What is the treatment for a patient with hypoferritinemia, low percent transferrin saturation, and low ferritin levels?

Treatment of Severe Iron Deficiency

This patient requires immediate iron supplementation given the severely depleted iron stores (ferritin 4 ng/mL), critically low transferrin saturation (7%), and low serum iron (32), which together indicate absolute iron deficiency requiring treatment. 1

Diagnostic Interpretation

Your laboratory results demonstrate absolute iron deficiency by all standard criteria:

• Ferritin <15 μg/L is highly specific (99% specificity) for absent iron stores 1
• Transferrin saturation <20% confirms impaired iron delivery to bone marrow 1
• These values fall well below any diagnostic threshold, even accounting for inflammation 1

Investigation for Underlying Cause

Before initiating treatment, the underlying cause must be identified, as recurrent blood loss accounts for 94% of iron deficiency anemia cases. 2

Key Clinical Considerations:

• In premenopausal women with plausible bleeding source (heavy menstrual bleeding): Treat the bleeding source and provide iron supplementation without extensive GI investigation 1

• In men and postmenopausal women: Bidirectional endoscopy (colonoscopy and upper endoscopy) is mandatory to exclude gastrointestinal malignancy, as 9% of patients over 65 with iron deficiency have GI cancer 3

• All patients should be tested for:

  • Helicobacter pylori infection (common cause of iron deficiency) 2
  • Celiac disease (noninvasive testing recommended) 2
  • Consider Hb electrophoresis if microcytosis present with appropriate ethnic background to exclude thalassemia 1

Treatment Approach

First-Line: Oral Iron Supplementation

Oral iron is the recommended first-line treatment for most patients with iron deficiency. 2, 4

Dosing strategy:

• Use preparations containing 28-50 mg elemental iron to minimize gastrointestinal side effects 5
• Standard ferrous sulfate tablets contain 65 mg elemental iron per 324 mg tablet 6
• Every-other-day dosing improves iron absorption compared to daily dosing 2
• Take on empty stomach when possible; if GI upset occurs, may take with food despite reduced absorption 5

Common pitfall: Approximately 50% of patients have decreased adherence due to adverse GI effects (constipation, nausea, abdominal discomfort) 2

Monitoring Response

Reassess hemoglobin in 2-4 weeks after initiating oral iron therapy: 2, 3

• Expected response: 1-2 g/dL increase in hemoglobin within one month 3
• Repeat complete iron panel (ferritin, transferrin saturation, hemoglobin) at 8-10 weeks 5
• Failure to respond indicates either malabsorption, continued bleeding, or unidentified lesion 3

Second-Line: Intravenous Iron

Intravenous iron should be used when: 2, 4

• Patient cannot tolerate oral iron despite optimization 2
• Inadequate response to oral iron after appropriate trial 2
• Iron malabsorption present (celiac disease, inflammatory bowel disease, atrophic gastritis) 4, 7
• Concomitant disease requiring urgent treatment 5
• Heart failure patients with iron deficiency (regardless of anemia status) to increase exercise capacity 2

Available IV formulations include iron dextran, iron gluconate, and iron sucrose, with hypersensitivity reactions <1% with newer formulations. 2, 4

Cautions with IV iron: Monitor for allergic reactions, hypophosphatemia/osteomalacia, iron overload, and vascular leakage, particularly with high-dose formulations 7

Long-Term Management

For patients with recurrent low ferritin despite treatment:

• Intermittent oral iron supplementation to maintain stores 5
• Monitor iron studies every 6-12 months 5
• Do NOT provide long-term daily oral or IV iron if ferritin normalizes or becomes elevated, as this is potentially harmful 5

Critical Thresholds to Remember

• Ferritin <15 μg/L = absent iron stores 1
• Ferritin <30 μg/L = low body iron stores in adults >15 years 1, 5
• Ferritin <45 μg/L = optimal sensitivity/specificity trade-off for iron deficiency 1
• Transferrin saturation <20% = impaired iron delivery 1