macrocytic anemia


Summary: Anemia characterized by larger than normal erythrocytes, increased mean corpuscular volume (MCV) and increased mean corpuscular hemoglobin (MCH).

Top Publications

  1. Trimarchi H, Forrester M, Schropp J, Pereyra H, Freixas E. Low initial vitamin B12 levels in Helicobacter pylori--positive patients on chronic hemodialysis. Nephron Clin Pract. 2004;96:c28-32 pubmed
    ..pylori-positive chronic hemodialysis patients may present with lower vitamin B12 blood levels and macrocytosis. H. pylori infection should be suspected in this population when low or low-normal vitamin B12 levels or macrocytosis exist. ..
  2. Metz J, McNeil A, Levin M. The relationship between serum cobalamin concentration and mean red cell volume at varying concentrations of serum folate. Clin Lab Haematol. 2004;26:323-5 pubmed
    ..Macrocytosis appears to retain its value as a marker of cobalamin deficiency in people with serum folate concentrations above the population average. ..
  3. Morris M, Jacques P, Rosenberg I, Selhub J. Folate and vitamin B-12 status in relation to anemia, macrocytosis, and cognitive impairment in older Americans in the age of folic acid fortification. Am J Clin Nutr. 2007;85:193-200 pubmed
    ..In seniors with low vitamin B-12 status, high serum folate was associated with anemia and cognitive impairment. When vitamin B-12 status was normal, however, high serum folate was associated with protection against cognitive impairment. ..
  4. Khawcharoenporn T, Shikuma C, Williams A, Chow D. Lamivudine-associated macrocytosis in HIV-infected patients. Int J STD AIDS. 2007;18:39-40 pubmed
    ..We found that lamivudine was strongly associated with macrocytosis (OR = 24.6 [2.9-3223.0], P = 0.001). This association may be due to lamivudine's effect on erythrocyte synthesis. ..
  5. Barlow J, Drynan L, Hewett D, Holmes L, Lorenzo Abalde S, Lane A, et al. A p53-dependent mechanism underlies macrocytic anemia in a mouse model of human 5q- syndrome. Nat Med. 2010;16:59-66 pubmed publisher
    ..Haploinsufficiency of the Cd74-Nid67 interval (containing Rps14, encoding the ribosomal protein S14) caused macrocytic anemia, prominent erythroid dysplasia and monolobulated megakaryocytes in the bone marrow...
  6. Murphy P, Fay M, Quinn J, O Donnell J. Remission of transfusion-dependent myelodysplastic syndrome in association with respiratory tract infection. Ann Hematol. 2005;84:614-5 pubmed
    ..Following an acute hospital admission with a respiratory tract infection, the patient entered a complete and sustained remission. ..
  7. Brigden M. A systematic approach to macrocytosis. Sorting out the causes. Postgrad Med. 1995;97:171-2, 175-7, 181-4 passim pubmed
    ..This initial evaluation should allow systematic consideration of the possible causes. Serum B12 and red cell folate determinations and other studies may then be undertaken as appropriate. ..
  8. Savage D, Ogundipe A, Allen R, Stabler S, Lindenbaum J. Etiology and diagnostic evaluation of macrocytosis. Am J Med Sci. 2000;319:343-52 pubmed
    ..Drugs and alcohol are the most common causes of macrocytosis in hospitalized patients in a New York City teaching hospital. We have formulated tentative guidelines for the evaluation of high MCV values in this setting. ..
  9. Lobetti R, Tasker S. Diagnosis of feline haemoplasma infection using a real-time PCR assay. J S Afr Vet Assoc. 2004;75:94-9 pubmed
    ..Cats that were positive for M. haemofelis showed macrocytic regenerative anaemia, monocytosis and thrombocytopaenia. This report documents the existence of both haemoplasma species in cats in South Africa. ..

