Iron Infusions Do Not Cause Thrombocytosis—They Actually Reduce Elevated Platelet Counts
Iron infusions treat, rather than cause, thrombocytosis by correcting the underlying iron deficiency that drives reactive platelet elevation. 1, 2
The Relationship Between Iron Deficiency and Thrombocytosis
Iron deficiency itself causes thrombocytosis, not iron replacement. Approximately 8-22% of patients with iron deficiency anemia present with elevated platelet counts (>400-450 × 10⁹/L) at baseline. 1, 2 The mechanism appears related to increased erythropoietin production in iron-deficient states, which may cross-stimulate platelet production. 3, 4
Key Clinical Evidence
Thrombocytosis resolves with iron replacement: In a study of 76 patients with iron deficiency anemia, 22% had thrombocytosis at baseline, but only 5% remained thrombocytotic after 3 months of iron therapy (oral or IV). 1
Platelet counts decrease with iron administration: The median platelet count dropped from 299 to 265 × 10⁹/L after iron replacement, regardless of whether thrombocytosis was present initially. 1
Rapid resolution with treatment: Among patients with IDA-induced thrombocytosis, 50% normalized their platelet counts within 2 weeks of iron supplementation, and all patients resolved thrombocytosis within 6 weeks. 2
Clinical Implications for ESA Therapy
The concern about thrombosis in cancer patients relates to ESA therapy combined with iron deficiency, not iron infusions themselves. 5 Venous thromboembolism risk may be partially mediated through thrombocytosis that correlates with iron deficiency occurring from rapid iron consumption during ESA-stimulated erythropoiesis. 5
IV iron administration actually decreases platelet counts in ESA-treated patients: In the DRIVE trial of hemodialysis patients, those receiving IV iron had a mean platelet decrease of 29,000/μL, while those not given iron had no change (p = 0.017). 3
Important Clinical Caveats
When Iron Deficiency Causes Thrombocytopenia Instead
Rarely, severe iron deficiency can paradoxically cause thrombocytopenia rather than thrombocytosis. 6 This represents profound iron deficiency and resolves with iron replacement. 6
Monitoring Recommendations
Patients with IDA and thrombocytosis should receive active iron treatment with increased follow-up frequency to prevent potential thrombotic events during the period before platelet counts normalize. 2
For persistent thrombocytosis despite adequate iron replacement, consider evaluating for a concomitant clonal myeloproliferative process. 2
Safety Considerations for IV Iron
All IV iron formulations carry risk of acute adverse events including anaphylactoid reactions (0.65-0.7% for iron dextran), hypotension, shortness of breath, and chills. 7, 8 Administration should only occur with trained staff available to manage anaphylaxis, with 30-minute post-infusion observation. 7, 8
IV iron should be used cautiously or avoided in patients with active infection due to concerns about promoting inflammation and bacterial growth. 7