What are RBC Indices?
RBC indices are calculated values that describe the average size and hemoglobin content of red blood cells. They are automatically calculated by hematology analyzers from measured parameters (RBC count, hemoglobin, hematocrit). The three primary indices are MCV, MCH, and MCHC.
MCV - Mean Corpuscular Volume
MCV measures the average volume (size) of red blood cells, expressed in femtoliters (fL).
- Formula: MCV = (Hematocrit ÷ RBC count) × 10
- Normal range: 80-100 fL
- Clinical use: Classifies anemia as microcytic (<80 fL), normocytic (80-100 fL), or macrocytic (>100 fL)
- Most important index: MCV is the key to anemia differential diagnosis
MCH - Mean Corpuscular Hemoglobin
MCH measures the average mass of hemoglobin per red blood cell, expressed in picograms (pg).
- Formula: MCH = (Hemoglobin ÷ RBC count) × 10
- Normal range: 27-31 pg
- Clinical use: Parallels MCV; low MCH indicates hypochromic RBCs (pale, less hemoglobin)
- Less useful clinically: Provides similar information to MCV but less commonly used for classification
MCHC - Mean Corpuscular Hemoglobin Concentration
MCHC measures the average concentration of hemoglobin within red blood cells, expressed in g/dL or %.
- Formula: MCHC = (Hemoglobin ÷ Hematocrit) × 100
- Normal range: 32-36 g/dL (or 32-36%)
- Clinical use: Identifies hypochromic (low MCHC) or hyperchromic (high MCHC) RBCs
- Quality control: MCHC >37 g/dL is physiologically impossible; suggests lab error
Why MCV Matters Most: Of the three indices, MCV is the most clinically important because it directly classifies anemia type, which dramatically narrows the differential diagnosis. Microcytic anemia → think iron deficiency or thalassemia. Macrocytic anemia → think B12/folate deficiency or alcohol. Normocytic anemia → think blood loss, hemolysis, or chronic disease.
RBC indices vary slightly by age, with infants and young children having lower MCV than adults. Values are generally similar between sexes.
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| Population | MCV (fL) | MCH (pg) | MCHC (g/dL) |
|---|---|---|---|
| Adults (male and female) | 80-100 | 27-31 | 32-36 |
| Newborns (0-2 weeks) | 95-121 | 32-38 | 30-36 |
| Infants (2-6 months) | 74-96 | 25-35 | 30-36 |
| Children (6 months-12 years) | 76-90 | 24-30 | 31-36 |
| Adolescents (13-18 years) | 78-98 | 25-33 | 31-36 |
Important Considerations:
- Age differences: Newborns have higher MCV; it decreases during first year of life
- MCHC upper limit: MCHC >37 g/dL is physiologically impossible (RBCs can't pack more hemoglobin); indicates lab error
- Borderline values: MCV 78-82 fL or 98-102 fL may represent early or mixed anemias
- Sample timing: RBCs swell over time; analyze within 6 hours for accurate MCV
Microcytic Anemia (MCV <80 fL)
Small red blood cells suggest impaired hemoglobin synthesis. The mnemonic "TAILS" helps remember causes:
T - Thalassemia
- Beta-thalassemia: Decreased beta-globin chain production; common in Mediterranean, Asian, African populations
- Alpha-thalassemia: Decreased alpha-globin chain production
- Clues: Family history, elevated HbA2 (beta-thalassemia), target cells on smear, RBC count normal or high despite low hemoglobin
A - Anemia of Chronic Disease
- Chronic inflammation: Cancer, chronic infections, autoimmune diseases
- Mechanism: Hepcidin sequesters iron, preventing RBC production
- Clues: Normal or high ferritin, low TIBC, low transferrin saturation
I - Iron Deficiency
- Most common cause worldwide: Blood loss (menstruation, GI bleeding), inadequate intake, malabsorption
- Stages: Iron depletion → iron-deficient erythropoiesis → iron deficiency anemia
- Clues: Low ferritin (<15 ng/mL), high TIBC, low transferrin saturation (<20%)
L - Lead Poisoning
- Inhibits heme synthesis: Lead interferes with ferrochelatase and ALA dehydratase
- Clues: Basophilic stippling on smear, elevated blood lead level, occupational exposure
S - Sideroblastic Anemia
- Defective heme synthesis: Despite adequate iron stores
- Causes: Hereditary (X-linked), acquired (alcohol, drugs, myelodysplasia)
- Clues: Ringed sideroblasts on bone marrow, high ferritin, high iron
Normocytic Anemia (MCV 80-100 fL)
Normal-sized red blood cells suggest recent blood loss, hemolysis, or production problems.
