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Abdul Mannan: Anemia in Myelofybrosis – Five Fires Behind One Falling Hb
Abdul Mannan/LinkedIn
May 6, 2026, 14:02

Abdul Mannan: Anemia in Myelofybrosis – Five Fires Behind One Falling Hb

Abdul Mannan, Consultant Haematologist at Betsi Cadwaladr University Health Board, shared a post on LinkedIn:

“Your myelofibrosis patient’s Hb keeps dropping.

EPO isn’t working. Iron studies look strange.

You’re not sure what to try next.

Here’s why that happens.

Anaemia in MF rarely comes from one place. It usually comes from five.

The five mechanisms:

  • Ineffective erythropoiesis: JAK2/CALR/MPL mutations dysregulate JAK-STAT signalling. Red cell progenitors (BFU-E, CFU-E) simply can’t mature normally.
  • Hepcidin lock: IL-6 drives ACVR1/BMP-SMAD signalling, HAMP rises, ferroportin gets degraded, and iron stays trapped inside cells. Ferritin goes up. TSAT goes down.
  • Fibrotic marrow: Reticulin and collagen replace haematopoietic space. Dry tap. MF grade 2/3. Almost no reserve left.
  • Splenic sequestration: Extramedullary haematopoiesis turns the spleen into a red cell trap. A massive spleen makes every cytopenia worse.
  • JAK-inhibitor cytopenia: JAK2 blockade suppresses EPOR signalling. Hb drop typically appears 8-12 weeks in. This was documented in both COMFORT-I and COMFORT-II trials.

The trap that catches everyone:

  • High ferritin and low TSAT in MF is not iron deficiency. It is functional iron restriction. Giving iron here misses the point entirely and helps no one.

Understand the fire before you reach for the extinguisher.

What’s your approach when a patient on ruxolitinib has a worsening Hb?”

Abdul Mannan: Anemia in Myelofybrosis - Five Fires Behind One Falling Hb

Other posts from Abdul Mannan on Hemostasis Today.

Abdul Mannan anemia CALR ferroportin gets degraded HAMP rises Hb Health Hematology Hemoglobin Hemostasis Hemostasis News Hemostasis Today JAK2 Medicine MF MPL myelofibrosis ruxolitinib thrombosis
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