| • 375 to 500 mL according to sex and weight, every 1–3 weeks according to SF level and severity of iron overload. The goal is to achieve SF around 50 mg/L |
| • Check Hb every month; if Hb <12 g/dL in men or <11 g/dL in women, discontinue or delay phlebotomies. Check SF every 4–8 phlebotomies according to baseline and follow-up levels |
| Phlebotomy—maintenance phase |
| • One phlebotomy every 2, 4 or 6 months to keep SF level between 50–100 mg/L; phlebotomies are performed lifelong, but can be slow down or stopped after 70 years |
| • Check SF every 6, 12 months, according to phlebotomy frequency; routine exams every year |
| Erythrocytapheresis |
| • Rapid, safe, but requires special apparatus and facility, and has limited availability; excellent in selected cases, but may require EPO stimulation to maintain adequate hemoglobin level |
| • May be preferred for patients with severe iron overload and patients whose clinical condition requires maintaining the isovolemic status or sparing of plasma proteins as in severe cardiopathy or advanced liver disease |
| Iron chelators |
| • Can be used when blood letting is contraindicated or in combination with phlebotomies in most severe iron overload (see below for dosages) |
| • Oral iron chelators can only be used as an off-label therapy |
| Ferroportin disease |
| Phlebotomy—induction phase |
| • 375 to 500 mL according to sex and weight every 3–4 weeks. The goal is to achieve SF around 100 mg/L |
| • Check Hb, and TSAT every month to prevent anemia; if Hb <12 g/dL in men or <11 g/dL in women, discontinue or delay phlebotomies. Check SF every 4–8 phlebotomies according to baseline and follow-up levels |
| Phlebotomy—maintenance phase |
| • One phlebotomy every 4, 6 or 12 months to keep SF level around 100 mg/L; phlebotomies are performed lifelong according to needs, but can be slow down or stopped after 70 years |
| • Check SF every 6–12 months, according to phlebotomy frequency |
| Atransferrinemia |
| Plasma transfusion (as a source of transferrin) |
| • One plasma transfusion every 2 weeks in the initial anemic stage and every 4 weeks in the maintenance phase; volume according to patient’s weight to obtain a post-transfusional transferrin level of 50–60 mg/dL |
| • Check Hb every week in early stages, every 1–3 month when Hb value is normal. Check SF every 3–6 months |
| Transferrin replacement therapy |
| • Clinical Trial Register: EudraCT Number: 2009-017409-13; protocol MD2009.04 |
| Iron chelators |
| • Deferoxamine: subcutaneous infusion; dose 25–40 mg/kg, 5–7 days/week. Deferiprone: oral, off-label therapy; dose 75–100 mg/kg, 5–7 days/week. Deferasirox: oral, off-label therapy; dose 10–25 mg/kg, 3–7 days/week |
| • Measure ferritin every 3–6 months; leukocyte count for deferiprone-dependent agranulocytosis risk; liver and renal function tests for deferasirox monitoring |
| DMT1 deficiency |
| Blood transfusion: often required according to needs |
| Erythropoietin: does not improve erythroid iron utilization, but likely reduces the degree or intensity of apoptosis |
| Oral iron supplementation: a rise of 1–2 g/dL in Hb concentration is expected |
| Oral iron chelators: ineffective |
| Aceruloplasminemia |
| Iron chelators |
| • Effective for removing liver iron excess, but less or no effective for brain iron excess; 1/3 reduced dosage every 3 days/week to avoid the risk of anemia aggravation; deferiprone and deferasirox preferred for their higher capacity to pass the BBB |
| • Check Hb, and TSAT every month to prevent anemia, SF every 3–6 months |
| Plasma transfusion (as a source of ceruloplasmin) + iron chelators |
| • Under evaluation |
