{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T15:44:44Z","timestamp":1786549484945,"version":"build-2736575974"},"reference-count":55,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T00:00:00Z","timestamp":1786492800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Nutr."],"abstract":"<jats:p>Vitamin B12 (cobalamin) deficiency remains a significant problem affecting both children and adults and is associated with a wide range of hematological manifestations that are largely preventable with timely diagnosis and treatment. Vitamin B12 deficiency can present with variable hematological, neuropsychiatric, and mucocutaneous changes. Hematological abnormalities are among the most common presentations. The classical peripheral blood smear shows macrocytosis with oval macrocytes, anisopoikilocytosis, and hypersegmented neutrophils. Anemia may be accompanied by leukopenia and thrombocytopenia due to ineffective hematopoiesis. Bone marrow examination typically reveals hypercellularity with erythroid hyperplasia and large megaloblasts exhibiting open chromatin and nuclear\u2013cytoplasmic asynchrony as a result of defective DNA synthesis. Ineffective erythropoiesis leads to intramedullary destruction of hematopoietic precursors, resulting in elevated lactate dehydrogenase, indirect hyperbilirubinemia, and reduced haptoglobin, thereby mimicking hemolytic anemias. Abnormal red cells and megaloblasts that enter the circulation have a shortened lifespan, leading to megaloblastic anemia, with reticulocyte counts that are inappropriately low for the degree of anemia. In pediatric patients, manifestations may be severe, particularly in infants born to cobalamin-deficient mothers. Presentations include profound anemia, pancytopenia, failure to thrive, recurrent infections, and bleeding manifestations due to thrombocytopenia, often misdiagnosed as aplastic anemia or myelodysplasias. Pigmentary changes in the form of hyperpigmentation of knuckles, oral mucosa and rarely Addisonian pigmentation have been described. In older children, isolated anemia or bicytopenia with subtle macrocytosis may delay diagnosis. Severe presentations, seen in approximately 10% of cases, include pancytopenia, hemolytic anemia, and pseudothrombotic microangiopathy, which may mimic hematological malignancies or thrombotic microangiopathies. Early recognition is crucial, as vitamin B12 replacement leads to rapid and often complete hematological recovery.<\/jats:p>","DOI":"10.3389\/fnut.2026.1898533","type":"journal-article","created":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T14:45:51Z","timestamp":1786545951000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Revisiting the hematological manifestations of vitamin B12 deficiency"],"prefix":"10.3389","volume":"13","author":[{"given":"Nupur","family":"Parakh","sequence":"first","affiliation":[{"name":"Department of Hematology, Bone Marrow Transplantation and Cellular Therapy, Vardhman Mahavir Medical College and Safdarjung Hospital, Guru Gobind Singh Indraprastha University","place":["New Delhi, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pooja","family":"Dewan","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University College of Medical Sciences, University of Delhi","place":["New Delhi, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,8,12]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"118896","DOI":"10.1016\/j.bbamcr.2020.118896","article-title":"The requirement for cobalt in vitamin B12: a paradigm for protein metalation.","volume":"1868","author":"Osman","year":"2021","journal-title":"Biochim Biophys Acta Mol Cell Res"},{"key":"B2","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1002\/9781119946045.ch22","article-title":"Vitamin B12.","volume-title":"Present Knowledge In Nutrition.","author":"Stabler","year":"2012"},{"key":"B3","first-page":"7","article-title":"The methionine-homocysteine cycle and its effects on cognitive diseases.","volume":"8","author":"Miller","year":"2003","journal-title":"Altern Med Rev."},{"key":"B4","doi-asserted-by":"publisher","first-page":"832","DOI":"10.1016\/s0140-6736(76)91213-7","article-title":"The neurology of vitamin B12 deficiency metabolic mechanisms","volume":"2","author":"Reynolds","year":"1976","journal-title":"Lancet"},{"key":"B5","volume-title":"Dietary Reference Intakes For Thiamin, Riboflavin, Niacin, Vitamin B(6), Folate, Vitamin B(12), Pantothenic Acid, Biotin, And Choline.","year":"1998"},{"key":"B6","doi-asserted-by":"publisher","first-page":"OC01","DOI":"10.7860\/JCDR\/2015\/16191.6866","article-title":"Opportunistic screening of vitamin B12 deficiency in IT professionals presenting for routine health check-up.","volume":"9","author":"Ingole","year":"2015","journal-title":"J Clin Diagn Res"},{"key":"B7","unstructured":"Nagral\n              N\n            \n            \n              Saluja\n              JG\n            \n            \n              Khanna\n              SS.\n            \n          \n          Vitamin B12 and Non-vegetarianism: Myth versus Reality.\n          \n          2024"},{"key":"B8","doi-asserted-by":"publisher","first-page":"149","DOI":"10.1056\/NEJMcp1113996","article-title":"Clinical practice. 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