Morbilidad y mortalidad de 599 pacientes con drepanocitosis en el Instituto de Hematología e Inmunología / Morbidity and mortality of 599 sickle cell disease patients in the Institute of Hematology and Immunology

Introducción: La drepanocitosis es la anemia hemolítica congénita más común del mundo. Entre el 5 y 15 por ciento de la población mundial es portadora de la hemoglobina S y en Cuba, la frecuencia es de 3,08 por ciento, lo que representa un problema de salud pública. Objetivo: Caracterizar el cuadro clínico, el perfil hematológico y la probabilidad de supervivencia de los pacientes con drepanocitosis en el Instituto de Hematología e Inmunología. Método: Se realizó estudio descriptivo, longitudinal y retrospectivo, que incluyó todos los enfermos seguidos, al menos dos años, en la institución, entre enero de 1973 y diciembre del 2009. Resultados: Se incluyeron 599 pacientes (285 masculinos), 439 SS/Sβ0tal y 160 SC/Sβ+tal. El seguimiento medio fue de 17,6±9,5 años. Predominaron los pacientes entre 20 y 59 años. Los eventos clínicos más frecuentes fueron las crisis vasoclusivas dolorosas, las infecciones, el síndrome torácico agudo y las complicaciones hepáticas. Los valores de reticulocitos, plaquetas, leucocitos y hemoglobina fetal fueron significativamente mayores en los pacientes SS/Sβ0tal; no así la hemoglobina total que fue mayor en los SC/Sβ+tal. La probabilidad de supervivencia global de los pacientes a los 45 años fue de 69 por ciento. Los accidentes vasculares encefálicos (17,5 por ciento), las complicaciones hepáticas (17,5 por ciento) y las cardíacas (14,28 por ciento) fueron las principales causas de muerte. Conclusiones: La distribución demográfica y por hemoglobinopatías, el cuadro clínico, y el perfil hematológico fueron similares a los encontrados en pacientes de otras regiones geográficas, excepto la frecuencia de complicaciones hepáticas que fue mayor. La probabilidad de supervivencia fue similar con los mejores centros de atención en el mundo(AU)

Introduction: Sickle cell disease is the most common congenital hemolytic anemia in the world. Between 5 to 15 percent of the world population is a carrier of hemoglobin S and in Cuba, the frequency is 3.08 percent, which represents a public health problem. Objective: To characterize the clinical picture, the hematological profile, and the probability of survival of patients with sickle cell disease at the Institute of Hematology and Immunology. Method: A descriptive, longitudinal and retrospective study was carried out, which included all patients followed up for at least two years at the institution between January 1973 and December 2009. Results: 599 patients (285 male), 439 SS/Sβ0tal and 160 SC/Sβ+tal, were included. The mean follow-up was 17.6±9.5 years. Patients between 20 and 59 years old predominated. The most frequent clinical events were painful vasocclusive crises, infections, acute chest syndrome, and liver complications. The reticulocytes, platelets, leukocytes and fetal hemoglobin values ​​were significantly higher in the SS/Sβ0tal patients, but not the total hemoglobin, which was higher in the SC/Sβ+tal. The overall survival probability of patients at 45 years was 70 percent. Stroke (17.5 percent), liver complications (17.5 percent), and cardiac complications (14.28 percent) were the main causes of death. Conclusions: The demographic distribution and by hemoglobinopathies, the clinical events, and the hematological profile were similar to those found in patients from other geographic regions, except the frequency of liver complications, which was higher. The probability of survival was comparable with the best care centers in the world(AU)

Diagnóstico diferencial de las anemias hemolíticas / Differential diagnosis of hemolytic anemias

