Why not remove iron from blood transfusions to prevent iron overload?

Why Iron Cannot Be Removed From Blood Transfusions

Iron cannot be removed from blood transfusions because it is an essential component of hemoglobin, which is necessary for oxygen transport and the therapeutic function of the transfusion itself. 1

Iron's Essential Role in Transfusions

• Iron is a critical component of hemoglobin in red blood cells, which is responsible for oxygen transport throughout the body 1
• Removing iron from blood would render the transfusion ineffective, as the primary purpose of red blood cell transfusions is to improve oxygen delivery to tissues 2
• Each unit of transfused blood contains approximately 200-250 mg of iron, which cannot be physiologically eliminated from the body 3

Consequences of Transfusional Iron Overload

• Humans lack a physiological mechanism to actively remove excess iron, leading to accumulation with repeated transfusions 4
• Transfusion-dependent patients develop secondary iron overload when the iron acquired from transfused red blood cells exceeds body storage capacity 5
• Iron overload significantly worsens survival in patients requiring regular red cell transfusion therapy, with a 30% increase in hazard for every 500 ng/mL increase in serum ferritin above 1,000 ng/mL 1
• Organ damage from iron overload primarily affects:
  • Heart (cardiac toxicity is the leading cause of death in transfusion-dependent patients) 3
  • Liver (dysfunction and fibrosis) 1
  • Endocrine system (hypothyroidism and diabetes) 1

Current Management Strategies for Iron Overload

Prevention Strategies

• Maintain hemoglobin transfusion threshold at about 10 g/dL to balance the need for transfusion with minimizing iron accumulation 1
• Consider restrictive transfusion strategies when appropriate (Hb < 7 g/dL) in hemodynamically stable patients 2
• Tailor transfusion decisions to individual patient needs based on symptoms and comorbidities 2

Iron Chelation Therapy

• Iron chelation therapy should be initiated when:

  • Serum ferritin levels exceed 1,000 ng/mL 6
  • Patient has received at least 20 units of packed red blood cells 7
  • Patient requires regular transfusions 1

• Available iron chelation options include:

  • Deferasirox (Exjade®) - oral, once-daily administration with a recommended initial dose of 14 mg/kg for patients with eGFR >60 mL/min/1.73m² 7
  • Deferoxamine - parenteral administration, well-established efficacy but limited by poor compliance due to demanding regimen 8
  • Deferiprone - oral agent, alternative option but with risk of serious side effects including agranulocytosis 8

• Chelation therapy should be continued until serum ferritin falls below 1,000 ng/mL 6

Monitoring Iron Overload

• Regular monitoring of serum ferritin levels (monthly) is recommended as a practical measure of body iron stores 1
• Liver iron concentration can be assessed by CT scan (increased Hounsfield units correlate with iron overload) 6
• Monitor organ function regularly:
  • Liver function tests 1
  • Cardiac function 3
  • Endocrine function 1

Clinical Implications

• Patients with longer life expectancy and chronic transfusion needs (like those with myelodysplastic syndromes, particularly low-risk subtypes) are at highest risk for complications from iron overload 1
• Elevated pre-transplantation serum ferritin levels are associated with lower overall and disease-free survival in patients undergoing allogeneic stem cell transplantation 1
• Early intervention with chelation therapy is crucial to prevent irreversible organ damage in transfusion-dependent patients 5