Causes of Lower MCHC
Lower Mean Corpuscular Hemoglobin Concentration (MCHC) is most commonly caused by iron deficiency anemia, which represents the final and most severe stage of iron depletion. 1
Primary Cause: Iron Deficiency Anemia
Iron deficiency is the predominant cause of low MCHC, occurring as a late-stage manifestation when iron stores are severely depleted. 1 The progression follows a predictable pattern:
- Stage 1: Anisocytosis and increased percentage of microcytic cells appear first, with normal hemoglobin and transferrin saturation <32% 1
- Stage 2: MCV and MCH decline, hemoglobin becomes subnormal (but >9 g/dL), transferrin saturation typically <16% 1
- Stage 3 (Low MCHC): MCHC drops below normal, hemoglobin falls below 9 g/dL, and transferrin saturation remains <16% 1
Low MCHC specifically indicates hypochromic red blood cells with decreased hemoglobin content per unit volume, reflecting severe iron-restricted erythropoiesis. 2
Secondary Causes
Thalassemia
**Thalassemia minor produces microcytic anemia with low MCHC but can be distinguished from iron deficiency by a normal or low RDW (<14.0%).** 2 In contrast, iron deficiency typically shows RDW >14.0% due to greater variation in red cell size. 2
Anemia of Chronic Disease
Chronic inflammatory conditions can cause low MCHC, though less commonly than iron deficiency. 2 The NCCN guidelines note that microcytic anemia (<80 fL) may result from anemia of chronic disease, particularly when accompanied by elevated inflammatory markers. 2
Sideroblastic Anemia
Sideroblastic anemia represents a rare cause of microcytic hypochromic anemia with low MCHC. 2 This condition involves defective hemoglobin synthesis despite adequate iron stores.
Special Population: Cyanotic Congenital Heart Disease
In cyanotic heart disease patients, low MCHC indicates iron deficiency anemia superimposed on polycythemia, creating a particularly dangerous situation. 2, 3
- Iron deficiency in these patients produces microcytic hypochromic red cells that are rigid and less deformable in microcirculation 2
- MCHC <31% in cyanotic children is associated with increased risk of cerebrovascular accidents 3
- The combination of increased red cell mass from polycythemia and iron-deficient cells with decreased oxygen-carrying capacity severely impairs tissue oxygenation 2
Clinical Significance and Diagnostic Approach
MCHC is more stable than MCV or MCH during progressive anemia and serves as a reliable late indicator of iron deficiency. 4 However, this stability means it changes only after significant iron depletion has occurred. 1
Critical Diagnostic Pitfall
Normal hemoglobin, hematocrit, and MCHC do NOT exclude iron deficiency. 5 Measuring CBC parameters alone without iron status indicators (serum iron, ferritin, transferrin saturation) will miss early iron depletion and lead to misdiagnosis of iron-deficient individuals as normal. 5
The minimum workup for suspected low MCHC must include: 2
- Complete blood count with RBC indices (MCV, MCH, MCHC, RDW)
- Serum ferritin
- Transferrin saturation
- C-reactive protein (to assess for inflammation)
False Elevation Caveat
Cold agglutination and lipemia can cause falsely elevated MCHC readings. 6 When MCHC appears abnormally high or inconsistent with clinical presentation, consider warming the sample to 37°C or performing plasma exchange to correct interference. 6
Prognostic Implications
Low MCHC (<32 g/dL) independently predicts nonatherosclerotic cardiovascular disease in dialysis patients, likely reflecting left atrial overload and left ventricular hypertrophy. 4 This association underscores that low MCHC represents not just a laboratory finding but a marker of significant physiologic compromise requiring intervention.