Flow cytometry-detected changes in megaloblastic anemia secondary to cobalamin deficiency.

Introduction: Megaloblastic anemias secondary to Vitamin B12 deficiency are a group of pathologies produced by defective nuclear DNA synthesis. Objective: To describe the maturation alterations found in hematopoietic precursors of the bone marrow in a series of patients with megaloblastic anemia. Methods: Were included patients attended at the Regional Hospital of Concepción with bone marrow samples sent for the study of cytopenia by flow cytometry whose final diagnosis was megaloblastic anemia. The immunophenotype was performed with CD45, CD34, CD117, HLA-DR, markers of neutrophil (CD13, CD11b, CD10, CD16) and/or erythroblast (CD105, CD71, CD36) maturation. Results: From the flow cytometry laboratory database, 8 patients with megaloblastic anemia were identified, and myelodysplastic syndromes (n=9) and normal or reactive bone marrow (n=10) were used as controls. 44% were men, with a median age of 58 years. Megaloblastic anemia was associated with a higher proportion of size and complexity of erythroid and myeloid progenitors compared to lymphocytes compared to controls. The total percentage of erythroblasts and the proportion of CD34+ myeloid cells associated with erythroid lineage was higher in megaloblastic anemia, associated with a maturation arrest in the CD105+ precursor stage (69% vs 19% and 23%, p<0.001). The heterogeneity of CD36 and CD71 in megaloblastic anemia was similar to myelodysplastic syndromes. Conclusions: Megaloblastic anemia produces a heterogeneous involvement of hematopoiesis, characterized by a greater size and cellular complexity of precursors of the neutrophil and erythroid series and a maturation arrest of the erythroblasts.

Introducción: Anemias megaloblásticas secundarias a la deficiencia de vitamina B12 son patologías producidas por una síntesis defectuosa del ADN nuclear. Objetivo: Describir las alteraciones madurativas encontradas en precursores hematopoyéticos de la médula ósea de una serie de pacientes con anemia megaloblástica. Métodos: Se incluyeron pacientes atendidos en el Hospital Regional de Concepción con muestras de médula ósea enviadas para estudio de citopenias por citometría de flujo cuyo diagnóstico fue anemia megaloblástica. El inmunofenotipo se realizó con CD45, CD34, CD117, HLA-DR, marcadores de maduración de serie de neutrófilo (CD13, CD11b, CD10, CD16) y/o eritroblasto (CD105, CD71, CD36). Resultados: Se identificaron 8 pacientes con anemia megaloblástica y como controles se utilizaron síndromes mielodisplásicos (n=9) y médula ósea normal o reactiva (n=10). El 44% eran hombres, con una mediana de edad de 58 años. La anemia megaloblástica se asoció con una mayor proporción de tamaño y complejidad de progenitores eritroides y mieloides con respecto de los linfocitos en comparación a los controles. El porcentaje total de eritroblastos y la proporción de células mieloides CD34+ comprometidas con el linaje eritroide fue mayor en anemia megaloblástica, asociado a una parada madurativa en la etapa de precursor CD105+ (69% vs 19% y 23%, p <0.001). La heterogeneidad de CD36 y CD71 en anemia megaloblástica fue similar a los síndromes mielodisplásicos. Conclusiones: la anemia megaloblástica produce una afectación heterogénea de la hematopoyesis, caracterizada por un mayor tamaño y complejidad celulares de precursores de la serie neutrófilo y eritroide y una detención madurativa de los eritroblastos.

Anemia y patología digestiva / Anemia and digestive diseases / Anemia e patologia digestiva

Cada vez más los pacientes diagnosticados con anemia son referidos al gastroenterólogo para su evaluación. La necesidad de realizar un adecuado planteo clínico y una correcta interpretación de las pruebas de diagnóstico ha motivado la revisión de este tema. Varios trastornos gastroenterológicos, con frecuencia, conducen a anemia como resultado de pérdidas sanguíneas, inflamación, malabsorción o a consecuencia de las terapias farmacológicas. En algunas patologías como la cirrosis, EII o neoplasias las causas son a menudo multifactoriales. Esta revisión, pretende proporcionar un enfoque útil para la práctica clínica. Para ello se ha revisado la información actualizada acerca de la patogénesis, diagnóstico y tratamiento de la anemia vinculada a patologías digestivas y se han confeccionados cuadros y algoritmos para facilitar su comprensión.

