Hematology & immune disorders


Folate deficiency anemia

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Last staff update: 4 October 2023

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PubMed Search: Folate deficiency anemia [title]

R. Amita, M.D.
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Cite this page: Amita R. Folate deficiency anemia. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/hematofolatedefanemia.html. Accessed July 13th, 2024.
Definition / general
  • Folate deficiency is a low level of folic acid (Vitamin B9) in the body
Essential features
  • Characterized by macrocytic anemia
  • Also called Vitamin B9 deficiency
  • Inadequate ingestion of folate containing foods due to: alcoholism (alcohol dehydrogenase binds folate), psychiatric morbidities, elderly
  • Impaired absorption: celiac disease, tropical sprue, achlorhydria, anticonvulsant drugs (Dilantin), zinc deficiency, bacterial overgrowth in blind loops, strictures, jejunal diverticula
  • Impaired metabolism, leading to inability to utilize absorbed folate: methotrexate and trimethoprim (folate antagonists)
  • Hypothyroidism (decreases hepatic levels of dihydrofolate reductase)
  • Congenital deficiency of enzymes of folate metabolism
  • Increased requirement: infancy, pregnancy, lactation, malignancy, concurrent infection (immunoproliferative response), chronic hemolytic anemia (increased hematopoiesis)
  • Increased excretion/loss: vitamin B12 deficiency (causes "folate trap"), chronic alcoholism (increased excretion of folate into bile), hemodialysis (may have excess folate loss)
  • Increased destruction: superoxide can inactivate folate
Clinical features
  • Symptoms due to anemia: weakness, fatigue, difficulty concentrating, irritability, headache, palpitations, shortness of breath, cardiac failure
  • Gastrointestinal symptoms: anorexia, nausea, vomiting, abdominal pain, diarrhea (especially after meals)
  • Neurologic: cognitive impairment, dementia, depression

  • Coronary artery disease, stroke
  • Pregnancy complications include spontaneous abortion, abruption placentae, congenital malformations (neural tube defects), severe language delay
  • Serum folate levels < 3 ng/mL and a red blood cell (RBC) folate level < 140 ng/mL indicate folate deficiency
  • Normal serum folate level is 2.5-20 ng/mL
  • Normal serum cobalamin is 200-900 pg/mL
  • The RBC folate level generally indicates folate stored in the body
  • Serum folate level tends to reflect acute changes in folate intake
  • Mild hyperhomocystinemia is total plasma concentration of 15-25 mmol/L; moderate hyperhomocystinemia is 26-50 mmol/L
Case reports
  • Important to rule out cobalamin (Vitamin B12) deficiency because folate treatment will not improve neurologic abnormalities due to cobalamin deficiency
Microscopic (histologic) images

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Megaloblastic erythroid precursors

Cytology description
  • Bone marrow biopsy and aspirate may show a hypercellular bone marrow with a megaloblastic maturation of cells, which morphologically resembles changes of vitamin B12 deficiency
Peripheral smear images

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Hypersegmented neutrophils, macro ovalocytes

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