What is the diagnosis and treatment for a patient with hypochromia (low MCHC), low transferrin, elevated Total Iron Binding Capacity (high TIBC), and normal hemoglobin levels?

Diagnosis: Iron Deficiency Anemia (Early Stage)

This laboratory pattern—low MCHC (hypochromia), low transferrin, high TIBC, and normal hemoglobin—is diagnostic of early iron deficiency anemia, and treatment should begin immediately with oral iron supplementation to prevent progression to overt anemia. 1

Understanding the Laboratory Pattern

The combination of these specific findings confirms iron-deficient erythropoiesis even before hemoglobin drops:

• Low MCHC indicates hypochromic red cells, a hallmark of iron-deficient erythropoiesis where red blood cells contain insufficient hemoglobin 1
• High TIBC reflects increased transferrin production by the liver attempting to capture any available iron, a compensatory mechanism in iron deficiency 2, 1
• Low transferrin with high TIBC creates a low transferrin saturation (TSAT), calculated as (serum iron/TIBC) × 100, which will be <16-20% and confirms iron deficiency 1
• Normal hemoglobin indicates this is early-stage iron deficiency before anemia has fully developed 2

Critical distinction: This pattern differs from congenital atransferrinemia (which presents with low iron, low TIBC, and high ferritin) 3, and from anemia of chronic disease (which typically shows low TIBC, not high) 2.

Essential Additional Testing Required

Before initiating treatment, obtain these specific tests:

• Serum ferritin is the most specific test for iron deficiency: <15 μg/L is highly specific, <30 μg/L indicates depleted iron stores, and <45 μg/L warrants investigation even with inflammation 1
• C-reactive protein (CRP) to identify inflammation that might falsely elevate ferritin 1
• Complete blood count with MCV and RDW to assess for microcytosis that may not yet be apparent 1
• Reticulocyte count to evaluate bone marrow response 1

Investigating the Underlying Cause

Any level of iron deficiency should be investigated, even without anemia. 2

For Men and Postmenopausal Women:

• Gastrointestinal blood loss is the most common cause and requires endoscopic evaluation 2, 4
• Begin with colonoscopy if age >50 years, as asymptomatic colonic and gastric carcinoma may present with iron deficiency 2, 5
• Consider dual pathology (bleeding from both upper and lower GI tracts) in 1-10% of patients, especially in older individuals 2
• NSAIDs and aspirin are common causes and should be stopped where clinically appropriate 2

For Premenopausal Women:

• Menstrual blood loss is the most common cause 2
• If history and examination are negative, a trial of iron is reasonable with hemoglobin recheck at one month 5
• If hemoglobin does not increase by 1-2 g/dL within one month, consider malabsorption, continued bleeding, or occult lesion 5

For All Patients:

• Screen for celiac disease with tissue transglutaminase (tTG) antibody at presentation, as malabsorption from celiac disease is common in the UK and similar populations 2
• Assess dietary history for poor iron intake 2
• Consider blood donation, gastrectomy, and family history of iron absorption disorders 2

Treatment Protocol

First-Line: Oral Iron Supplementation

Oral iron is the initial treatment for most patients with iron deficiency, with expected response of 1-2 g/dL hemoglobin increase within one month. 1, 4

• Initiate oral iron immediately while investigating the underlying cause 4, 6
• Standard dosing: 200 mg elemental iron daily 2
• Continue supplementation to replenish iron stores even after hemoglobin normalizes 4

Second-Line: Intravenous Iron

IV iron is preferred when oral iron intolerance or non-adherence, malabsorption, heavy ongoing blood loss, or rapid iron repletion is needed. 1

Available formulations include:

• Iron sucrose (Venofer): dissociates into iron and sucrose, with iron transported as a complex with transferrin to erythroid precursor cells 7
• Ferric gluconate (Ferrlecit): effective in iron-deficient patients, particularly those on hemodialysis 8

Caution with IV iron: Monitor for allergic reactions, hypophosphatemia/osteomalacia, iron overload, and vascular leakage, particularly with high-dose formulations 9

Monitoring Treatment Response

Assess these parameters to confirm adequate response:

• Hemoglobin and hematocrit should increase by 1-2 g/dL within one month 1, 5
• Serum ferritin should rise, indicating iron store repletion 1
• Transferrin saturation should normalize to >20% 1
• Reticulocyte hemoglobin content provides early indication of functional iron sufficiency 1

If no response occurs: Consider malabsorption, continued blood loss, incorrect diagnosis, or non-adherence 5. Parenteral therapy may be necessary in patients who cannot tolerate or absorb oral preparations 4, 6.