More Information


  1. Deugnier Y, Gandon Y, Juhel C, Olivie D, Jouanolle A, Turlin B. [Diagnosis of iron overload]. Rev Prat. 2006;56:2118-22 pubmed
  2. Uprichard J, Bain B. Case 39: an elderly man with red cell aplasia. Leuk Lymphoma. 2008;49:1810-2 pubmed publisher
    An elderly man presented with a macrocytic anemia with severe reticulocytopenia. The observation of trilineage dysplasia in addition to red cell aplasia led to a diagnosis.
  3. KatipoÄŸlu N, Karapinar T, Demir K, Aydin Köker S, NalbantoÄŸlu Ã, Ay Y, et al. Infantile-onset thiamine responsive megaloblastic anemia syndrome with SLC19A2 mutation: a case report. Arch Argent Pediatr. 2017;115:e153-e156 pubmed publisher
    ..which presented with sensorineural deafness treated with a hearing prosthesis, insulin requiring diabetes, macrocytic anemia, treated with thiamine (100 mg/day). Hemoglobin level improved to 12...
  4. Singh I, Nunia V, Sharma R, Barupal J, Govindaraj P, Jain R, et al. Mutational analysis of telomere complex genes in Indian population with acquired aplastic anemia. Leuk Res. 2015;: pubmed publisher
    ..AAA patients showed hematologic abnormalities (macrocytic anemia, thrombocytopenia, & granulocytopenia) in peripheral blood and severe hypoplastic bone marrows...
  5. Fogarasi A, Neuwirth M, Bekesi A, Bocskai E. [Macrocytic anemia and neurological signs due to vitamin B-12 deficiency in a breast-fed infant of a strict vegetarian mother]. Orv Hetil. 2001;142:2581-5 pubmed
    ..Beside reviewing the literature they emphasize the importance of early recognition and intervention and the need of an appropriate doctor-parent cooperation in this disease. ..
  6. Mukai Y, Asanuma K, Mori A, Kamada M, Kawabata Y, Nodera H, et al. [Copper deficiency with SMON-like neurological symptoms and macrocytic anemia]. Nihon Naika Gakkai Zasshi. 2008;97:1876-8 pubmed
  7. Wolf N. Dissecting the hematopoietic microenvironment. II. The kinetics of the erythron of the S1/S1d mouse and the dual nature of its anemia. Cell Tissue Kinet. 1978;11:325-34 pubmed
    ..The cause of the moderately high level of erythropoiesis in the S1/S1d is a mean daily loss of 2.5--3.0% of its total blood volume via the intestinal tract. ..
  8. Varela Moreiras G. What have animal studies told us about the role of folic acid and vitamin B12 in health?. Forum Nutr. 2003;56:49-51 pubmed
  9. Rivera Campos J, Leyva González F, Leyva Salas C. [Developing undergraduate medical boarding's clinical aptitude in anemic deficiencies with a participation promotive educational strategy]. Rev Invest Clin. 2005;57:784-93 pubmed
    ..It must be considerated to propitiate changes to develop a more reflexive and critical education. ..
  10. Figueroa Jiménez L, González Márquez A, Alicea Guevara R, Santiago Casiano M, de la Paz López M, Negrón Garcia L, et al. A Hispanic female patient with heartburn: A rare presentation of Paroxysmal Nocturnal Hemoglobinuria. Bol Asoc Med P R. 2015;107:9-12 pubmed
    ..CBC showed leukopenia (WBC 2.9 x 103 /µL) with neutropenia (segmented neutrophils 48%), macrocytic anemia (Hgb 6.1 g/dL, hematocrit 20%, MCV,113 fL) and thrombocytopenia (platelet count 59 x 109/L)...
  11. Schoeman T, Lobetti R, Jacobson L, Penzhorn B. Feline babesiosis: signalment, clinical pathology and concurrent infections. J S Afr Vet Assoc. 2001;72:4-11 pubmed
    ..A close correlation was evident between peripheral and central parasite counts. Concurrent infections with Haemobartonella felis, feline immunodeficiency virus and/or feline leukemia virus were identified in a number of cats. ..
