The most likely diagnosis in this patient is acquired sideroblastic anemia.  Sideroblastic anemias consist of different types of anemias characterized by defects in heme synthesis (eg, in mitochondria) and ring sideroblasts (nucleated erythroblasts with mitochondrial iron granules surrounding the nucleus).  They can be congenital (presenting in children or adolescents) or acquired (most common).  Although acquired sideroblastic anemias may be related to clonal abnormalities (eg, myelodysplastic syndrome), they are frequently due to reversible etiologies (eg, alcohol, malnutrition, medications) that lead to pyridoxine-dependent impairment in the early steps of protoporphyrin synthesis within mitochondria.

This patient is on isoniazid (INH), a well-known pyridoxine (vitamin B6) antagonist that can cause acquired sideroblastic anemia.  It frequently manifests as microcytic hypochromic anemia, simulating iron deficiency anemia.

• As can sometimes be seen with iron deficiency anemia, usually 2 groups of red blood cells (RBCs) can be demonstrated on microscopy: hypochromic and normochromic ("dimorphic" RBC population), likely reflecting the defective heme synthesis.
• Unlike iron deficiency anemia, iron studies typically reveal increased serum iron concentration and normal or decreased total iron binding capacity due to mitochondrial mishandling of iron (explaining the mitochondrial iron granules seen in ring sideroblasts); in contrast, iron deficiency anemia is characterized by decreased serum iron concentration and high total iron binding capacity.

In this patient with an easily identifiable cause of vitamin B6 deficiency (ie, INH), administration of pyridoxine is the most reasonable next step.  Bone marrow sampling can confirm the diagnosis by demonstrating ring sideroblasts (a specific finding in sideroblastic anemia), but it is not necessary in this patient (Choice A).

(Choices C and D)  Folic acid or the combination of folic acid with vitamin B12 is employed in patients with macrocytic anemia (which would cause an elevated mean corpuscular volume).

Educational objective:
Sideroblastic anemia usually manifests as microcytic/hypochromic anemia simulating iron-deficiency anemia, but iron studies reveal elevated serum iron level and normal or decreased total iron binding capacity.  In patients with an identifiable cause of vitamin B6 deficiency (alcohol, medications), the administration of pyridoxine can easily correct the problem.