Indications for Phlebotomy in Iron Overload without HFE C282Y Mutation

Diagnostic Evaluation Before Phlebotomy

The American Association for the Study of Liver Diseases recommends liver biopsy for diagnosis and prognosis in patients with phenotypic markers of iron overload who are not homozygous C282Y or compound heterozygous 1, 2
In patients with non-HFE hemochromatosis, data on hepatic iron concentration are useful, along with histopathological iron staining, to determine the degree and cellular distribution of iron present 1, 2
Magnetic resonance imaging should be used to quantify hepatic iron concentrations and assess extrahepatic organ involvement in patients with biochemical iron overload (increased transferrin saturation and ferritin) or positive hepatic iron staining 3

Phlebotomy is indicated in patients with confirmed iron overload (via MRI or liver biopsy), but this decision requires individualized clinical evaluation 3
Patients with non-HFE iron overload should undergo phlebotomy when they have a high hepatic iron concentration (HIC) 4
The presence of symptoms related to iron overload (fatigue, skin pigmentation, abdominal pain, insulin requirements for diabetics) that may benefit from phlebotomy should be considered in the treatment decision 1, 2

Check hematocrit/hemoglobin before each phlebotomy, allowing a decrease of no more than 20% from the previous level 4
Check serum ferritin level every 10-12 phlebotomies 4
Stop frequent phlebotomy when serum ferritin reaches 50-100 μg/L 4
Continue phlebotomy at intervals to maintain serum ferritin between 50 and 100 μg/L 4

In patients with secondary iron overload due to dyserythropoiesis, consider the use of deferasirox (Exjade) orally as an alternative to phlebotomy 4
Avoid vitamin C supplements during iron overload treatment 4
Phlebotomy may be useful in some forms of secondary iron overload, such as porphyria cutanea tarda, chronic hepatitis C, and NAFLD, but the decision should be based on the severity of the iron overload 4

Patients with cirrhosis should continue screening for hepatocellular carcinoma after adequate phlebotomy, as the risk persists 1, 2