Conditions That Increase Mean Corpuscular Hemoglobin Concentration (MCHC)
Hereditary spherocytosis is the primary pathologic condition that causes elevated MCHC, while hemoglobin SC disease and laboratory artifacts from cell dehydration are other important causes to consider. 1, 2, 3
Primary Pathologic Causes
Hereditary Spherocytosis
- Hereditary spherocytosis (HS) characteristically produces elevated MCHC above the reference range in 50-67% of patients due to red blood cell membrane defects that lead to progressive cellular dehydration 1, 4
- The membrane transport abnormalities in HS result in increased sodium extrusion, reduced total cation content (Na+ + K+), and consequent water loss, which concentrates the hemoglobin within the cell 3
- MCHC correlates significantly with RBC cationic content in HS patients (r=0.51, P<0.05), reflecting the degree of cellular dehydration 3
- When HS coexists with beta-thalassemia trait, the MCHC may be lower than in isolated HS but can still be elevated compared to normal controls 4
Hemoglobin SC Disease
- SC erythrocytes demonstrate abnormally high intracellular hemoglobin concentration and elevated MCHC due to cellular dehydration mechanisms 2
- The elevated MCHC in SC disease contributes to multiple pathophysiologic consequences including decreased oxygen affinity, increased viscosity of deoxygenated cells, accelerated sickling rate, and enhanced potassium efflux 2
Hemochromatosis
- Patients with hemochromatosis show increased MCHC related to enhanced iron availability for erythropoiesis 5
- Reports demonstrate elevated hemoglobin levels, hematocrit, mean corpuscular volume, mean corpuscular hemoglobin, and MCHC in hemochromatosis patients 5
Laboratory Artifacts and Technical Considerations
Measurement Inaccuracies
- Electronic cell counters systematically underestimate MCHC when true values exceed 36 g/dL, with increasing error as MCHC rises 6
- For dehydrated or undeformable cells, inaccuracies in measured mean cell volume lead to spurious MCHC values on automated analyzers 6
- Values of MCHC significantly above the reference range are not physiologically possible due to hemoglobin solubility limitations, suggesting either pathologic dehydration or measurement artifact 1
Clinical Approach
When to Suspect Elevated MCHC
- High MCHC should prompt critical evaluation of the peripheral blood smear to identify spherocytes, target cells, or other morphologic abnormalities 1
- Consider hereditary spherocytosis when elevated MCHC is accompanied by hemolytic anemia, splenomegaly, and family history 3
- Evaluate for hemoglobinopathies (particularly SC disease) in patients with appropriate ethnic background and elevated MCHC 2
Important Caveats
- The finding of anemia in a patient with hemochromatosis should prompt investigation for other unrelated causes, as hemochromatosis typically increases rather than decreases MCHC 5
- Automated MCHC measurements may be unreliable in conditions causing significant red cell dehydration, requiring manual verification 6
- Combined HS and beta-thalassemia can produce confusing red cell indices with lower MCHC than isolated HS 4