Introducción: El término hemólisis hace referencia a la destrucción de los eritrocitos y ocurre en un amplio rango de condiciones clínicas fisiológicas y patológicas. Es empleado para definir situaciones en la que la vida media de los eritrocitos está disminuida por causas mecánicas, tóxicas, autoinmunes o infecciosas. Objetivo: Describir los principales marcadores de hemólisis que se encuentran variablemente alterados en las diferentes formas de anemias hemolíticas. Métodos: Se realizó una revisión de la literatura, en inglés y español, a través del sitio web PubMed y el motor de búsqueda Google Académico de artículos publicados en los últimos 10 años. Se hizo un análisis y resumen de la información. Análisis y síntesis de la información: La hemoglobina es el marcador más directo de la gravedad clínica en las enfermedades hemolíticas. Sus valores pueden estar muy próximos a los valores de referencia en las formas ligeras (Hb > 100 g/L) o significativamente reducidos en las moderadas (Hb entre 80-100 g/L), graves (Hb entre 60-80 g/L) y muy graves (Hb < 60 g/L). Sin embargo, existen otros marcadores esenciales para diferenciar las formas de presentación aguda y crónica, la hemólisis extravascular de la intravascular y la presencia de signos extrahematológicos tales como: los reticulocitos y esquistocitos, la deshidrogenasa láctica, la haptoglobina, la bilirrubina, la ferritina y la hemosiderinuria. Conclusiones: Los parámetros hemolíticos pueden estar diferencialmente alterados en varias condiciones lo cual ayuda en la realización del diagnóstico diferencial de las anemias hemolíticas(AU)

Introduction: The term hemolysis refers to the destruction of erythrocytes, a process occurring in a wide range of physiological and pathological clinical conditions. The term is used to define situations in which mean erythrocyte lifespan is reduced due to mechanical, toxic, autoimmune or infectious causes. Objective: Describe the main markers of hemolysis found to be variably altered in the different forms of hemolytic anemias. Methods: A review was conducted of the literature about the topic published in English and Spanish in the website PubMed and the search engine Google Scholar in the last 10 years. Data were analyzed and summarized. Data analysis and synthesis: Hemoglobin is the most direct marker of clinical severity in hemolytic diseases. Its values may be very close to reference levels in mild disease (Hb > 100 g/l), whereas they will be significantly reduced in moderate (Hb 80-100 g/l), severe (Hb 60-80 g/l) and very severe disease (Hb < 60 g/l). However, other markers are also essential to distinguish acute from chronic presentation, extravascular from intravascular hemolysis, and the presence of extrahematological signs such as reticulocytes and schistocytes, lactate dehydrogenase, haptoglobin, bilirubin, ferritin and hemosiderinuria. Conclusions: Differentially altered hemolytic parameters may be found in several conditions, which makes them useful for the differential diagnosis of hemolytic anemias(AU)

Xerocitosis hereditaria. Presentación de dos casos clínicos pediátricos / Hereditary xerocytosis. Presentation of two pediatric cases

La xerocitosis hereditaria es un desorden poco frecuente causado por defectos en la permeabilidad eritrocitaria, que se caracteriza por anemia hemolítica de gravedad variable y sobrecarga de hierro. El diagnóstico suele ser tardío y confundirse con otras anemias hemolíticas, lo que puede llevar a indicaciones de procedimientos, como la esplenectomía, contraindicados en estos pacientes. Se reportan las características clínicas, hematológicas y moleculares de dos pacientes pediátricos no relacionados con diagnóstico de xerocitosis hereditaria. Ambos presentaban eritrocitos deshidratados con alta concentración de hemoglobina corpuscular media, frotis no patognomónico, marcadores de hemólisis y una curva de fragilidad osmótica resistente. El diagnóstico se confirmó por la secuenciación del gen PIEZO.Se resalta la importancia de reconocer la causa de la anemia hemolítica para dar un enfoque terapéutico preciso y dar adecuado consejo genético

Hereditary xerocytosis is a rare disorder caused by defects of red blood cell permeability that are characterized by hemolytic anemia of variable degree and iron overload. Diagnosis is usually late and confused with other hemolytic anemias, which can lead to procedural indications, such as splenectomy, contraindicated in these patients. We report the clinical, haematological, and molecular characteristics of two patients from two unrelated families affected by hereditary xerocytosis. Both patients had dehydrated erythrocytes with a high concentration of mean corpuscular hemoglobin, non-pathognomonic smears, markers of hemolysis and a resistant osmotic fragility curve. The diagnosis was confirmed by the sequencing of the PIEZO gene. We emphasize the importance of recognizing the cause of hemolytic anemia to give an accurate therapeutic approach and give adequate genetic counseling.

