What is the appropriate treatment for a patient with iron overload indicated by a low Total Iron-Binding Capacity (DTIBC) of 230?

Treatment for Low TIBC (230) with Iron Overload

Iron chelation therapy should be initiated when serum ferritin reaches ≥1,000 ng/mL or when transfusion burden is ≥2 units per month sustained for more than one year, as these thresholds are associated with significantly worsened survival and organ damage. 1, 2

Understanding Your Laboratory Finding

A low Total Iron-Binding Capacity (TIBC) of 230 suggests iron overload, as TIBC decreases when iron stores are elevated. However, treatment decisions should not be based on TIBC alone—you must obtain serum ferritin and transferrin saturation to guide therapy. 1, 3

Diagnostic Workup Required

Before initiating treatment, obtain:

• Serum ferritin level (primary indicator for treatment decisions) 1
• Transferrin saturation (essential to differentiate true iron overload from inflammatory states) 1, 3
• Transfusion history (document cumulative units received and monthly transfusion rate) 1
• HFE genetic testing (screen for C282Y and H63D mutations if primary hemochromatosis suspected) 3

Treatment Algorithm Based on Clinical Scenario

For Primary Iron Overload (Hereditary Hemochromatosis)

Therapeutic phlebotomy is first-line treatment once diagnosis is confirmed, with a target ferritin <50 μg/L during depletion phase. 3 This applies when the patient has adequate hemoglobin and no contraindications to phlebotomy.

For Transfusion-Dependent Iron Overload

Iron chelation therapy is the treatment of choice, with deferasirox as the primary oral chelating agent at a starting dose of 14-20 mg/kg/day. 3, 4

Initiate chelation if ANY of the following criteria are met:

• Serum ferritin ≥1,000 ng/mL with ongoing transfusions 1, 2
• Transfusion burden ≥2 units/month for >1 year 1, 2
• Evidence of organ dysfunction from iron overload (regardless of ferritin level) 1, 2, 5
• Candidate for allogeneic stem cell transplant with elevated iron stores (ferritin >1,000 ng/mL at transplant is associated with higher mortality) 1, 2
• Life expectancy ≥1 year 1, 2

Available Chelation Options

Three chelators are currently licensed and have demonstrated efficacy:

• Deferasirox (oral): First-line oral agent, dosed once daily 3, 4
• Deferoxamine (parenteral): Most effective for severe cardiac iron overload, requires subcutaneous infusions 8-12 hours on 4-6 days weekly 4, 6
• Deferiprone (oral): Alternative oral agent at 75 mg/kg/day, though less effective than deferoxamine 4, 6

For patients with cardiac abnormalities due to iron overload (cardiac T2 <20 milliseconds), continuous intravenous deferoxamine is essential to eliminate toxic plasma non-transferrin bound iron.* 2, 6

Monitoring During Therapy

Check serum ferritin every 3 months (monthly if possible) in transfusion-dependent patients. 1, 3

Additional monitoring includes:

• Liver function tests and imaging (ultrasound or FibroScan for cirrhosis assessment) 3
• Cardiac echocardiogram if symptoms or significantly elevated ferritin 3
• MRI for liver iron content every 1-2 years using validated R2, T2*, or R2* methods 5
• Cardiac T2 MRI* for patients with high iron burden (LIC >15 mg/g for ≥2 years) 5
• Endocrine screening for diabetes and hypogonadism 3

Treatment Targets and Duration

The target ferritin decline is <1,000 ng/mL during treatment, and chelation should be continued as long as transfusion therapy continues and iron overload remains clinically relevant. 1, 3

Withhold chelation when ferritin declines to <1,000 ng/mL and no additional transfusions are needed. 3

Critical Contraindications

Do NOT initiate chelation if life expectancy <1 year without existing organ damage. 1, 2 Iron overload complications generally take greater than one year to become apparent. 1

Avoid post-transplant chelation during ongoing immunosuppressive therapy due to overlapping renal toxicity. 1, 2, 3 In these cases, phlebotomy is preferred for iron unloading in patients with favorable prognosis >1 year after transplant and adequate, stable hemoglobin. 1

Common Pitfalls to Avoid

• Do not rely on TIBC or transferrin saturation alone—these are influenced by inflammation and day-to-day variability 1
• Do not use excessive deferoxamine dosages (mean daily dose should not exceed 40 mg/kg to avoid growth retardation, ototoxicity, and ocular toxicity) 7
• Monitor for deferiprone-associated agranulocytosis (occurs in 0.6-4% of patients, requiring frequent white blood cell counts) 7
• Ensure adherence to therapy—poor compliance is the primary reason for treatment failure 4, 7