessity of blood transfusions respectively. The hematologic variables analyzed in the post-surgery period showed a favorable answer to surgical treatment. Conclusions: partial splenectomy led to a hematologic and clinical improvement in patients with congenital hemolytic anemia, tributary of surgical treatment, without significant complications in a 5-year follow-up period (AU).

Esplenectomía parcial en niños con anemias hemolíticas congénitas en el Hospital Pediátrico Docente de Matanzas Eliseo Noel Caamaño / Partial splenectomy in children with congenital hemolytic anemia in the Pediatric Hospital Eliseo Noel Caamaño of Matanzas

Introducción: las anemias hemolíticas se caracterizan por una destrucción precoz de los hematíes, con un acortamiento de su vida media. Estos pacientes pueden requerir para el control de la enfermedad o por el desarrollo de complicaciones esplénicas, la necesidad de ser sometidos a una esplenectomía. Por la morbilidad y posibles complicaciones letales como la sepsis post-esplenectomía de la esplenectomía total en niños, se ha empleado la esplenectomía parcial como opción de tratamiento quirúrgico. Objetivo: evaluar los resultados de la esplenectomía parcial en los pacientes con anemias hemolíticas congénitas. Materiales y Métodos: se realizó un estudio prospectivo, descriptivo longitudinal, del universo de los 15 pacientes con anemias hemolíticas congénitas a los que se les realizó esplenectomía parcial. Resultados: se encontró que la drepanocitosis y la esferocitosis hereditaria fueron los diagnósticos más frecuentes dentro de los casos operados. Las principales indicaciones de la esplenectomía parcial fueron la crisis de secuestro esplénico y la necesidad de transfusiones de sangre respectivamente. Las variables hematológicas analizadas en el período postoperatorio mostraron una respuesta favorable al tratamiento quirúrgico. Conclusiones: la esplenectomía parcial llevó a un mejoramiento clínico y hematológico en los pacientes con anemias hemolíticas congénitas, tributarios de tratamiento quirúrgico, sin complicaciones significativas en un período de seguimiento de 5 años (AU).

Introduction: congenital hemolytic anemia are characterized by an early destruction of red blood cells, with a shortening of their average life. For the control of the disease or due to the development of splenic complications, these patients may require to undergo splenectomy. Due to the morbidity and possible lethal complications such as post-splenectomy sepsis of total splenectomy in children, partial splenectomy has been used as a surgical treatment option. Objective: to evaluate the results of partial splenectomy in patients with congenital hemolytic anemia. Materials and Methods: a longitudinal prospective, descriptive study was performed in 15 patients with congenital hemolytic anemia who underwent partial splenectomy. Results: sickle cell disease and hereditary spherocytosis were the most frequent diagnoses in the group of operated cases. The main indications of partial splenectomy were splenic sequester crises and the necessity of blood transfusions respectively. The hematologic variables analyzed in the post-surgery period showed a favorable answer to surgical treatment. Conclusions: partial splenectomy led to a hematologic and clinical improvement in patients with congenital hemolytic anemia, tributary of surgical treatment, without significant complications in a 5-year follow-up period (AU).

Coinheritance of Hb Bristol-Alesha [ß67(E11)Val→Met; HBB: c.202G>A] and the α212 Patchwork Allele in a Brazilian Child with Severe Congenital Hemolytic Anemia.

Hb Bristol-Alesha [HBB: c.202G>A; ß 67 Val>Met] is a rare structural variant of hemoglobin (Hb) resulting from a GTG>ATG substitution at codon 67 of the ß-globin gene that leads to the replacement of valine by methionine in the corresponding position of the ß-globin chain. The methionine residue is subsequently modified to aspartic acid [ß67(E11)Val-Met→Asp], possibly by autoxidation mechanisms. This substitution prevents normal non-polar binding of Val67 to the heme group, resulting in molecular instability and severe hemolysis. We identified Hb Bristol-Alesha (in the heterozygous state), as the cause of severe congenital hemolytic anemia in an 11-month-old girl of mixed (native Indian and European) ethnic origin from the Midwestern region of Brazil, whose parents were clinically and hematologically normal. The mutation on the ß-globin gene was found to have been coinherited with the α212 patchwork allele.

