What is the treatment for a patient with low ferritin (iron storage protein) levels and high iron binding capacity (total iron-binding capacity, TIBC)?

Treatment of Low Ferritin and High Iron Binding Capacity (Iron Deficiency)

Iron supplementation should be initiated immediately for patients with low ferritin and high total iron-binding capacity (TIBC), as this pattern indicates absolute iron deficiency requiring treatment. 1

Diagnostic Confirmation

Low ferritin with elevated TIBC represents classic iron deficiency anemia, where:

• Low ferritin (<30-40 ng/mL) indicates depleted iron stores 2, 3
• Elevated TIBC (>370 mg/dL or >66 mmol/L) reflects the body's compensatory attempt to bind more iron 1
• This pattern occurs before inflammation is present, as both markers are affected by inflammatory states 1

Treatment Algorithm

First-Line: Oral Iron Supplementation

Oral iron is the initial treatment of choice for most patients with iron deficiency. 1, 2

Dosing:

• Ferrous sulfate 325 mg daily (containing 65 mg elemental iron) 4, 2
• Alternate-day dosing (every other day) may provide better absorption with fewer gastrointestinal side effects 1
• Typical therapeutic doses range 100-200 mg elemental iron per day in divided doses 1

Duration and Monitoring:

• Continue treatment for 8-10 weeks before reassessing iron studies 1
• Expect hemoglobin increase of 1-2 g/dL within one month if treatment is effective 3
• Target ferritin levels depend on clinical context (see below) 1

Common pitfalls: Gastrointestinal side effects (constipation, diarrhea, nausea) occur frequently with oral iron 1. If these develop, consider alternate-day dosing rather than discontinuing treatment 1.

Second-Line: Intravenous Iron

Intravenous iron is indicated when oral iron fails or specific conditions exist. 1, 2

Specific indications for IV iron:

• Oral iron intolerance or gastrointestinal side effects 1, 2
• Malabsorption conditions (celiac disease, post-bariatric surgery, atrophic gastritis) 2, 5
• Ongoing blood loss requiring rapid iron replacement 1, 2
• Chronic inflammatory conditions (chronic kidney disease, heart failure, inflammatory bowel disease, cancer) 2, 5
• Pregnancy (second and third trimesters) 2
• Failure to respond to oral iron after adequate trial 1, 6

IV iron formulations:

• Modern formulations include ferric carboxymaltose, iron sucrose, ferric gluconate, and low molecular weight iron dextran 1
• Ferric carboxymaltose allows rapid administration of large single doses (up to 1000 mg over 15 minutes) 1
• Risk of infusion reactions is very low (<1:250,000) with recent formulations, but avoid high molecular weight iron dextran due to higher risk 1

Safety monitoring for IV iron:

• Monitor for hypophosphatemia/osteomalacia, allergic reactions, and iron overload 5
• Ferritin levels are falsely elevated immediately after IV iron; wait 8-10 weeks before rechecking 1
• Target ferritin should not exceed 500 mg/L to avoid toxicity, especially in children and adolescents 1

Target Ferritin Levels by Clinical Context

General population (non-inflammatory conditions):

• Treat until ferritin reaches >30-40 ng/mL at minimum 2, 3
• Some patients require ferritin >100 ng/mL for symptom resolution 6

Restless legs syndrome:

• Target ferritin ≥75 ng/mL or transferrin saturation ≥20% 1
• Consider IV iron if ferritin is 75-100 ng/mL 1
• In children with RLS, target ferritin ≥50 ng/mL 1

Chronic kidney disease patients:

• Target ferritin >100-200 ng/mL with transferrin saturation >20% 1
• Higher targets may reduce erythropoiesis-stimulating agent requirements 1

Adjunctive Measures

Dietary modifications:

• Increase heme iron intake (red meat, though consumption should be limited in some contexts) 1
• Integrate iron-rich foods regularly into diet 1
• Avoid iron absorption inhibitors (tea, coffee, calcium supplements) near iron supplementation 1
• Dietary changes alone are insufficient as primary treatment but provide additional benefit 1, 7

Address underlying causes:

• Investigate and treat sources of blood loss (menstrual, gastrointestinal) 2, 3
• Evaluate for malabsorption disorders 2, 5
• Consider Helicobacter pylori testing in refractory cases 5
• In patients >50 years or with concerning symptoms, endoscopic evaluation is recommended 3

Avoid:

• Supplemental vitamin C should be avoided, especially before iron repletion 1
• Iron-fortified foods may be avoided where possible in certain conditions 1