  12. Bentley D, Harrison C, Ketchen A, Redhead N, Samuel K, Waterfall M, et al. DNA ligase I null mouse cells show normal DNA repair activity but altered DNA replication and reduced genome stability. J Cell Sci. 2002;115:1551-61 pubmed
  13. Gentilella A, Morón Duran F, Fuentes P, Zweig Rocha G, Riaño Canalias F, Pelletier J, et al. Autogenous Control of 5?TOP mRNA Stability by 40S Ribosomes. Mol Cell. 2017;67:55-70.e4 pubmed publisher
    ..The importance of this mechanism is underscored in 5q? syndrome, a macrocytic anemia caused by a large monoallelic deletion, which we found to also encompass the LARP1 gene...
  14. Oh R, Holt S, Hitchcock K, Hoekzema G. How do you evaluate macrocytosis without anemia?. J Fam Pract. 2008;57:548-50 pubmed
  15. Ghanayem B, Long P, Ward S, Chanas B, Nyska M, Nyska A. Hemolytic anemia, thrombosis, and infarction in male and female F344 rats following gavage exposure to 2-butoxyethanol. Exp Toxicol Pathol. 2001;53:97-105 pubmed
    ..Thrombosis may be related to intravascular hemolysis, which could be triggered by procoagulant release and/or alterations in erythrocyte morphology, as well as increased rigidity...
  16. De La Garza A, Cameron R, Nik S, Payne S, Bowman T. Spliceosomal component Sf3b1 is essential for hematopoietic differentiation in zebrafish. Exp Hematol. 2016;44:826-837.e4 pubmed publisher
  17. Taney F, Vasilenko P, Steinetz B, Weiss G, Cole D, Goldsmith L. The role of estrogen and relaxin in the reproductive abnormalities of mice with Hertwig's anemia. Biol Reprod. 1991;45:719-26 pubmed
    Mice homozygous for a mutant allele (an/an) causing a lifelong macrocytic anemia (Hertwig's anemia) also demonstrate an inability to deliver their offspring, despite normal ovulation, conception, implantation, and fetal development...
  18. Li Harms X, Milasta S, Lynch J, Wright C, Joshi A, Iyengar R, et al. Mito-protective autophagy is impaired in erythroid cells of aged mtDNA-mutator mice. Blood. 2015;125:162-74 pubmed publisher
    ..mutations via a targeted defect in the proofreading function of the mtDNA polymerase, PolgA, and develop macrocytic anemia similar to that of patients with MDS...
  19. van der Weyden M, Campbell L. Clinching the diagnosis: macrocytic anemia. Pathology. 1988;20:353-7 pubmed
    ..The utility of these changes for dictating further investigation and the appropriate "modus operandi" in diagnostic strategies for the adult and the younger patient are outlined...
  20. Meznarich J, Draper L, Christensen R, Yaish H, Luem N, Pysher T, et al. Fetal presentation of congenital dyserythropoietic anemia type 1 with novel compound heterozygous CDAN1 mutations. Blood Cells Mol Dis. 2018;71:63-66 pubmed publisher
    ..present in utero with hydrops fetalis, but more often it presents in childhood or adulthood with moderate macrocytic anemia, jaundice, and progressive iron-overload...
  21. Ziarkiewicz M, Dwilewicz Trojaczek J, Pastwińska A, Chmarzyńska E, Paszkowska Kowalewska M, Koperski Ł, et al. Refractory anaemia with ringed sideroblasts associated with marked thrombocytosis (RARS-T) with superimposed 5q-syndrome. Pol J Pathol. 2010;61:105-9 pubmed
    ..After the description of the clinical data, we summarize the histopathologic, cytogenetic and molecular findings, as well as introduced treatment. Next, we discuss possible diagnostic options with reference to the relevant literature. ..
  22. Green R, Dwyre D. Evaluation of Macrocytic Anemias. Semin Hematol. 2015;52:279-86 pubmed publisher
    b>Macrocytic anemia, defined as a mean cell volume (MCV) ≥100 fL in adults, has a narrow differential diagnosis that requires evaluation of the peripheral blood smear as well as additional laboratory testing taken in conjunction with ..
