Why do patients with iron deficiency anemia (IDA) often have thrombocytosis (high platelet count)?

Why Iron Deficiency Causes Thrombocytosis

Iron deficiency anemia is frequently associated with reactive thrombocytosis (elevated platelet counts), which occurs due to increased erythropoietin levels that stimulate megakaryocyte production in response to anemia. 1

Mechanism of Iron Deficiency-Induced Thrombocytosis

Iron deficiency leads to thrombocytosis through several pathways:

1. Erythropoietin (EPO) Stimulation:

   • When iron deficiency causes anemia, the body increases EPO production
   • High EPO levels stimulate not only red blood cell production but also megakaryocyte proliferation
   • This cross-stimulation leads to increased platelet production 2

2. Altered Thrombopoiesis Regulation:

   • Iron is required for normal thrombopoiesis regulation
   • In iron deficiency, this regulatory mechanism is disrupted, leading to increased platelet production

3. Inflammatory Response:

   • Iron deficiency may trigger mild inflammatory responses
   • Inflammation can stimulate platelet production through cytokine pathways

Clinical Significance

• Prevalence: About 8.1% of patients with iron deficiency anemia develop thrombocytosis (platelet count >450 × 10^9/L) 3

• Severity Correlation: Patients with iron deficiency and thrombocytosis typically show:

  • More severe anemia
  • Lower ferritin levels
  • More advanced iron deficiency compared to iron-deficient patients without thrombocytosis 3

• Thromboembolic Risk:

  • Elevated platelet counts in iron deficiency may increase thromboembolic risk in both arterial and venous systems
  • This risk is particularly notable in patients with inflammatory bowel diseases, chronic kidney disease, or cancer 1

Response to Treatment

Iron replacement therapy effectively resolves thrombocytosis:

• 50% of patients with iron deficiency-induced thrombocytosis normalize their platelet counts within 2 weeks of iron supplementation
• Nearly all patients resolve thrombocytosis within 6 weeks of treatment 3

Unusual Presentation: Iron Deficiency-Associated Thrombocytopenia

While thrombocytosis is common, in rare cases of severe iron deficiency, thrombocytopenia may occur:

• This is known as iron deficiency-associated thrombocytopenia (IDAT)
• IDAT is characterized by:
  • Low platelet counts (median ~30.5 × 10^9/L)
  • Lower mean platelet volume (MPV) compared to immune thrombocytopenia
  • Rapid recovery (median 6 days) with iron therapy 4
• IDAT is often misdiagnosed as immune thrombocytopenia 4

Clinical Implications

• Iron deficiency should be considered an underestimated thromboembolic risk factor
• Patients with iron deficiency and thrombocytosis should receive prompt iron replacement therapy
• Iron supplementation can serve as an effective preventive strategy against thromboembolic events in at-risk populations 1
• For patients with persistent thrombocytosis despite iron therapy, evaluation for concomitant clonal processes should be considered 3