What is low MCHC (Mean Corpuscular Hemoglobin Concentration) characteristic of?

Low MCHC is Characteristic of Iron Deficiency Anemia

Low Mean Corpuscular Hemoglobin Concentration (MCHC) is most characteristic of iron deficiency anemia, particularly in its advanced stages. 1, 2, 3

Understanding MCHC and Its Significance

MCHC measures the average concentration of hemoglobin in a given volume of packed red blood cells. It is calculated from hemoglobin, hematocrit, and red blood cell count measurements and is reported as part of a complete blood count (CBC).

The progression of iron deficiency affects red blood cell parameters in stages:

1. Early stage: Anisocytosis (variation in cell size) and increased percentage of microcytic cells appear first, with normal hemoglobin and transferrin saturation <32% 3
2. Intermediate stage: MCV (Mean Corpuscular Volume) and MCH (Mean Corpuscular Hemoglobin) decline, with hemoglobin typically below normal but not <9 g/dL, and transferrin saturation usually <16% 3
3. Advanced stage: MCHC decreases, hemoglobin falls below 9 g/dL, and transferrin saturation remains <16% 3

Laboratory Parameters in Iron Deficiency Anemia

Iron deficiency anemia presents with the following characteristic laboratory findings:

• Low MCHC (hypochromia)
• Low MCV (microcytosis)
• Low serum ferritin (<15 μg/L)
• Low transferrin saturation
• Elevated RDW (Red cell Distribution Width)
• Low or normal RBC count 2

The British Society of Gastroenterology guidelines note that automated cell counters provide measurements of red cell changes that accompany iron deficiency, including reduced MCH (hypochromia) and reduced MCV (microcytosis). MCH is considered a more reliable marker of iron deficiency as it is less dependent on storage and counting machines, and shows changes in both absolute and functional iron deficiency. 1

Differential Diagnosis of Microcytic Anemia

When evaluating low MCHC, it's important to differentiate between various causes of microcytic anemia:

Condition	MCHC	MCV	Ferritin	Transferrin Saturation	Other Features
Iron Deficiency Anemia	Low	Low	Low (<15 μg/L)	Low	Elevated RDW
Anemia of Chronic Disease	Normal or low	Low or normal	Normal/high	Low	Normal/slightly elevated RDW
Thalassemia	Normal	Very low	Normal	Normal	Normal RDW, elevated RBC count
Hemoglobinopathies (HbC, D, E, S)	Often higher	Variable	Variable	Variable	Less sensitive MCHC response to iron deficiency [4]

Clinical Implications and Pitfalls

Important Considerations:

• Timing matters: MCHC decreases in the later stages of iron deficiency, making it less sensitive for early detection 3
• MCH may be more sensitive: Some evidence suggests MCH changes occur earlier than MCHC in developing iron deficiency 1
• Hemoglobinopathies affect interpretation: In patients with hemoglobin variants (HbC, D, E, or S traits), MCHC values may be higher than expected even with coexisting iron deficiency, making MCHC less reliable for detecting iron deficiency in these patients 4
• Technical limitations: Values of MCHC significantly above reference range are not physiologically possible due to limitations on hemoglobin solubility, so very high values should prompt review of the peripheral smear 5

Common Pitfalls:

• Relying solely on MCHC for diagnosis without considering other iron studies
• Failing to investigate underlying causes of iron deficiency
• Not recognizing that normal MCHC doesn't exclude early iron deficiency
• Overlooking the possibility of mixed deficiencies (e.g., concurrent B12 or folate deficiency) 2

Diagnostic Approach

For accurate diagnosis of iron deficiency anemia:

1. Obtain complete iron studies including serum ferritin, transferrin saturation, serum iron, and total iron binding capacity 2
2. Consider inflammatory markers (CRP, ESR) as ferritin is an acute phase reactant that may be falsely elevated in inflammatory conditions 1, 2
3. Evaluate reticulocyte count to assess bone marrow response 1
4. Consider hemoglobin electrophoresis in patients with microcytosis and normal iron studies to rule out hemoglobinopathies 1
5. Check vitamin B12 and folate levels to identify potential mixed deficiencies 2

By understanding the relationship between low MCHC and iron deficiency anemia, clinicians can more effectively diagnose and manage this common condition while avoiding diagnostic pitfalls.