What is the management plan for a patient with increased storage iron and confirmed iron overload?

Management of Increased Storage Iron (3+) with Confirmed Iron Overload

The management hinges on determining the underlying cause and quantifying the degree of iron overload through serum ferritin and transferrin saturation measurements, followed by either phlebotomy for primary iron overload or chelation therapy for transfusion-dependent conditions.

Immediate Diagnostic Workup Required

You must obtain the following tests immediately to guide treatment decisions:

• Serum ferritin level - This is the single most critical value to determine treatment thresholds and monitor response 1, 2
• Transferrin saturation (TSAT) - Essential to differentiate true iron overload (TSAT >45-50%) from inflammatory states (TSAT <20% with elevated ferritin) 3
• HFE genetic testing - Screen for C282Y and H63D mutations to diagnose hereditary hemochromatosis, the most common primary cause 2, 4
• Liver MRI (T2)* - Quantify hepatic iron concentration and assess for organ damage 2
• Cardiac MRI (T2)* - Indicated if any cardiac symptoms or markedly elevated ferritin 2

Treatment Algorithm Based on Etiology

For Primary Iron Overload (Hereditary Hemochromatosis)

Therapeutic phlebotomy is first-line treatment once diagnosis is confirmed 2, 5:

• Remove 1 unit (450-500 mL) of blood weekly until serum ferritin reaches 10-20 μg/L 5
• Target ferritin <50 μg/L during depletion phase to achieve iron deficiency and normalize tissue iron 3
• Maintenance therapy: Phlebotomy every 3-6 months to maintain ferritin at 50-100 μg/L 3
• Initiate treatment when ferritin ≥300 μg/L in men or ≥200 μg/L in women, regardless of symptoms 5

For Transfusion-Dependent Iron Overload

Iron chelation therapy is the treatment of choice when phlebotomy is not feasible 1, 2:

Indications to Initiate Chelation 1:

• Serum ferritin ≥1,000 ng/mL
• Transfusion requirement ≥2 units/month for >1 year
• Patient becomes unresponsive to or ineligible for primary therapy
• Need to preserve organ function (cardiac, hepatic, endocrine)

Patient Selection - Most Likely to Benefit 1:

• Low-risk MDS patients (IPSS low or intermediate-1; WHO classification RA, RARS, or 5q-)
• Life expectancy ≥1 year (iron complications take >1 year to manifest)
• No comorbidities limiting prognosis
• Candidates for allogeneic stem cell transplant (chelation reduces procedure-related hepatic complications and mortality) 1

Critical caveat: Patients with life expectancy <1 year should NOT receive chelation unless already showing iron-related organ complications requiring preservation 1

Chelation Regimens

Deferasirox is the primary oral chelating agent 3, 2:

• Starting dose: 14-20 mg/kg/day for transfusional iron overload 2, 6
• Maximum dose: 28-40 mg/kg/day depending on age (60 mg/kg/day for adults in severe cases) 3, 6
• Adjust dose to achieve decreasing ferritin trends 3

Deferoxamine (parenteral alternative) 6:

• Subcutaneous: 40 mg/kg/day over 8-12 hours, 5-7 nights/week via portable pump
• Intravenous: 40-50 mg/kg/day over 8-12 hours at rate up to 15 mg/kg/hour, 5-7 days/week
• Maximum: 60 mg/kg/day in adults; 40 mg/kg/day in children

Deferiprone is a third option available in some regions 1

Duration and Monitoring of Chelation Therapy

Continue chelation as long as the patient requires transfusions and iron overload remains clinically relevant 1, 7:

• Withhold chelation when ferritin declines to <1,000 ng/mL and no additional transfusions needed 1
• Monitor ferritin at minimum every 3 months, monthly if possible, commensurate with transfusion frequency 1, 7
• Target ferritin decline to <1,000 ng/mL during treatment 7

Critical Safety Warnings

Avoid these potentially life-threatening complications:

• Do NOT overchelate - Continuing chelation when ferritin approaches normal range can cause life-threatening adverse events 3
• Interrupt chelation during volume depletion - Resume only when renal function and hydration normalize 3
• Post-transplant chelation - Avoid during ongoing immunosuppressive therapy due to overlapping renal toxicity; phlebotomy is preferred >1 year post-SCT with stable hemoglobin 1

Special Populations

Patients Undergoing Allogeneic Stem Cell Transplant

• Initiate chelation pre-transplant if ferritin >1,000 ng/mL to decrease hepatic complications and mortality 1
• Switch to phlebotomy >1 year post-transplant if prognosis favorable and hemoglobin adequate 1

Idiopathic Myelofibrosis

• Consider chelation in patients with favorable/intermediate prognostic score who are transfusion-dependent and meet iron overload criteria 1

Adjunctive Management

Vitamin C supplementation enhances iron chelation 6:

• Start after 1 month of regular deferoxamine treatment
• Dose: 50 mg daily for children <10 years; 100 mg daily for older children; up to 200 mg daily in divided doses for adults
• Vitamin C increases iron availability for chelation 6

Dietary modifications 5:

• Avoid medicinal iron and mineral supplements
• Avoid excess vitamin C supplementation
• Avoid uncooked seafood (reduces Vibrio infection risk in liver disease)

Organ-Specific Monitoring

Assess for target organ damage 2, 8:

• Liver: Function tests, ultrasound or FibroScan for cirrhosis assessment
• Cardiac: Echocardiogram if symptoms or significantly elevated ferritin
• Endocrine: Screen for diabetes, hypogonadism (especially critical in children)
• Joints: Assess for arthropathy

The absence of ring sideroblasts in your patient excludes sideroblastic anemia as a cause, narrowing the differential to hereditary hemochromatosis, transfusional overload, or other secondary causes requiring the diagnostic workup outlined above 4.