At what ferritin level should a patient with hereditary hemochromatosis (HH) undergo phlebotomy?

From the Guidelines

Phlebotomy should be performed in hemochromatosis patients until serum ferritin levels are reduced to a target range of 50 lg/L, but not lower, to avoid iron deficiency, as recommended by the most recent guidelines 1. The goal of phlebotomy therapy is to deplete excess iron stores and prevent associated organ damage, while also avoiding iron deficiency.

• The target ferritin level for the induction phase is 50 lg/L, as stated in the EASL clinical practice guidelines on haemochromatosis 1.
• In the maintenance phase, serum ferritin can be maintained with some flexibility in the range of 50-100 lg/L, according to the same guidelines 1.
• It is essential to monitor serum ferritin levels regularly to ensure that the target value is achieved and maintained, and to avoid overtreatment, which can lead to unnecessary bloodletting or iron deficiency 1.
• The frequency and volume of phlebotomies should be adjusted based on the patient's iron status, body weight, and tolerance, with typical volumes of 400-500 mL weekly or every 2 weeks during the induction phase, and every 1-4 months during the maintenance phase 1.
• Serum haemoglobin should also be monitored during both induction and maintenance phases to prevent anemia, and phlebotomy should be discontinued if haemoglobin concentrations are <11 g/dl 1.

From the Research

Ferritin Levels for Phlebotomy in Hemochromatosis Patients

• The ideal ferritin level for initiating phlebotomy in hemochromatosis patients is not universally agreed upon, but some studies provide guidance:
  • Therapeutic phlebotomy should be started in men with serum ferritin levels of 300 μg/l or more and in women with serum ferritin levels of 200 μg/l or more 2
  • The goal of phlebotomy is to reduce serum ferritin levels to 10 to 20 μg/l and maintain them at 50 μg/l or lower thereafter 2
• It is essential to monitor serum ferritin levels and adjust the frequency of phlebotomies accordingly to prevent iron deficiency:
  • Sustained iron deficiency in hemochromatosis patients can be prevented by monitoring hemoglobin levels and serum ferritin 3
  • Iron deficiency can occur due to excessive therapeutic phlebotomy, and symptoms can persist for an extended period before diagnosis 3
• Phlebotomy is the initial treatment of choice in haemochromatosis, while chelation is a mainstay in the treatment of transfusional siderosis:
  • Phlebotomy and chelation are the two most important treatment options for iron overload 4
  • Combined treatment with subcutaneous and oral iron chelators may hold promise for certain patients 4

Key Considerations

• Serum ferritin levels should be monitored regularly to guide phlebotomy therapy:
  • Ferritin values are not always useful guides to the pace of phlebotomy, and other indicators like MCV and Hb may be more reliable 5
  • Transferrin saturation and serum ferritin levels can fluctuate during treatment, and regular monitoring is necessary to adjust the frequency of phlebotomies 5, 6
• Patient compliance with phlebotomy therapy is crucial for effective management of hemochromatosis:
  • Most patients with hemochromatosis achieve iron depletion with phlebotomy, but compliance with maintenance therapy decreases over time 6