  23. Freund Y, Dousman L, MacGregor J, Mohagheghpour N. Oral treatment with trimethoprim-sulfamethoxazole and zidovudine suppresses murine accessory cell-dependent immune responses. Toxicol Sci. 2000;55:335-42 pubmed
    ..ZDV at 240 mg/kg/day was not immunosuppressive but caused a mild macrocytic anemia. Combined treatment produced severe pancytopenia, a significant drop in splenic cellularity, and a 61% ..
  24. Eyer Silva W, Arabe J, Pinto J, Morais de Sá C. Macrocytosis in patients on stavudine. Scand J Infect Dis. 2001;33:239-40 pubmed
    ..Macrocytosis was commonly observed among patients on stavudine-based regimens although the MCV usually stabilized at a lower level than that observed with zidovudine. ..
  25. Tefferi A, Dingli D, Li C, Mesa R. Microcytosis in agnogenic myeloid metaplasia: prevalence and clinical correlates. Leuk Res. 2006;30:677-80 pubmed
    ..In the current study, we show that microcytosis is a frequent laboratory feature in agnogenic myeloid metaplasia and investigate its clinical relevance in the particular setting. ..
  26. Ear J, Hsueh J, Nguyen M, Zhang Q, Sung V, Chopra R, et al. A Zebrafish Model of 5q-Syndrome Using CRISPR/Cas9 Targeting RPS14 Reveals a p53-Independent and p53-Dependent Mechanism of Erythroid Failure. J Genet Genomics. 2016;43:307-18 pubmed publisher
    ..MDS is characterized by bone marrow failures, including macrocytic anemia. Genetic mapping and studies using various models support the notion that ribosomal protein S14 (RPS14) is ..
  27. Doty R, Phelps S, Shadle C, Sanchez Bonilla M, Keel S, Abkowitz J. Coordinate expression of heme and globin is essential for effective erythropoiesis. J Clin Invest. 2015;125:4681-91 pubmed publisher
    ..Mice lacking the heme exporter FLVCR1 have a severe macrocytic anemia; however, the mechanisms that underlie erythropoiesis dysfunction in these animals are unclear...
  28. Beyan C, Beyan E, Kaptan K, Ifran A, Uzar A. Post-gastrectomy anemia: evaluation of 72 cases with post-gastrectomy anemia. Hematology. 2007;12:81-4 pubmed
    ..In conclusion, gastrectomized patients should be followed for anemia and treated appropriately based on the cause of anemia. ..
  29. Alford K, Slender A, Vanes L, Li Z, Fisher E, Nizetic D, et al. Perturbed hematopoiesis in the Tc1 mouse model of Down syndrome. Blood. 2010;115:2928-37 pubmed publisher
    ..We show that although Tc1 mice do not develop leukemia, they have macrocytic anemia and increased extramedullary hematopoiesis...
  30. Chan C, Liu S, Kho C, Lau K, Liang Y, Chu W, et al. Diagnostic clues to megaloblastic anaemia without macrocytosis. Int J Lab Hematol. 2007;29:163-71 pubmed
  31. Tauro G, Danks D, Rowe P, van der Weyden M, Schwarz M, Collins V, et al. Dihydrofolate reductase deficiency causing megaloblastic anemia in two families. N Engl J Med. 1976;294:466-70 pubmed
    ..A satisfactory clinical response in both patients followed parenteral therapy with 5-formyl tetrahydrofolic acid. One sibling in each family died of a similar illness. Autosomal recessive inheritance is probable. ..
  32. Terade H, Niikura H, Mori H, Hagiwara S, Takizawa Y, Okada S, et al. [Megaloblastic anemia and platelet function--a qualitative platelet defect in pernicious anemia]. Rinsho Ketsueki. 1990;31:254-5 pubmed
    ..In summary, the acquired defects of platelet function in pernicious anemia are regarded as a secondary storage pool disease, and its defects improve after Vitamin B12 therapy. ..