Transient erythroblastopenia of childhood is an underdiagnosed and self-limiting disease.

AIM: Transient erythroblastopenia of childhood (TEC) is an uncommon, benign normocytic anaemia of unknown cause, characterised by reduced or absent mature erythroid precursors in otherwise normocellular bone marrow and a complete spontaneous recovery. We present epidemiological data on paediatric TEC cases in a single centre over 30 years and compare them with published data. METHODS: In this retrospective study, epidemiological data on children diagnosed with TEC between 1978 and 2008 were collected and compared with published data. RESULTS: A total of 36 children (median age 19 months, 56% male children) were diagnosed. At presentation, median haemoglobin was 44 g/L with absolute reticulocyte count 0 × 10(9) /L; seventeen (47%) patients were neutropenic and 23 (64%) had platelet counts of more than 400 × 10(9) /L. The majority (78%) presented from 1983 to 1997, and 78% of articles reviewing 10 or more TEC patients were published between 1983 and 1992. CONCLUSION: Transient erythroblastopenia of childhood is now diagnosed less frequently in our institution than in the last two decades. Although the aetiology remains largely unknown, it is possible that changes in causative environmental factors contribute to making TEC a rare disease. Clinicians need to be aware of TEC in order to prevent unnecessary diagnostic and therapeutic measurements.

Coexistence of Gilbert syndrome with hereditary haemolytic anaemias.

BACKGROUND: Gilbert syndrome is an inherited disease characterised by mild unconjugated hyperbilirubinaemia caused by mutations in UGT1A1 gene which lead to decreased activity of UDP-glucuronosyltransferase 1A1. The most frequent genetic defect is a homozygous TA dinucleotide insertion in the regulatory TATA box in the UGT1A1 gene promoter. METHODS AND RESULTS: 182 Polish healthy individuals and 256 patients with different types of hereditary haemolytic anaemias were examined for the A(TA)(n)TAA motif. PCR was performed using sense primer labelled by 6-Fam and capillary electrophoresis was carried out in an ABI 3730 DNA analyser. The frequency of the (TA)(7)/(TA)(7) genotype in the control group was estimated at 18.13%, (TA)(6)/(TA)(7) at 45.05% and (TA)(6)/(TA)(6) at 36.26%. There was a statistically significant difference in the (TA)(6)/(TA)(6) genotype distribution between healthy individuals and patients with glucose-6-phosphate dehydrogenase deficiency (p=0.041). Additionally, uncommon genotypes, (TA)(5)/(TA)(6), (TA)(5)/(TA)(7) and (TA)(7)/(TA)(8) of the promoter polymorphism, were discovered. CONCLUSION: Genotyping of the UGT1A1 gene showed distinct distribution of the common A(TA)(n)TAA polymorphism relative to other European populations. Because of a greater risk of hyperbilirubinaemia due to hereditary haemolytic anaemia, the diagnosis of Gilbert syndrome in this group of patients is very important.

Experiencia en el manejo de las esferocitosis hereditarias en un solo centro a largo plazo / Long term experience in the management of hereditary spherocytosis in a single center

No disponible

Incidence of congenital hemolytic anemias in young cholelithiasis patients.

