What is the evaluation and management of a child with a high Mean Corpuscular Hemoglobin Concentration (MCHC)?

Evaluation and Management of High MCHC in Children

A high MCHC in a child is not physiologically possible above certain thresholds and should immediately trigger critical examination of the peripheral blood smear to identify the underlying cause, which is most commonly hereditary spherocytosis, hemolytic anemia, or laboratory artifact. 1

Understanding High MCHC

• MCHC values significantly above the reference range (>36 g/dL) are not physiologically possible due to limitations on hemoglobin solubility 1
• An elevated MCHC provides a critical clue to specific types of hemolytic anemia and necessitates systematic peripheral smear examination 1
• The first and most important step is obtaining a peripheral blood smear reviewed by an experienced pathologist or hematologist 2, 1

Common Causes to Consider

Hereditary Spherocytosis (Most Common True Elevation)

• Children with >4% hyperchromic red cells (intracellular hemoglobin >410 g/L) typically have significantly higher MCHC values, elevated reticulocyte counts, higher hemoglobin distribution width (HDW), and lower mean cell volume (MCV) 3
• These patients show a profile of red blood cell changes characteristic of hereditary spherocytosis, though laboratory features may be subtle 3
• Look for spherocytes on peripheral smear, family history of anemia or splenectomy, and evidence of hemolysis (elevated reticulocyte count, indirect bilirubin) 1, 3

Laboratory Artifacts (Common False Elevation)

• Cold agglutinins and lipemia are the two most common causes of falsely elevated MCHC 4
• Cold agglutination causes red blood cells to clump at room temperature, artificially decreasing measured cell count and falsely elevating MCHC 4
• Lipemic samples interfere with hemoglobin measurement, causing spuriously high MCHC 4
• Correct suspected cold agglutinin interference by warming the sample to 37°C and rerunning 4
• Correct lipemia interference by plasma exchange and retesting 4

Other Hemolytic Anemias

• Autoimmune hemolytic anemia can present with elevated MCHC due to spherocyte formation 1
• Examine the peripheral smear for schistocytes, spherocytes, or other abnormal red cell morphology 5, 1

Diagnostic Algorithm

Step 1: Verify the Result

• Review the complete blood count for other abnormalities (anemia, reticulocytosis, elevated HDW, low MCV) 3
• Check for hemolysis indicators: elevated indirect bilirubin, elevated LDH, low haptoglobin 1
• If MCHC is only slightly elevated (36-37 g/dL) with no other abnormalities, consider laboratory artifact first 4

Step 2: Rule Out Artifact

• Inspect the sample for lipemia (milky appearance) 4
• Warm sample to 37°C and retest if cold agglutinins suspected 4
• If artifact corrected, MCHC should normalize and no further workup needed 4

Step 3: Obtain Peripheral Smear

• This is mandatory for all confirmed high MCHC cases 1
• Look specifically for: spherocytes (hereditary spherocytosis), schistocytes (microangiopathic hemolysis), agglutination, or other abnormal morphology 5, 1, 3
• The smear must be reviewed by an experienced pathologist or hematologist 2, 1

Step 4: Additional Testing Based on Smear Findings

If spherocytes present:

• Osmotic fragility test or eosin-5-maleimide (EMA) binding test for hereditary spherocytosis 3
• Direct antiglobulin test (DAT/Coombs) to exclude autoimmune hemolytic anemia 1
• Reticulocyte count (typically elevated) 3
• Family history assessment 3

If no clear morphologic abnormality:

• Reticulocyte count to assess for hemolysis 3
• Consider hemoglobin electrophoresis or HPLC if microcytic component present, as some hemoglobinopathies can occasionally present with elevated MCHC 6

Critical Pitfalls to Avoid

• Never ignore a significantly elevated MCHC (>37 g/dL) without investigation - this represents either serious hemolytic disease or laboratory error requiring correction 1, 4
• Do not assume hereditary spherocytosis without peripheral smear confirmation - artifact is common and must be excluded first 4
• Do not delay hematology referral if peripheral smear shows abnormal cells, evidence of hemolysis, or if the child has anemia with elevated MCHC 2, 1
• Avoid attributing isolated mild MCHC elevation (36-37 g/dL) to disease without excluding technical factors 4

When to Refer to Pediatric Hematology

• Confirmed elevated MCHC with spherocytes on peripheral smear 1
• Elevated MCHC with evidence of hemolysis (anemia, reticulocytosis, elevated bilirubin) 1, 3
• Elevated MCHC with other cytopenias or abnormal cell lines 2
• Persistent unexplained MCHC elevation after artifact exclusion 1