A 55-year-old man presents to the clinic for a follow-up visit regarding his treatment for pulmonary tuberculosis. He has been taking isoniazid, rifampin, pyrazinamide, and ethambutol for the past three months. He reports increasing fatigue and difficulty climbing stairs. He denies any chest pain, shortness of breath, or bleeding. Vital signs are within normal limits. Physical examination reveals mild conjunctival pallor. Laboratory studies show a hemoglobin of 9.5 g/dL, mean corpuscular volume (MCV) of 74 fL, and a platelet count of 240,000/μL. His iron studies demonstrate a serum iron of 180 μg/dL (normal: 50–170), serum ferritin of 450 ng/mL (normal: 20–250), and a total iron-binding capacity (TIBC) of 220 μg/dL (normal: 240–450).
A bone marrow biopsy is performed. Which of the following findings is most likely to be present?
The correct answer is:
D) Ringed sideroblasts
This patient has developed anemia due to his isoniazid therapy. Isoniazid is a pyridoxine (vitamin B6) antagonist. Pyridoxine is a required cofactor for δ-aminolevulinic acid (ALA) synthase, the rate-limiting enzyme in heme synthesis. Inhibition of this enzyme impairs heme production, leading to the accumulation of iron within the mitochondria of developing erythroblasts. This accumulation creates the classic ringed sideroblasts seen on bone marrow examination when stained with Prussian blue. This is a form of acquired sideroblastic anemia. Laboratory findings classically show iron overload (high serum iron, high ferritin) and often a decreased TIBC, as the body attempts to compensate for the fact that it cannot effectively utilize the iron for heme synthesis.
Answer choice A: Basophilic stippling, is incorrect. Basophilic stippling represents aggregated ribosomal RNA and is classically associated with lead poisoning or thalassemia. While lead poisoning can also cause a sideroblastic anemia, the patient's presentation with isoniazid use makes drug-induced sideroblastic anemia the primary diagnosis, and ringed sideroblasts are the defining hallmark of the condition.
Answer choice B: Heinz bodies, is incorrect. Heinz bodies represent denatured hemoglobin precipitates. They are characteristic of glucose-6-phosphate dehydrogenase (G6PD) deficiency, which leads to episodic hemolytic anemia, not the microcytic, iron-overloaded picture seen in this patient.
Answer choice C: Hypersegmented neutrophils, is incorrect. Hypersegmented neutrophils are a classic finding in megaloblastic anemia, most commonly caused by folate or vitamin B12 deficiency. These conditions present with macrocytic anemia (high MCV), which contrasts with this patient's microcytic anemia.
Answer choice E: Target cells, is incorrect. Target cells are red blood cells with a central area of pigment surrounded by a clear ring. They are most commonly associated with hemoglobinopathies such as thalassemia, liver disease, or post-splenectomy states, rather than the mitochondrial iron overload characterizing sideroblastic anemia.
Key Learning Point
Sideroblastic anemia is a defect in heme synthesis, most commonly due to a failure in the incorporation of iron into protoporphyrin. This leads to iron accumulation in the mitochondria of erythroid precursors (ringed sideroblasts). The laboratory profile typically shows high serum iron, high ferritin, and a normal or low TIBC. Common causes include hereditary defects (ALAS2 mutation), alcohol use, lead poisoning, and vitamin B6 deficiency which can occur secondary to isoniazid therapy.
