Can thalassemia cause elevated ferritin levels?

Thalassemia and Elevated Ferritin Levels

Yes, thalassemia commonly causes elevated ferritin levels, particularly in transfusion-dependent patients, due to iron overload from multiple transfusions, increased gastrointestinal iron absorption, and ineffective erythropoiesis.

Mechanism of Elevated Ferritin in Thalassemia

Ferritin elevation in thalassemia occurs through several mechanisms:

1. Blood transfusions: Regular transfusions in transfusion-dependent thalassemia introduce excess iron (0.47 mg/mL in whole blood) 1
2. Ineffective erythropoiesis: Leads to increased intestinal iron absorption 2
3. Increased gastrointestinal iron absorption: Even without transfusions, thalassemia patients absorb more iron than normal 2

Ferritin Levels in Thalassemia Patients

• 87.4% of beta thalassemia major patients show very high ferritin levels, with mean values around 2767.52 ng/mL 2
• 44.4% of patients have ferritin between 1000-2500 ng/mL, while 43.05% have values above 2500 ng/mL 2
• Ferritin levels are higher in beta-thalassemia/Hb E than in Hb H disease 3
• Splenectomized patients with beta-thalassemia/Hb E disease have significantly higher ferritin levels than non-splenectomized patients 3

Monitoring Iron Overload in Thalassemia

The American Heart Association recommends:

• Initiating iron chelation when serum ferritin exceeds 1000 ng/mL to prevent irreversible organ damage 1
• Using MRI for liver iron content assessment every 1-2 years with validated R2, T2*, or R2* methods 1
• Cardiac T2* MRI for patients with high iron burden, evidence of end-organ damage, or cardiac dysfunction 1

Limitations of Ferritin as a Marker

While ferritin generally correlates with iron stores, several factors affect its reliability:

• Inflammation or infection (especially hepatitis C) can falsely elevate ferritin levels 4, 1
• Vitamin C deficiency may decrease ferritin levels despite iron overload 4
• Chronic hepatitis: Ferritin levels are higher in patients with chronic hepatitis than in those with hepatic siderosis only for a given level of iron stores 5
• Single measurements may be misleading: They may not reflect long-term iron levels 4

Clinical Implications

• A ferritin level >2500 μg/L indicates increased risk of cardiac complications, but risk increases even at levels of 1000 μg/L 4
• Long-term elevations in ferritin predict cardiac mortality in thalassemia patients 4
• Low ferritin does not guarantee freedom from heart failure in thalassemia patients 4

Management Considerations

• Iron chelation therapy should be initiated when serum ferritin exceeds 1000 ng/mL 1
• Options include:
  • Deferasirox (oral)
  • Deferiprone (75 mg/kg/day in 3 divided doses)
  • Deferoxamine (40-50 mg/kg/day subcutaneous or intravenous) 1
• Combination therapy with deferiprone and deferoxamine shows superior efficacy for severe iron overload 1

Monitoring Recommendations

• Regular monitoring of ferritin trends is useful but should be supplemented with:
  • Liver MRI for iron content using validated methods consistently over time 4, 1
  • Cardiac T2* MRI for high-risk patients 4, 1
• The American Heart Association recommends a 3-tier risk model based on cardiac T2*:
  • Low risk: >20 ms
  • Intermediate risk: 10-20 ms
  • High risk: <10 ms 4

In conclusion, elevated ferritin is a common and expected finding in thalassemia patients, particularly those who are transfusion-dependent, but its interpretation requires consideration of multiple factors including inflammation, hepatitis, and the need for complementary testing with MRI.