  33. Provan D, Weatherall D. Red cells II: acquired anaemias and polycythaemia. Lancet. 2000;355:1260-8 pubmed
    ..Aplastic anaemia is caused by an intrinsic defect of haemopoietic stem cells; both inherited and acquired forms occur. Primary polycythaemia is a myeloproliferative disorder, a non-malignant stem-cell disease. ..
  34. Maruyama S, Hirayama C, Yamamoto S, Koda M, Udagawa A, Kadowaki Y, et al. Red blood cell status in alcoholic and non-alcoholic liver disease. J Lab Clin Med. 2001;138:332-7 pubmed
    ..b>Macrocytic anemia was mostly found in cirrhotic patients, in which the Child-Pugh score was closely related to the development ..
  35. Zsebo K, Williams D, Geissler E, Broudy V, Martin F, Atkins H, et al. Stem cell factor is encoded at the Sl locus of the mouse and is the ligand for the c-kit tyrosine kinase receptor. Cell. 1990;63:213-24 pubmed
    ..In vivo administration of SCF can reverse the macrocytic anemia and locally repair the mast cell deficiency of Sl/Sld mice...
  36. Ploemacher R, Molendijk W, Brons N, de Ruiter H. Defective support of S1/S1d splenic stroma for humoral regulation of stem cell proliferation. Exp Hematol. 1986;14:9-15 pubmed
  37. Nilsson Ehle H, Landahl S, Lindstedt G, Netterblad L, Stockbruegger R, Westin J, et al. Low serum cobalamin levels in a population study of 70- and 75-year-old subjects. Gastrointestinal causes and hematological effects. Dig Dis Sci. 1989;34:716-23 pubmed
    ..Megaloblastic hematopoiesis was found in 10 individuals, four of whom had macrocytic anemia. Our results indicate that low serum cobalamin concentration in the elderly is usually a consequence of ..
  38. Bamba T, Kosugi S, Kanda T, Tsubono T, Sakai Y, Musha N, et al. Multiple carcinoids in the duodenum, pancreas and stomach accompanied with type A gastritis: a case report. World J Gastroenterol. 2007;13:2247-9 pubmed
    ..Laboratory tests revealed that the patient was associated with macrocytic anemia and hypergastrinemia, and type A gastritis was shown by gastrofiberscopy...
  39. Al Safi S, Tashtoush B, Abdul Razzakl K. Azathioprine-induced fatal macrocytic anemia in rabbits. Pol J Pharmacol. 2002;54:513-6 pubmed
    ..of AZA (10 mg/kg/day) to rabbits for two weeks induced reversible thrombocytosis and delayed fatal macrocytic anemia. Moreover, neither the hemoglobin level nor the white blood cell count was affected by AZA...
  40. Hwang S, Kang Y, Sung B, Kim M, Kim D, Lee Y, et al. Folic acid promotes the myogenic differentiation of C2C12 murine myoblasts through the Akt signaling pathway. Int J Mol Med. 2015;36:1073-80 pubmed publisher
    ..folic acid can lead to folic acid deficiency and can therefore result in several health problems, including macrocytic anemia, elevated plasma homocysteine levels, cardiovascular disease, birth defects, carcinogenesis, muscle weakness ..
  41. Neggers Y. The Relationship between Folic Acid and Risk of Autism Spectrum Disorders. Healthcare (Basel). 2014;2:429-44 pubmed publisher
    ..The role of folic acid in the prevention of macrocytic anemia and neural tube defects is well established...
  42. Tasker S, Peters I, Papasouliotis K, Cue S, Willi B, Hofmann Lehmann R, et al. Description of outcomes of experimental infection with feline haemoplasmas: copy numbers, haematology, Coombs' testing and blood glucose concentrations. Vet Microbiol. 2009;139:323-32 pubmed publisher
    ..haemofelis infection, in contrast to 'Candidatus M. haemominutum' and 'Candidatus M. turicensis' infection, can result in a severe macrocytic anaemia and the development of cold and warm reactive erythrocyte-bound antibodies...
