Main Article Content


Megaloblastic anemias secondary to Vitamin B12 deficiency are a group of pathologies produced by defective nuclear DNA synthesis.

To describe the maturation alterations found in hematopoietic precursors of the bone marrow in a series of patients with megaloblastic anemia.

Included patients attended the Regional Hospital of Concepción with bone marrow samples sent to study 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.

Eight patients with megaloblastic anemia were identified from the flow cytometry laboratory database, 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.

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.


Vania Belén Briones Muñoz, Universidad de Concepción


Fernanda Isabel Figueroa Faúndez, Universidad de Concepción


Catalina Monserrat Vidal Rojas, Universidad de Concepción


Vicente Tomás Micolich Espejo, Universidad de Concepción


Mauricio Andrés Chandia Cabas, Universidad de Concepción


Briones Muñoz, V. B., Figueroa Faúndez, F. I., Vidal Rojas, C. M., Micolich Espejo, V. T., & Chandia Cabas, M. A. (2024). Flow cytometry-detected changes in megaloblastic anemia secondary to cobalamin deficiency. Colombia Medica, 54(2), e2005494. (Original work published June 28, 2023)

Koury MJ, Horne DW, Brown ZA, et al. Apoptosis of late-stage erythroblasts in megaloblastic anemia:association with DNA damage and macrocyte production. Blood. 1997; 89(12): 4617-4623. PMid:9192787

Ballas SK, Pielichowski HJ, Stoll DB. Further characterization of the erythrocyte membrane protein abnormality in megaloblastic anemia. J Med. 1982;13(1-2):15-34.

Stabler SP. Vitamin B12 Deficiency. N Engl J Med. 2013; 368(2): 149-160. PMid:23301732

Green R. Vitamin B12 deficiency from the perspective of a practicing hematologist. Blood. 2017; 129(19): 2603-2611. PMid:28360040

Sutton L, Mba N. Hematogones detected by flow cytometry in a child with vitamin B12 deficiency: a case report. Pediatr Dev Pathol. 2017; 20(2):172-175. PMid:28326965

van Dongen JJM, Lhermitte L, Böttcher S, Almeida J, van der Velden VHJ, Flores-Montero J, et al. EuroFlow antibody panels for standardized n-dimensional flow cytometric immunophenotyping of normal, reactive and malignant leukocytes. Leukemia. 2012; 26(9): 1908-1975. PMid:22552007 PMCid:PMC3437410

Matarraz S, López A, Barrena S, Fernandez C, Jensen E, Flores-Montero J,et al. Bone marrow cells from myelodysplastic syndromes show altered immunophenotypic profiles that may contribute to the diagnosis and prognostic stratification of the disease: a pilot study on a series of 56 patients. Cytometry B Clin Cytom. 2010; 78(3): 154-168. PMid:20198685

Orfao A, Matarraz S, Pérez-Andrés M, Almeida J, Teodosio C, Berkowska MA, et al. Immunophenotypic dissection of normal hematopoiesis. J Immunol Methods. 2019;475:112684. PMid:31676343

Mello FV, Land MGP, Costa ES, Teodósio C, Sanchez ML, Bárcena P, et al. Maturation-associated gene expression profiles during normal human bone marrow erythropoiesis. Cell Death Discov. 2019;5(1):1-12. PMid:30854228 PMCid:PMC6395734

Green R, Datta Mitra A. Megaloblastic anemias: nutritional and other causes. Med Clin North Am. 2017;101(2):297-317. PMid:28189172

Matarraz S, López A, Barrena S, Fernandez C, Jensen E, Flores J, et al. The immunophenotype of different immature, myeloid and B-cell lineage-committed CD34+ hematopoietic cells allows discrimination between normal/reactive and myelodysplastic syndrome precursors. Leukemia. 2008; 22(6): 1175-1183. PMid:18337765


Download data is not yet available.
Received 2022-12-28
Accepted 2023-06-25
Published 2024-04-12