Why does my patient with alcoholic cirrhosis have macrocytic anemia?

Macrocytic anemia is commonly due to folate or vitamin B12 (cobalamin) deficiency.1 Deficiency in these vitamins can be related broadly to poor intake, poor absorption, or drug interference. In patients with chronic excess alcohol consumption, both intake and/or absorption of these vitamins may be affected.

Although folate deficiency is increasingly rare in many developed countries due to mandatory folate fortification of flour and uncooked-grain, alcohol use can be associated with malnourishment severe enough to causes folate deficiency. In addition, alcohol itself can alter folate metabolism and absorption.  More specifically, chronic alcohol consumption has been shown to be associated with decreased folate absorption by the small intestine, altered intrahepatic processing and distribution between the systemic and enterohepatic folate circulations as well as increased folate urinary excretion. 2 Though uncommon,3 alcohol can also be associated with a food B12 malabsorption process, whereby despite adequate intake, B12 is not released or absorbed from food. 4

But what if serum folate and B12 levels return as normal in our patient with macrocytosis? It turns out that alcohol consumption, independent of folate or B12 deficiency, may also cause macrocytosis. 5 Though the exact mechanism is unknown, it may be related to alcohol’s direct toxicity or that of its metabolites; alcohol is oxidized to acetaldehyde, which affects membranes of red blood cells (RBCs) and their precursors by forming adducts with erythroid proteins,6 and interfering with cell division.7 Interestingly, alcohol-related macrocytosis may appear before anemia is detected and can resolve within 2-4 months of abstinence.

In addition to alcohol, cirrhosis itself may be associated with macrocytic anemia caused by lipid deposition on RBC membranes.1

See also a related pearl at  https://pearls4peers.com/2019/07/26/my-patient-with-anemia-has-an-abnormally-high-mean-red-blood-cell-corpuscular-volume-mcv-what-conditions-should-i-routinely-consider-as-a-cause-of-his-macrocytic-anemia   


  1. Hoffbrand V, Provan D. ABC of clinical haematology: macrocytic anaemias. BMJ 2011;314(7078):430–430. https://www.ncbi.nlm.nih.gov/pubmed/9040391
  2. Medici V, Halsted CH. Folate, alcohol, and liver disease. Mol Nutr Food Res 2013;57(4):596–606. https://www.ncbi.nlm.nih.gov/pubmed/23136133
  3. Bode C, Bode CJ. Effect of alcohol consumption on the gut. Best Pract Res Clin Gastroenterol [Internet] 2003;17(4):575–92. https://www.sciencedirect.com/science/article/pii/S1521691803000349
  4. Dali-Youcef N, Andrès E. An update on cobalamin deficiency in adults. QJM 2009;102(1):17–28. https://academic.oup.com/qjmed/article/102/1/17/1502492
  5. Savage DG, Ogundipe A, Allen RH, Stabler SP, Lindenbaum J. Etiology and diagnostic Evaluation of macrocytosis. Am J Med Sci [Internet] 2000;319(6):343–52. http://dx.doi.org/10.1016/S0002-9629(15)40772-4 https://www.ncbi.nlm.nih.gov/pubmed/10875288
  6. Latvala J, Parkkila S, Melkko J, Niemelä O. Acetaldehyde adducts in blood and bone marrow of patients with ethanol-induced erythrocyte abnormalities. Mol Med 2001;7(6):401–5. https://www.ncbi.nlm.nih.gov/pubmed/11474133
  7. Wickramasinghe SN, Malik F. Acetaldehyde causes a prolongation of the doubling time and an increase in the modal volume of cells in culture. Alcohol Clin Exp Res 1986;10(3):350–4. https://www.ncbi.nlm.nih.gov/pubmed/3526962


Contributed by Kim Schaefer, Harvard medical student, Boston, MA

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Why does my patient with alcoholic cirrhosis have macrocytic anemia?

What is the significance of teardrop cells (dacrocytes) on the peripheral smear of my patient with newly-discovered pancytopenia?

The presence of teardrop cells (dacrocytes) (Figure below) in the peripheral blood, named for their tear drop shape, is a prominent feature of myelophthisic (marrow infiltrative) conditions, including myelofibrosis, hematologic malignancies, cancer metastatic to the bone marrow, and granulomatous diseases. Teardrop cells may also be seen in beta-thalassemia, autoimmune and microangiopathic hemolytic anemia and severe iron deficiency (1-4).

When evaluating patients with leucoerythroblastic smears (defined by the presence of early myeloid and erythroid forms), the presence of teardrop cells can be helpful in distinguishing often malignant marrow infiltrative conditions from a benign reactive process.  Conditions where teardrop cells are seen with high frequency may also have extramedullary hematopoiesis, particularly in the spleen (1,2).
The mechanism of teardrop cell formation may be multifactorial but appears to involve distortion of the red cells as they pass through marrow or splenic sinusoids.


Teardrop cells resulting from conditions such as cancer metastatic to the bone marrow likely involve primarily a marrow origin of the cells whereas primary myelofibrosis with prominent extramedullary hematopoiesis include a splenic mechanism of teardrop cell formation (2).

Supporting the possible splenic contribution to teardrop cell formation is the observation that teardrop cells may be reduced in number or eliminated entirely after splenectomy in patients with myelofibrosis and autoimmune hemolytic anemia (1,4).


Figure. Teardrop cells


1. DiBella NJ, Sliverstein MN, Hoagland HC. Effect of splenectomy on teardrop-shaped erythrocytes in agnogenic myeloid metaplasia. Arch Intern Med 1977; 137: 380-381. https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/586447
2. Gutgemann I, Heimpel H, Nebe CT. Significance of teardrop cells in peripheral blood smears. J Lab Med 2014; DOI: 10.1515/labmed-2014-0005 https://www.researchgate.net/publication/272430111_Significance_of_teardrop_cells_in_peripheral_blood_smears
3. Korber C, Wolfler A, Neubauer M, Robier Christoph. Red blood cell morphology in patients with β-thalassemia minor. J Lab Med 2016-12-10 | https://www.researchgate.net/publication/311564128_Red_blood_cell_morphology_in_patients_with_b-thalassemia_minor DOI: https://doi.org/10.1515/labmed-2016-0052
4. Robier C, Klescher D, Reicht G,Amouzadeh-Ghadikolai O, Quehenberger F, Neubauer M. Dacrocytes are a common morphologic feature of autoimmune and microangiopathic haemolytic anaemia. Clin Chem Lab Med. 2015;53:1073-6. https://www.ncbi.nlm.nih.gov/pubmed/25503671

Contributed by Tom Spitzer, MD, Director of Cellular Therapy and Transplantation Laboratory,  Massachusetts General Hospital, Boston, MA.

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What is the significance of teardrop cells (dacrocytes) on the peripheral smear of my patient with newly-discovered pancytopenia?