What is Macrocytic Anaemia?
Macrocytic anaemia is a blood disorder characterized by the presence of unusually large red blood cells (macrocytes) in the peripheral blood smear, with a mean corpuscular volume (MCV) typically above 100 fL. It signals a disruption in red blood cell production and maturation.
Understanding its causes, clinical significance, and diagnostic approach is crucial for students, clinicians, and healthcare professionals. A handy mnemonic to remember its differential diagnosis is "FAT RBC"—an engaging and memory-friendly way to tackle a complex topic.
Macrocytic anaemia refers to the reduction in haemoglobin concentration associated with enlarged red blood cells. It’s defined by:
- MCV >100 fL
- Hemoglobin below age/sex reference ranges
- Seen on peripheral smear as large, oval (megaloblastic) or round (non-megaloblastic) RBCs
Megaloblastic vs Non-Megaloblastic Macrocytic Anaemia
| Feature | Megaloblastic Anaemia | Non-Megaloblastic Anaemia |
|---|---|---|
| Common Cause | B12 / Folate deficiency | Alcoholism, Liver disease |
| RBC Shape | Oval macrocytes | Round macrocytes |
| Bone Marrow | Hypercellular, megaloblasts | No megaloblasts |
| Neutrophils | Hypersegmented | Normal |
| MCV | Very high (>110 fL) | Mild increase (100–110 fL) |
FAT RBC Mnemonic – Differential Diagnosis Made Easy
To simplify recall for medical students, use the mnemonic FAT RBC:
- F – Fetus (Pregnancy)
- A – Alcohol (Excessive)
- T – Thyroid Disease (Hypothyroidism)
- R – Reticulocytosis
- B – B12 & Folate Deficiency
- C – Cirrhosis and Chronic Liver Disease
Let’s now understand each in detail.
F – Fetus (Pregnancy)
Pregnancy is a physiological state associated with mild macrocytosis due to:
- Increased plasma volume
- Dilutional anaemia
- Raised demand for folate and B12
Note: Always check folate levels in pregnant women to rule out neural tube defects in the fetus.
A – Alcohol (Excessive Consumption)
Chronic alcoholism leads to macrocytic anaemia by:
- Direct marrow toxicity
- Folate deficiency
- Liver dysfunction
- Acetaldehyde interfering with DNA synthesis
Clue: Elevated GGT + macrocytosis without anaemia is often alcohol-related.
T – Thyroid Disease (Hypothyroidism)
Hypothyroidism slows metabolism and erythropoiesis, causing:
- Mild macrocytosis
- Normochromic anaemia
- Associated hyperlipidemia and fatigue
Lab hint: TSH > 5 mIU/L and low Free T4
R – Reticulocytosis
Reticulocytes are larger than mature RBCs. Seen in:
- Haemolytic anaemia
- Acute blood loss
- Post-treatment of megaloblastic anaemia
Retic count >2% with elevated LDH and indirect bilirubin confirms hemolysis.
B – B12 & Folate Deficiency
Most common cause of macrocytic anaemia. Caused by:
- Poor diet (vegans, alcoholics)
- Malabsorption (Crohn’s, celiac)
- Pernicious anaemia (anti-IF antibodies)
- Drugs: Methotrexate, phenytoin
Neurological symptoms (loss of proprioception, ataxia) → Think B12 deficiency!
C – Cirrhosis & Chronic Liver Disease
In liver disease:
- Lipid changes alter RBC membrane
- Alcohol affects marrow
- Coexisting vitamin deficiencies
Peripheral smear: target cells, macrocytes, spur cells (acanthocytes)
Diagnostic Workup: Labs & Clues
| Test | Findings in Macrocytic Anaemia |
|---|---|
| CBC | Low Hb, High MCV |
| Peripheral Smear | Macrocytes ± hypersegmented neutrophils |
| Reticulocyte Count | Increased in haemolysis |
| Serum B12/Folate | Low in deficiency |
| LFT | Elevated in liver disease |
| TSH | High in hypothyroidism |
| Bone Marrow | Megaloblasts (if megaloblastic) |
Macrocytic Anaemia in Different Age Groups
- Infants: Inborn errors, maternal deficiency
- Adolescents: Vegan diet, menorrhagia
- Adults: Alcohol, hypothyroidism, pregnancy
- Elderly: Pernicious anaemia, MDS (Myelodysplastic Syndrome)
Macrocytosis Without Anaemia: Is It Dangerous?
Yes, macrocytosis without anaemia can be:
- An early clue to evolving disease (e.g., MDS)
- Linked to alcohol abuse
- A sign of thyroid or liver dysfunction
Never ignore an MCV >100 even with normal Hb.
Treatment Strategies Based on Cause
| Cause | Treatment |
|---|---|
| B12 Deficiency | B12 injections or oral |
| Folate Deficiency | Folic acid 5 mg/day |
| Hypothyroidism | Levothyroxine |
| Alcoholism | Abstinence + nutrition |
| Liver Disease | Manage underlying cause |
| Pregnancy | Iron, folate supplements |
Avoid giving folate alone in B12 deficiency → may worsen neuropathy.
Clinical Pearls for NEET PG & MBBS Exams
- Hypersegmented neutrophils = hallmark of megaloblastic anaemia
- MCV >110 fL → suspect B12/folate deficiency
- Peripheral smear is more cost-effective than bone marrow
- MCV 100–110 fL → consider alcohol, liver disease, hypothyroidism
- MCV may remain high even after anaemia corrects in alcoholism
Mnemonic Recap: FAT RBC
Here's the mnemonic again for easy recall:
- F – Fetus (Pregnancy)
- A – Alcohol abuse
- T – Thyroid disease (Hypothyroidism)
- R – Reticulocytosis
- B – B12 & Folate deficiency
- C – Cirrhosis & Chronic liver disease
Tip: Use the smiling RBC character in the diagram as a visual cue for exam recall!
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