Management of Elevated Iron and Iron Saturation in Males
Therapeutic phlebotomy is the first-line treatment for males with elevated serum iron and transferrin saturation index of 0.63, and should be initiated immediately to prevent organ damage and improve survival. 1
Diagnostic Evaluation
Before initiating treatment, a comprehensive workup should include:
- Complete iron studies (serum ferritin, transferrin, TIBC)
- Liver function tests
- Fasting glucose and HbA1c
- Genetic testing for HFE mutations (C282Y, H63D)
- Liver imaging (ultrasound or MRI)
This evaluation helps differentiate between hereditary hemochromatosis and secondary causes of iron overload such as alcoholic liver disease, non-alcoholic fatty liver disease (NAFLD), or inflammatory conditions 1.
Treatment Protocol
Therapeutic Phlebotomy
Initial Phase: Weekly phlebotomy (removal of 450-500 mL of blood) until serum ferritin reaches 50 μg/L 1, 2
Monitoring During Initial Phase:
- Check hemoglobin before each procedure
- Monitor ferritin monthly or after every 4th phlebotomy
- When ferritin falls below 200 μg/L, check after every 1-2 sessions 1
Maintenance Phase: Once target ferritin (50 μg/L) is reached, continue phlebotomy every 1-4 months to maintain ferritin between 50-100 μg/L 1
Monitoring During Maintenance: Check ferritin every 6 months to adjust treatment schedule 1
Alternative Treatment: Erythrocytapheresis
For patients who cannot tolerate frequent phlebotomy or need more rapid iron depletion, erythrocytapheresis is an effective alternative that selectively removes red blood cells and can reduce the number of treatment procedures by approximately 57-67% compared to phlebotomy 1, 3. However, this option has higher material costs.
Iron Chelation Therapy
Iron chelation with deferasirox should only be considered when phlebotomy is contraindicated or not tolerated 1, 4. Important considerations include:
- Starting dose: 5-7 mg/kg/day (maximum 40 mg/kg/day) 4
- Contraindicated in patients with eGFR <40 mL/min/1.73 m² 4
- Requires dose reduction (50%) in patients with moderate hepatic impairment or renal impairment (eGFR 40-60 mL/min/1.73 m²) 4
- Monitor renal and hepatic function regularly 4
- Associated with significant side effects including gastrointestinal disturbances and potential kidney function impairment 1
Dietary and Lifestyle Modifications
- Avoid iron supplements and iron-fortified foods 1
- Limit supplemental vitamin C, especially before iron depletion 1
- Reduce red meat consumption 1
- Restrict alcohol intake, with complete abstention if cirrhosis is present 1
- Avoid raw or undercooked shellfish due to risk of Vibrio vulnificus infection 1
Monitoring for Complications
- Regular liver function tests to assess for hepatic damage 1
- Screening for diabetes mellitus 1
- Cardiac evaluation if symptoms are present 1
- Monitoring for joint disease 1
Common Pitfalls to Avoid
- Overtreatment: Reducing ferritin below 50 μg/L can increase dietary iron absorption and cause symptomatic iron deficiency 1
- Undertreatment: Inadequate iron removal can lead to continued organ damage 1
- Misdiagnosis: Elevated ferritin can be due to inflammation, not just iron overload 1, 5
- Overlooking NAFLD: Non-alcoholic fatty liver disease is frequently associated with iron metabolism disorders and may require additional management 5
- Inaccurate prediction of treatment requirements: Initial iron parameters cannot accurately predict the total number of phlebotomies needed 6
Phlebotomy has been shown to improve survival and prevent complications when initiated before the development of cirrhosis and/or diabetes, with established efficacy and a good safety profile 1, 2, 7.