  43. Baker H. Nutrition in the elderly: hypovitaminosis and its implications. Geriatrics. 2007;62:22-6 pubmed
    ..The astute clinician will determine which factors are most likely at work in a specific patient and determine the best course of action to replenish vitamin levels. ..
  44. Becaria A, Campbell A, Bondy S. Aluminum as a toxicant. Toxicol Ind Health. 2002;18:309-20 pubmed
    ..This review encompasses the general toxicology of aluminum with emphasis on the potential mechanisms by which it may accelerate the progression of chronic age-related neurodegenerative disorders. ..
  45. Garcia Perez A, Sancho P, Pinilla M. Surface and metabolic properties of microcytic and macrocytic human anaemic red blood cells detected in polymer aqueous two-phase systems. J Chromatogr B Biomed Sci Appl. 1998;711:301-7 pubmed
    ..Bisphosphoglycerate mutase specific activity did not change along the fractionation profile of any cell population under study, thus providing 2,3-bisphosphoglycerate during the life-span of the red blood cells from anaemic patients. ..
  46. Ralapanawa D, Jayawickreme K, Ekanayake E, Jayalath W. B12 deficiency with neurological manifestations in the absence of anaemia. BMC Res Notes. 2015;8:458 pubmed publisher
    Vitamin B12 deficiency is often diagnosed with hematological manifestations of megaloblastic macrocytic anemia, which is usually the initial presentation...
  47. Torres Gomez A, Casaño J, Sanchez J, Madrigal E, Blanco F, Alvarez M. Utility of reticulocyte maturation parameters in the differential diagnosis of macrocytic anemias. Clin Lab Haematol. 2003;25:283-8 pubmed
    ..measurement of reticulocyte maturation parameters may be a very useful tool in the differential diagnosis of macrocytic anemia. The presence of extremely high values of IRF (>16%), MFI (>18) and MRV (>129 fl), makes the ..
  48. Geissler E, Russell E. Analysis of the hematopoietic effects of new dominant spotting (W) mutations of the mouse. I. Influence upon hematopoietic stem cells. Exp Hematol. 1983;11:452-60 pubmed
    ..Even non-anemic W44/W44 recipients are repopulated with +/+ donor red cells, indicating that W44/W44 stem cells are at a disadvantage when competing with normal counterparts. ..
  49. Bouree P. [Tropical sprue]. Presse Med. 2007;36:723-6 pubmed
    ..Pathogenesis is still unknown but an infectious cause is suspected. Macrocytic anemia and hypoalbuminemia are present, together with progressive villus atrophy of the small intestine...
  50. Chetty M, Stewart G. Pseudohyperkalaemia and pseudomacrocytosis caused by inherited red-cell disorders of the 'hereditary stomatocytosis' group. Br J Biomed Sci. 2001;58:48-55 pubmed
    ..All are inherited as dominants, although new mutations can be seen. ..
  51. Mangles S, Abdalla S, Gabriel C, Bain B. Case 37: Neutropenia and macrocytosis in a middle-aged man. Leuk Lymphoma. 2007;48:1846-8 pubmed
    ..The correct non-neoplastic diagnosis was not made for 5 years. It is of crucial importance to exclude treatable causes of cytopenia and dysplasia when MDS is suspected. ..
  52. Borgna Pignatti C, Marradi P, Pinelli L, Monetti N, Patrini C. Thiamine-responsive anemia in DIDMOAD syndrome. J Pediatr. 1989;114:405-10 pubmed
    ..We propose that an inherited abnormality of thiamine metabolism is responsible for the multisystem degenerative disorder known as DIDMOAD syndrome. ..
  53. Janus J, Moerschel S. Evaluation of anemia in children. Am Fam Physician. 2010;81:1462-71 pubmed
    ..Common tests used in the evaluation of macrocytic anemias include vitamin B12 and folate levels, and thyroid function testing. A peripheral smear can provide additional information in patients with anemia of any morphology. ..