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).

Prevalencia de anemia drepanocitica en dos comunidades de Omoa, Cortés durante el año 2017 / Prevalence of sickle-cell anemia in two communities Omoa Cortés, during the year 2017

La anemia drepanocítica (AD) es la anemia hemolítica congénita más común en el mundo. La frecuencia del estado de portador de hemoglobina S (AS) abarca un rango que oscila entre 5 y 15% de la población mundial. Objetivo: Identificar la prevalencia de anemia drepanocítica en las comunidades de Masca y Pueblo Nuevo, Omoa Cortés, duran- te el año 2017. Pacientes y Métodos: Estu- dio con enfoque cuantitativo, diseño no expe- rimental, longitudinal y alcance descriptivo. El Universo, estuvo constituido por (2545 perso- nas): 1511 de Masca y 1,034 de Pueblo Nuevo. Se calculó muestra probabilística aleatoria, de 369. La primera fase del estudio incluyó la realización de hemograma y meta- bisulfito de sodio al 2%, la segunda fase con- sistió en la toma de electroforesis de Hemog- lobina a los pacientes con metabisulfito posi- tivo. Las pruebas fueron procesadas en un laboratorio clínico certificado. Los datos fueron analizados con SPSS. Resultados De los 369 participantes: las edades estuvieron comprendidas entre 1-83 años, 250 (67.8%) eran femeninos y 119 (32.2%) masculinos, los valores de hemoglobina estuvieron com- prendidos entre 7.85- 17.4 g/dl y 20 resulta- ron con metabisulfito positivo haciendo una prevalencia de 5.4%. En la segunda fase del estudio, se encontró que 13 (65%) de los pacientes eran del sexo femenino, 12 (60%) eran asintomáticos. Se realizó electroforesis de hemoglobina, encontrando, 18 (94.7%) Artículos Originales con HbAS y 1 (5.3%) paciente con 100% de HbSS. Conclusión: La prevalencia obtenida es similar a otros estudios encontrados, pero cabe recalcar que la raza predominante para heterocigotos fue la mestiza y no la afrodes- cendiente.

Treatment and Management of Late Complications in Hereditary Hemolytic Anemia / 임상소아혈액종양

Hereditary hemolytic anemia is a very heterogeneous disorder in which abnormalities of red blood cell structural protein, globin protein, or enzyme defect lead to shortened life span. There has been much progress in revealing its pathophysiology and genetic backgrounds, but the lifelong plans for caring these patients are not well established yet. All patients with hereditary hemolytic anemic have three common problems: transfusion dependency, iron overload and iron chelation therapy. Patients with hereditary spherocytosis (HS) usually manifest severe anemia in neonatal period and infancy, but transfusion requirements may decrease in adulthood. But patients with thalassemia or sickle cell disease usually transfusion-dependent throughout life. Maintaining the optimal hemoglobin (Hb) levels in these patients is crucial because correction of anemia and dilution of abnormal Hb helps prevent certain complications that frequently occur in these patients. Frequent transfusion leads to transfusion-mediated infection and hemochromatosis. Iron chelation therapy should be started early to prevent permanent organ damage. Folate therapy can be helpful in patients with hereditary spherocytosis. Regular evaluations for cholestasis should be started at age 5, and splenectomy with concurrent cholecystectomy can be considered if the patient has cholecystitis. Hydroxyurea can be used to reduce transfusion requirements and prevent complications in patients with β-thalassemia and sickle cell disease. Consensus on long-term management of patients with hereditary hemolytic anemia is lacking, especially for adult patients. But further efforts to build guidelines for long-term follow-up and management of the patients with hereditary hemolytic anemia in the context of Korean society are needed.

