Evaluation and Management of Abnormal MCHC
When MCHC is abnormal, immediately obtain a complete blood count with MCV, reticulocyte count, serum ferritin, transferrin saturation, and CRP to classify the anemia and guide treatment. 1
Understanding MCHC in Clinical Context
MCHC (Mean Corpuscular Hemoglobin Concentration) measures hemoglobin concentration within red blood cells and serves as a key parameter for anemia classification alongside MCV and MCH. 1
Critical Pitfall: False Elevations
- Significantly elevated MCHC above physiologic limits (>37 g/dL) is not biologically possible and indicates laboratory interference. 2, 3
- Common causes include cold agglutinins or lipemia—correct by warming sample to 37°C or plasma exchange before interpreting results. 2
- True elevated MCHC may indicate hereditary spherocytosis or other hemolytic anemias requiring peripheral smear examination. 3
Diagnostic Algorithm for Low MCHC
Step 1: Minimum Initial Workup
Obtain these tests when hemoglobin is below normal (women <12 g/dL, men <13 g/dL): 1
- Complete blood count with RBC indices (MCV, MCH, MCHC, RDW)
- Reticulocyte count
- Serum ferritin
- Transferrin saturation (TfS)
- CRP concentration
Step 2: Classify by MCV Pattern
Microcytic Pattern (Low MCV + Low MCHC):
- Iron deficiency anemia is most likely when: 1
- Ferritin <30 μg/L without inflammation
- Ferritin <100 μg/L with inflammation present
- High RDW (>16.1%) supports iron deficiency 4
- Consider thalassemia trait if: 1, 5
- Microcytosis disproportionate to anemia severity
- Family history or ethnic predisposition
- Normal or elevated ferritin
- Requires hemoglobin electrophoresis for confirmation 5
Normocytic Pattern (Normal MCV + Low/Normal MCHC):
- Suggests anemia of chronic disease (ACD) 1
- May indicate early iron deficiency before MCV drops 1
- Check ferritin and CRP to distinguish from functional iron deficiency 1
Macrocytic Pattern (High MCV):
- Indicates vitamin B12 or folate deficiency 1, 6
- Obtain methylmalonic acid (MMA) and homocysteine—both elevated in B12 deficiency 6
- Consider medication effects (thiopurines), alcohol, hypothyroidism 1
Step 3: Evaluate Reticulocyte Response
Low or "normal" reticulocytes: 1
- Indicates inadequate bone marrow response
- Suggests nutritional deficiencies or bone marrow disease
- In CKD patients with adequate iron/B12/folate, indicates erythropoietin deficiency or inflammation 1
Elevated reticulocytes: 1
- Excludes nutritional deficiencies
- Investigate for hemolysis: obtain haptoglobin, LDH, bilirubin
- Peripheral smear examination mandatory 1
Treatment Approach Based on Diagnosis
Iron Deficiency Anemia
Without inflammation: 1
- Ferritin <30 μg/L confirms diagnosis
- Investigate for GI bleeding in non-menstruating patients 1
- Initiate iron replacement therapy
With inflammation (IBD, CKD): 1
- Ferritin up to 100 μg/L may still indicate iron deficiency
- Transferrin saturation more reliable than ferritin in inflammatory states 1
- Consider intravenous iron in inflammatory conditions 1
When to Consult Hematology
Refer when: 1
- Cause remains unclear after extended workup (B12, folate, haptoglobin, LDH)
- Abnormalities in multiple cell lines (pancytopenia)
- Suspected hemoglobinopathy requiring electrophoresis 5
- Persistently elevated MCHC suggesting hemolytic process 3
Key Clinical Pearls
- MCV alone can be misleading when microcytosis and macrocytosis coexist—high RDW reveals this mixed picture. 1
- MCHC has limited utility for predicting iron deficiency compared to MCV, MCH, and RDW. 4, 7
- In CKD patients, MCV is a late marker of iron deficiency—ferritin and transferrin saturation are superior. 1
- Hemoglobin is preferred over hematocrit for anemia assessment due to better reproducibility and lack of interference from glucose or storage time. 1