AIM: To clarify the incidence of congenital hemolytic anemias (CHA) in young cholelithiasis patients and to determine a possible screening test based on the results. METHODS: Young cholelithiasis patients (< 35 years) were invited to our outpatient clinic. Participants were asked for comorbidities and family history. The number of gallstones were recorded. Blood samples were obtained to perform a complete blood count, standard Wright-Giemsa staining, reticulocyte count, hemoglobin (Hb) electrophoresis, serum lactate dehydrogenase and bilirubin levels, and lipid profile. RESULTS: Of 3226 cholecystectomy patients, 199 were under 35 years, and 190 with no diagnosis of CHA were invited to take part in the study. Fifty three patients consented to the study. The median age was 29 years (range, 17-35 years), 5 were male and 48 were female. Twelve patients (22.6%) were diagnosed as thalassemia trait and/or iron-deficiency anemia. Hb levels were significantly lower (P = 0.046), and mean corpuscular volume (MCV) and hematocrit levels were slightly lower (P = 0.072 and 0.082, respectively) than normal. There was also a significantly lower number of gallstones with the diagnosis (P = 0.007). CONCLUSION: In endemic regions, for young cholelithiasis patients (age under 35) with 2-5 gallstones, the clinician/surgeon should pay attention to MCV and Hb levels as indicative of CHA.

Inherited hemoglobin disorders in Andhra Pradesh, India: a population study.

BACKGROUND: The hemoglobinopathies are a very heterogeneous group of congenital hemolytic anemias. They include thalassemias, hemoglobin variants and hereditary persistence of fetal hemoglobin. Beta-thalassemia is the most common monogenic disorder in India. Molecular characterization of this disease has revealed an extremely heterogeneous picture. METHODS: 1592 blood samples from suspected cases were studied using high performance liquid chromatography, amplification refractory mutation system polymerase chain reaction and reverse dot blot techniques. RESULTS: Out of 1592 cases, we found 119 cases of beta-thalassemia major, and 347 cases of beta-thalassemia trait. In addition to this, cases with structural variants like sickle cell anemia, sickle cell trait, D-thalassemia (Hb DD), E-thalassemia (Hb EE), double heterozygotes and the hereditary persistence of fetal hemoglobin were also found. Molecular analysis revealed the presence of different beta-thalassemia mutations in the population under study. CONCLUSIONS: Molecular analysis revealed that IVS1-5(G-C) and 619 bp deletion are the most common mutations in the population under study. The knowledge about the frequency of predominant mutations in the present population helps in offering prenatal diagnosis to the families having fetus at risk.

Differential diagnosis and management of anemia in the newborn.

Neonatal anemia is a condition with a diverse etiologic spectrum.Therefore, in order to form a focused differential diagnosis, it is important for the caregiver to have some knowledge of the more common causes of low hemoglobin and hematocrit concentrations in the neonate. Proper history taking, physical examination, and interpretation of diagnostic tests can narrow this focus and aid in establishing an accurate diagnosis and in directing the appropriate therapeutic interventions.

Frequency of glucose 6 phosphate dehydrogenase deficiency and related hemolytic anemia in Riyadh, Saudi Arabia.

BACKGROUND: Glucose 6 Phosphate dehydrogenase deficiency is present in over 400 million people world wide. It is more common iin tropical and subtropical countries and is one of the important causes of hemolytic anemia and neonatal jaundice. We studied the frequency of glucose-6-phosphate dehydrogenase deficiency and associated complications in Central Region (Riyadh) of Saudi Arabia. METHODS: A total of 1740 subjects referred by Ministry of Interior and different hospitals in Riyadh were investigated for glucose-6-phosphate dehydrogenase deficiency. Glucose 6 phosphate dehydrogenase activity was determined by a screening test described by Beutler. RESULTS: Out of these, 106 (6.09%) subjects were deficient. The subjects were divided into marriage and hospital groups. In marriage group deficiency was 4.1% while in hospital group it was 13.3%. In 54 glucose-6-phosphate dehydrogenase deficient patients red blood cell count and haemoglobin levels were determined to see the degree of anaemia. Sixty one percent (61%) had anaemia. In hospital patients 8% patients had severe anaemia while in marriage group no patients had severe anaemia. However mild anaemia was seen in 25% subjects in marriage group. CONCLUSIONS: In conclusion the study indicates that glucose-6-phosphate dehydrogenase deficiency is common in the central region of Saudi Arabia and a lot of patients present with haemolytic episodes. The haemolytic crisis however is not related to the intake of fava beans. The type of variant causing anaemia and suggestions for prevention in marriage group are outlined.