Treatment and Management of Late Complications in Hereditary Hemolytic Anemia / 임상소아혈액종양

Hereditary hemolytic anemia is a very heterogeneous disorder in which abnormalities of red blood cell structural protein, globin protein, or enzyme defect lead to shortened life span. There has been much progress in revealing its pathophysiology and genetic backgrounds, but the lifelong plans for caring these patients are not well established yet. All patients with hereditary hemolytic anemic have three common problems: transfusion dependency, iron overload and iron chelation therapy. Patients with hereditary spherocytosis (HS) usually manifest severe anemia in neonatal period and infancy, but transfusion requirements may decrease in adulthood. But patients with thalassemia or sickle cell disease usually transfusion-dependent throughout life. Maintaining the optimal hemoglobin (Hb) levels in these patients is crucial because correction of anemia and dilution of abnormal Hb helps prevent certain complications that frequently occur in these patients. Frequent transfusion leads to transfusion-mediated infection and hemochromatosis. Iron chelation therapy should be started early to prevent permanent organ damage. Folate therapy can be helpful in patients with hereditary spherocytosis. Regular evaluations for cholestasis should be started at age 5, and splenectomy with concurrent cholecystectomy can be considered if the patient has cholecystitis. Hydroxyurea can be used to reduce transfusion requirements and prevent complications in patients with β-thalassemia and sickle cell disease. Consensus on long-term management of patients with hereditary hemolytic anemia is lacking, especially for adult patients. But further efforts to build guidelines for long-term follow-up and management of the patients with hereditary hemolytic anemia in the context of Korean society are needed.

Glucose-6-phosphate Dehydrogenase Deficiency / 임상소아혈액종양

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common enzyme disorder. There are more than 400 million people worldwide with G6PD deficiency, and its distribution is similar to that of malaria. G6PD deficiency is an X-linked recessive disorder. Most patients with G6PD deficiency may be asymptomatic throughout their lives. They may present as neonatal jaundice, or acute and chronic hemolysis. The most important point in the management of G6PD deficiency is to avoid oxidative stress. The prevalence of G6PD deficiency in Korea is about 0.9%. However, a nationwide survey has revealed that the number of patients with enzymopathy is increasing. Immigration of different ethnicities into Korea, and the rise of interracial marriages will likely lead to an increase in the number of patients with G6PD deficiency.

Glucose-6-phosphate Dehydrogenase Deficiency / 임상소아혈액종양

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common enzyme disorder. There are more than 400 million people worldwide with G6PD deficiency, and its distribution is similar to that of malaria. G6PD deficiency is an X-linked recessive disorder. Most patients with G6PD deficiency may be asymptomatic throughout their lives. They may present as neonatal jaundice, or acute and chronic hemolysis. The most important point in the management of G6PD deficiency is to avoid oxidative stress. The prevalence of G6PD deficiency in Korea is about 0.9%. However, a nationwide survey has revealed that the number of patients with enzymopathy is increasing. Immigration of different ethnicities into Korea, and the rise of interracial marriages will likely lead to an increase in the number of patients with G6PD deficiency.

Deficiencia de glucosa-6-fosfatodeshidrogenasa: De lo clínico a lo bioquímico / Glucose-6-phosphate dehydrogenase: From the clinical to the biochemical aspects / Deficiência de glicose-6-fosfato desidrogenase: Aspectos clínicos e bioquímicos