Acute Blood Loss
- Trauma: Major hemorrhage from injury
- GI bleeding: Peptic ulcer, varices, malignancy
- Surgery: Perioperative blood loss
Hemolytic Anemia
- Autoimmune: Warm or cold antibodies destroy RBCs
- Hereditary spherocytosis: Membrane defect causes premature RBC destruction
- G6PD deficiency: Oxidative stress triggers hemolysis
- Sickle cell disease: HbS causes sickling and hemolysis
- Microangiopathic: Mechanical destruction (DIC, TTP, HUS, prosthetic valves)
Bone Marrow Disorders
- Aplastic anemia: Bone marrow failure affecting all cell lines
- Myelodysplastic syndromes: Ineffective hematopoiesis
- Leukemia: Marrow infiltration by malignant cells
Chronic Diseases
- Chronic kidney disease: Decreased erythropoietin production
- Anemia of chronic disease: Can be normocytic or microcytic
- Endocrine disorders: Hypothyroidism, hypopituitarism
Macrocytic Anemia (MCV >100 fL)
Large red blood cells suggest impaired DNA synthesis or accelerated RBC production (reticulocytosis).
Megaloblastic (Impaired DNA Synthesis)
- Vitamin B12 deficiency: Pernicious anemia, malabsorption, strict veganism, gastric bypass
- Folate deficiency: Inadequate intake (alcohol, elderly), malabsorption, increased demand (pregnancy, hemolysis)
- Medications: Methotrexate, hydroxyurea, 5-FU, trimethoprim
Non-Megaloblastic
- Alcohol use: Direct toxic effect on marrow, often with folate deficiency
- Liver disease: Impaired folate metabolism, lipid abnormalities affecting RBC membranes
- Hypothyroidism: Decreased metabolic demand and impaired erythropoiesis
- Reticulocytosis: Young RBCs are larger; seen in hemolysis or bleeding with bone marrow response
- Myelodysplastic syndromes: Dysplastic RBC production
Abnormal MCH and MCHC
Low MCH and MCHC (Hypochromic RBCs)
- Iron deficiency: Most common cause; RBCs pale due to low hemoglobin
- Thalassemia: Impaired globin synthesis
- Anemia of chronic disease: Iron sequestration
High MCHC (Hyperchromic RBCs)
- Hereditary spherocytosis: Spherical RBCs have decreased surface area/volume ratio
- Lab error: MCHC >37 g/dL is physiologically impossible
Step-by-Step Approach to Anemia Using MCV
Step 1: Confirm anemia
- Hemoglobin <13.0 g/dL (men) or <12.0 g/dL (women)
Step 2: Check MCV to classify anemia type
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| MCV Category | Value (fL) | Primary Differential |
|---|---|---|
| Microcytic | <80 | Iron deficiency, thalassemia, anemia of chronic disease |
| Normocytic | 80-100 | Acute blood loss, hemolysis, chronic disease, renal failure |
| Macrocytic | >100 | B12/folate deficiency, alcohol, liver disease, hypothyroidism |
Step 3: Order targeted testing based on MCV
Microcytic Anemia Workup:
- Iron studies: Ferritin, serum iron, TIBC, transferrin saturation
- Hemoglobin electrophoresis: If thalassemia suspected (family history, ethnicity, normal/high RBC count)
- Lead level: If occupational exposure or pica
Normocytic Anemia Workup:
- Reticulocyte count: High suggests bleeding or hemolysis; low suggests production problem
- Hemolysis labs: LDH, haptoglobin, indirect bilirubin, peripheral smear
- Renal function: Creatinine, BUN
- Bone marrow biopsy: If unexplained or concern for malignancy
Macrocytic Anemia Workup:
- Vitamin levels: B12, folate
- Thyroid function: TSH
- Liver function tests: AST, ALT, bilirubin, albumin
- Reticulocyte count: High suggests reticulocytosis (hemolysis, bleeding response)
- Peripheral smear: Hypersegmented neutrophils suggest megaloblastic anemia
Distinguishing Iron Deficiency from Thalassemia (Both Microcytic)
Both cause microcytic anemia, but distinguishing them avoids unnecessary iron therapy in thalassemia.
