Medical Knowledge: Hematologic Pathophysiology
Core concepts
Medical knowledge questions test mechanistic understanding across benign and malignant hematology. Key frameworks include: hemoglobin structure and oxygen dissociation (shift with pH, 2,3-BPG, temperature), iron homeostasis (hepcidin, ferroportin), and the coagulation cascade with the cell-based model. Malignant hematology requires familiarity with WHO classification, prognostic markers (e.g., cytogenetics in AML, IPSS-R in MDS, CLL FISH), and targeted therapies (tyrosine kinase inhibitors, BTK inhibitors, venetoclax).
Traps
- Confusing anemia of chronic disease (low iron, low TIBC, high ferritin) with iron deficiency (low iron, high TIBC, low ferritin).
- Assuming a normal PT/PTT excludes a factor deficiency-factor XIII deficiency gives normal screening tests.
- Missing that a left shift with toxic granulation suggests infection rather than leukemia.
- Forgetting that B12 deficiency can cause both macrocytic anemia and neurologic findings without anemia.
Worked example
A patient with fatigue, MCV 112, hypersegmented neutrophils, and paresthesias: check B12 and methylmalonic acid. Elevated MMA confirms B12 deficiency even if serum B12 is borderline. Treat before assuming folate deficiency, since folate replacement can mask B12 neurologic progression.
Rule of thumb
Match the morphologic and laboratory pattern to a mechanism-never diagnose on a single number.