What is the best course of action for a patient with depleted iron stores, as indicated by a ferritin level of 25, and a history of elevated hemoglobin (Hb) and hematocrit (Hct) levels?

Management of Ferritin 25 with History of Elevated Hemoglobin/Hematocrit

A ferritin of 25 ng/mL indicates depleted iron stores requiring iron supplementation, but the history of elevated hemoglobin and hematocrit suggests this patient may have secondary erythrocytosis or polycythemia, which fundamentally changes the management approach—you must first investigate the cause of the elevated Hgb/Hct before initiating iron therapy, as iron supplementation in polycythemia vera or other myeloproliferative disorders could be contraindicated.

Initial Diagnostic Approach

Confirm Iron Deficiency Status

• Ferritin 25 ng/mL definitively indicates depleted iron stores in the absence of inflammation, as values <30 ng/mL reflect absolute iron deficiency 1
• Check transferrin saturation (TSAT) to assess functional iron status—TSAT <20% confirms iron deficiency 1
• In patients with inflammatory conditions, ferritin cutoffs should be raised to 100 ng/mL, but at 25 ng/mL, iron deficiency is present regardless of inflammatory status 1

Investigate the Elevated Hemoglobin/Hematocrit

This is the critical step that distinguishes this case from routine iron deficiency:

• Obtain complete blood count with differential to assess for polycythemia vera (elevated RBC mass, WBC, platelets) 2
• Measure erythropoietin level—low EPO suggests primary polycythemia (polycythemia vera), while elevated EPO suggests secondary causes 2
• Assess for secondary causes of erythrocytosis: chronic hypoxemia, sleep apnea, smoking, renal disease, testosterone use, or other causes of elevated hemoglobin 2
• Consider JAK2 mutation testing if polycythemia vera is suspected based on elevated Hgb/Hct with low-normal EPO 2

Management Algorithm

If Polycythemia Vera or Primary Polycythemia is Diagnosed:

• Do NOT supplement with iron—iron deficiency in polycythemia vera is often therapeutic, as it limits excessive red cell production 2
• Therapeutic phlebotomy is the primary treatment to reduce hematocrit and can be used to mobilize iron stores 1, 2
• Hematology consultation is essential for ongoing management 1

If Secondary Erythrocytosis is Identified:

• Treat the underlying cause (e.g., CPAP for sleep apnea, smoking cessation, discontinue testosterone) 2
• Iron supplementation may be appropriate once the secondary cause is addressed and hemoglobin normalizes 1
• Monitor response carefully as correcting iron deficiency may further increase already-elevated hemoglobin 1

If No Cause for Elevated Hgb/Hct is Found and Values Normalize:

Proceed with standard iron deficiency treatment:

Oral Iron Therapy (First-Line)

• Ferrous sulfate 324 mg (65 mg elemental iron) daily is the gold standard, with doses up to 200 mg elemental iron daily for optimal repletion 1, 3, 4
• Take on empty stomach for best absorption, or with meals if gastrointestinal side effects occur 1
• Avoid taking within 2 hours of tetracycline antibiotics due to absorption interference 3
• Duration: 3-12 weeks to correct anemia and replenish stores 4
• Monitor ferritin and hemoglobin at 4-6 weeks—ferritin should not rise significantly in the first 3 weeks with standard dosing unless iron is absorbed in excess of erythropoietic needs 5

Intravenous Iron (Alternative)

Consider IV iron if:

• Intolerance to oral iron (nausea, constipation, diarrhea) 1, 3, 4
• Malabsorption conditions (celiac disease, inflammatory bowel disease, prior gastric surgery) 1
• Need for rapid correction prior to surgery or other urgent situations 4
• Chronic kidney disease where oral iron is often insufficient 1

Dosing for IV iron:

• Ferric carboxymaltose or ferric derisomaltose: 500-1000 mg in single infusion with excellent safety profiles 1, 4
• Iron dextran: 500-1000 mg after 25 mg test dose in adults 1
• Must be administered in medical facilities by trained providers due to rare hypersensitivity risk 4
• Monitor phosphate levels as IV iron (especially ferric carboxymaltose) can cause hypophosphatemia 4

Critical Monitoring Parameters

• Recheck hemoglobin and ferritin after 4-6 weeks of oral iron therapy 5
• Target ferritin >100 ng/mL for adequate iron stores in most patients 1
• Watch for paradoxical rise in hemoglobin during iron repletion—if Hgb/Hct becomes elevated again, stop iron and reassess for underlying polycythemia 2
• Assess for gastrointestinal blood loss in men and postmenopausal women with iron deficiency, as this is the most common cause 1, 6

Common Pitfalls to Avoid

• Never assume iron deficiency is the only problem when hemoglobin/hematocrit has been elevated—this combination is unusual and demands investigation 2
• Do not reflexively start iron supplementation without understanding why Hgb/Hct was previously elevated, as you may worsen polycythemia 2
• Ferritin can be falsely elevated by inflammation, liver disease, or malignancy, but at 25 ng/mL, iron deficiency is certain 1
• Standard oral iron dosing may not raise ferritin for several weeks despite hematologic response 5