Iron Deficiency Without Anemia
You have iron deficiency without anemia. Your hemoglobin of 13.1 g/dL is below your facility's reference range (≥14 g/dL) but above the threshold that defines anemia in most clinical contexts, while your ferritin of 20.5 ng/mL confirms depleted iron stores.
Diagnostic Classification
Your laboratory values fit the following pattern:
Hemoglobin 13.1 g/dL: This is below your local reference range but typically above the WHO anemia threshold for adult males (13 g/dL) or females (12 g/dL). The declining trend from 13.8 to 13.1 g/dL suggests progressive iron depletion. 1
Ferritin 20.5 ng/mL: This definitively confirms iron deficiency. In adults without inflammation, ferritin <30 ng/mL is diagnostic of absolute iron deficiency. 2, 1, 3 Your ferritin is well below this threshold, indicating severely depleted iron stores.
Transferrin saturation 24%: Although measured 8 months ago and now potentially outdated, this value was above the diagnostic threshold for iron deficiency (<16-20%). 2, 4 However, TSAT can remain falsely normal early in iron deficiency before stores are completely exhausted, and your current ferritin confirms true deficiency regardless of the prior TSAT. 4
Why This Matters Clinically
Iron deficiency without anemia is a distinct clinical entity that causes symptoms and warrants treatment. You are in the early-to-intermediate stage of iron deficiency, where stores are depleted (low ferritin) but hemoglobin has not yet fallen to anemic levels. 1, 3
Common symptoms at this stage include:
- Fatigue, irritability, and difficulty concentrating
- Exercise intolerance and dyspnea on exertion
- Restless legs syndrome (32-40% prevalence)
- Pica (40-50% prevalence)
- These symptoms can occur even when hemoglobin remains "normal" 1
Recommended Diagnostic Work-Up
Before starting treatment, the underlying cause must be identified:
1. Repeat Iron Studies Now
Your TSAT is 8 months old and should be remeasured alongside a complete iron panel:
- Serum iron, TIBC, transferrin saturation, and ferritin
- Complete blood count with red cell indices (MCV, MCH)
- C-reactive protein to assess for inflammation that might elevate ferritin 2, 4, 3
2. Identify the Source of Iron Loss
The most common causes of iron deficiency are:
Gastrointestinal blood loss (94% of cases in adults): In men and postmenopausal women, bidirectional endoscopy (upper endoscopy and colonoscopy) is mandatory to exclude malignancy. 1, 3
Menstrual blood loss: In premenopausal women, assess menstrual patterns. Heavy menstrual bleeding (≥4 days duration or excessive volume) is the leading cause. 1, 3
Malabsorption: Test for celiac disease (tissue transglutaminase antibody) and Helicobacter pylori infection, both common and treatable causes. 3
Dietary insufficiency: Assess iron intake, particularly in vegetarians/vegans or those with restricted diets. 1
Medications: NSAIDs, aspirin, and anticoagulants increase gastrointestinal blood loss. 1
3. Screen for Chronic Inflammatory Conditions
If CRP is elevated, consider:
- Chronic kidney disease (check creatinine and eGFR)
- Heart failure (assess for symptoms, BNP if indicated)
- Inflammatory bowel disease (if gastrointestinal symptoms present)
- Malignancy (age-appropriate cancer screening) 1, 3
Treatment Algorithm
First-Line: Oral Iron Supplementation
For iron deficiency without inflammation and no contraindications to oral therapy:
Ferrous sulfate 325 mg (65 mg elemental iron) every other day is the preferred regimen. Alternate-day dosing improves absorption and reduces gastrointestinal side effects compared to daily dosing. 1, 3
Take on an empty stomach (1 hour before or 2 hours after meals) to maximize absorption. If gastrointestinal upset occurs, take with food despite reduced absorption. 3
Avoid taking with calcium supplements, antacids, proton pump inhibitors, or tea/coffee, which impair absorption. 3
Common side effects include constipation, nausea, and dark stools; approximately 50% of patients experience reduced adherence due to adverse effects. 3
Monitoring Response
Recheck hemoglobin and iron studies (ferritin, TSAT) 8-10 weeks after starting oral iron. 4, 5
Expected response: Hemoglobin should rise by 1-2 g/dL within 4-8 weeks, and ferritin should increase toward the target range. 4
Target ferritin after repletion: ≥30-45 ng/mL with TSAT ≥20% in patients without chronic inflammation. 4
When to Use Intravenous Iron
Switch to IV iron if:
- Intolerance to oral iron (gastrointestinal side effects)
- Lack of response after 8-10 weeks of adequate oral therapy
- Malabsorption (celiac disease, post-bariatric surgery, atrophic gastritis)
- Ongoing blood loss that exceeds oral replacement capacity
- Chronic inflammatory conditions (CKD, heart failure, IBD, cancer) where hepcidin blocks intestinal iron absorption 2, 1, 3
IV iron formulations (ferric carboxymaltose, iron sucrose, low-molecular-weight iron dextran) bypass intestinal absorption and directly replenish stores. 2, 4
Common Pitfalls to Avoid
Do not assume normal hemoglobin excludes clinically significant iron deficiency. Symptoms and progression to anemia occur as stores deplete further. 1, 3
Do not rely on the 8-month-old TSAT value. Iron parameters change over time, and current values are needed to guide treatment. 4
Do not skip the evaluation for underlying causes. Treating iron deficiency without identifying the source (especially occult malignancy) can delay critical diagnoses. 3
Do not measure iron studies within 4 weeks of starting IV iron if that route is chosen, as circulating iron interferes with assays and produces falsely elevated results. 4
Do not use daily oral iron dosing. Alternate-day dosing is superior for absorption and tolerability. 3