A 38-year-old woman from rural India presents with fatigue and pallor. Peripheral blood smear examination shows numerous target cells (codocytes), polychromasia, and occasional nucleated RBCs. Which is the most common cause of target cells on peripheral blood smear?

Explanation

## Target Cells (Codocytes) — Most Common Cause **Key Point:** Target cells result from an increased surface-area-to-volume ratio of RBCs. The **most common cause globally** of target cells on peripheral blood smear is **iron deficiency anemia (IDA)**, which is also the most prevalent anemia worldwide and in rural India. ### Pathophysiology of Target Cell Formation Target cells form when: 1. RBC membrane surface area is relatively increased compared to hemoglobin content 2. In IDA, reduced hemoglobin synthesis leads to hypochromic, microcytic RBCs with excess membrane relative to cell volume 3. The central pallor widens, creating the characteristic "target" or "Mexican hat" appearance ### Comparison of Common Causes | Cause | Mechanism | Associated Findings | Frequency | | --- | --- | --- | --- | | **Iron deficiency anemia** | Reduced Hb synthesis → excess membrane-to-volume ratio | Microcytic, hypochromic RBCs; low serum ferritin; low serum iron; high TIBC | **Most common globally** | | Thalassemia major | Defective β-globin synthesis; chronic hemolysis | Nucleated RBCs, polychromasia, anisopoikilocytosis, hepatosplenomegaly | Common in Mediterranean/Asian populations | | Liver cirrhosis | Increased cholesterol/phospholipid in RBC membrane | Splenomegaly, ascites, coagulopathy; also produces acanthocytes | Common | | Hereditary spherocytosis | Membrane protein defects (spectrin/ankyrin) | Spherocytes (NOT target cells), osmotic fragility positive | Rare | **High-Yield:** Iron deficiency anemia is the **most common cause of target cells** because: - IDA is the single most common anemia worldwide (WHO data) - Rural India has extremely high prevalence of nutritional iron deficiency - Reduced hemoglobin content per cell directly increases the surface-area-to-volume ratio - Target cells are a classic peripheral smear finding in IDA alongside pencil cells and hypochromic microcytes **Clinical Pearl:** While thalassemia major also produces prominent target cells with nucleated RBCs and polychromasia, it is less prevalent than IDA. The question asks for the **most common cause** of target cells overall — that distinction belongs to iron deficiency anemia. Hemoglobin electrophoresis and serum ferritin help differentiate the two conditions. **Warning:** Do not confuse target cells with spherocytes. Spherocytes appear dense and lack central pallor; target cells have prominent central pallor. Hereditary spherocytosis produces spherocytes, NOT target cells. [cite: Wintrobe's Clinical Hematology 13e; Harrison's Principles of Internal Medicine 20e Ch 93; Robbins Basic Pathology 10e Ch 14]