More and more patients diagnosed with anemia are referred to the gastroenterologist for evaluation. The need to carry out an adequate clinical approach and a correct interpretation of diagnostic tests has motivated this review. Several digestive diseases frequently lead to anemia because of blood loss, inflammation, malabsorption, or drug therapies. In some of them such as cirrhosis, IBD or neoplasms, the etiology is multifactorial. This review is intended to provide a useful approach to clinical practice. To this aim, updated information on the pathogenesis, diagnosis, and treatment of anemia related to digestive diseases has been reviewed, and tables and algorithms have been built to favor its understanding.

Cada vez mais pacientes diagnosticados com anemia são encaminhados ao gastroenterologista para avaliação. A necessidade de realizar uma abordagem clínica adequada e uma interpretação correta dos testes de diagnóstico motivou a revisão deste tema. Vários distúrbios gastroenterológicos freqüentemente levam à anemia como resultado de perda de sangue, inflamação, má absorção ou pelas próprias terapias farmacológicas. Em algumas patologias como cirrose, DII ou neoplasias, as causas costumam ser multifatoriais. Esta revisão visa fornecer uma abordagem útil à prática clínica. Para esse fim, foram revisadas informações atualizadas sobre a patogênese, o diagnóstico e o tratamento da anemia associada à patologia digestiva e foram elaboradas tabelas e algoritmos para facilitar seu entendimento.

Compromiso neurológico y hematológico por déficit de vitamina B12 en lactante hijo de madre vegetariana: caso clínico / Hematological and neurological compromise due to vitamin B12 deficit in infant of a vegetarian mother: case report

Introducción: La deficiencia de vitamina B12 es una de las complicaciones del vegetarianismo y sus variantes. Los lactantes de madres vegetarianas tienen mayor riesgo de deficiencia y son más lábiles a sus efectos. Objetivo: Relatar un caso para alertar sobre la importancia de la sospecha de deficiencia de vitamina B12 en hijos de madres con hábito vegetariano. Caso clínico: Se presenta una lactante de 12 meses, hija de una mujer vegetariana de larga data, que se presenta con compromiso neurológico y hematológico por déficit de vitamina B12. Luego de un corto período de administración de cianocobalamina parenteral y apoyo enteral nutricional, evoluciona con una notoria mejoría clínica y de laboratorio, aunque aún presenta retraso del desarrollo residual. Conclusiones: La deficiencia de vitamina B12 no es frecuentemente sospechada por el pediatra en lactantes sanos. Sus manifestaciones clínicas pueden ser tan inespecíficas, como la apatía, el rechazo alimentario y el deterioro progresivo del desarrollo psicomotor. Una anamnesis nutricional breve realizada a la madre (con mayor énfasis en aquellas vegetarianas) para estimar sus reservas en el periodo previo, durante y después del parto pueden ser fundamentales para detectar el riesgo déficit de esta vitamina en el niño pequeño.

Introduction: Vitamin B12 deficiency is extremely common in strict vegetarians and their variants. Infants of vegetarian mothers have a higher risk of deficiency and are more prone to its effects. Objective: To report a case in order to warn people about the importance of suspected vitamin B12 deficiency in children of vegetarian mothers. Case report: A 12-month old infant, daughter of a longtime vegetarian woman, who presented neurological and hematological compromise due to vitamin B12 deficiency, is discussed. After a short period of parenteral administration of cyanocobalamin and enteral nutrition, the patient evolved with clinical and laboratory improvement, although she still had residual development delay. Conclusions: Vitamin B12 deficiency is often not suspected by the pediatrician in healthy infants. Clinical manifestations can be nonspecific, such as apathy, food refusal and progressive impairment of psychomotor development. A nutritional anamnesis performed on the mother (with great emphasis on those strict vegetarians) to estimate her reserves in the period prior to, during and after delivery can be critical to detect the risk of this vitamin deficiency in young children.

Difilobotríase: atualidades e perspectivas / Diphyllobothriasis: updates and perspectives

A difilobotríase é uma moléstia intestinal provocada por cestódeos do gênero Diphyllobothrium (tênia) que até pouco tempo havia poucos relatos em nosso país. Porém, em decorrência do aumento do consumo de peixes crus, mal cozidos ou defumados e da falta de cuidado nos seus preparos, vêm sendo identificados casos autóctones no Brasil. O número de pessoas parasitadas pelo platelminto difilobotríase, presente em várias regiões do mundo, vem aumentando desde 2003. A doença pode ser assintomática ou causar desconforto abdominal e interferir na absorção da vitamina B12, podendo causar anemia megaloblástica. Abster-se do consumo de pescado cru, defumado em temperaturas inadequadas ou mal cozido é a principal medida para a sua prevenção.

