Indices

Overview of CBC Indices

Definition: The red blood cell (RBC) indices are a set of calculations derived from the complete blood count (CBC) that provide information about the size, hemoglobin content, and concentration of hemoglobin in red blood cells
Clinical Significance:
- Classification of Anemias: RBC indices are essential for classifying anemias as microcytic, normocytic, or macrocytic, and for determining the degree of hemoglobinization (hypochromic vs. normochromic)
- Differential Diagnosis: Help narrow down the differential diagnosis and guide further testing
- Monitoring Treatment: Useful for monitoring the response to treatment for anemia
Measured Parameters:
- The RBC indices are calculated from the following parameters, which are directly measured by automated hematology analyzers:
  - Red Blood Cell Count (RBC): Number of red blood cells per unit volume of blood (e.g., x 10^12/L)
  - Hemoglobin (HGB): Concentration of hemoglobin in whole blood (g/dL)
  - Hematocrit (HCT): Percentage of blood volume occupied by red blood cells (%)
Calculated Indices:
- The RBC indices are calculated using the measured parameters and the following formulas:
  - Mean Corpuscular Volume (MCV)
  - Mean Corpuscular Hemoglobin (MCH)
  - Mean Corpuscular Hemoglobin Concentration (MCHC)

Key RBC Indices and Their Significance

Mean Corpuscular Volume (MCV):
- Definition: The average volume of individual red blood cells
- Formula: MCV (fL) = (HCT / RBC) x 10
- Units: femtoliters (fL)
- Reference Range: Typically 80-100 fL (varies slightly by laboratory)
- Clinical Significance:
  - MCV < 80 fL: Microcytic Anemia (small RBCs)
    - Iron deficiency anemia
    - Thalassemia
    - Sideroblastic anemia
    - Anemia of chronic disease (in some cases)
  - MCV 80-100 fL: Normocytic Anemia (normal-sized RBCs)
    - Acute blood loss
    - Hemolytic anemia
    - Aplastic anemia
    - Anemia of chronic disease (in many cases)
    - Early iron deficiency
  - MCV > 100 fL: Macrocytic Anemia (large RBCs)
    - Vitamin B12 deficiency
    - Folate deficiency
    - Alcoholism
    - Liver disease
    - Hypothyroidism
    - Myelodysplastic syndromes (MDS)
Mean Corpuscular Hemoglobin (MCH):
- Definition: The average amount of hemoglobin per red blood cell
- Formula: MCH (pg) = HGB / RBC x 10
- Units: picograms (pg)
- Reference Range: Typically 27-33 pg (varies slightly by laboratory)
- Clinical Significance:
  - MCH is generally proportional to MCV, so it is useful for assessing the hemoglobin content in relation to cell size
  - Increased MCH: Macrocytic anemias
  - Decreased MCH: Microcytic anemias
  - Note: MCH is less useful than MCV and MCHC for classifying anemias
Mean Corpuscular Hemoglobin Concentration (MCHC):
- Definition: The average concentration of hemoglobin in a given volume of red blood cells
- Formula: MCHC (g/dL) = HGB / HCT x 100
- Units: grams per deciliter (g/dL) or grams per liter (g/L)
- Reference Range: Typically 32-36 g/dL (varies slightly by laboratory)
- Clinical Significance:
  - MCHC Provides information about the degree of hemoglobinization of red blood cells (i.e., how “full” the RBCs are with hemoglobin)
  - Increased MCHC: Hyperchromia (rare); seen in:
    - Hereditary spherocytosis: Due to dehydration of red blood cells
    - Cold agglutinin disease: Due to interference with hemoglobin measurement
  - Decreased MCHC: Hypochromia (pale RBCs)
    - Iron deficiency anemia
    - Thalassemia
    - Sideroblastic anemia
    - Note: The MCHC is a critical index for quality control. MCHC values > 36 g/dL are rare and often indicate a laboratory error (e.g., lipemia, cold agglutinins)
Red Cell Distribution Width (RDW):
- Definition: A measure of the variation in red blood cell size (anisocytosis)
- Units: Expressed as a coefficient of variation (CV) or standard deviation (SD)
- Reference Range:
  - RDW-CV: Typically 11.5-14.5%
  - RDW-SD: Typically 35-56 fL
- Clinical Significance:
  - Increased RDW: Indicates greater variation in RBC size
  - Used in combination with MCV to narrow down the differential diagnosis of anemia
  - Helpful in Distinguishing Different Anemias:
    - Iron Deficiency Anemia: High RDW (due to increased variation in RBC size)
    - Thalassemia: Normal or slightly elevated RDW (RBCs are uniformly small)
    - Anemia of Chronic Disease: Normal RDW (unless coexisting with iron deficiency)

