What are the lab guidelines for phlebotomy in patients with iron overload?

Lab Guidelines for Phlebotomy in Iron Overload

Patients with iron overload should undergo weekly therapeutic phlebotomy of 450-500 mL until serum ferritin reaches 50-100 μg/L, with hemoglobin/hematocrit checked before each session to ensure adequate levels for safe blood removal. 1, 2

Pre-Treatment Laboratory Assessment

Before initiating phlebotomy therapy, obtain the following baseline studies:

• Serum ferritin to quantify total body iron burden 2
• Transferrin saturation to confirm iron overload (typically >45%) 3
• Complete blood count with hemoglobin and hematocrit to ensure patient can tolerate blood removal 2
• Liver function tests (ALT, AST) to assess hepatic involvement and guide need for liver biopsy 1, 2
• Renal function to establish baseline 2

C282Y homozygotes with ferritin <1000 μg/L and normal liver enzymes can proceed directly to phlebotomy without liver biopsy. 1

Induction Phase Monitoring

Pre-Phlebotomy Requirements

• Check hemoglobin/hematocrit before every phlebotomy session 2, 4
• Minimum hemoglobin threshold: ≥140 g/L at baseline; postpone if drops to <120 g/L (women) or <130 g/L (men) 5
• Remove 450-500 mL of whole blood weekly as tolerated 1, 2, 6

Frequency of Laboratory Monitoring During Induction

• Serum ferritin every 10-12 phlebotomies initially, then more frequently as levels approach target range 2, 3
• Hemoglobin/hematocrit at each visit to prevent excessive anemia 2, 4
• MCV can serve as an inexpensive physiologic indicator - it increases transiently from reticulocytosis, stabilizes, then decreases sharply when iron-limited erythropoiesis occurs, signaling approaching iron depletion 7

Target Endpoints for Induction

Continue weekly phlebotomy until serum ferritin reaches 50-100 μg/L (some sources suggest 10-20 μg/L for initial depletion, then maintain at 50-100 μg/L). 1, 2, 6

Maintenance Phase Monitoring

Laboratory Schedule

• Serum ferritin monthly during initial maintenance phase, then every 3-6 months once stable 2, 3
• Hemoglobin/hematocrit before each maintenance phlebotomy 2
• Liver function tests periodically to monitor for hepatic complications 2

Maintenance Phlebotomy Frequency

• Perform phlebotomy every 2-4 months (typically every 7.5 weeks, range 6-16 weeks) to maintain ferritin 50-100 μg/L 2, 7
• Transferrin saturation should remain <35% during maintenance therapy 7
• Restart phlebotomy when ferritin approaches upper limit of normal if using an alternative monitoring approach 3

Critical Monitoring Pitfalls

Avoiding Iron Deficiency

Sustained iron deficiency can develop from excessive phlebotomy - monitor for symptoms (fatigue, weakness), microcytosis, and ferritin <10 μg/L. 8 Recovery without iron supplementation takes 8-24 months; brief ferrous sulfate (325 mg daily for 2-6 weeks) can be used if symptomatic, though generally unnecessary. 8

Avoiding Overchelation

Do not allow ferritin to drop below 50 μg/L during maintenance to prevent iron deficiency while maintaining adequate depletion. 3 Ferritin levels can be misleading in secondary iron overload due to inflammation, unlike in hereditary hemochromatosis where it reliably reflects iron burden. 1

Special Population Considerations

In patients with cardiac hemochromatosis or severe heart failure, phlebotomy may not be tolerated - consider slower schedules or iron chelation therapy instead. 6 Rapid iron mobilization increases risk of sudden death in those with cardiomyopathy. 2

For patients developing anemia during phlebotomy despite elevated ferritin (as in ferroportin disease), extend the phlebotomy interval or consider adding erythropoietin. 1

Laboratory Parameters That Are Less Useful

• Transferrin saturation fluctuates considerably during treatment and is not a reliable guide for phlebotomy pace 7
• Ferritin values alone are not useful guides to the pace of individual phlebotomies, though they remain essential for monitoring overall progress 7

Compliance Monitoring

Approximately 96% of patients achieve iron depletion, but only 33% tolerate weekly phlebotomy schedules. 9 Compliance with maintenance therapy decreases by 6.8% annually, with mean follow-up of 4.1 years. 9 C282Y homozygotes show significantly better compliance than other genotypes. 9