How should a low mean corpuscular hemoglobin concentration (MCHC) of 31.2 g/dL be managed?

Management of Low MCHC of 31.2 g/dL

A low MCHC of 31.2 g/dL indicates hypochromic anemia and requires immediate iron studies (serum ferritin, transferrin saturation, and complete blood count with indices) to confirm iron deficiency anemia, which is the most common cause and should be treated with oral iron supplementation while investigating the underlying source of blood loss. 1, 2

Diagnostic Workup

Order the following tests immediately:

• Complete blood count with MCV, MCH, RDW, and reticulocyte count to classify the anemia pattern 1
• Serum ferritin (the single most specific test for iron deficiency) 1, 2
• Transferrin saturation (TSAT) to assess circulating iron availability 1, 2
• C-reactive protein to identify inflammation that may falsely elevate ferritin 2

Interpret ferritin based on inflammatory status:

• Without inflammation: Ferritin <30 μg/L confirms iron deficiency 1, 3
• With inflammation: Ferritin up to 100 μg/L may still indicate iron deficiency 1, 3
• Ferritin >150 μg/L essentially excludes absolute iron deficiency even with concurrent inflammation 3

Additional diagnostic criteria for iron deficiency:

• TSAT <20% with ferritin <100 μg/L confirms inadequate iron for hemoglobin synthesis 4, 1
• MCV <80 fL and MCHC <27 g/dL are indicative of iron deficiency 4
• Low MCHC (31.2 g/dL is below the normal range of 32-36 g/dL) represents the final stage of iron deficiency when hemoglobin is typically <9 g/dL and TSAT is usually <16% 5

Differential Diagnosis

If iron studies confirm deficiency, iron deficiency anemia is the diagnosis. 1, 3 However, consider these alternatives if iron studies are normal:

• Thalassemia trait: MCV disproportionately low relative to anemia degree, normal iron studies, requires hemoglobin electrophoresis 2, 3
• Anemia of chronic disease: Ferritin >100 μg/L with TSAT <20% 1, 3
• Combined deficiency: Ferritin 30-100 μg/L suggests both iron deficiency and chronic disease 3
• Sideroblastic anemia: Rare cause requiring bone marrow evaluation 3

Investigation of Underlying Cause

In adult men and post-menopausal women, gastrointestinal evaluation is mandatory as GI blood loss is the most common cause: 1, 3

• Upper endoscopy and colonoscopy to exclude GI malignancy 1
• Small bowel biopsy during endoscopy to rule out celiac disease (present in 2-3% of iron deficiency cases) 1, 3

In pre-menopausal women:

• Assess menstrual blood loss as the primary cause 1
• If menstrual losses are normal, proceed with GI evaluation 1

Screen for additional causes:

• NSAID use causing occult GI bleeding 1
• Malabsorption syndromes in patients with GI symptoms 1
• Chronic kidney disease (anemia develops early in CKD and is nearly universal in stage 5) 4

Treatment Protocol

Initiate oral iron supplementation immediately:

• Ferrous sulfate 325 mg (65 mg elemental iron) 1-3 times daily taken between meals for optimal absorption 2
• Expected response: Hemoglobin increase of 1-2 g/dL every 2-4 weeks 2
• Duration: Continue for 3-6 months after hemoglobin normalizes to replenish iron stores 1, 2

Consider intravenous iron in these situations:

• Intolerance to oral iron 2
• Poor response to oral iron after 4-8 weeks 2
• Malabsorption (inflammatory bowel disease, celiac disease) 1
• Severe anemia requiring rapid correction 2
• Preoperative setting with expected blood loss (reduces transfusion requirements within 2-4 weeks) 4, 3

Monitoring and Follow-up

Repeat CBC after 4-8 weeks of treatment to assess response 1, 2

Expected response confirming diagnosis:

• Hemoglobin rise of ≥1 g/dL within 2 weeks strongly confirms iron deficiency even if initial iron studies were equivocal 2, 3
• Reticulocyte count should increase within 7-10 days 1

Monitor serum ferritin to ensure adequate repletion of iron stores (target >100 ng/mL) 1

If no response to oral iron after 4-8 weeks:

• Reassess compliance with therapy 1
• Consider repeat endoscopic evaluation for ongoing blood loss 1
• Evaluate for occult sources of blood loss 1
• Switch to intravenous iron 2

Critical Pitfalls to Avoid

Do not rely on MCV alone as iron deficiency can present with normal MCV in early stages; MCHC and MCH are more sensitive early markers 2, 3, 5

Do not dismiss normal ferritin in inflammatory states (infection, malignancy, chronic inflammatory disease, liver disease) as ferritin is an acute-phase reactant and can mask true iron deficiency 2, 3

Do not forget to investigate the underlying cause as iron deficiency in adults almost always indicates ongoing blood loss requiring evaluation 1, 3

Do not stop iron therapy prematurely as iron stores must be replenished even after hemoglobin normalizes, requiring 3-6 months of continued supplementation 1, 2

Special Considerations

Low MCHC with normal MCV may represent early iron deficiency before microcytosis develops 1

In chronic kidney disease patients with MCHC <27 g/dL and ferritin <100 ng/mL or TSAT <20%, iron therapy (oral or intravenous) is reasonable to reduce transfusions and increase hemoglobin 4

Combined deficiencies (iron plus B12 or folate) can present with low MCHC but normal MCV, requiring evaluation of B12 and folate levels 1, 2