Interpretation of RBC Indices

Microcytic Anemias (MCV < 80 fL):
- Iron Deficiency Anemia: Low MCV, low MCH, low MCHC, high RDW, low serum iron and ferritin, high TIBC
- Thalassemia: Low MCV, low MCH, normal or high RBC count, normal or elevated serum iron and ferritin, normal or low RDW
- Sideroblastic Anemia: Low or normal MCV, normal or high serum iron and ferritin, ringed sideroblasts in bone marrow
- Anemia of Chronic Disease: Low or normal MCV, low serum iron, normal or high ferritin
Normocytic Anemias (MCV 80-100 fL):
- Acute Blood Loss: Normal RBC indices initially, but can develop into microcytic anemia over time if iron stores are depleted
- Hemolytic Anemias: Normal or slightly elevated MCV, elevated reticulocyte count, elevated bilirubin and LDH, decreased haptoglobin
- Aplastic Anemia: Normal RBC indices, pancytopenia, hypocellular bone marrow
- Anemia of Chronic Disease: Normal RBC indices, low serum iron, normal or high ferritin
Macrocytic Anemias (MCV > 100 fL):
- Vitamin B12 Deficiency: High MCV, oval macrocytes, hypersegmented neutrophils, low serum vitamin B12, elevated MMA and homocysteine
- Folate Deficiency: High MCV, oval macrocytes, hypersegmented neutrophils, low serum folate, elevated homocysteine
- Alcoholism: High MCV, round macrocytes, normal vitamin B12 and folate levels
- Liver Disease: High MCV, round macrocytes, abnormal liver function tests
- Hypothyroidism: High MCV, round macrocytes, abnormal thyroid function tests
- Myelodysplastic Syndromes (MDS): High MCV, dysplastic features in bone marrow

Sources of Error and Troubleshooting

Cold Agglutinins: Cause falsely elevated MCV and MCHC and falsely decreased RBC count
- Corrective Action: Warm the sample to 37°C and reanalyze
Lipemia: Falsely elevates hemoglobin, which can affect MCV and MCHC calculations
- Corrective Action: Perform saline replacement or use a lipemia clearing agent
High White Blood Cell Count (Leukocytosis): Can interfere with hemoglobin measurement and affect RBC indices
- Corrective Action: Dilute the sample and correct the results for the dilution factor
Clotted Sample: Invalidates the results and requires recollection of a new sample

Key Terms

MCV (Mean Corpuscular Volume): Average volume of red blood cells
MCH (Mean Corpuscular Hemoglobin): Average amount of hemoglobin per red blood cell
MCHC (Mean Corpuscular Hemoglobin Concentration): Average concentration of hemoglobin in red blood cells
RDW (Red Cell Distribution Width): Measure of the variation in red blood cell size (anisocytosis)
Microcytic: Small red blood cells
Normocytic: Normal-sized red blood cells
Macrocytic: Large red blood cells
Hypochromic: Decreased hemoglobin content (pale color)
Hyperchromic: Increased hemoglobin content (intensely colored)
Anisocytosis: Variation in red blood cell size
Anemia: Deficiency of red blood cells or hemoglobin

Hematocrit

Hemolysis