How should I interpret a red blood cell (RBC) count?

Interpreting Red Blood Cell (RBC) Count

Interpret the RBC count in the context of hemoglobin, hematocrit, and red cell indices (MCV, MCH, MCHC, RDW) rather than in isolation, as the RBC count alone provides limited diagnostic value without these complementary parameters. 1

Essential Components to Evaluate Alongside RBC Count

When interpreting an RBC count, you must simultaneously assess:

• Hemoglobin concentration: The oxygen-carrying capacity of blood; more clinically relevant than RBC count alone for assessing anemia 2
• Hematocrit (Hct): The proportion of blood volume occupied by red cells 1
• Mean Cell Volume (MCV): Average size of red blood cells, measured in femtoliters; helps classify anemia as microcytic (low MCV), normocytic (normal MCV), or macrocytic (high MCV) 1
• Red Cell Distribution Width (RDW): Variability in red cell size; RDW >14.0% indicates significant size variation 1

Algorithmic Approach to RBC Interpretation

Step 1: Assess if RBC Count is Truly Abnormal

• Consider patient-specific factors: Age affects normal ranges, with MCV highest at birth, decreasing during the first 6 months, then gradually increasing to adult levels 1
• Gender considerations: For transgender patients on gender-affirming hormone therapy (GAHT) ≥12 months, interpret RBC indices using reference ranges for affirmed gender rather than sex assigned at birth, as testosterone increases hemoglobin to male reference range and estradiol decreases it to female reference range 1
• Recognize spurious results: RBC agglutination from EDTA, cryoglobulins, lipids, or elevated glucose can falsely alter RBC counts 3

Step 2: Classify the Pattern Using MCV and RDW

Low MCV (microcytic pattern):

• Low MCV + RDW >14.0%: Iron-deficiency anemia is most likely 1
• Low MCV + RDW ≤14.0%: Thalassemia minor is most likely 1
• Exclude lead poisoning, chronic inflammatory disease, and infection before confirming iron deficiency 1

High MCV (macrocytic pattern):

• High MCV + elevated RDW: Vitamin B12 or folate deficiency, or mixed deficiency states 4
• Measure vitamin B12, folate, reticulocyte count, and assess for hemolysis 4
• Immediate treatment for B12 deficiency is critical to prevent irreversible neurologic damage 4

Normal MCV with abnormal RBC count:

• Consider acute blood loss, hemolysis, chronic disease, or early nutritional deficiency 1

Step 3: Evaluate Mean Cell Hemoglobin Concentration (MCHC)

• MCHC is the most important calculated index for detecting spurious results and technical errors 3
• Abnormal MCHC should prompt verification of hemoglobin, hematocrit, and RBC count accuracy 3

Critical Pitfalls to Avoid

• Do not rely on RBC count alone: Hemoglobin concentration is influenced by both red cell mass and plasma volume; it may remain falsely elevated despite significant blood loss if fluid resuscitation is inadequate 1
• Do not assume anemia equals iron deficiency: Only 50% of children with anemia (hemoglobin <5th percentile) are iron deficient 1
• Do not ignore conditions affecting RBC turnover: Hemolytic anemia, recent acute blood loss, iron deficiency anemia, and chronic kidney disease falsely lower hemoglobin A1c regardless of assay method 1
• Verify unexpected results with peripheral blood smear: Essential for assessing schistocytes, hemolysis, and red cell morphology when automated indices are discordant 5

When to Obtain Additional Testing

• Measure ferritin and transferrin saturation: Ferritin <30 μg/L confirms iron deficiency; ferritin <100 μg/L with inflammation may still indicate deficiency 4
• Check reticulocyte count: Elevated reticulocytes suggest hemolysis or bleeding with bone marrow response; low reticulocytes suggest production defect 4
• Obtain hematology consultation: Required if cause remains unclear after complete workup, suspicion for myelodysplastic syndrome, confirmed hemolytic anemia, pancytopenia, or no response to appropriate replacement therapy after 2-3 weeks 5, 4