A 38-year-old man with a 10-year history of Crohn's disease presents with macrocytic anemia. Serum B12 and folate levels are both low. Which of the following findings is NOT expected in the peripheral blood film of this patient?

Explanation

## Peripheral Blood Film Findings in Megaloblastic Anemia **Key Point:** Megaloblastic anemia is characterized by **nuclear-cytoplasmic asynchrony** — nuclear maturation lags behind cytoplasmic maturation. This produces distinctive morphologic changes on blood film. ### Expected Findings in Megaloblastic Anemia | Finding | Mechanism | Significance | |---------|-----------|---------------| | Hypersegmented neutrophils (>5 lobes) | Prolonged maturation of granulocyte nucleus | Highly specific for megaloblastosis; normal is 3–4 lobes | | Macro-ovalocytes | Increased MCV (100–140 fL); oval shape from nuclear enlargement | Pathognomonic morphology | | Anisocytosis | Mixed population of large and normal RBCs | Reflects asynchronous maturation | | Polychromasia | Immature RBCs released early due to ineffective erythropoiesis | Indicates bone marrow response | | Howell-Jolly bodies | Nuclear remnants from abnormal nuclear extrusion | Seen in severe cases | ### Why Polychromasia and Reticulocytosis Are NOT Expected **High-Yield:** Megaloblastic anemia is characterized by **ineffective erythropoiesis** — most developing RBCs die in the bone marrow before reaching the peripheral blood. This results in: 1. **Low reticulocyte count** (inappropriately low for the degree of anemia) 2. **Absence of polychromasia** (few young RBCs escape to circulation) 3. **High LDH and indirect bilirubin** (from intramedullary hemolysis) **Clinical Pearl:** The hallmark of megaloblastic anemia is a **low reticulocyte count despite severe anemia** — this distinguishes it from hemolytic anemia or acute blood loss, where reticulocytosis is brisk. **Mnemonic: INEFFECTIVE** — Inadequate DNA synthesis → Nuclear-cytoplasmic asynchrony → Erythroid precursor death IN marrow → Fewer RBCs reach blood → Elevated intramedullary hemolysis → Corrected reticulocyte count LOW (not elevated) → Typical findings: Macro-ovalocytes, hypersegmented neutrophils, anisocytosis ### Bone Marrow Findings (Supportive) - Megaloblastic erythroblasts (large, immature nucleus with fine chromatin) - Giant metamyelocytes and band forms - Hypercellular marrow with erythroid predominance - Increased mitotic activity (paradoxically, despite low reticulocytes) **Warning:** Do not confuse megaloblastic anemia with hemolytic anemia. Both cause macrocytosis, but hemolytic anemia shows **high reticulocytosis and polychromasia**, while megaloblastic anemia shows **low reticulocytosis and absent polychromasia**.