La deficiencia de Glucosa-6-fosfato deshidrogenasa (G6PD) es la enzimopatíamás frecuente, con una prevalencia global del 4,9% y con alrededor de 330 a 400 millones de personas afectadas en el mundo. La G6PD desempeña un papel fundamental en el equilibrio redox intracelular, especialmente en los eritrocitos; en condiciones de estrés oxidativo inducido (por ejemplo,por exposición a agentes externos como fármacos, alimentos o infecciones),los hematíes portadores de la variante enzimática y con deficiencia de la actividad enzimática, sufren daños irreversibles que condicionan su destrucción acelerada. La hemólisis explica el espectro de manifestaciones clínicas de esta enfermedad, que incluyen ictericia neonatal, episodios de hemólisis aguda inducida por agentes externos o anemia hemolítica crónica. El presente trabajo hace una reseña de los aspectos epidemiológicos y clínicos de esta enfermedad y revisa los aspectos fisiopatológicos a nivel bioquímico-molecular, con particular énfasis en la caracterización genética,estructural y funcional de las variantes asociadas a la deficiencia de G6PD.

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most frequent enzymopathy in humans with a global prevalence of 4.9 % and around 330 to 400 million patients affected worldwide. G6PD plays a fundamental role in the intracellular redox equilibrium, especially in red blood cells (RBC). Under oxidative stress (induced by exposure to external agents like drugs, infections or diet) RBC carrying the deficient variant suffer irreversible damage resulting in their accelerated destruction. This hemolysis explains the clinical manifestations of the disease that include neonatal jaundice, inducedacute hemolysis or chronic hemolytic anemia. This work summarizes the epidemiologic and clinical features of G6PD deficiency, and reviews the molecular pathophysiology of this disease with special emphasis on the genetical, structural and functional characterization of variants causing this pathology.

A deficiência da Glicose-6-FosFato desidrogenase (G6PD) é a enzimopatia mais Frequente, com uma prevalência global do 4,9%, e com aproximadamente 330 a 400 milhões de pessoas afetadas no mundo. A G6PD tem um importante papel no equilíbrio celular redox intracelular, especialmente nos eritrócitos; em condições de estresse oxidativo induzido, (por exemplo, pela exposição a agentes externos como Fármacos, alimentos, ou infecções) as hemácias portadoras da variante enzimática e com defciência da atividade enzimática, sofrem danos irreversíveis que condicionam a sua destruição acelerada. A hemólise explica o espectro de manifestações clínicas desta doença, que incluem icterícia neonatal, episódios de hemólise aguda induzida por agentes externos ou anemia hemolítica crônica. Este trabalho faz uma resenha dos aspectos epidemiológicos e clínicos desta doença, e revisa os aspectos fsiopatológicos no nível bioquímico-molecular, com ênfase especial na caracterização genética, estrutural e funcional das variantes associadas à defciência de G6PD.

Sobrecarga de ferro em adolescente com xerocitose: a importância da ressonância nuclear magnética / Iron overload in a teenager with xerocytosis: the importance of nuclear magnetic resonance imaging

Relatar um caso de sobrecarga de ferro secundária à xerocitose, uma doença rara, em uma adolescente, diagnosticada por meio de ressonância magnética em T2*. Relatamos o caso de uma paciente sintomática com xerocitose, nível de ferritina de 350ng/mL e sobrecarga de ferro cardíaca significativa. Ela foi diagnosticada por ressonância magnética em T2* e recebeu terapia de quelação. Análise por ectacitometria confirmou o diagnóstico de xerocitose hereditária. Na sequência, a ressonância magnética em T2* demonstrou resolução completa da sobrecarga de ferro em vários órgãos e novo ecocardiograma revelou resolução completa das alterações cardíacas anteriores. A paciente permanece em terapia de quelação. Xerocitose é uma desordem genética autossômica dominante rara, caracterizada por estomatocitose desidratada. O paciente pode apresentar fadiga intensa e sobrecarga de ferro. Sugerimos o uso regular de ressonância magnética em T2* para o diagnóstico e controle da resposta à quelação de ferro em xerocitose e acreditamos que o exame pode ser útil também em outras anemias hemolíticas que necessitam de transfusões.

