What are the next steps for a 12-year-old female with heavy menstrual bleeding, iron deficiency anemia (low iron 17, iron saturation 5%), elevated ferritin, and elevated liver enzymes, who recently experienced syncope (passed out)?

Immediate Management of Iron Deficiency with Paradoxical Hyperferritinemia in Adolescent with Heavy Menstrual Bleeding

This 12-year-old requires immediate oral iron supplementation (3 mg/kg/day of elemental iron between meals) and urgent gynecologic evaluation for heavy menstrual bleeding management, while the elevated ferritin and liver enzymes necessitate investigation for an underlying inflammatory or hepatic condition causing functional iron deficiency. 1

Understanding the Paradox: True Iron Deficiency Despite High Ferritin

This patient presents with a critical diagnostic challenge—severe iron deficiency (iron 17, saturation 5%) coexisting with elevated ferritin. This is functional iron deficiency, where ferritin acts as an acute phase reactant rather than reflecting true iron stores. 1

Key Diagnostic Points:

• Iron saturation of 5% confirms absolute iron deficiency (normal >16%), regardless of ferritin level 1
• Elevated ferritin with low iron saturation indicates inflammation or liver disease blocking iron utilization 1
• The elevated liver enzymes and neutrophilia (7.1) support an inflammatory or hepatic process 1
• Syncope in the setting of recent menarche with heavy bleeding suggests acute hemodynamic compromise from blood loss 2

Immediate Next Steps (First 24-48 Hours)

1. Iron Replacement Therapy - Start Immediately

• Prescribe oral iron: 3 mg/kg/day of elemental iron (ferrous sulfate) taken between meals 1, 3
• For a 12-year-old (approximate weight 40-50 kg), this translates to 120-150 mg elemental iron daily 1
• Consider adding ascorbic acid (250-500 mg twice daily with iron) to enhance absorption 1
• Recheck hemoglobin in 4 weeks—expect rise of ≥1 g/dL if compliant and no ongoing losses 1

2. Evaluate Heavy Menstrual Bleeding

• Obtain menstrual history: duration, frequency, clot size (≥1 inch suggests HMB), "flooding" episodes 2
• Refer to gynecology urgently for HMB management—hormonal therapy may be needed to stop ongoing losses 2, 4
• Heavy menstrual bleeding is the most common cause of iron deficiency in adolescent females 1

3. Investigate the Elevated Ferritin and Liver Enzymes

• Obtain complete hepatic panel: AST, ALT, alkaline phosphatase, bilirubin, GGT 1
• Check inflammatory markers: CRP, ESR to quantify inflammation 1
• Screen for celiac disease: tissue transglutaminase antibody (tTG) with total IgA level 1
• Consider transferrin saturation calculation if not already done: (serum iron ÷ TIBC) × 100 1

Differential Diagnosis for Elevated Ferritin with Iron Deficiency

The combination demands investigation for:

Most Likely in This Age Group:

• Inflammatory bowel disease (elevated ferritin as acute phase reactant with malabsorption) 1
• Celiac disease (impaired iron absorption, can cause elevated liver enzymes) 1
• Autoimmune hepatitis (liver inflammation causing elevated ferritin and transaminases) 1
• Non-alcoholic fatty liver disease (increasingly common in adolescents, causes elevated ferritin) 1

Less Common but Important:

• Hemochromatosis variants (unlikely given low iron saturation, but compound heterozygotes can present atypically) 1
• Chronic infection or occult malignancy (ferritin as acute phase reactant) 1

Follow-Up Algorithm (Next 4-12 Weeks)

Week 4:

• Repeat CBC with hemoglobin/hematocrit 1
• If hemoglobin increased ≥1 g/dL: continue iron for 3 months total after anemia correction to replenish stores 1
• If no response despite compliance: consider parenteral iron (intravenous) if malabsorption confirmed 1

Weeks 4-8:

• Complete workup results review: celiac serology, hepatic panel, inflammatory markers
• Liver imaging (ultrasound or MRI) if transaminases remain elevated to assess for structural disease 1
• Gynecologic intervention for HMB if not already initiated 2, 4

Month 3:

• Recheck iron studies: ferritin, iron, TIBC, transferrin saturation 1
• Target ferritin >15 μg/L (ideally >35 μg/L in menstruating females) with normal hemoglobin 1
• Continue iron supplementation for 2-3 months after anemia correction 1

Months 3-12:

• Monitor hemoglobin every 3 months for first year 1
• Reassess at 6 months post-treatment completion 1
• Address underlying HMB definitively to prevent recurrence 2, 4

Critical Pitfalls to Avoid

1. Do Not Delay Iron Therapy Based on High Ferritin

The iron saturation of 5% is diagnostic of iron deficiency requiring immediate treatment, regardless of ferritin level. 1 Ferritin >100 ng/mL with TSAT <20% represents functional iron deficiency or inflammatory block. 1

2. Do Not Assume Menstruation Alone Explains Everything

While HMB is the likely primary cause, the elevated liver enzymes and ferritin mandate investigation for inflammatory/hepatic conditions that may impair iron absorption or utilization. 1

3. Do Not Use Parenteral Iron as First-Line

Oral iron is appropriate initial therapy in this stable patient. 1 Reserve intravenous iron for documented malabsorption, intolerance to multiple oral preparations, or failure to respond after 4 weeks of compliant oral therapy. 1

4. Do Not Forget to Replenish Stores

Iron therapy must continue for 3 months after hemoglobin normalization to replenish body stores, not just correct anemia. 1 Premature discontinuation leads to rapid recurrence.

5. Monitor for Non-Response

If hemoglobin fails to rise ≥1 g/dL after 4 weeks of compliant therapy, consider: ongoing blood loss, malabsorption (celiac disease), misdiagnosis, or inflammatory iron block requiring intravenous therapy. 1

Special Considerations for Adolescent Females

• Screen annually for anemia in adolescent females with risk factors (HMB, previous iron deficiency, low dietary iron intake) 1
• Dietary counseling: emphasize iron-rich foods (red meat, seafood) and vitamin C co-ingestion with non-haem iron sources 1
• Address contraceptive needs if HMB management requires hormonal therapy 2, 5
• Premenopausal women <45 years with iron deficiency should have celiac screening but do not routinely require GI endoscopy unless symptoms present 1