Anemia questions: here’s exactly where to start 🩸

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Greetings Gang 😈😜

When a CBC flags for anemia at the bench, nobody sits there reciting every anemia ever named. We look at the MCV, then the retic, then the smear. Done. The exam works the same way.

Every anemia case, I run the same 3 questions:

𝟭. 𝗪𝗵𝗮𝘁'𝘀 𝘁𝗵𝗲 𝗠𝗖𝗩? (small, normal or big cells)

𝟮. 𝗪𝗵𝗮𝘁'𝘀 𝘁𝗵𝗲 𝗿𝗲𝘁𝗶𝗰? (is the marrow keeping up or not)

𝟯. 𝗪𝗵𝗮𝘁'𝘀 𝘁𝗵𝗲 𝗼𝗻𝗲 𝗰𝗹𝘂𝗲 𝘁𝗵𝗮𝘁 𝗰𝗹𝗼𝘀𝗲𝘀 𝗶𝘁? (iron studies, smear, or the patient's story)

Let's run 5 cases exactly like you'd see them on the exam.

🩸 CASE 1

A 28-year-old woman complains of fatigue and heavy periods. She says she's been craving ice.

Hgb 9.1 g/dL | MCV 71 fL | RDW 18.5% (high)

Ferritin 5 ng/mL (low) | Serum iron 25 µg/dL (low) | TIBC 480 µg/dL (high)

Breaking it down:

MCV 71 → small cells → think iron deficiency, chronic disease, thalassemia, sideroblastic

RDW high → lots of variation in cell size, which fits iron deficiency

Ferritin LOW + TIBC HIGH → her iron stores are empty, and her body is grabbing for more

Story clues: heavy periods (blood loss) + craving ice (pica)

✅ Answer: Iron deficiency anemia

Trap answer: anemia of chronic disease. It's also low iron, but ferritin is normal or HIGH and TIBC is LOW. If ferritin is low, you're done: it's iron deficiency.

🩸 CASE 2

A 24-year-old man of Mediterranean descent has a routine physical. He feels fine.

Hgb 11.8 g/dL | MCV 64 fL | RBC 6.1 x10¹²/L (high) | RDW 13.5% (normal)

Ferritin 85 ng/mL (normal)

Smear: target cells, basophilic stippling

Breaking it down:

MCV 64 → very small cells, but he's barely anemic and has no symptoms

RBC count HIGH → his marrow is pumping out LOTS of tiny cells. That's a classic thalassemia clue. Iron deficiency usually has a LOW RBC count.

RDW normal → the cells are all evenly small

Ferritin normal → this is NOT an iron problem

✅ Answer: Beta Thalassemia (likely beta thalassemia minor)

Next best test: hemoglobin electrophoresis. Look for Hb A2 > 3.5%.

Trap answer: "Start iron supplements." Giving iron to a thalassemia patient with normal iron stores can cause iron overload.

🩸 CASE 3

A 67-year-old man had gastric bypass surgery 5 years ago. He now has numbness and tingling in his feet.

Hgb 8.9 g/dL | MCV 118 fL | WBC 3.8 x10⁹/L (low) | PLT 120 x10⁹/L (low)

Retic: low | LD: very high

Smear: oval macrocytes, hypersegmented neutrophils

Methylmalonic acid: increased

Breaking it down:

MCV 118 → big cells

Hypersegmented neutrophils → megaloblastic anemia (B12 or folate)

Numbness/tingling + gastric bypass → no stomach acid or intrinsic factor to absorb B12

MMA increased → confirms B12 (MMA is normal in folate deficiency)

✅ Answer: Vitamin B12 deficiency

Trap: the high LD can make you think "hemolysis!" But look at the retic. It's LOW. In megaloblastic anemia, the cells die inside the marrow before they ever get out. In true hemolysis, the retic goes UP.

🩸 CASE 4

A 19-year-old woman has fatigue and yellow eyes. Her mom had her spleen removed when she was young.

