Can iron deficiency cause thrombocytopenia (low platelet count)?

Can Iron Deficiency Cause Thrombocytopenia?

Yes, severe iron deficiency can cause thrombocytopenia, though this is uncommon—iron deficiency typically causes thrombocytosis, making this a rare but important differential diagnosis that can be mistaken for immune thrombocytopenic purpura (ITP). 1, 2

Mechanism and Clinical Context

Iron deficiency-associated thrombocytopenia represents a central production defect with decreased platelet formation in the bone marrow, distinguishing it from peripheral destruction seen in ITP. 1

Key Pathophysiologic Features:

• The thrombocytopenia occurs through decreased megakaryopoiesis despite increased megakaryocyte numbers in the bone marrow 2
• Immature platelet fraction (IPF) is characteristically low, indicating reduced platelet production rather than increased peripheral destruction 1
• The "two-compartment model" suggests iron plays a direct role in maintaining platelet counts beyond its effects on erythropoiesis 3

Clinical Presentation Pattern

Severe iron deficiency thrombocytopenia typically presents with profound anemia (hemoglobin often <5 g/dL), microcytic hypochromic red cells, and platelet counts ranging from 30,000-150,000/mm³. 2, 3, 4

Characteristic Laboratory Findings:

• Marked microcytic anemia with mean corpuscular volume (MCV) typically <50 fL 2
• Ferritin levels profoundly low (often <3 μg/L) 2
• Increased red cell distribution width (RDW) 3
• Low iron saturation 3
• Bone marrow shows increased megakaryocytes (mimicking ITP) but with absent iron stores 2

Critical Diagnostic Pitfall

The presence of increased megakaryocytes on bone marrow examination can lead to misdiagnosis as immune thrombocytopenic purpura, resulting in inappropriate corticosteroid therapy when iron supplementation is the correct treatment. 2

Distinguishing Features from ITP:

• Profound microcytic anemia is present (ITP typically has isolated thrombocytopenia) 5, 2
• Low immature platelet fraction indicates central production defect 1
• Ferritin is markedly low 2
• No abnormalities in white blood cell count (ITP guidelines suggest investigating other cytopenias) 5

Treatment Response

Iron supplementation rapidly corrects the thrombocytopenia, typically normalizing platelet counts within 48 hours to 2 weeks, confirming the diagnosis retrospectively. 2, 3

Treatment Approach:

• Initiate iron supplementation (oral or intravenous depending on severity and tolerance) 2, 3
• Platelet count recovery occurs in 9 ± 3 days on average 6
• Continue iron therapy for 3-6 months to fully replenish stores 7
• Monitor for underlying causes of iron deficiency, particularly gastrointestinal bleeding 5, 7

Important Caveat: Iron Replacement-Induced Thrombocytopenia

Paradoxically, iron replacement therapy itself can cause transient thrombocytopenia, particularly with parenteral administration, though this is typically self-limited. 6, 4

Key Features of Iron-Induced Thrombocytopenia:

• Occurs 9 ± 3 days after starting iron replacement 6
• Platelet counts drop to average of 121 ± 112 × 10⁹/L 6
• More commonly reported with intravenous iron 6
• Usually self-corrects with continued supplementation 6, 4
• Rarely requires discontinuation of therapy 6

Clinical Context from Guidelines

While the provided guidelines primarily address thrombocytopenia in other contexts (cyanotic heart disease, myelodysplastic syndromes, ITP), they establish important principles:

• The American Society of Hematology recommends investigating abnormalities in complete blood count beyond isolated thrombocytopenia before diagnosing ITP 5
• Microcytic anemia attributed to chronic blood loss should prompt iron studies 5
• In cyanotic congenital heart disease, iron deficiency can worsen polycythemia-associated complications and contribute to platelet abnormalities 5