What does a low Mean Corpuscular Hemoglobin Concentration (MCHC) indicate and how is it treated?

Low MCHC: Clinical Significance and Management

A low MCHC most commonly indicates iron deficiency anemia and requires immediate iron studies (serum ferritin and transferrin saturation) to confirm the diagnosis, followed by investigation of the underlying cause—particularly gastrointestinal blood loss in adult men and postmenopausal women. 1, 2

What Low MCHC Indicates

Primary Diagnostic Considerations:

• Iron deficiency is the most common cause of reduced MCHC, occurring when insufficient iron is available for hemoglobin synthesis 2
• Low MCHC suggests hypochromia (reduced hemoglobin concentration in red cells), which often accompanies iron deficiency even when MCV remains normal 1
• MCHC decreases in the final stage of iron deficiency, typically when hemoglobin falls below 9 g/dL and transferrin saturation drops below 16% 3
• Thalassemia (particularly alpha and beta thalassemia trait) also causes low MCHC with microcytosis and hypochromia 2
• Chronic inflammatory conditions can occasionally cause reduced MCHC, though this is less common than iron deficiency 2
• Sideroblastic anemia may present with low MCHC 2

Important Clinical Context:

• MCH (mean corpuscular hemoglobin) is actually a more reliable marker than MCHC for detecting iron deficiency because it is less dependent on storage conditions and counting equipment 1, 2
• In combined deficiencies (iron plus B12/folate), MCV may appear normal while MCHC remains low 2

Diagnostic Workup

Essential Initial Testing:

• Obtain serum ferritin as the single most powerful test for iron deficiency: levels <15 μg/L indicate absent iron stores, and <30 μg/L indicate low body iron stores 2
• Measure transferrin saturation: levels <15-16% support iron deficiency and indicate insufficient circulating iron for erythropoiesis 1, 2
• Complete blood count with red cell indices including MCV, MCH, and RDW 1
• Reticulocyte count to evaluate bone marrow response to anemia 1, 2

Interpreting Iron Studies:

• Ferritin is an acute phase protein and can be falsely normal or elevated during inflammation, infection, malignancy, or liver disease despite true iron deficiency 2
• In the presence of inflammation, ferritin up to 100 μg/L may still indicate iron deficiency, but ferritin >150 μg/L essentially excludes absolute iron deficiency even with concurrent inflammation 2
• Combined assessment of ferritin and transferrin saturation is useful for diagnosing absolute versus functional iron deficiency 2

When Iron Studies Are Normal:

• If iron studies are normal with persistent low MCHC and microcytosis, obtain hemoglobin electrophoresis to evaluate for thalassemia, particularly in patients with appropriate ethnic background 2
• Low MCV with RDW >14.0% suggests iron deficiency, while low MCV with RDW ≤14.0% suggests thalassemia minor 2
• Consider chronic disease and assess for underlying inflammatory conditions 2

Investigation of Underlying Cause

Mandatory Evaluations:

• In adult men and postmenopausal women with confirmed iron deficiency, gastrointestinal evaluation is mandatory as GI blood loss is the most common cause 4, 2
• Upper gastrointestinal endoscopy with small bowel biopsy (to exclude celiac disease, which occurs in 2-3% of iron deficiency anemia patients) 4
• Colonoscopy or barium enema to exclude gastrointestinal malignancy 4
• In premenopausal women, assess menstrual blood loss as the most common cause 4
• Evaluate for NSAID use, previous gastrectomy, and dietary intake 4

Treatment Approach

Iron Replacement:

• First-line treatment is oral iron once iron deficiency is confirmed 5
• Intermittent dosing (rather than daily or twice-daily) is as effective with fewer side effects 5
• Therapeutic response to 3 weeks of oral iron supplementation confirms iron deficiency diagnosis when other tests are equivocal 2
• For patients who cannot tolerate, cannot absorb, or do not respond to oral iron, intravenous iron is preferred 5
• In patients with chronic kidney disease, IV iron (such as iron sucrose) significantly increases hemoglobin compared to oral iron 6

Treating the Underlying Cause:

• Treatment of the underlying cause will cure the anemia 4
• Even when no cause is detected, the long-term outlook is good 4

Critical Pitfalls to Avoid

• Do not assume low MCHC is always iron deficiency—normal iron studies warrant evaluation for thalassemia 2
• Do not rely solely on ferritin in inflammatory states—it can be falsely elevated despite true iron deficiency 2
• Do not skip gastrointestinal evaluation in adult men and postmenopausal women with iron deficiency, as asymptomatic malignancy may present with iron deficiency anemia 4
• Do not ignore mild anemia—there is no evidence that mild anemia is less indicative of important disease than severe anemia 4