Will transfusion of packed red blood cells (PRBCs) affect peripheral blood smear results?

Will Transfusion of Packed Red Blood Cells Affect Peripheral Blood Smear Results?

Yes, transfusion of packed red blood cells will significantly affect peripheral blood smear results by introducing normal donor red blood cells into the circulation, which can mask underlying red cell abnormalities and interfere with diagnostic testing for up to 90-120 days post-transfusion. 1

Mechanism of Interference

Donor red blood cells contaminate the patient's native red cell population, diluting or obscuring morphological abnormalities that may be present on the peripheral smear. 1 The extent of contamination depends on:

• Volume transfused: One unit of PRBCs (approximately 180 mL) results in about 12% donor RBC contamination immediately post-transfusion in a 60 kg adult with pre-transfusion hemoglobin of 8 g/dL 1
• Two units result in approximately 24% donor contamination 1
• Time since transfusion: Transfused RBCs have a lifespan of 90-110 days with approximately 1% daily loss 1

Timeline of Interference

The degree of donor RBC contamination decreases predictably over time:

• At 50 days post-transfusion: 6-12% donor contamination remains (for 1-2 units transfused) 1
• At 90-120 days: Minimal to no donor contamination expected 1
• Ideally, delay peripheral smear evaluation for diagnostic purposes for 120 days after the last transfusion 1

Clinical Impact on Specific Diagnoses

For enzyme deficiency testing (such as pyruvate kinase deficiency), donor RBCs cause false-negative results by contributing normal enzyme activity that masks the patient's deficiency. 1 This same principle applies to peripheral smear morphology—normal donor cells will dilute abnormal cell populations.

When urgent clinical assessment is required and transfused cells are still present, interpret results with extreme caution:

• Morphological findings may underestimate the severity of the underlying red cell disorder 1
• The presence of some abnormal cells despite recent transfusion actually supports the diagnosis of an underlying hemolytic disorder 1
• Document the transfusion history and timing when reporting smear results 1

Practical Recommendations

If diagnostic evaluation of red cell morphology is needed:

• Obtain peripheral smear BEFORE transfusion whenever possible 1
• If the patient has already been transfused, delay diagnostic smears for as long as clinically feasible—minimum 50 days, ideally 90-120 days 1
• Record the date of last transfusion and number of units transfused in the laboratory requisition 1

For patients requiring frequent transfusions (every few weeks), obtaining a pre-transfusion sample may be impossible. 1 In these cases:

• Genetic/molecular testing becomes the preferred diagnostic approach rather than relying on morphology or enzyme assays 1
• Any abnormal morphology detected despite donor cell contamination strongly supports an underlying disorder 1

Common Pitfalls to Avoid

Do not assume that peripheral smear results obtained shortly after transfusion accurately reflect the patient's baseline red cell morphology—the presence of normal donor cells will mask abnormalities. 1 This is particularly problematic when evaluating for:

• Hereditary hemolytic anemias (spherocytosis, elliptocytosis)
• Enzyme deficiencies
• Hemoglobinopathies
• Membrane disorders

Do not wait exactly 120 days if the patient requires multiple transfusions—this creates a diagnostic window that may never open. 1 Instead, pursue alternative diagnostic methods such as molecular genetic testing. 1

Always document transfusion history when ordering or interpreting peripheral smears for diagnostic purposes. 1 Failure to account for recent transfusion is a common cause of missed diagnoses in hemolytic disorders.