To report a case of iron overload secondary to xerocytosis, a rare disease in a teenager, diagnosed, by T2* magnetic resonance imaging. We report the case of a symptomatic patient with xerocytosis, a ferritin level of 350ng/mL and a significant cardiac iron overload. She was diagnosed by T2* magnetic resonance imaging and received chelation therapy Ektacytometric analysis confirmed the diagnosis of hereditary xerocytosis. Subsequent T2* magnetic resonance imaging demonstrated complete resolution of the iron overload in various organs, as a new echocardiography revealed a complete resolution of previous cardiac alterations. The patient remains in chelation therapy. Xerocytosis is a rare autosomal dominant genetic disorder characterized by dehydrated stomatocytosis. The patient may present with intense fatigue and iron overload. We suggest the regular use of T2* magnetic resonance imaging for the diagnosis and control of the response to iron chelation in xerocytosis, and we believe it can be used also in other hemolytic anemia requiring transfusions.

Hb Southampton B106 G8 Leu PRO, CTG CCG in a Uruguayan woman

Hemoglobin Southampton (also known as hemoglobin Casper) is a rare hemoglobin structural variant resulting from a substitution of a leucine residue for proline at codon beta106 [beta106(G8)Leu→Pro, CTG→CCG]. It is very unstable and associated with severe hemolytic anemia. We detected this mutation in a 37-year-old Uruguayan woman with a history of severe chronic hemolytic anemia since her childhood. According to our knowledge this is the first time that this variant has been found in the Uruguayan population.

Hereditary hemolytic anemia in Korea from 2007 to 2011: A study by the Korean Hereditary Hemolytic Anemia Working Party of the Korean Society of Hematology

BACKGROUND: The number of patients diagnosed with hereditary hemolytic anemia (HHA) has increased since the advent of novel diagnostic techniques that accurately identify this disorder. Here, we report data from a survey on the prevalence and characteristics of patients diagnosed with HHA in Korea from 2007 to 2011. METHODS: Information on patients diagnosed with HHA in Korea and their clinical and laboratory results were collected using a survey questionnaire. Globin gene and red blood cell (RBC) enzyme analyses were performed. In addition, we analyzed data collected by pediatricians. RESULTS: In total, 195 cases of HHA were identified. Etiologies identified for HHA were RBC membranopathies, hemoglobinopathies, and RBC enzymopathies, which accounted for 127 (64%), 39 (19.9%), and 26 (13.3%) cases, respectively. Of the 39 patients with hemoglobinopathies, 26 were confirmed by globin gene analysis, including 20 patients with beta-thalassemia minor, 5 patients with alpha-thalassemia minor, and 1 patient with unstable hemoglobin disease. CONCLUSION: The number of patients diagnosed with hemoglobinopathies and RBC enzymopathies has increased considerably since the previous survey on HHA in Korea, dated from 1997 to 2006. This is likely the result of improved diagnostic techniques. Nevertheless, there is still a need for more sensitive diagnostic tests utilizing flow cytometry and for better standardization of test results to improve the accuracy of diagnosis of RBC membranopathies in Korea. Additionally, more accurate assays for the identification of RBC enzymopathies are warranted.

RBC Enzyme Analysis / 임상소아혈액종양

Among ~20 RBC enzyme deficiencies causing hereditary hemolytic anemia (HRA), deficiencies involving three RBC enzymes such as glucose-6-phosphatase, pyruvate kinase and pyrimidine 5'-nucleodiase were known to be relatively common. The methods that have been used for RBC enzyme analysis are based on the kinetic spectrophotometry. This method, however, usually requires multiple step reactions and manual manipulations which are labor-intensive and time-consuming, and carry a greater risk of error due to their complexity. To solve this problem, we had successfully developed the multiplex enzyme analysis for galactose using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). We are now trying to adopt this method to other RBC enzymes associated with HRA. The devised method will allow simple, rapid, sensitive and reproducible quantification of RBC enzymes and should be helpful for the confirmatory diagnosis of HRA caused by RBC enzyme deficiencies.

