Is marked nucleated red blood cell count (nRBCemia) in a peripheral blood smear report sufficient for clinical decision-making in a 4-day-old male with a high total leukocyte count (leukocytosis)?

Marked nRBCemia is NOT an adequate impression for this peripheral blood smear report

This report requires immediate clarification of the underlying etiology and correction of the automated WBC count, as the presence of 150 nRBCs/100 WBCs in a 4-day-old neonate with extreme leukocytosis (89,000/mm³) represents a critical finding that demands urgent clinical correlation and may indicate severe pathology requiring immediate intervention.

Why This Impression is Inadequate

Automated WBC Count is Falsely Elevated

• The automated analyzer cannot distinguish nRBCs from WBCs, resulting in a spuriously elevated total leukocyte count 1
• The corrected WBC count must be calculated and reported: With 150 nRBCs/100 WBCs, the true WBC is approximately 35,600/mm³ (89,000 ÷ 2.5), which is still markedly elevated but changes clinical interpretation significantly 1, 2
• Failure to provide the corrected WBC count can lead to inappropriate clinical decisions regarding sepsis workup, antibiotic therapy, and monitoring 1

Extreme nRBC Elevation Demands Etiologic Investigation

• 150 nRBCs/100 WBCs is profoundly abnormal even for a 4-day-old neonate and suggests severe underlying pathology 3
• In preterm neonates, nRBC counts >70/100 WBCs beyond day 3-4 of life predict major morbidity with 82% sensitivity and 96% specificity 3
• Persistence of elevated nRBCs beyond day 4 strongly predicts mortality: 80% of survivors clear nRBCs by day 4, versus only 35% of non-survivors 3

Critical Differential Diagnoses Must Be Addressed

The report must guide clinicians toward specific etiologies:

• Severe perinatal hypoxia/asphyxia: nRBCs are markers of placental dysfunction and fetal hypoxemia; correlation with cord pH, Apgar scores, and clinical status is essential 3
• Sepsis: The combination of extreme leukocytosis (corrected WBC ~35,600) and marked nRBCemia in a 4-day-old raises urgent concern for bacterial sepsis 1, 2
• Hemolytic disease: ABO/Rh incompatibility can cause both marked nRBCemia and reactive leukocytosis; direct antiglobulin test results must be correlated 3
• Congenital infections: TORCH infections can present with this pattern 3
• Bone marrow infiltrative processes: Though rare in neonates, congenital leukemia or neuroblastoma must be excluded with this degree of abnormality 4, 5

What the Report Should Include

Mandatory Elements for Adequate Reporting

1. Corrected WBC count: Calculate and report the true leukocyte count after accounting for nRBCs 1, 2

2. Detailed morphologic description:

   • Stage of nRBC maturation (orthochromatic vs. polychromatophilic vs. basophilic)
   • Presence of left shift in neutrophils (absolute band count, toxic granulation, Döhle bodies) 1, 2
   • RBC morphology (polychromasia, spherocytes, fragmentation)
   • Platelet count and morphology

3. Clinical correlation statement: "Marked nRBCemia (150/100 WBCs) in a 4-day-old neonate is abnormal and requires urgent clinical correlation. Differential diagnosis includes severe perinatal asphyxia, sepsis, hemolytic disease, and congenital infection. Recommend immediate clinical assessment and additional laboratory evaluation as indicated."

4. Specific recommendations:

   • Blood cultures if not already obtained 1, 6
   • Direct antiglobulin test if not performed 3
   • Reticulocyte count 3
   • Lactate dehydrogenase and bilirubin levels 3
   • Clinical assessment for signs of sepsis, respiratory distress, or hemolysis 1, 2

Critical Clinical Context

Prognostic Significance

• nRBCs in peripheral blood of critically ill patients predict mortality: 30% mortality in nRBC-positive versus 14% in nRBC-negative patients 7
• A cutoff of 2.5 nRBCs/100 WBCs shows high mortality risk with 91% sensitivity in critically ill patients 7
• This neonate's count of 150/100 WBCs is 60-fold higher than this threshold 7

Urgency of Evaluation

• The combination of extreme corrected leukocytosis (~35,600/mm³) with absolute band count assessment is critical: band count ≥1,500/mm³ has a likelihood ratio of 14.5 for bacterial infection 1, 2
• Left shift (≥16% bands) has a likelihood ratio of 4.7 for bacterial infection even with normal WBC 1, 2
• Manual differential is mandatory to accurately assess band forms and immature neutrophils 1

Common Pitfalls to Avoid

• Never report only "marked nRBCemia" without correcting the WBC count - this leads to misinterpretation of the degree of leukocytosis 1, 2
• Do not assume nRBCemia is "normal for a neonate" at this magnitude on day 4 of life - it is not 3
• Do not delay clinical notification - this finding requires immediate communication with the treating physician 7, 3
• Do not ignore the need for etiologic workup - simply describing the finding without guiding clinical action is inadequate 1, 6