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| Parameter | Iron Deficiency | Thalassemia |
|---|---|---|
| Ferritin | Low (<15 ng/mL) | Normal or high |
| RBC Count | Low or low-normal | Normal or high |
| Mentzer Index | >13 (MCV/RBC) | <13 (MCV/RBC) |
| RDW | High (anisocytosis) | Normal or mildly elevated |
| HbA2 | Normal | Elevated (beta-thalassemia) |
Clinical Pearl
Mentzer Index: MCV ÷ RBC count. If >13, think iron deficiency. If <13, think thalassemia. For example, MCV 75 fL with RBC 3.5 million/μL: Mentzer = 75/3.5 = 21.4 → suggests iron deficiency. MCV 75 fL with RBC 6.0 million/μL: Mentzer = 75/6.0 = 12.5 → suggests thalassemia.
Factors That Increase MCV
- Alcohol use: Direct toxic effect on RBC production (most common cause of mild macrocytosis)
- Reticulocytosis: Young RBCs are larger; seen in active bleeding or hemolysis
- Medications: Hydroxyurea, methotrexate, zidovudine (AZT), azathioprine
- Hypothyroidism: Decreased metabolism and RBC turnover
- Sample storage: RBCs swell over time; must analyze within 6 hours
Factors That Decrease MCV
- Iron deficiency: Impaired hemoglobin synthesis causes small RBCs
- Thalassemia trait: Genetic; common in certain ethnic groups
- Chronic disease: Inflammation sequesters iron
Mixed Anemias
- Combined deficiencies: Iron + B12 deficiency may yield normal MCV (microcytic and macrocytic cancel out)
- Dimorphic population: Two distinct RBC populations (e.g., transfused blood, recent iron treatment)
- RDW elevated: Red cell distribution width increases when RBC sizes vary widely
Pre-analytical Errors
- Cold agglutinins: Cause RBC clumping, falsely elevate MCV and falsely lower RBC count
- Hyperglycemia: Extreme hyperglycemia causes RBC swelling
- Leukocytosis: Extreme WBC elevation can interfere with RBC measurement
- Sample delay: RBCs swell over time; analyze within 6 hours for accurate MCV
Clinical Pearl
"MCV is your anemia roadmap": The MCV classification (microcytic, normocytic, macrocytic) immediately narrows your differential diagnosis from dozens of causes to 3-5 likely culprits. Always start your anemia workup by checking MCV.
Clinical Pearl
TAILS for microcytic anemia: Thalassemia, Anemia of chronic disease, Iron deficiency, Lead poisoning, Sideroblastic anemia. This mnemonic covers 99% of microcytic anemias you'll encounter.
Mentzer Index distinguishes iron deficiency from thalassemia: MCV ÷ RBC count. >13 suggests iron deficiency. <13 suggests thalassemia. Both are microcytic, but thalassemia has many small RBCs (high RBC count), while iron deficiency has fewer RBCs overall.
Beware combined deficiencies: Patients with both iron deficiency (microcytic) and B12 deficiency (macrocytic) may have normal MCV because the effects cancel out. Check RDW (red cell distribution width) - it will be elevated, indicating mixed RBC sizes. Also check ferritin and B12 levels.
Clinical Pearl
Alcohol causes macrocytosis even without anemia: Chronic alcohol use commonly causes MCV 100-110 fL without anemia. This is a direct toxic effect on bone marrow. If MCV >115 fL, also check B12 and folate (alcoholics often have folate deficiency).
Clinical Pearl
Reticulocytes are macrocytic: Active bleeding or hemolysis triggers reticulocytosis (release of young RBCs). Since reticulocytes are larger than mature RBCs, this can cause mild macrocytosis (MCV 100-105 fL). Check reticulocyte count to confirm.
MCHC >37 g/dL is impossible: RBCs cannot physically pack more hemoglobin than 37 g/dL. If you see MCHC >37, there's a lab error (lipemia, hemolysis, cold agglutinins). Repeat the sample. The only true cause of high MCHC (35-37 g/dL) is hereditary spherocytosis.
Clinical Pearl
RDW helps differentiate causes: Red cell distribution width measures variation in RBC size. High RDW with microcytic anemia suggests iron deficiency (many different-sized RBCs). Normal RDW with microcytic anemia suggests thalassemia (uniformly small RBCs).
Don't give iron to thalassemia patients: Both iron deficiency and thalassemia cause microcytic anemia, but thalassemia patients have normal or high iron stores. Giving iron to thalassemia patients causes iron overload (hemochromatosis). Always check ferritin before starting iron therapy for microcytic anemia.
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