Hgb 9.5 g/dL | MCV 88 fL | MCHC 37.5 g/dL (high) | Retic 9% (high)

Indirect bilirubin ↑ | LD ↑ | Haptoglobin ↓

DAT: negative

Smear: spherocytes

Breaking it down:

MCV 88 → normal size, so go straight to the retic

Retic HIGH → the marrow is working hard, so cells are being destroyed (hemolysis)

Indirect bili ↑ + LD ↑ + haptoglobin ↓ → confirms hemolysis

Spherocytes → hereditary spherocytosis OR warm autoimmune hemolytic anemia

DAT NEGATIVE → not autoimmune

Family history + high MCHC → hereditary

✅ Answer: Hereditary spherocytosis

Confirm with: osmotic fragility (increased) or EMA binding by flow cytometry

Trap answer: warm autoimmune hemolytic anemia. It also has spherocytes, but the DAT is POSITIVE.

🩸 CASE 5: B12 deficiency vs. pernicious anemia

Two patients, same CBC. Can you tell them apart?

PATIENT A: A 64-year-old man who has taken metformin for diabetes and an acid reducer (PPI) for heartburn for over 10 years

PATIENT B: A 62-year-old woman with Hashimoto's thyroiditis and no long-term medications

Both patients:

Hgb 9.0 g/dL | MCV 115 fL | Hypersegmented neutrophils

Vitamin B12: low | Methylmalonic acid ↑ | Homocysteine ↑

So far they look IDENTICAL. Both have a B12 deficiency. The question is WHY.

Patient B's extra labs:

Anti-intrinsic factor antibodies: POSITIVE

Anti-parietal cell antibodies: POSITIVE

Serum gastrin: ↑

Breaking it down:

Intrinsic factor (IF) is a protein made by the parietal cells in the stomach. B12 has to bind to IF to be absorbed in the ileum. No IF = no B12 absorbed, no matter how much you take in.

Patient A's medications are the problem. Long-term metformin and acid reducers both interfere with B12 absorption. His stomach still makes intrinsic factor, and his antibodies are negative.

✅ Answer A: Medication-related B12 deficiency. Fix: B12 supplements (by mouth can work) and review his medications.

Patient B's immune system is attacking her parietal cells and her intrinsic factor. She can't absorb B12 from food or pills.

✅ Answer B: Pernicious anemia (autoimmune). Fix: B12 shots, because oral B12 can't be absorbed well without IF.

How to tell them apart on the exam:

Anti-IF antibodies = very SPECIFIC for pernicious anemia (if positive, that's your answer)

Anti-parietal cell antibodies = more SENSITIVE but less specific (can show up in other autoimmune diseases)

Gastrin ↑ = the stomach isn't making acid, so it keeps calling for more

Other autoimmune disease (Hashimoto's, type 1 diabetes, vitiligo) = big story clue for pernicious anemia

Remember: ALL B12 deficiencies have low B12, high MMA, high homocysteine and hypersegs. Those labs tell you it's B12. The 𝗮𝗻𝘁𝗶𝗯𝗼𝗱𝗶𝗲𝘀 tell you it's pernicious anemia.

Throwback the exam still loves: the Schilling test. Patients took radioactive B12 by mouth, and the lab measured how much came out in the urine. In pernicious anemia, absorption improved when IF was given with the B12.

🧐 Your turn (answer in the comments!):

A 32-year-old man of Mediterranean descent eats a big plate of fava beans at a family dinner. Two days later he has dark urine, yellow eyes and fatigue.

Hgb 8.2 g/dL (was 14.5) | MCV 90 fL | Retic ↑ | Haptoglobin ↓ | DAT negative

Smear: bite cells

Supravital stain: Heinz bodies

What's the diagnosis?

Drop your answer below, and I'll reply to every one.

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1 comment

Anemia questions: here’s exactly where to start 🩸