What is the appropriate management for an adult patient with no significant medical history presenting with low Mean Corpuscular Hemoglobin (MCH) and Hemoglobin (Hgb) levels, indicating anemia?

Management of Low MCH and Hemoglobin in Adults

For an adult patient with low MCH and low hemoglobin, initiate oral iron supplementation immediately with ferrous sulfate 325 mg daily (or on alternate days to improve tolerability) after confirming iron deficiency with serum ferritin, and expect a hemoglobin rise of ≥10 g/L within 2 weeks if iron deficiency is the cause. 1

Initial Diagnostic Workup

Low MCH combined with low hemoglobin strongly suggests iron deficiency anemia, which is the most common cause of microcytic anemia. 1, 2

Essential laboratory tests to order:

• Serum ferritin is the single most useful marker for confirming iron deficiency, with levels <30 μg/L definitively indicating iron deficiency in the absence of inflammation 3, 1
• Complete blood count with RBC indices to assess MCV (mean corpuscular volume) and RDW (red cell distribution width) 3
• Transferrin saturation and TIBC if ferritin is equivocal or inflammation is suspected, with transferrin saturation <15% confirming iron deficiency 4
• Reticulocyte count to assess bone marrow response 3

Critical caveat: MCH is actually more reliable than MCV for detecting iron deficiency because it is less dependent on storage conditions and laboratory equipment. 1 However, do not assume microcytosis must be present—coexisting macrocytic causes (like B12 or folate deficiency) can mask the typical microcytic picture. 3

Treatment Algorithm

Step 1: Initiate Iron Replacement

Start oral iron therapy immediately with ferrous sulfate 324 mg (containing 65 mg elemental iron) once daily or on alternate days. 1, 5 The alternate-day dosing may improve tolerability while maintaining efficacy.

• Continue therapy for 3 months total to replenish iron stores if response is positive 1
• For menstruating women, higher doses and longer duration may be necessary 1

Step 2: Assess Response at 2-4 Weeks

Check hemoglobin, MCV, and MCH after 2-4 weeks of iron therapy. 1

• A hemoglobin rise of ≥10 g/L within 2 weeks strongly confirms iron deficiency, even if initial iron studies were equivocal 3, 1
• If no response occurs, evaluate for non-adherence, malabsorption, ongoing blood loss, or alternative diagnoses 2

Step 3: Investigate Underlying Cause

Identify the source of iron deficiency while treating:

• Gastrointestinal bleeding is found in 60-70% of patients with iron deficiency anemia referred for endoscopy 2
• Consider menstrual blood loss, dietary inadequacy, malabsorption disorders (celiac disease, inflammatory bowel disease), and medications 3
• Investigation should be considered at any level of anemia, with stronger indication for more severe degrees 3

Special Clinical Scenarios

When Inflammation is Present

In patients with chronic inflammatory conditions, ferritin may appear falsely normal despite true iron deficiency. 3, 1

• Use a higher ferritin cutoff of <45 μg/L (or even up to 100 μg/L in severe inflammation) to diagnose iron deficiency 3
• Check CRP or inflammatory markers to guide ferritin interpretation 3

When Oral Iron Fails or Cannot Be Used

Consider parenteral iron when: 2

• Oral iron is not tolerated or absorbed
• Inflammatory bowel disease is present (parenteral iron may be preferred) 1
• Rapid correction is needed
• Patient has chronic kidney disease with erythropoietin deficiency 1

If MCV is Normal or High Despite Low MCH

Do not exclude iron deficiency—this pattern suggests combined deficiencies. 3

• Check vitamin B12 and folate levels before treating, as coexisting macrocytic causes can mask microcytosis 3
• A high RDW indicates mixed cell sizes, confirming combined deficiencies 3
• Treat B12 deficiency first and immediately if present, as folate treatment alone can cause irreversible neurological damage 3

Common Pitfalls to Avoid

• Do not rely on MCV alone—low MCH with normal or high MCV can still represent iron deficiency with concurrent B12/folate deficiency 3
• Do not assume normal ferritin excludes iron deficiency in inflammatory states; ferritin up to 45-100 μg/L may still represent deficiency with inflammation 3
• Do not delay treatment waiting for extensive workup in symptomatic patients—start iron therapy and investigate concurrently 1
• Do not stop iron therapy prematurely—continue for 3 months to replenish stores, not just until hemoglobin normalizes 1

Monitoring and Follow-up

Recheck hemoglobin at 2-4 weeks to confirm response, then monitor periodically until stores are replenished. 1 If the patient does not respond to appropriate iron therapy, consider referral to hematology for evaluation of less common causes including sideroblastic anemia, genetic disorders of iron metabolism, or anemia of chronic disease. 1, 2