Do we need to treat an elevated Mean Corpuscular Hemoglobin Concentration (MCHC) when all other blood counts are normal?

Management of Isolated Elevated MCHC with Normal Blood Counts

An isolated elevation of MCHC with all other blood counts normal typically does not require treatment, as it most commonly represents a laboratory artifact or measurement error rather than true pathology requiring intervention. 1, 2

Initial Diagnostic Approach

Verify the Abnormality

• Repeat the complete blood count immediately to confirm the elevated MCHC is reproducible, as spurious elevations are common with automated analyzers 1, 2
• Request a peripheral blood smear examination to assess red cell morphology and identify spherocytes, agglutination, or other abnormalities that could explain the finding 1
• Review the sample quality with the laboratory, specifically asking about lipemia, cold agglutinins, or hemolysis that can falsely elevate MCHC 1

Rule Out Technical Interference

• Cold agglutinins cause false MCHC elevation by inducing red cell clumping that interferes with automated cell counting; warming the sample to 37°C before reanalysis corrects this artifact 1
• Severe lipemia interferes with hemoglobin measurement by light scattering, artificially raising the calculated MCHC; plasma exchange or ultracentrifugation can eliminate this interference 1
• Dehydrated or undeformable red cells cause automated counters to underestimate mean cell volume (MCV), resulting in spuriously elevated MCHC calculations 2

When Treatment Is NOT Indicated

No treatment is required when:

• The elevated MCHC is an isolated finding with normal hemoglobin, hematocrit, MCV, and red cell morphology 1, 2
• Repeat testing after correcting for technical interference normalizes the MCHC 1
• The patient is asymptomatic without evidence of hemolysis, anemia, or other hematologic abnormalities 3

When Further Investigation IS Indicated

Pursue additional workup only if:

• Spherocytes are present on blood smear, suggesting hereditary spherocytosis—a true cause of elevated MCHC that may require treatment if causing significant hemolysis 4
• The patient has symptoms of hemolytic anemia (jaundice, dark urine, fatigue) despite normal hemoglobin, which could indicate compensated hemolysis 3
• MCHC remains persistently elevated >36 g/dL on multiple samples processed without technical interference, warranting evaluation for red cell membrane disorders 2

Specific Testing for Persistent Elevation

• Osmotic fragility testing or eosin-5-maleimide (EMA) binding test to diagnose hereditary spherocytosis if spherocytes are present 4
• Reticulocyte count to assess for compensated hemolysis 3
• Direct antiglobulin test (DAT) to exclude autoimmune hemolytic anemia 3

Critical Pitfalls to Avoid

• Do not initiate treatment based solely on an isolated MCHC elevation without confirming it represents true pathology rather than laboratory artifact 1, 2
• Do not overlook cold agglutinins, which are particularly common in elderly patients and can cause persistent false MCHC elevations if samples are not warmed before analysis 1
• Do not assume hereditary spherocytosis without spherocytes on smear, as true pathologic MCHC elevation without morphologic changes is extremely rare 4, 2
• Recognize that MCHC >37 g/dL is physiologically implausible and almost always indicates measurement error requiring investigation of the pre-analytical and analytical phases 2

Clinical Context

The MCHC is a calculated value (hemoglobin/hematocrit × 100) that is highly susceptible to measurement errors affecting either the numerator or denominator 2. Unlike hemoglobin or MCV, which are directly measured parameters, MCHC abnormalities frequently reflect technical issues rather than clinical disease 1. In the absence of anemia, hemolysis, or characteristic red cell morphology, an isolated MCHC elevation warrants laboratory investigation rather than patient treatment 1, 2.