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Hub / Organ Systems / Hematology & Oncology
COMLEX Level 1 • Level 2-CE • COMAT • 8–11% Blueprint Weight

Hematology & Oncology Command Center

High-yield hematology pathophysiology, algorithmic MCV-based anemia workups, peripheral blood smear cytology exhibits, coagulation cascade and mixing studies, leukemia and lymphoma cytogenetics, and plasma cell dyscrasias.

Erythrocyte Size: MCV < 80 fL

Microcytic Hypochromic Anemia Differential Matrix

Iron • Ferritin • TIBC • Mentzer Index
Condition Serum Iron Serum Ferritin TIBC (Transferrin) % Transferrin Saturation Diagnostic Hallmark & Board Pearl
Iron Deficiency Anemia (IDA) ↓↓ Low ↓↓ Low (< 15 ng/mL) ↑↑ High ↓↓ Low (< 15%) #1 cause worldwide. Increased RDW (anisocytosis); microcytic hypochromic RBCs with pencil cells; in adult males or postmenopausal females, always order colonoscopy to rule out occult GI malignancy!
Anemia of Chronic Disease (ACD) ↓ Low ↑ Normal to High ↓ Low Normal to ↓ (15–25%) Inflammatory IL-6 stimulates hepatic production of Hepcidin → degrades ferroportin → traps iron inside macrophages and enterocytes, preventing release into circulation.
Thalassemia Trait (α or β) Normal to High Normal to High Normal Normal to High Mentzer Index (MCV / RBC count) < 13 strongly favors thalassemia! Normal RDW; Target cells (codocytes) on smear; β-thalassemia trait shows elevated HbA2 (> 3.5%) on hemoglobin electrophoresis.
Sideroblastic Anemia ↑↑ High ↑↑ High Normal to ↓ ↑↑ High (> 50%) Defect in heme synthesis (X-linked ALAS2, lead poisoning, alcoholism, isoniazid/vitamin B6 deficiency); Prussian blue stain of bone marrow reveals ringed sideroblasts (iron trapped in perinuclear mitochondria).
Blood Smear Exhibit

Megaloblastic Anemia: Hypersegmented PMN

≥ 6 Lobes
Peripheral blood smear showing hypersegmented neutrophil with six nuclear lobes in megaloblastic anemia

Cytological Clue: Neutrophil with ≥ 6 lobes (or ≥ 5% of neutrophils with 5 lobes) indicating impaired DNA synthesis with nuclear-cytoplasmic dyssynchrony.

B12 vs. Folate Differentiation:

  • • Vitamin B12 Deficiency: Elevated Methylmalonic Acid (MMA) AND Homocysteine. Causes Subacute Combined Degeneration (SCD) of spinal cord (dorsal columns + lateral corticospinal tracts; ataxia + paresthesias).
  • • Folate Deficiency: NORMAL MMA and elevated Homocysteine. No neurological deficits!
Hemolytic Anemia Exhibit

Hereditary Spherocytosis (HS)

Osmotic Fragility
Peripheral smear showing small dense spherical erythrocytes without central pallor in hereditary spherocytosis

Molecular Defect: Autosomal dominant mutation in RBC membrane skeleton proteins (Ankyrin, Spectrin, or Band 3) → membrane blebbing and loss of surface area → sphere-shaped RBCs without central pallor.

Triad & Labs: Hemolytic anemia, jaundice, and splenomegaly. Elevated MCHC (> 36%), negative direct Coombs test, and positive Eosin-5-maleimide (EMA) binding / acidified glycerol lysis test.

Definitive Treatment: Splenectomy (resolves hemolysis; spherocytes persist on smear, accompanied by newly visible Howell-Jolly bodies!).