Indications for Therapeutic Phlebotomy
Therapeutic phlebotomy is indicated for hemochromatosis with iron overload, polycythemia vera, porphyria cutanea tarda, and select cases of secondary iron overload including non-alcoholic fatty liver disease with hyperferritinemia. 1, 2, 3
Primary Indications
Hemochromatosis and Iron Overload
All patients with confirmed hemochromatosis and iron overload require weekly therapeutic phlebotomy (500 mL) until ferritin reaches 50-100 μg/L, followed by lifelong maintenance phlebotomy to maintain this target range. 1, 4
C282Y homozygotes with elevated ferritin below 1000 μg/L and no signs of significant liver disease (normal ALT/AST) should proceed directly to phlebotomy without liver biopsy. 1
Patients with end-organ damage from iron overload (cirrhosis, cardiomyopathy, diabetes) require regular phlebotomy to the same ferritin endpoints of 50-100 μg/L. 1, 4
Non-HFE iron overload with elevated hepatic iron concentration also warrants phlebotomy treatment. 1
Polycythemia Vera
All patients with polycythemia vera require therapeutic phlebotomy to maintain hematocrit below 45%, combined with low-dose aspirin if no contraindications exist. 3
This indication applies regardless of age or thrombosis risk, as maintaining hematocrit below 45% reduces thrombotic complications. 3
Phlebotomy addresses the erythrocytosis (hemoglobin >16.5 g/dL in men or >16.0 g/dL in women) that defines this myeloproliferative neoplasm. 3
Secondary Iron Overload Conditions
Porphyria cutanea tarda clearly benefits from phlebotomy, resulting in reduction of skin manifestations, with total iron stores rarely exceeding 4-5 grams. 1, 2
Non-alcoholic fatty liver disease with hyperferritinemia shows benefit from therapeutic phlebotomy, with improvement in insulin resistance parameters and reduction in elevated ALT levels. 1, 2
Chronic hepatitis C with secondary iron overload may benefit from phlebotomy for ALT reduction and marginal histopathologic improvement, though it does not affect viral clearance. 1
Contraindications and When NOT to Use Phlebotomy
Phlebotomy is not recommended for mild secondary iron overload (hepatic iron concentration <2500 μg/g dry weight) in chronic hepatitis C. 1
No published evidence supports phlebotomy benefit in alcoholic liver disease with secondary iron overload. 1
Secondary iron overload from ineffective erythropoiesis (β-thalassemia, myelodysplastic syndromes) requires iron chelation therapy with deferoxamine or deferasirox rather than phlebotomy, as these patients cannot tolerate blood removal. 1
Critical Monitoring Parameters Before Each Session
Check hemoglobin and hematocrit before every phlebotomy session to prevent excessive anemia. 4, 5
Postpone phlebotomy if anemia develops until hemoglobin recovers to safe levels. 5
Monitor serum ferritin every 10-12 phlebotomies during induction phase, then monthly during maintenance to avoid overchelation. 4, 5
Common Pitfalls and Caveats
In patients with cardiac involvement (cardiomyopathy or arrhythmias), rapid iron mobilization increases risk of sudden death—consider slower phlebotomy schedules or iron chelation instead. 4
Avoid vitamin C supplements entirely during active iron depletion, as vitamin C accelerates iron mobilization and increases oxidative stress. 1, 4, 5
Patients with cirrhosis and iron overload must avoid raw shellfish due to Vibrio vulnificus infection risk. 5, 6
In elderly patients, consider more relaxed ferritin targets during maintenance (up to 200 μg/L for women, 300 μg/L for men) to avoid excessive treatment burden. 4