Hereditary red blood cell disorders in middle eastern patients.

Hereditary disorders of erythrocytes are common in many areas of the world, including the Middle East. In some regions of the Middle East more than 10% of the population are carriers of a gene for one of these conditions. When patients from the Middle East seek medical care in the West, an unrecognized but clinically important erythrocyte disorder can result in serious complications during routine medical care, such as a drug-induced hemolytic crisis. This article reviews the most important and most common inherited red blood cell disorders in Middle Eastern patients, including glucose-6-phosphate dehydrogenase deficiency, the thalassemias, and sickle cell disorders. We discuss when to suspect such conditions, how to determine their presence, and how to avoid potential complications related to them. Although a detailed discussion of treatment of erythrocyte disorders is beyond the scope of this article, some general management principles are described.

Hereditary Red Cell Membrane Disorders in Japan: Their Genotypic and Phenotypic Features in 1014 Cases Studied.

This study describes the characteristic features of the incidence of hereditary red cell membrane disorders in the Japanese population based on studies of 1014 cases of these disorders from 605 kindred. Among them, there were 581 cases of hereditary spherocytosis (HS) from 303 kindred, 137 cases of hereditary elliptocytosis (HE) from 68 kindred, 104 cases of hereditary stomatocytosis (HSt) from 64 kindred, and 34 cases of protein 4.2 (P4.2) anomalies from 20 kindred, and 41 cases of membrane lipid anomalies from 27 kindred. In HS patients, eleven mutations of the band 3 (B3) gene, 15 mutations of the ankyrin gene, and three mutations of the protein 4.2 (P4.2) gene, which are pathognomonic for this disorder, were identified. Most of these mutations had not been reported and, with few exceptions, were specific to the Japanese population. P4.2 abnormalities also appear to be unique to the Japanese population. The biochemical and biophysical functions of P4.2 are associated with stabilization of the cytoskeletal network by anchoring it to integral proteins (especially B3). Biochemical and genetic analyses of the HE patients revealed one family with an α-spectrin (Sp) anomaly (HE [α(1/74)]) and three kindred with ß-spectrin abnormalities (ß-Sp Yamagata, ß-Sp Tokyo, and ß-Sp Nagoya) due to abnormal splicings of the ß-Sp gene. On the basis of these observations, the relationship between the genotypes and phenotypes is reviewed. In addition, the morphogenesis of red cell membranes with regard to the sequential expression of these membrane proteins was also discussed. Finally, from the standpoint of gene expression, a possible role of gene methylation as an epigenetic control was proposed.

Two British families with variants of the 'cryohydrocytosis' form of hereditary stomatocytosis.

We describe two British families with similar, dominantly-inherited, temperature-related variants of hereditary stomatocytosis, consistent with the original description of 'cryohydrocytosis'. The cells show a 5-6-fold increase in passive permeability at 37 degrees C with abnormal intracellular Na and K levels at 15-20 and 60-65 mmol/(l cells) respectively. Marked temperature effects were evident: lysis of red cells on storage in the cold was blatant and when whole heparinized blood was stored at room temperature, K accumulated in the plasma, producing 'pseudohyperkalaemia'. Studies of the temperature dependence of passive permeability showed that the minimum in the passive permeability, which is seen in normal cells at 8-10 degrees C, was shifted up to 23 degrees C in these abnormal cells, such that the permeability at 0 degrees C exceeded that at 37 degrees C. The abnormal temperature dependence in these genetically abnormal red cells strongly resembles that seen in normal cells when suspended in media in which either Na or Cl has been replaced by an organic cation or anion: it could be said these cells had a genetic mutation that somehow rendered the cell resistant to the stabilizing action of NaCl at low temperatures.