Mili Jain: Key Causes and Diagnosis of Macrocytic Anemia
Mili Jain, Assistant Professor at Pacific Medical College and Hospital, shared a post on LinkedIn:
” ‘Macrocytic Anemia’
Macrocytic anemia is anemia in which the red blood cells are larger than normal, typically with MCV greater than 100 fL.
Important causes
1. Vitamin B12 deficiency:
- Pernicious anemia
- Malabsorption
- Gastrectomy/bariatric surgery
- Ileal disease
- Poor dietary intake
- Certain drugs, e.g. metformin
2. Folate deficiency:
- Poor diet/alcoholism
- Pregnancy
- Malabsorption
- Increased requirement
- Methotrexate and other antifolate drugs
3. Other causes:
- Alcohol
- Liver disease
- Hypothyroidism
- Myelodysplastic syndrome
- Reticulocytosis after hemolysis/bleeding
- Drugs such as hydroxyurea, zidovudine, and some anticonvulsants
Main Classification:
- ‘Megaloblastic’:– Vitamin B12 deficiency, folate deficiency, drugs affecting DNA synthesis
Key Clues: increased MCV
* Macro-ovalocytes
* Hypersegmented neutrophils, Sometimes leukopenia and thrombocytopenia
- ‘Non-megaloblastic’:– Alcohol, liver disease, hypothyroidism, reticulocytosis
Key Clues: No typical megaloblastic morphology.
Important PBF findings in Macrocytic Anemia
‘Megaloblastic anemia’ — classic PBF findings:
- Macro-ovalocytes — most characteristic
- Hypersegmented neutrophils — 5 or more lobes in a significant proportion of neutrophils, and 1% 6 lobes neutrphil.
- Anisocytosis and poikilocytosis
- Oval macrocytes
- Howell–Jolly bodies, basophilic stippling and may be seen
- Pancytopenia may occur in severe cases
Useful investigations
CBC, followed by a peripheral blood smear, followed by a reticulocyte count, followed by vitamin B12 and folate testing.
‘Non-megaloblastic macrocytosis’:
- Round macrocytes/macrocytic RBCs
- Reticulocytosis may be present
- Target cells may suggest liver disease
- No hypersegmented neutrophils.
Depending on the findings:
- Serum B12
- Serum/RBC folate
- Methylmalonic acid (MMA) – increased in B12 deficiency
- Homocysteine – increased in both B12 and folate deficiency
- TSH
- Liver function tests
- LDH, bilirubin, haptoglobin if hemolysis suspected
- Consider bone marrow examination if MDS or another marrow disorder is suspected.
B12 vs Folate — high-yield distinction
Finding:
B12 deficiency:
- MCV , Hypersegmented neutrophils- Present ,increased Homocysteine, increased Methylmalonic acid, Neurological manifestations- Common
Folate deficiency:
- increased MCV, Hypersegmented neutrophils – Present, increased Homocysteine , Methylmalonic acid- Normal, Neurological manifestations- Usually absent
Macro-ovalocytes and hypersegmented neutrophils: think B12/folate deficiency (megaloblastic anemia).
Important: If B12 deficiency is possible, check B12 before treating with folate alone, because folate can correct the anemia while allowing neurological damage from B12 deficiency to progress.”
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