What is the diagnosis and treatment for a patient with low Mean Corpuscular Hemoglobin (MCH) and low Mean Corpuscular Hemoglobin Concentration (MCHC) indicating anemia?

Low MCH and Low MCHC: Diagnosis and Management

Low MCH and low MCHC indicate microcytic hypochromic anemia, most commonly caused by iron deficiency anemia, which requires confirmation through iron studies (ferritin, transferrin saturation) followed by oral iron supplementation as first-line treatment. 1

Diagnostic Approach

Initial Laboratory Evaluation

• Obtain iron studies immediately: Serum ferritin <30 μg/L without inflammation confirms iron deficiency; with inflammation present, ferritin up to 100 μg/L may still indicate iron deficiency 1

• Measure transferrin saturation: Values <20% support iron deficiency diagnosis 1

• Check inflammatory markers (CRP, ESR): Elevated markers suggest anemia of chronic disease, which can also present with microcytosis 1

• Obtain reticulocyte count: Normal or low reticulocytes with microcytic anemia narrows the differential to iron deficiency, anemia of chronic disease, thalassemia, or lead poisoning 1

Key Diagnostic Criteria

A ferritin <30 μg/L with MCV <80 fL and MCHC <27 g/dL definitively indicates iron deficiency anemia 1. The combination of low MCH and low MCHC is highly sensitive for iron deficiency, with MCH showing the highest correlation with hemoglobin among all red cell indices 2, 3.

Critical Differential Diagnosis

Exclude these conditions before assuming simple iron deficiency:

• Thalassemia minor: Consider when microcytosis is disproportionate to anemia severity; requires hemoglobin electrophoresis 1

• Anemia of chronic disease: Typically shows elevated ferritin (>100 μg/L) with elevated CRP despite microcytosis 1

• Polycythemia vera with iron deficiency: The combination of elevated red blood cell count with low MCV, MCH, and MCHC creates a distinctive pattern requiring serum erythropoietin measurement 4

• Lead poisoning: Rare but important to exclude in appropriate clinical contexts 1

Treatment Algorithm

Step 1: Confirm Iron Deficiency

Once iron deficiency is confirmed with ferritin <30 μg/L (or <100 μg/L with inflammation) and transferrin saturation <20%, proceed with treatment 1

Step 2: Identify Underlying Cause

In patients over 50 years or with alarm symptoms, gastrointestinal blood loss must be excluded:

• Upper endoscopy to exclude gastric cancer, peptic ulcer disease, celiac disease 5
• Colonoscopy to exclude colonic cancer, polyps, inflammatory bowel disease 5

In women of reproductive age, assess for:

• Menorrhagia (most common cause) 6
• Pregnancy-related iron depletion 6

Step 3: Initiate Iron Supplementation

Oral iron is first-line treatment 1, 6:

• Dosing: 100-200 mg elemental iron daily 6
• Intermittent dosing (every other day) is as effective as daily dosing with fewer side effects 6
• Response should be evident within 2-4 weeks with reticulocyte count increase 1
• Continue treatment for 3-6 months after hemoglobin normalization to replenish iron stores 6

Intravenous iron is indicated when 1, 6:

• Oral iron is not tolerated due to gastrointestinal side effects 6
• Malabsorption is present (inflammatory bowel disease, celiac disease, gastric bypass) 1
• Rapid correction is needed preoperatively 1
• Oral iron fails to correct anemia after 4-6 weeks 6

Step 4: Monitor Response

• Repeat complete blood count after 4-8 weeks of treatment 4
• Hemoglobin should increase by 1-2 g/dL within 3-4 weeks 6
• Failure to respond requires reassessment for ongoing blood loss, malabsorption, or alternative diagnosis 6

Critical Pitfalls to Avoid

Do not assume all microcytic anemia is simple iron deficiency: Combined deficiencies (iron plus B12/folate) can mask each other, resulting in normal MCV despite significant abnormalities 1

Do not give iron supplementation in polycythemia vera before establishing diagnosis: This can worsen hyperviscosity and increase thrombotic risk 4

Do not rely solely on hemoglobin and hematocrit: Normal CBC parameters do not exclude iron depletion, as they decrease only with severe deficiency 7

Do not overlook gastrointestinal malignancy: Asymptomatic colon cancer commonly presents with iron deficiency anemia in older adults 5

Special Populations

Inflammatory Bowel Disease

• Optimize IBD treatment first, as disease control improves anemia 1
• Intravenous iron is preferred over oral due to better absorption and tolerability 1
• Consider erythropoiesis-stimulating agents only after optimizing IBD therapy and iron repletion, with target hemoglobin not above 12 g/dL 1

Preoperative Anemia

• Screen for iron deficiency using ferritin <100 ng/mL, transferrin saturation <20%, or MCV <80 fL with MCHC <27 g/dL 1
• Administer oral or intravenous iron 2-4 weeks preoperatively to reduce transfusion requirements and complications 1
• Consider tranexamic acid intraoperatively to reduce blood loss 1