What is the diagnosis and management for a patient with low ferritin, low iron, low transferrin saturation, hypochromic red blood cells (RBC), low hemoglobin (Hg), low mean corpuscular volume (MCV), low mean corpuscular hemoglobin (MCH), and high red blood cell distribution width (RDW)?

Iron Deficiency Anemia (IDA)

This clinical presentation is diagnostic of iron deficiency anemia, characterized by microcytic hypochromic anemia with depleted iron stores, and should be treated with iron supplementation after identifying and addressing the underlying cause of iron loss or malabsorption. 1

Diagnosis

The laboratory pattern presented is pathognomonic for iron deficiency anemia:

• Low ferritin confirms depleted iron stores (absolute iron deficiency when <30 μg/L without inflammation, or <100 μg/L with inflammation) 1
• Low serum iron and low transferrin saturation (<16-20%) indicate insufficient circulating iron for erythropoiesis 1
• Low MCV and low MCH reflect microcytic hypochromic red blood cells characteristic of iron-restricted erythropoiesis 1, 2
• High RDW indicates anisocytosis from mixed populations of older normocytic cells and newer microcytic cells 1, 2
• Low hemoglobin confirms anemia (defined as Hb <12 g/dL in women, <13 g/dL in men) 1

Diagnostic Considerations

In the absence of inflammation (normal CRP, no clinical signs of active disease), a ferritin <30 μg/L and transferrin saturation <16% definitively establish iron deficiency 1

If inflammation is present (elevated CRP, active inflammatory disease), ferritin thresholds must be adjusted upward to 100 μg/L, as ferritin is an acute-phase reactant that can be falsely elevated despite true iron deficiency 1

Identifying the Underlying Cause

Before initiating treatment, investigate the source of iron deficiency:

• Gastrointestinal blood loss (most common in adults): Evaluate for peptic ulcer disease, gastritis, inflammatory bowel disease, celiac disease, malignancy, or angiodysplasia 1, 3
• Helicobacter pylori infection can impair iron absorption and should be tested 1
• Menstrual blood loss in premenopausal women 1
• Dietary insufficiency or malabsorption (celiac disease, atrophic gastritis, post-gastrectomy) 1, 3
• Increased demand (pregnancy, rapid growth in children) 2, 3
• Rare genetic causes (TMPRSS6 mutations causing iron-refractory iron deficiency anemia) should be considered only if refractory to standard therapy 1, 3

Treatment Strategy

First-Line: Oral Iron Supplementation

Initiate oral iron as first-line therapy in most patients with iron deficiency anemia 1

• Ferrous sulfate 324 mg (65 mg elemental iron) daily is the standard initial regimen 1, 4
• Take on an empty stomach for optimal absorption, though taking with food improves tolerance in patients with gastrointestinal side effects 1
• Add vitamin C 500 mg to enhance absorption, particularly if taken with meals 1
• Alternate-day dosing may improve absorption by avoiding hepcidin upregulation that occurs with daily dosing 1
• Common side effects include nausea, constipation, and abdominal discomfort, which cause poor compliance 1

Second-Line: Intravenous Iron

Switch to intravenous iron if:

• Oral iron is not tolerated due to gastrointestinal side effects 1
• Malabsorption is present (inflammatory bowel disease, celiac disease, atrophic gastritis) 1
• Rapid iron repletion is needed (severe anemia, perioperative setting, symptomatic patients) 1, 3
• Inadequate response to oral iron after 4-6 weeks of therapy 1
• Active inflammation with hepcidin upregulation blocking intestinal iron absorption 1

Intravenous iron formulations include iron sucrose, ferric carboxymaltose, iron isomaltoside, ferumoxytol, and low molecular weight iron dextran 1, 3

Calculate total iron deficit using standard formulas accounting for hemoglobin deficit and iron store repletion 1

Monitor serum ferritin and avoid exceeding 500 μg/L to prevent iron overload toxicity, particularly in children and adolescents 1

Potential complications of intravenous iron include allergic reactions, hypophosphatemia, and rarely iron overload 3

Monitoring Response to Therapy

• Hemoglobin should increase by ≥2 g/dL within 4-6 weeks of initiating therapy 1
• Reticulocyte count typically rises within 1-2 weeks, indicating bone marrow response 2, 5
• Continue iron supplementation for 3-6 months after hemoglobin normalization to replete iron stores 1, 2
• Recheck ferritin to confirm adequate iron repletion (target >100 μg/L in most patients) 1

Common Pitfalls

Failure to identify the underlying cause leads to recurrent anemia; gastrointestinal evaluation is mandatory in adults without obvious source 1

Underestimating iron deficiency in inflammatory conditions when ferritin is 30-100 μg/L (combination of true iron deficiency and anemia of chronic disease) 1

Premature discontinuation of therapy before iron stores are repleted results in rapid recurrence 1

Not considering intravenous iron early enough in patients with malabsorption or active inflammation where oral iron is ineffective 1