Vitamin B12 Deficiency / Pernicious Anemia vs Folate Deficiency Anemia
Vitamin B12 Deficiency / Pernicious Anemia and Folate Deficiency Anemia are easy to mix up on the boards. Here's a side-by-side comparison — presentation, workup, imaging, and first-line treatment — drawn from our full outlines.
Vitamin B12 Deficiency / Pernicious Anemia vs Folate Deficiency Anemia at a glance
- Vitamin B12 Deficiency / Pernicious Anemia: Macrocytic megaloblastic anemia with neurologic features from cobalamin deficiency.
- Folate Deficiency Anemia: Macrocytic megaloblastic anemia without neurologic features — develops faster than B12 deficiency due to smaller body stores.
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Side-by-side comparison
| Feature | Vitamin B12 Deficiency / Pernicious Anemia | Folate Deficiency Anemia |
|---|---|---|
| At a glance | Macrocytic megaloblastic anemia with neurologic features from cobalamin deficiency. | Macrocytic megaloblastic anemia without neurologic features — develops faster than B12 deficiency due to smaller body stores. |
| Classic presentation | Subacute combined degeneration — dorsal column + lateral corticospinal tract demyelination causing posterior column sensory loss with UMN signs. Neurologic deficits can occur WITHOUT anemia.; Fatigue, dyspnea on exertion, pallor; Glossitis (smooth, beefy red, painful tongue), angular cheilitis; Anorexia, weight loss, diarrhea;… | Megaloblastic anemia in an alcoholic or pregnant patient with hypersegmented neutrophils and a normal neurologic exam.; Fatigue, dyspnea on exertion, pallor; Glossitis, angular cheilitis; Diarrhea, anorexia, weight loss; NO paresthesias, NO ataxia, NO cognitive deficit (distinguishes from B12 deficiency); Pallor, tachycardia, mild… |
| Workup / key labs | Low serum B12 (<200 pg/mL) OR borderline B12 with elevated MMA, plus clinical/laboratory features consistent with deficiency. Pernicious anemia confirmed by positive anti-intrinsic factor antibody.; CBC — macrocytic anemia (MCV often >110 fL), pancytopenia in advanced cases; Peripheral smear — oval macrocytes, hypersegmented neutrophils… | Macrocytic megaloblastic anemia + low serum/RBC folate + normal B12 + elevated homocysteine with normal MMA.; CBC — macrocytic anemia, often pancytopenia in severe cases; Peripheral smear — oval macrocytes, hypersegmented neutrophils, anisopoikilocytosis; Serum folate — low (<2-4 ng/mL); reflects recent intake and rises within 24 hours… |
| Imaging | MRI cervical/thoracic spine — T2 hyperintensity in dorsal columns ('inverted V sign') in subacute combined degeneration; EGD with biopsy if pernicious anemia suspected — atrophic gastritis; ~3x risk of gastric adenocarcinoma and carcinoid | Not generally indicated; targeted workup for underlying cause (celiac serology, EGD if malabsorption suspected) |
| First-line treatment | Cyanocobalamin or hydroxocobalamin IM — 1000 mcg IM daily for 1 week, then weekly for 4 weeks, then monthly for life (pernicious anemia) or until cause corrected; High-dose oral cyanocobalamin 1000-2000 mcg daily — alternative for non-PA causes and stable PA patients; ~1% absorbed passively independent of intrinsic factor; Sublingual… | Folic acid 1-5 mg orally daily for 1-4 months until hematologic recovery, then continue or address underlying cause; Confirm B12 status FIRST — never give folate alone to a patient with possible B12 deficiency; Folinic acid (leucovorin) for methotrexate/trimethoprim-induced deficiency (bypasses dihydrofolate reductase block); Treat… |
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