What are the diagnostic and treatment approaches for iron deficiency?

Iron Deficiency Diagnosis

Serum ferritin is the most powerful diagnostic test for iron deficiency, with a threshold of <30 μg/L in patients without inflammation, but up to 100 μg/L may still indicate iron deficiency when inflammation is present. 1

Diagnostic Approach

Initial Laboratory Workup

The minimum diagnostic workup should include 1:

• Complete blood count (CBC) with mean corpuscular volume (MCV) and red cell distribution width (RDW)
• Serum ferritin
• Transferrin saturation (TSAT)
• C-reactive protein (CRP) to assess for inflammation
• Reticulocyte count

Interpreting Ferritin Levels

The ferritin threshold varies critically based on inflammatory status 1:

• Without inflammation: Ferritin <30 μg/L confirms iron deficiency 1
• With inflammation present: Ferritin up to 100 μg/L may still indicate iron deficiency 1
• Ferritin >100 μg/L: Iron deficiency is almost certainly not present 1

Critical caveat: Ferritin is an acute phase reactant and can be falsely elevated in patients with chronic inflammation, malignancy, or hepatic disease, masking true iron deficiency 1. In these cases, transferrin saturation <20% helps confirm iron deficiency 1, 2.

Using MCV and Reticulocyte Count

Follow this algorithmic approach 1:

1. Check MCV first:

   • Microcytosis (low MCV) suggests iron deficiency but can also occur in thalassemia or anemia of chronic disease 1
   • Normal MCV does not exclude iron deficiency, especially when microcytosis and macrocytosis coexist 1
   • High RDW indicates iron deficiency when MCV is normal 1

2. Then assess reticulocyte count 1:

   • Low or normal reticulocytes indicate deficiency states or bone marrow disease 1
   • Elevated reticulocytes exclude deficiencies and suggest hemolysis instead 1

Confirmatory Testing When Diagnosis Unclear

If ferritin is equivocal (30-100 μg/L) or inflammation is present, obtain 1, 2:

• Transferrin saturation: <20% confirms iron deficiency 2
• Soluble transferrin receptor (if available) 1
• Reticulocyte hemoglobin equivalent 1

Extended Workup for Non-Responders

If anemia does not respond to iron therapy after 4 weeks despite compliance, perform 1:

• Repeat ferritin (confirm <15 μg/L for iron deficiency) 1
• Vitamin B12 and folate levels 1
• Haptoglobin, lactate dehydrogenase, and bilirubin to assess for hemolysis 1
• Consider hematology consultation if cause remains unclear 1

Population-Specific Screening Recommendations

Who Should Be Screened

Screen routinely 1:

• All pregnant women at first prenatal visit 1
• Infants at 9-12 months and again at 15-18 months 1
• Adolescent girls and nonpregnant women every 5-10 years 1
• Patients with chronic heart failure at diagnosis and 1-2 times yearly 1
• All patients with inflammatory bowel disease 1

Do not screen routinely 1:

• Men (unless symptomatic or high-risk) 1
• Postmenopausal women (unless symptomatic or high-risk) 1

High-Risk Groups Requiring Annual Screening 1

• Heavy menstrual bleeding 1
• Low iron intake or restricted diets 1
• Previous iron deficiency anemia 1
• Chronic kidney disease 2
• Inflammatory bowel disease 1

Treatment Approaches

Oral Iron Therapy

First-line treatment for most patients 2:

• Ferrous sulfate 325 mg daily or on alternate days 2
• Administer between meals to enhance absorption 3
• Continue for 2-3 months after hemoglobin normalizes to replenish stores 1

Expected response: Hemoglobin should increase by ≥1 g/dL or hematocrit by ≥3% after 4 weeks 1

Intravenous Iron Therapy

Use IV iron when 1, 2:

• Oral iron intolerance or malabsorption 2
• Active inflammatory bowel disease with compromised absorption 1
• Chronic kidney disease, heart failure, or cancer 2
• Ongoing blood loss exceeding oral replacement capacity 2
• Second or third trimester of pregnancy 2

For chronic kidney disease patients on hemodialysis: Administer 100 mg IV iron sucrose per dialysis session, total course 1000 mg 4

Common Pitfalls to Avoid

1. Do not rely on ferritin alone in inflammatory conditions—always check TSAT simultaneously 1
2. Do not use MCV, MCH, or MCHC as sole markers in heart failure patients—they are unreliable 1
3. Do not assume dietary deficiency is the sole cause—always investigate for gastrointestinal blood loss in men and postmenopausal women 1, 3
4. Do not stop investigating if initial ferritin is normal—functional iron deficiency can occur with normal or elevated ferritin in inflammatory states 1