What is the diagnosis and treatment for a patient with low Mean Corpuscular Hemoglobin Concentration (MCHC), low transferrin, and high Total Iron Binding Capacity (TIBC)?

Iron Deficiency Anemia

This laboratory pattern—low MCHC, low transferrin, and high TIBC—is diagnostic of iron deficiency anemia (IDA), and treatment should begin with oral iron supplementation unless specific contraindications exist. 1

Understanding the Laboratory Pattern

The combination you describe represents classic iron deficiency:

• Low MCHC (Mean Corpuscular Hemoglobin Concentration) indicates hypochromic red cells, a hallmark of iron-deficient erythropoiesis 1
• High TIBC (Total Iron Binding Capacity) reflects increased transferrin production by the liver attempting to capture any available iron 1, 2
• Low transferrin in your description likely refers to low transferrin saturation (TSAT), not low transferrin protein levels—since TIBC is high, transferrin protein is actually elevated 2

Key diagnostic point: TSAT is calculated as (serum iron / TIBC) × 100, and values <16-20% confirm iron deficiency 2. The elevated TIBC with low iron creates this low saturation pattern 1, 2.

Complete Diagnostic Workup Required

Before initiating treatment, obtain these additional tests:

• Serum ferritin (most specific test): <15 μg/L is highly specific for iron deficiency (specificity 0.99); <30 μg/L indicates depleted iron stores; <45 μg/L warrants investigation even with inflammation 1
• Complete blood count with MCV and RDW to assess microcytosis 1
• Reticulocyte count to evaluate bone marrow response 1
• CRP to identify inflammation that might elevate ferritin falsely 1

Critical caveat: Ferritin is an acute phase reactant—apparently normal levels (30-150 μg/L) can mask iron deficiency in inflammatory conditions 1. In chronic disease with inflammation, ferritin up to 100 ng/mL may still indicate iron deficiency 2.

Identifying the Underlying Cause

Investigation for blood loss is mandatory at any level of anemia with iron deficiency, particularly in:

• Men and non-menstruating women: Gastrointestinal evaluation (colonoscopy first if >50 years) is essential, as 9% of patients >65 years with IDA have GI malignancy 1, 3
• Premenopausal women: If history and examination suggest menorrhagia alone, a trial of iron is reasonable with hemoglobin recheck at one month 3
• Fast-track referral criteria: Hemoglobin <110 g/L in men or <100 g/L in non-menstruating women warrants urgent GI investigation 1

Other causes to consider:

• Malabsorption (celiac disease, atrophic gastritis, H. pylori, gastric bypass) 4, 5
• Inadequate dietary intake 5
• Increased demand (pregnancy, adolescence) 3
• Rare: TMPRSS6 mutations causing iron-refractory IDA 5

Important: In patients with microcytosis and normal iron studies, obtain hemoglobin electrophoresis to exclude thalassemia, particularly in appropriate ethnic backgrounds 1.

Treatment Algorithm

First-Line: Oral Iron Supplementation

Oral iron is the initial treatment for most patients with IDA 4, 6:

• Standard dosing provides adequate iron replacement 4, 6
• Expected response: 1-2 g/dL (10-20 g/L) hemoglobin increase within one month 3
• Reticulocyte count increases within days 7
• Continue treatment to replenish iron stores, not just correct hemoglobin 7

Common pitfall: Patient adherence is poor due to gastrointestinal side effects (nausea, constipation, abdominal discomfort) 4. If no hemoglobin response at one month, consider malabsorption, continued bleeding, or non-adherence 3.

Second-Line: Intravenous Iron

IV iron is preferred when:

• Oral iron intolerance or non-adherence 4, 6
• Malabsorption (gastric bypass, inflammatory bowel disease, celiac disease) 4, 5
• Heavy ongoing blood loss (menorrhagia, hereditary hemorrhagic telangiectasia) 4
• Rapid iron repletion needed 5
• Chronic kidney disease or heart failure with iron deficiency 5

Available formulations include iron dextran, ferric gluconate, and iron sucrose 7, 8, 6:

• Modern formulations have very low rates of serious adverse events 4
• Full replacement doses can be administered in minutes to hours 4
• Monitoring: Check CBC and iron parameters (ferritin, TSAT) 4-8 weeks after last infusion; do not check within 4 weeks of total dose infusion as circulating iron interferes with assays 2
• Goal: TSAT ≥20% to ensure adequate iron for erythropoiesis 2

Potential complications of high-dose IV iron (newer formulations): allergic reactions, hypophosphatemia/osteomalacia, iron overload, vascular leakage 5. Despite safety concerns, IV iron is underutilized and should be moved forward in treatment algorithms 4.

Dosing Calculations for IV Iron

For iron dextran, total dose calculation 7:

• Adults >15 kg: Dose (mL) = 0.0442 × (Desired Hb - Observed Hb) × Lean Body Weight + (0.26 × Lean Body Weight)
• This accounts for hemoglobin restoration plus iron store replenishment 7

Monitoring Treatment Response

• Hemoglobin and hematocrit are simple, accurate monitoring tools 7
• Serum ferritin usually correlates with iron stores, though this may not be valid in chronic renal dialysis patients receiving IV iron 7
• Transferrin saturation should normalize with adequate treatment 8
• Reticulocyte hemoglobin content improves within 2 weeks of IV iron 8

If treatment fails: Consider functional iron deficiency (normal/elevated ferritin with low TSAT in chronic inflammation), continued blood loss, malabsorption, or incorrect diagnosis 2, 6.