RBC Enzyme Analysis / 임상소아혈액종양

Among ~20 RBC enzyme deficiencies causing hereditary hemolytic anemia (HRA), deficiencies involving three RBC enzymes such as glucose-6-phosphatase, pyruvate kinase and pyrimidine 5'-nucleodiase were known to be relatively common. The methods that have been used for RBC enzyme analysis are based on the kinetic spectrophotometry. This method, however, usually requires multiple step reactions and manual manipulations which are labor-intensive and time-consuming, and carry a greater risk of error due to their complexity. To solve this problem, we had successfully developed the multiplex enzyme analysis for galactose using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). We are now trying to adopt this method to other RBC enzymes associated with HRA. The devised method will allow simple, rapid, sensitive and reproducible quantification of RBC enzymes and should be helpful for the confirmatory diagnosis of HRA caused by RBC enzyme deficiencies.

A new paradigm in the diagnosis of hereditary hemolytic anemia

No abstract available.

Resistencia osmótica eritrocitaria en el diagnóstico de anemias hereditarias en Tucumán, Argentina / Red cell osmotic resistance in the hereditary anemias diagnosis in Tucumán, Argentina / Resistência osmótica eritrocitária no diagnóstico de anemias hereditárias em Tucumán, Argentina

Las anemias hereditarias más frecuentes en Tucumán (Argentina) son el rasgo beta talasémico (RBT), las hemoglobinopatías estructurales (HBP) y la esferocitosis hereditaria (EH). La resistencia osmótica eritrocitaria inmediata y 24 horas post-incubación constituye el método diagnóstico de la EH, y como tubo único (ROETU) es usada para cribado de RBT. El propósito del trabajo fue determinar el comportamiento de ROETU (4,0 y 5,5 g/L de NaCl) en el diagnóstico de anemias hereditarias. Se estudiaron 125 pacientes: 34 normales (GN), 59 con RBT (GRBT), 21 con HBP (GHBP) y 11 con EH (GEH), que fueron agrupados en niños (≤12 años), mujeres y hombres (>12 años). Se realizaron hemograma (Coulter AcT10 y Sysmex KX-21N), índices de Mentzer y de Shine&Lal, ROETU, hierro, transferrina y saturación de transferrina (Wiener Lab), reticulocitos (azul brillante de cresilo), prueba de falciformación y electroforesis de hemoglobina a pH alcalino y ácido. GRBT presentó anemia microcítica hipocrómica, y GEH y GHBP, anemia normocítica normocrómica. El hierro fue normal. GRBT y GHBP fueron resistentes en ROETU 4,0 g/L, aunque GRBT mostró mayor resistencia (p<0,05). GEH fue menos resistente que GN en ROETU 5,5 g/L (p<0,05). ROETU 4,0 y 5,5 g/L serían recomendables en el diagnóstico presuntivo de RBT y EH, respectivamente.

Beta thalassaemia trait (BTT), structural hemoglobinopathies (SHB) and hereditary spherocytosis (HS) are the most frequent hereditary anaemias in Tucumán (Argentina). Immediately and 24 hours post-incubation red cell osmotic resistance is the diagnosis method of HS, and as a single tube (RORST), it is used for clínicamenBTT screening. The purpose of this study was to determine the RORST (NaCl 4.0 and 5.5 g/L) behaviour in the diagnosis of hereditary anemia. The study encompassed 125 patients : 34 normal patients (NG), 59 with BTT (BTTG), 21 with SHB (SHBG) and 11 with HS (HSG), who were divided into children (≤12 years), women and men (> 12 years). Blood count (Coulter AcT10 and Sysmex KX-21N), Mentzer and Shine&Lal indexes, RORST, iron, transferrin and transferrin saturation (Wiener Lab), reticulocytes (brilliant cresyl blue), sickling and hemoglobin electrophoresis at alkaline and acid pH were performed. BTTG showed hypochromic microcytic anemia, and SHBG and HSG, normochromic normocytic anemia. Iron was normal. BTTG and SHBG were resistant in RORST 4.0 g/L, but BTTG showed more resistance (p<0.05). SHG was less resistant than NG at RORST 5.5 g/L (p<0.05). RORST at values of 4.0 and 5.5 g/L would be recommended for the presumptive diagnosis of BTT and SH, respectively.

