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William Aird: Understanding the Ferritin Surge After IV Iron
William Aird/X
Oct 9, 2025, 13:11

William Aird: Understanding the Ferritin Surge After IV Iron

William Aird, Professor of Medicine at Harvard Medical School, posted on X:

”IV Iron and Ferritin

I recently posted a question about the spike in serum ferritin after IV iron. It can shoot from <10 to >1000, yet transferrin saturation (TSAT) only rises to normal — it barely moves.

What’s going on? This is macrophage physiology in action.

Step 1 – Uptake

IV iron–carbohydrate complexes (e.g., iron dextran) are endocytosed by macrophages in the liver, spleen, and marrow. Inside, the iron is released and floods the labile Fe²⁺ pool, the cell’s internal “iron bank.”

Step 2 – Ferritin synthesis explodes

  • High intracellular Fe²⁺ flips the IRP–IRE switch, unleashing translational ferritin synthesis.
  • Cytokines add a transcriptional boost.
  • Ferritin production ↑↑ → serum ferritin rises via a regulated, non-classical secretion pathway.

Step 3 – The lab pattern

During the first 1–3 weeks after infusion:

  • Ferritin ↑↑ (macrophage storage + secretion)
  • TSAT ↑ to normal (as a small fraction of iron slowly transfers to transferrin)

Step 3 (cont’d)

Fe release is slow, because hepcidin levels rise after IV iron, throttling ferroportin and keeping iron temporarily trapped in macrophages (only a slow trickle of iron is exported via ferroportin into the bloodstream). This is redistribution, not overload.

Step 4 – Resolution

  • As macrophages slowly export iron via ferroportin, their intracellular iron falls. The IRP–IRE system re-engages, ferritin synthesis drops, cytokine signals fade.
  • Serum ferritin settles to a new, steady level.

Bottom line:

Ferritin spikes after IV iron because:

  1. Macrophages are suddenly iron-loaded → ↑ ferritin translation
  2. Cytokines transiently ↑ transcription
  3. Ferritin is secreted into plasma

As iron normalizes, ferritin synthesis and secretion taper.

Clinical takeaway: If you see ferritin >1000 and TSAT merely normal after IV iron, think macrophage response, not iron overload. Ferritin is telling you iron has arrived; it just hasn’t moved on yet.”

William Aird

Stay updated with Hemostasis Today.

Ferritin Ferroportin Health Hematology Hemostasis Hemostasis Today Iron Dextran IV Iron Macrophage Medicine Transferrin Transferrin Saturation TSAT William Aird
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