In a 69‑year‑old man with a recent 7‑day history of melena that resolved with a proton‑pump inhibitor, is the low ferritin despite a normal hemoglobin level concerning?

Is This Concerning? Yes—Investigate Immediately for Occult Gastrointestinal Blood Loss

This 69-year-old man's declining ferritin (64 → 34 μg/L) following a melena episode, despite normal hemoglobin, is highly concerning and mandates urgent bidirectional endoscopy to exclude gastrointestinal malignancy or ongoing occult bleeding. 1

---

Why This Pattern Demands Investigation

The Ferritin Decline Signals Ongoing Iron Loss

• Ferritin <45 μg/L has 92% specificity for iron deficiency, and this patient's current level of 34 μg/L indicates depleted iron stores. 1
• The drop from 64 to 34 μg/L over time represents progressive iron depletion, which in an older adult male without obvious blood loss strongly suggests occult gastrointestinal bleeding. 1
• Normal hemoglobin (149 g/L) does not exclude iron deficiency—this represents Stage 1 iron deficiency where stores are depleted before anemia develops. 1

The Melena History Is a Critical Red Flag

• Melena indicates upper gastrointestinal bleeding, and while PPI therapy resolved the acute episode, the declining ferritin suggests either incomplete healing, recurrent bleeding, or an underlying lesion (ulcer, malignancy, angiodysplasia) that continues to bleed at a subclinical rate. 2, 3
• In adult men and postmenopausal women, iron deficiency may be the sole manifestation of gastrointestinal malignancy, making urgent investigation mandatory. 1

PPI Use May Be Masking Ongoing Blood Loss AND Impairing Iron Absorption

• PPIs reduce gastric acid secretion, which impairs absorption of non-heme iron from both diet and oral supplements. 2, 3, 4
• Studies show that only 16% of iron-deficient patients on omeprazole achieve normal hemoglobin response to oral ferrous sulfate, with mean hemoglobin increases of only 0.8 g/L after 3 months. 4
• Long-term PPI use (even 25 years) can cause iron deficiency anemia through reduced iron absorption, independent of bleeding. 3
• However, in this case, the prior melena episode makes ongoing occult bleeding the more likely primary cause, with PPI-induced malabsorption potentially contributing. 2, 5

---

Immediate Diagnostic Algorithm

Step 1: Urgent Bidirectional Endoscopy (Upper GI + Colonoscopy)

• This is mandatory in a 69-year-old man with iron deficiency and prior melena, regardless of current symptom resolution. 1
• Look for:
  • Upper GI sources: peptic ulcer disease, gastric/esophageal malignancy, angiodysplasia, Cameron lesions (hiatal hernia erosions)
  • Lower GI sources: colorectal cancer, polyps, colitis, angiodysplasia

Step 2: Calculate Transferrin Saturation (TSAT)

• TSAT = (serum iron × 100) ÷ TIBC. 1
• TSAT <16-20% confirms iron deficiency and indicates insufficient iron available for red blood cell production. 1
• This helps quantify the severity of iron-restricted erythropoiesis.

Step 3: Screen for Celiac Disease

• Measure tissue transglutaminase IgA antibodies—celiac disease accounts for 3-5% of iron deficiency cases and can coexist with other pathology. 1

Step 4: Test for Helicobacter pylori

• Use stool antigen or urea breath test (non-invasive)—H. pylori impairs iron absorption and can cause chronic gastritis/ulcers. 1

---

Treatment Strategy While Awaiting Investigation

Do NOT Wait for Endoscopy Results to Start Iron Replacement

• Initiate oral ferrous sulfate 65 mg elemental iron daily (or alternate-day dosing to improve absorption and reduce GI side effects). 1
• However, oral iron will likely fail in this patient due to:
  1. Ongoing PPI use impairing absorption 4, 5
  2. Possible ongoing occult bleeding exceeding oral replacement capacity 1

Plan for Intravenous Iron if Oral Therapy Fails

• Intravenous ferric carboxymaltose (15 mg/kg, max 1000 mg per dose) is indicated if: 1
  • No hemoglobin rise ≥10 g/L after 2 weeks of oral iron
  • Ongoing blood loss is confirmed on endoscopy
  • Oral iron intolerance develops
• IV iron produces reticulocytosis within 3-5 days and mean hemoglobin increase of ~8 g/L over 8 days. 1
• 95% of PPI-associated iron deficiency cases respond to IV iron when oral therapy fails. 5

---

Critical Pitfalls to Avoid

Do Not Assume PPI-Resolved Melena Means the Problem Is Solved

• PPIs suppress acid and promote ulcer healing, but they do not address underlying structural lesions (malignancy, large ulcers, vascular malformations) that may continue to bleed intermittently. 2, 3
• Declining ferritin despite PPI therapy indicates ongoing iron loss that requires investigation. 1

Do Not Rely on Normal Hemoglobin to Exclude Significant Pathology

• Iron deficiency without anemia (Stage 1) can persist for months before hemoglobin drops, during which time malignancy or other serious pathology may progress. 1
• Ferritin is the earliest and most specific marker of iron deficiency, and a level of 34 μg/L demands action. 1

Do Not Continue PPI Without Reassessing Need

• Long-term PPI use is a recognized cause of iron deficiency anemia through impaired absorption. 2, 3, 4, 5, 6
• Once endoscopy is complete and any lesions are treated, consider switching to an H2-receptor antagonist (e.g., famotidine) if acid suppression is still needed—one case report showed anemia resolution within 3 months after switching from rabeprazole to famotidine. 2

Do Not Overlook Celiac Disease

• Celiac disease is present in 3-5% of iron deficiency cases and can cause treatment failure if missed. 1
• Serologic screening is simple and should be done in all cases.

---

Follow-Up and Monitoring

• Repeat CBC and ferritin at 8-10 weeks after starting iron therapy to assess response. 1
• Target ferritin >100 ng/mL to fully replenish iron stores and prevent recurrence. 1
• If no improvement occurs despite adequate oral iron, this confirms either malabsorption (PPI effect, celiac disease) or ongoing blood loss, and IV iron should be initiated. 1, 5
• If endoscopy reveals a bleeding source, treat it definitively (e.g., ulcer therapy, polypectomy, angiodysplasia ablation) and monitor for recurrence.

---

Summary of Key Actions

1. Urgent bidirectional endoscopy—mandatory in a 69-year-old man with iron deficiency and prior melena 1
2. Start oral ferrous sulfate 65 mg daily—but anticipate failure due to PPI use 1, 4
3. Screen for celiac disease and H. pylori—both impair iron absorption 1
4. Plan for IV iron if oral therapy fails after 8-10 weeks—95% response rate in PPI-associated cases 1, 5
5. Reassess PPI necessity—consider switching to H2-blocker after endoscopy if continued acid suppression is needed 2