What is the diagnosis and treatment plan for a patient with hypoferritinemia, low iron saturation, and normal ferritin levels, presenting with iron deficiency anemia?

Diagnosis: Functional Iron Deficiency (Iron-Restricted Erythropoiesis)

Your patient has functional iron deficiency—characterized by low serum iron (20), critically low transferrin saturation (7%), but normal-range ferritin (90 μg/L)—indicating insufficient iron availability for red blood cell production despite adequate storage iron. 1, 2

Understanding the Laboratory Pattern

• Transferrin saturation of 7% is severely below the diagnostic threshold of 16-20%, confirming impaired iron delivery to the bone marrow for hemoglobin synthesis 1, 2
• Ferritin of 90 μg/L falls in the "gray zone" (30-100 μg/L), which in the presence of inflammation suggests a mixed picture of true iron deficiency and anemia of chronic disease 1
• This pattern indicates iron is sequestered and unavailable for erythropoiesis, even though storage levels appear adequate 1, 2

Critical Next Step: Rule Out Inflammation

You must immediately check inflammatory markers (CRP and ESR) to determine if ferritin is falsely elevated by inflammation, which would mask true iron deficiency: 1, 2

• If CRP/ESR are elevated: Anemia of chronic disease (inflammatory iron block) is present—the primary intervention is treating the underlying inflammatory condition (IBD, chronic kidney disease, heart failure, malignancy) 1, 3
• If CRP/ESR are normal: This represents true functional iron deficiency with depleted stores that require iron supplementation 1, 2

Investigation for Underlying Cause

All patients with iron deficiency require investigation for the source of iron loss or impaired absorption: 1, 3

• Check celiac serology (tissue transglutaminase antibody) at presentation—present in 3-5% of iron deficiency cases 1, 2
• Test for H. pylori non-invasively (stool antigen or urea breath test) 1, 2
• Assess menstrual history in premenopausal women—the most common cause in this population 2, 3
• Screen for NSAID use—a common and reversible cause of gastrointestinal blood loss 1, 3

When to Pursue Gastrointestinal Endoscopy

Reserve bidirectional endoscopy (gastroscopy and colonoscopy) for: 1, 2

• Age ≥50 years (higher risk of GI malignancy) 2
• Any gastrointestinal symptoms (abdominal pain, change in bowel habits, blood in stool) 1, 2
• Positive celiac or H. pylori testing requiring confirmation 1, 2
• Failure to respond to adequate oral iron therapy after 8-10 weeks 2, 4
• Men or postmenopausal women (always investigate) 1, 5

For young, asymptomatic premenopausal women with heavy menses and negative celiac/H. pylori testing, empiric iron supplementation alone is reasonable without immediate endoscopy 2

Treatment Protocol

Oral Iron Supplementation (First-Line)

Initiate oral iron immediately without waiting for investigation results: 2, 4

• Ferrous sulfate 325 mg daily OR ferrous bisglycinate 30-60 mg elemental iron daily 2, 3
• Alternate-day dosing (60 mg every other day) may improve absorption and reduce gastrointestinal side effects compared to daily dosing 2, 4
• Take on empty stomach for optimal absorption, or with meals if gastrointestinal symptoms occur 2, 4
• Expected side effects include constipation, nausea, or diarrhea—minimize by taking with food or switching to alternate-day dosing 2, 4

When to Use Intravenous Iron

Intravenous iron is indicated for: 3, 6

• Oral iron intolerance (gastrointestinal side effects preventing compliance) 3, 6
• Malabsorption conditions (celiac disease, inflammatory bowel disease, post-bariatric surgery) 1, 3
• Chronic inflammatory conditions (chronic kidney disease, heart failure, IBD, cancer) 3
• Ongoing blood loss requiring rapid repletion 3
• Second and third trimesters of pregnancy 3

Follow-Up and Monitoring

Repeat CBC, serum iron, transferrin saturation, and ferritin in 8-10 weeks to assess response: 2, 4

• Target ferritin >100 μg/L to restore iron stores and prevent recurrence 2
• Expected response: hemoglobin should increase by 1-2 g/dL and ferritin should rise 4, 5

If No Improvement After 8-10 Weeks

Consider the following causes of treatment failure: 2, 4

• Malabsorption (undiagnosed celiac disease, IBD, post-bariatric surgery) 2, 3
• Non-compliance with oral iron 4, 6
• Ongoing blood loss exceeding iron replacement 2, 7
• Need for intravenous iron 3, 6
• Unrecognized chronic inflammatory condition blocking iron utilization 1, 3

Long-Term Management

For patients with recurrent low ferritin (menstruating females, vegetarians, athletes, blood donors), screen ferritin every 6-12 months 2, 4

Do not continue daily iron supplementation once ferritin normalizes—this is potentially harmful and can lead to iron overload 2, 4

Common Pitfalls to Avoid

• Do not assume normal ferritin excludes iron deficiency—transferrin saturation is the key parameter for assessing iron availability for erythropoiesis 1, 2
• Do not overlook celiac disease—it is present in 3-5% of iron deficiency cases and easily missed without serologic screening 1, 2
• Do not perform extensive GI investigation in young, asymptomatic premenopausal women with heavy menses—the yield is extremely low (0-6.5%) 2
• Do not continue iron supplementation indefinitely without monitoring ferritin—iron overload concerns arise when ferritin chronically exceeds 1000 ng/mL 2, 4