The Anemia Sorting Hat

Drag Each Anemia Into Its MCV Bucket

If you get one wrong, it bounces back — try again.

Iron Deficiency — The #1 Anemia on Earth

Most common anemia worldwide. The body doesn't have enough iron to make hemoglobin, so the cells come out small and pale.

• Smear: microcytic, hypochromic (pencil cells = ovalocytes flattened by low hemoglobin) 🔑Pencil cells = pencil thin on iron — they're writing a letter asking for more
• Iron studies: ↓ ferritinFerritin = storage form of iron. Low ferritin = empty warehouse. Most specific single test for iron deficiency., ↓ serum iron, ↑ TIBCTotal Iron Binding Capacity — how many empty seats are on the transferrin bus. High TIBC = lots of empty seats = body desperate for iron., ↓ % saturation
• Causes: Blood loss (#1 in adults — menstruation, GI bleed), poor intake (infants, vegans), poor absorption (celiac, gastrectomy)

Thalassemia — Genes Made Less Hemoglobin

Genetic defect → less globin chain production → small cells. But the body has iron — it just can't use it properly for hemoglobin.

• Smear: microcytic but with target cells (bullseye appearance) 🔑Target cells = Thalassemia. Both start with T. Bullseye = genetic target.
• Iron studies: NORMAL (this is the key differentiator from iron deficiency!)
• Diagnosis: Hemoglobin electrophoresisSeparates hemoglobin types by charge. HbA2 ↑ in beta-thal trait. HbF ↑ in beta-thal major. Normal in alpha-thal (deletion doesn't change Hb type, just quantity).
• Red cell count: Often ↑ (body compensates by making MORE small cells)

Sideroblastic Anemia — Iron Trapped in the Wrong Place

The body HAS iron. It just can't put it into hemoglobin. Iron accumulates in mitochondriaThe iron deposits form a ring around the nucleus of developing red cells in the bone marrow — "ringed sideroblasts." The iron is literally stuck in the wrong compartment. of developing red cells → ringed sideroblasts on bone marrow biopsy.

• Iron studies: ↑ ferritin, ↑ serum iron (iron is there, just misplaced)
• Causes: Lead poisoning, alcohol, B6 (pyridoxine) deficiency, isoniazid, myelodysplastic syndrome
• Smear: microcytic + basophilic stipplingBlue dots in the red cell from precipitated RNA. Classic for lead poisoning and sideroblastic anemia. The ribosomal RNA that should have been cleared out is stuck because enzyme pathways are broken.

Lead Poisoning — A Special Sideroblastic

Lead inhibits two enzymes in heme synthesis: ALA dehydrataseFirst enzyme hit by lead. ALA (aminolevulinic acid) builds up in urine. This is the screening marker. and ferrochelataseLast enzyme — inserts iron into protoporphyrin. When it's blocked, free erythrocyte protoporphyrin (FEP) skyrockets. Iron can't get into the ring.. Result: iron can't get into heme → sideroblastic picture.

• Classic presentation: Kid eating paint chips. Or adult with occupational exposure.
• Labs: ↑ free erythrocyte protoporphyrin (FEP), ↑ ALA in urine, basophilic stippling on smear
• Other symptoms: Lead lines on gums/bones, wrist/foot drop, abdominal colic, encephalopathy in kids

B12 Deficiency — The Neuro One

Megaloblastic anemia + neurological symptoms. B12 is needed for DNA synthesis AND myelin maintenance.

• Smear: macro-ovalocytes + hypersegmented neutrophils (≥5 lobes = pathognomonic for megaloblastic anemia)
• Neuro: Subacute combined degeneration — loss of position sense, vibration sense, ataxia. Affects dorsal columnsPosterior columns of the spinal cord carry proprioception and vibration. B12 deficiency demyelinates these first. Patient can't tell where their feet are without looking. and lateral corticospinal tractsUpper motor neuron tracts. Damage here causes spasticity, hyperreflexia, positive Babinski. Combined with dorsal column loss = "subacute combined degeneration."
• Causes: Pernicious anemia (#1 — autoimmune destruction of parietal cells → no intrinsic factorMade by parietal cells. Binds B12 in the stomach, carries it to the terminal ileum for absorption. No IF = no B12 absorption regardless of intake.), vegan diet, Crohn's/ileal resection, Diphyllobothrium latum (fish tapeworm)

Folate Deficiency — The Diet One

Same megaloblastic picture as B12 — hypersegmented neutrophils, macro-ovalocytes. But NO neuro symptoms.

• Causes: Poor diet (#1 — alcoholics, elderly), pregnancy (↑ demand), methotrexate/phenytoin/TMP-SMX (folate antagonists)
• Key difference from B12: Folate stores only last ~4 months. B12 stores last ~3-4 years. Folate deficiency develops FAST.

Non-Megaloblastic Macrocytic

Big cells but NO hypersegmented neutrophils. DNA synthesis is fine — the cell membrane is just weird.

• Alcohol: Direct toxic effect on RBC membrane + usually folate-deficient too
• Liver disease: Excess cholesterol deposits in RBC membranes → cells swell
• Hypothyroidism, reticulocytosis (reticulocytes are bigger than mature RBCs), myelodysplastic syndrome

Hemolytic Anemias — Cells Dying Too Fast

Red cells are being destroyed before their 120-day lifespan. The marrow tries to compensate → ↑ reticulocytes.

• General labs: ↑ LDHLactate dehydrogenase — released when cells burst. Elevated in any hemolysis. Not specific but very sensitive., ↑ indirect bilirubin, ↓ haptoglobinHaptoglobin binds free hemoglobin released from lysed cells. When lots of cells lyse, haptoglobin gets used up → levels drop. Low haptoglobin = hemolysis until proven otherwise., ↑ reticulocytes
• Intravascular hemolysis (in the blood vessels): hemoglobinuria, hemoglobinemia, schistocytes on smear
• Extravascular hemolysis (in the spleen): splenomegaly, spherocytes on smear

Anemia of Chronic Disease — The Body's Sabotage

Chronic inflammation → liver pumps out hepcidinHepcidin is the iron gatekeeper. It blocks ferroportin on gut cells and macrophages, trapping iron inside cells. The body HIDES iron from bacteria during infection — but also from your own red cells. → iron gets LOCKED in storage → can't get to the marrow.

• Iron studies: ↑ ferritin (iron is there, just locked up), ↓ TIBC (body isn't looking for more iron), ↓ serum iron
• Usually normocytic but can be mildly microcytic
• Treatment: Treat the underlying disease. Iron supplements won't help — the iron is already there.