As anemias hereditárias mais comuns em Tucumán (Argentina) são o traço beta talassemia minor (BTM), as hemoglobinopatias estruturais (HBP) e esferocitose hereditária (EH). A resistência osmótica dos eritrócitos imediata e 24 horas pós-incubação é o método de diagnóstico da EH, e como um único tubo (ROETU) é usado para a detecção de BTM. O objectivo deste estudo foi determinar o comportamento de ROETU (4,0 e 5,5 g/L de NaCl) para o diagnóstico de anemias hereditárias. Foram estudados 125 pacientes: 34 normais (GN), 59 com BTM (GBTM), 21 com HBP (GHBP) e 11 com EH (GEH), que foram reunidos em crianças (≤12 anos), mulheres e homens (>12 anos). Foi realizado hemograma (Coulter AcT10 e Sysmex KX-21N), índices de Mentzer e Shine&Lal, ROETU, ferro, transferrina e saturação de transferrina (Wiener Lab), reticulócitos (azul de cresil brilhante), teste de falcização e eletroforese de hemoglobina em pH alcalino e ácido. GBTM mostrou anemia microcítica hipocrômica, e GEH e GHBP, anemia normocítica normocrômica. O ferro foi normal. GRBT e GHBP foram resistentes em ROETU 4,0 g/L, mas GBTM mostrou maior resistência (p<0,05). GEH foi menos resistente que GN em ROETU 5,5 g/L (p<0,05). ROETU 4,0 e 5,5 g/L seria recomendado para o diagnóstico presuntivo da BTM e EH, respectivamente.

Red Blood Cell Enzymopathies Causing Hereditary Hemolytic Anemia / 임상소아혈액종양

The RBC enzyme deficiencies causing hereditary hemolytic anemia (HHA) can be divided into three groups: those participating in the glycolytic (E-M) pathway; those involved with the maintenance of a high ratio of reduced to oxidized glutathione; one enzyme in the nucleotide degradation and salvage pathway. Although RBC enzyme deficiencies causing HHA are rare, 3 of the 15 kinds of important and relatively frequently reported enzyme deficiencies such as pyruvate kinase, glucose-6-phosphate-dehydrogenase and pyrimidine-5'-nucleotidase deficiencies are briefly reviewed. The molecular genetics, clinical symptoms, diagnosis and therapeutic approaches of each enzyme deficiencies are summerized. As these enzyme deficiencies are reported throughout the world as well as in Korea with the identification of the mutations, considering a broad spectrum of etiologies for the diagnosis of HHA seems to be warranted.

Red Blood Cell Enzymopathies Causing Hereditary Hemolytic Anemia / 임상소아혈액종양

The RBC enzyme deficiencies causing hereditary hemolytic anemia (HHA) can be divided into three groups: those participating in the glycolytic (E-M) pathway; those involved with the maintenance of a high ratio of reduced to oxidized glutathione; one enzyme in the nucleotide degradation and salvage pathway. Although RBC enzyme deficiencies causing HHA are rare, 3 of the 15 kinds of important and relatively frequently reported enzyme deficiencies such as pyruvate kinase, glucose-6-phosphate-dehydrogenase and pyrimidine-5'-nucleotidase deficiencies are briefly reviewed. The molecular genetics, clinical symptoms, diagnosis and therapeutic approaches of each enzyme deficiencies are summerized. As these enzyme deficiencies are reported throughout the world as well as in Korea with the identification of the mutations, considering a broad spectrum of etiologies for the diagnosis of HHA seems to be warranted.