What is the typical iron level in patients with Autoimmune Hemolytic Anemia (AIHA)?

Iron Studies in Autoimmune Hemolytic Anemia (AIHA)

In AIHA, serum iron levels are typically elevated or normal-high, ferritin is markedly elevated (often >1000 μg/L), and transferrin saturation is increased (often >50%), reflecting the release of iron from hemolyzed red blood cells rather than true iron deficiency. 1

Expected Iron Panel Results

Serum Ferritin

• Significantly elevated in hemolytic episode AIHA patients compared to healthy controls 1
• Can reach levels of 4933 μg/L in severe hemolytic crises requiring multiple transfusions 2
• Ferritin correlates with the severity of AIHA and serves as a marker of disease activity 1
• Remains elevated even in remission patients compared to healthy controls 1

Transferrin Saturation (TSAT)

• Markedly increased with mean values around 57% (±9%) in AIHA patients 1
• This is well above the normal range of 20-50% and reflects iron release from hemolyzed cells 1
• Contrasts sharply with iron deficiency anemia where TSAT would be <20% 3

Serum Hepcidin

• Significantly elevated in both hemolytic episode and remission AIHA patients compared to healthy controls 1
• Hepcidin levels correlate with disease severity 1
• Elevated hepcidin leads to decreased hepatic ferroportin 1 (FPN1) protein expression, trapping iron intracellularly 1

Pathophysiology of Iron Elevation

The iron overload in AIHA results from:

• Intravascular and extravascular hemolysis releasing hemoglobin, heme, and free iron into circulation 1
• Chronic inflammation driving hepcidin production, which blocks iron export from cells 1
• Transfusion burden in severe cases adding exogenous iron (approximately 200-250 mg per unit of red blood cells) 3, 2

Clinical Implications

Distinguishing AIHA from Iron Deficiency Anemia

This iron pattern is diagnostically useful because:

• Iron deficiency anemia shows: low ferritin (<30 ng/mL), low TSAT (<20%), elevated TIBC 3
• AIHA shows: high ferritin (often >1000 μg/L), high TSAT (>50%), normal-low TIBC 1
• Both may present with anemia, but the iron studies move in opposite directions 1

Transfusional Iron Overload Risk

• Patients requiring >20 units of red blood cells during severe hemolytic crises develop significant transfusional iron overload 2
• Post-crisis management may require serial phlebotomies (16+ sessions) to reduce ferritin from >4000 μg/L to target levels <100 μg/L 2
• Each unit of blood contains approximately 200-250 mg of iron, and overload can occur after 20-25 transfusions 3

Monitoring During Treatment

• Erythropoietin (EPO) levels are also elevated in hemolytic AIHA, reflecting appropriate bone marrow response to anemia 1
• Iron parameters should be monitored during immunosuppressive therapy as they normalize with disease control 1
• Hepatic hepcidin mRNA expression decreases and FPN1 protein increases as hemolysis resolves 1

Critical Pitfall to Avoid

Do not treat elevated ferritin in AIHA as iron overload requiring chelation therapy acutely—the elevated ferritin primarily reflects acute inflammation and hemolysis, not necessarily tissue iron deposition 1. Iron chelation is only indicated after massive transfusion burden (>75-100 units historically) or when ferritin remains persistently elevated after hemolysis resolution 3, 2.