What does a low Mean Corpuscular Hemoglobin Concentration (MCHC) indicate in an adult patient?

What is MCHC and What Does Low MCHC Mean?

Low MCHC indicates hypochromic red blood cells containing less hemoglobin than normal, most commonly signaling iron deficiency anemia that requires immediate iron studies and investigation of the underlying cause, particularly gastrointestinal blood loss in adults. 1, 2

Definition of MCHC

Mean Corpuscular Hemoglobin Concentration (MCHC) measures the average concentration of hemoglobin within each red blood cell, expressed in grams per deciliter (g/dL). 1

• MCHC reflects the degree of hemoglobin saturation in red cells and is calculated as hemoglobin divided by hematocrit. 3
• Normal MCHC ranges approximately 32-36 g/dL, though this varies slightly by laboratory. 3

Clinical Significance of Low MCHC

Primary Cause: Iron Deficiency Anemia

Low MCHC represents hypochromia—red cells with insufficient hemoglobin—and iron deficiency is the predominant cause requiring urgent evaluation. 1, 2

• Low MCHC appears as a late marker of iron deficiency, occurring only after iron stores are severely depleted and hemoglobin typically falls below 9 g/dL. 4
• This represents the final stage of progressive iron deficiency, when transferrin saturation drops below 16%. 4
• Mean cell hemoglobin (MCH) is actually a more reliable and earlier marker than MCHC for detecting iron deficiency, as it decreases in both absolute and functional iron deficiency. 5, 1

Differential Diagnosis

Other conditions causing low MCHC include: 2

• Thalassemia trait: Distinguished by normal or low RDW (<14.0%), elevated red cell count, and normal iron studies. 2
• Anemia of chronic disease: Less commonly causes low MCHC than iron deficiency; check C-reactive protein to identify inflammatory contribution. 2
• Sideroblastic anemia: Rare cause occurring with microcytosis and normal iron studies. 5

Diagnostic Workup Algorithm

Step 1: Confirm Iron Deficiency

Order iron studies immediately when low MCHC is detected: 1, 2

• Serum ferritin is the single most specific test for iron deficiency. 5

  • Ferritin <15 μg/L confirms absent iron stores (specificity 0.99). 5
  • Ferritin <30 μg/L indicates low body iron stores in patients without inflammation. 5, 1
  • Ferritin 30-100 μg/L with elevated CRP may still indicate iron deficiency in inflammatory states. 1
  • Ferritin >150 μg/L essentially excludes absolute iron deficiency even with inflammation. 5, 2

• Transferrin saturation <16-20% supports iron deficiency and is less affected by inflammation than ferritin. 1, 4

• C-reactive protein identifies inflammation that may falsely elevate ferritin. 1

Step 2: Investigate the Underlying Cause

All adult men and post-menopausal women with confirmed iron deficiency require gastrointestinal evaluation to exclude malignancy, even without overt bleeding: 2

• Perform both upper endoscopy (with small bowel biopsy) and colonoscopy. 2
• Gastrointestinal blood loss is the predominant cause in these populations, making exclusion of colonic and gastric carcinoma the prime concern. 2
• This applies regardless of anemia severity—mild anemia is equally indicative of important disease. 2

In pre-menopausal women: 2

• Menstrual blood loss is the most common etiology. 2
• However, do not attribute low MCHC to menstruation alone without excluding gastrointestinal pathology if other concerning features are present. 2

If iron studies are normal despite low MCHC: 1

• Consider thalassemia trait (especially with appropriate ethnic background), anemia of chronic disease, or sideroblastic anemia. 5, 1
• Hemoglobin electrophoresis is recommended in those with microcytosis and normal iron studies. 5

Treatment Approach

Once iron deficiency is confirmed, initiate oral iron supplementation as first-line therapy: 1

• Ferrous sulfate 325 mg (65 mg elemental iron) 1-3 times daily between meals. 1
• Expect hemoglobin increase of approximately 1-2 g/dL every 2-4 weeks. 1
• Continue iron for 3-6 months after hemoglobin normalizes to replenish iron stores. 1
• Check hemoglobin, reticulocytes, and iron studies after 4-8 weeks of therapy. 1

Consider parenteral iron if: 1

• Patient is intolerant to oral iron
• Poor response to oral iron occurs
• Severe anemia requires rapid correction

A hemoglobin rise ≥10 g/L within 2 weeks is highly suggestive of absolute iron deficiency, even if initial iron studies were equivocal. 5

Critical Pitfalls to Avoid

• Do not rely on MCHC alone: Low MCHC is a late finding; MCH and MCV may be more sensitive early markers of iron deficiency. 5, 1
• Do not dismiss normal ferritin in inflammatory states: Use higher cutoffs (45-100 μg/L) depending on inflammation severity. 5, 1
• Do not skip gastrointestinal investigation: Iron deficiency in adults often indicates ongoing blood loss requiring evaluation, regardless of anemia severity. 2
• Do not attribute findings to diet or menstruation without excluding malignancy in appropriate populations. 2
• In patients with hemoglobin C, D, E, or S traits: MCHC and hypochromic cell percentage are less sensitive indicators of iron deficiency than in those with normal hemoglobin phenotype. 6

High-Risk Clinical Scenarios

In patients with cyanotic congenital heart disease: 2

• Low MCHC indicates iron deficiency superimposed on polycythemia, creating a particularly dangerous situation. 2
• Iron-deficient microcytic hypochromic cells become rigid and less deformable, significantly increasing cardiovascular risk. 2

In chronic kidney disease patients: 2

• Anemia in CKD is typically normochromic and normocytic, so low MCHC suggests additional iron deficiency requiring assessment for gastrointestinal bleeding. 2