Bone Marrow Causes of Iron Deficiency Anemia
Iron deficiency anemia itself does not originate from primary bone marrow pathology—rather, the bone marrow demonstrates an appropriate but inadequate response to iron depletion. However, certain bone marrow conditions can mimic or coexist with iron deficiency anemia, and understanding the bone marrow's role in iron-deficient states is clinically important.
Understanding the Bone Marrow Response in Iron Deficiency
The bone marrow in true iron deficiency anemia shows absent iron stores on bone marrow biopsy, which remains the gold standard for confirming iron deficiency 1. This is a diagnostic finding rather than a causative pathology—the marrow is responding appropriately to lack of available iron.
Key Diagnostic Features:
- Low reticulocyte index (RI < 1.0-2.0) indicates decreased RBC production, which occurs in iron deficiency because the bone marrow lacks the iron substrate needed for hemoglobin synthesis 2
- The bone marrow examination in iron deficiency reveals absence of stainable iron stores (hemosiderin) in macrophages, distinguishing it from other microcytic anemias 1
- Bone marrow aspiration can confirm true iron deficiency when serum markers are equivocal, particularly in patients with concurrent inflammation where ferritin may be falsely elevated 2
True Bone Marrow Pathologies That Cause Microcytic Anemia
While iron deficiency itself is not a bone marrow disorder, several primary bone marrow conditions can present with microcytic anemia and must be differentiated:
Sideroblastic Anemia
- Sideroblastic anemia is characterized by the presence of ring sideroblasts in the bone marrow, representing iron-loaded mitochondria surrounding RBC nuclei 2
- This represents a defect in heme synthesis within the bone marrow despite adequate or increased iron stores 2
- Unlike iron deficiency, ferritin levels are typically normal or elevated 1
Bone Marrow Failure Syndromes
- Aplastic anemia and myelodysplastic syndromes (MDS) cause decreased RBC production with low reticulocyte counts 2, 3
- These conditions typically present with abnormalities in two or more cell lines (pancytopenia), which should prompt hematology consultation 2
- MDS can cause macrocytosis rather than microcytosis, distinguishing it from iron deficiency 4, 5
Bone Marrow Infiltration
- Bone marrow infiltration by cancer (such as prostate or breast cancer metastases) can cause anemia 4
- Hematological malignancies affecting the bone marrow can impair erythropoiesis 3
- These typically present as normocytic or macrocytic rather than microcytic anemia 2
Critical Distinction: Production vs. Supply Problem
The fundamental concept is that iron deficiency anemia represents a supply problem (lack of iron substrate) rather than a primary bone marrow production defect 6:
- In iron deficiency, the bone marrow is functionally normal but cannot produce adequate hemoglobin due to absent iron stores 1
- The low reticulocyte count reflects appropriate bone marrow response to lack of available iron, not intrinsic marrow failure 2
- Bone marrow dysfunction from cancer or chemotherapy causes anemia through direct impairment of erythropoiesis, which is mechanistically different 2
Clinical Pitfalls to Avoid
- Do not assume microcytic anemia with low reticulocytes automatically means simple iron deficiency—consider sideroblastic anemia if iron studies show adequate stores 2
- In patients with chronic inflammation or malignancy, ferritin may be elevated (>100 μg/dL) despite true iron deficiency, making bone marrow examination the definitive test 2
- Anemia of chronic disease can present with microcytosis and represents functional iron deficiency (iron sequestration in macrophages) rather than true depletion 2, 6
- Check for pancytopenia—if present, this suggests primary bone marrow pathology requiring different evaluation than isolated iron deficiency 2