The intestinal diphyllobotriasis is a disease caused by Diphyllobothrium (cestodes of the genus Taenia [tapeworm]) that until recently had a few reports in our country. However, as a result of increased consumption of raw fish, soft-boiled or smoked and lack of care in their staging have been identified indigenous cases in Brazil. The number of people by the flatworm diphyllobotriasis parasitized, present in various regions of the world, comes increasing since 2003. The disease may be asymptomatic or cause abdominal discomfort and interferes in the absorption of vitamin B12, leading to megaloblastic anemia. Avoid from eating raw, smoked or soft-boiled fish is the primaries beware of their prevention.

Acute neurologic decompensation in an infant with cobalamin deficiency exposed to nitrous oxide.

After exposure to nitrous oxide, an infant with unrecognized cobalamin deficiency developed neurologic deterioration and pancytopenia. Hematologic recovery and partial resolution of his neurologic changes followed repletion of the vitamin. Nitrous oxide depletes bioavailable cobalamin and may be a dangerous anesthetic in patients with cobalamin deficiency.

Vitamina B12 metabolismo y aspectos clínicos de su deficiencia / Vitamin B12: metabolism and clinical aspects of its deficiency

Se hace una revisión sobre el metabolismo de la vitamina B12, su estructura química, fuentes dietéticas y requerimientos en los diferentes grupos de edades, así como su absorción y distribución en el organismo. Se explica además la función metabólica de las cobalaminas y su papel en la etiología de las anemias megaloblásticas, así como las causas de deficiencia de esta vitamina y su tratamiento

Anemias carenciais na infancia / Nutritional deficiency-related anemias in children

Na faixa etaria pediatrica, a carencia alimentar se constitui na causa mais comum de anemia, particularmente nos paises em desenvolvimento. O acesso irregular a uma alimentacao balanceada, a elevada incidencia de parasitoses intestinais e o requerimento continuo e elevado de nutrientes devido ao crescimento, tornam as criancas propensas a desenvolver anemia carencial. Apesar de ser um problema clinico de resolucao relativamente facil apos instalado, estaria nos esforcos de prevencao a atitude mais correta dos pontos de vista medico, social e politico. Os autores fazem uma revisao da literatura abordando as tres principais deficiencias alimentares que resultam em anemia (ferropenia e as deficiencias de vitamina B12 e folato), com especial enfase as suas causas, manifestacoes clinicas, diagnostico tratamento

Papel del ácido fólico en la etiología de las anemias megaloblásticas / Role of folic acid in the etiology of megaloblastic anemias

Se hace una revisión sobre el metabolismo de los folatos, su estructura química, fuentes dietéticas y requerimientos diarios en lso diferentes grupos de edades y estados patológicos, así como su absorción y distribución en el organismo. Se expone además la función matabólica del ácido fólico y su papel etiológico en el desarrollo de las anemias megaloblásticas, las causas de la deficiencia de este metabolilto y su tratamiento

[Megaloblastic anemia: rapid and economical study]. / Anemia megaloblástica: su estudio en forma rápida y económica.

The diagnosis of megaloblastic anaemias caused by cobalamine or folate deficiency are still difficult. The dosage of these two substances help to differenciate between both carencies, but it is not determinant of any of them and is an expensive method. Homocisteinuria (HC), methylmalonuria (MMA) and formiminoglutamic acid (FIGLU) are cheap tests which could help in the differential diagnosis, if they are used properly. We report 62 patients to whom we made these test simultaneously. All of the patients received 10 micrograms of vit B12 and after 72 hours, 1 mg/day of folic acid (for 3 days). In both cases waiting for the increase of reticulocytyes up to 150 x 10(9)/L as a form of therapeutic test of diagnosis. By this simple way we have detected 97.9% of specificity for cobalamin deficiency of the MMA test, and only 4.2% for HC. This last test had increased its specificity up to 91.6% in association with the negative FIGLU test. We have also found a high specificity (92.3%) for FIGLU due to the detection of folate deficiency, in opposition with other authors who had described it as low as 50%. We have also compared the costs of the 3 tests with the dosage of cobalamine and folate, and we have found that the formers are 11 times less expensive than the last ones.

Anemia megalobástica Asociada a Diarrea crónica.Estudio prospectivo y multicéntrico en Lima / Megaloblástic anemia associated to chronic diarrhea. Prospective and multicentric study in Lima

A partir de 1986 hemos observado un incremento de Anemia Megaloblástica (AM) asociada a diarrea crónica, en 60 por ciento no se encontró ninguna relación causal. En los últimos 3 años hemos utilizado un protocolo multicéntrico prospectivo en Lima (Perú), se incluyeron adultos con AM confirmada por aspirado de médula ósea, excluyendo: ancianos, gestantes, alcohólicos, portadores de neoplasias, etc. Los pacientes fueron 45 con promedio de edad de 37.5 años. Se encontraron dosajes disminuídos de B12 + ácido fólico: 64 por ciento, B12: 20 por ciento, y ácido fólico:16 por ciento. Las biopsias gástricas demostraron atrofia: 33 por ciento (fondo), 7,6 por ciento (cuerpo) y 12 por ciento(antro). El pH gástrico menor o igual a 4.5 en 50 por ciento. El cultivo microbiológico del jugo duodenal fué positivo en 35.2 por ciento 96/17), la mayoría coliformes gram negativos. Presentaron diversas alteraciones estructurales 5/8 (62.5 por ciento) biopsias duodenales, 5/6 (83 por ciento) biopsias yeyunales y 4/4 (100 por ciento) biopsias ileales. Los estudios parasitológicos excluyeron diphillobothrium pacificum. Estos hallazgos nos llevan a sugerir que un significativo número de pacientes con AM y diarrea crónica (con o sin síndrome espruiforme) en Lima, son consecuencia del sobrecrecimiento bacteriano intestinal, lo que los configuraría como casos de Esprue Tropical

[Megaloblastic anemia associated with chronic diarrhea. A prospective and multicenter study in Lima]. / Anemia megaloblástica asociada a diarrea crónica. Estudio prospectivo y multicéntrico en Lima.

Since 1986 we have been observing an increased number of patients with megaloblastic anaemia (MA) associated to chronic diarrhea. In 60% of the cases we could not identify any etiologic factor. In the last three years a prospective study in Lima (Peru) has been carried on aimed to investigate this aspect; patients with diseases recognized to be associated to MA were excluded. 45 patients were included age average 37.5 years, all of them have a confirmed diagnosis by bone marrow; 64% with low serum B12 and folic acid, 20% with low serum B12, and 16% with low serum folic acid. Gastric biopsies did not show atrophy in 67%; intragastric pH was lower than 4 in 50% duodenal content culture was positive in 35% (6/17) to aerobic gram negative agents; 62% (5/8) of duodenal biopsies, 83% (5/6) of jejunal biopsies, 4/4 (100%) of ileal biopsies, showed diverse structural changes; 100% did not show Diphyllobothrium pacificum. All these findings make us suggest that a significative number of patients with MA and chronic diarrhea in Lima are related to small bowel bacterial overgrowth. These bacteria can "sequestrate" or consume folates and cobalamines besides the direct damage they can cause to intestinal morphology. Future studies are needed to confirm our proposal and define if these cases belong to a variety of tropical sprue.

[Tropical sprue revealed by severe anemia in a woman from Guadeloupe]. / Sprue tropicale révélée par une anémie sévère chez une femme d'origine guadeloupéenne.

The case of a young woman from Guadeloupe developing severe megaloblastic anemia is reported. She presented with fever and hemolysis (she had heterozygotic beta-thalassemia) after a six month history of diarrhea. She was shown to have folate deficiency, steatorrhea, vitamin K and B12 malabsorption. She responded well to intravenous folinic acid and tetracyclines. Diagnosis was based on the following criteria: a) no other cause of malabsorption was found despite a comprehensive inquiry, b) the pattern of the illness corresponded to the definition of disease. Three particular aspects are outlined: the acute onset, malabsorption of vitamin B12 requiring prolonged and combined treatment, and the unusual place in which the disease was contracted.

Anemia megaloblástica em idosos / Megaloblastic anemia in the elderly

Foram estudados retrospectivamente os prontuários de 20 pacientes idosos internados no Hospital das Clínicas da FMUSP, durante o período de 1974 a 1984, com diagnóstico de anemia megaloblástica. Dez doentes eram do sexo masculino e dez do feminino, com idades variando de 62 a 84 anos (média: 70,4 anos). Em todos os casos as manifestaçöes foram múltiplas e acentuadas, predominando as hematológicas, cardiocirculatórias, neurológicas, digestivas e o grave comprometimento do estado geral. Anemia com volume corpuscular médio elevado, aumento do índice de segmentaçäo dos neutrófilos, leucopenia, plaquetopenia e hemólise foram os achados hematológicos mais freqüentes, ocorrendo muitas vezes associadamente. Em todos os casos em que foi realizado o estudo endoscópico e a biópsia gástrica, encontraram-se alteraçöes. Näo houve diferença quanto às manifestaçöes entre os portadores de deficiência de vitamina B12 ou de ácido fólico. A resposta à terapêutica foi observada em 18 pacientes (90,0%) sendo, em geral, brilhante e rápida; porém, certas manifestaçöes neurológicas podem persistir. Por outro lado, os casos näo tratados podem até evoluir para óbito, em decorrência principalmente de complicaçöes cardiocirculatórias, hemorrágicas e infecciosas