What does it mean to have high polysegmented neutrophils (high polysegmenters)?

High Polysegmented Neutrophils: Meaning and Clinical Significance

High polysegmenters (neutrophil hypersegmentation) most commonly indicates folate or vitamin B12 (cobalamin) deficiency, but can also occur in iron deficiency anemia, infection, or as an artifact of specimen processing. 1, 2

Definition and Diagnostic Criteria

Neutrophil hypersegmentation is defined as:

• Five or more neutrophils with 5 lobes per 100 neutrophils counted, OR
• Any neutrophils with 6 or more lobes 1, 2

The predominant morphologic change is a shift from three-lobed to five-lobed neutrophils rather than an increase in extremely hypersegmented forms. 1

Primary Causes (Ranked by Clinical Importance)

1. Megaloblastic Anemia (Most Important)

• Folate deficiency is the most common cause and shows a significant negative correlation between average neutrophil lobe count and serum folate levels. 1
• Neutrophil hypersegmentation can be an early indicator of incipient folate deficiency before other hematologic indices (hemoglobin, MCV) become abnormal. 1
• Vitamin B12 (cobalamin) deficiency produces similar findings and must be excluded. 3, 4

2. Iron Deficiency Anemia

• Iron deficiency alone causes neutrophil hypersegmentation in 62% of cases (31/50 patients in controlled study), compared to only 4% in controls. 2
• Mean neutrophil lobe count in iron deficiency is significantly elevated (3.36 vs 2.96 in controls). 2
• The mechanism is unclear but this finding is reproducible and statistically significant. 2

3. Infection-Related Hypersegmentation

• Acute pyogenic meningitis and epidural abscess can cause florid neutrophil hypersegmentation in cerebrospinal fluid. 4
• This represents a pathologic response to severe bacterial infection rather than a nutritional deficiency. 4

4. Technical Artifact

• Cytocentrifugation can artifactually produce neutrophil hypersegmentation, particularly in CSF specimens. 4
• The striking hypersegmentation may result from combined effects of infection and specimen processing. 4

Diagnostic Algorithm

When you encounter neutrophil hypersegmentation:

1. First, check serum folate and vitamin B12 levels - these are the most common and clinically significant causes. 1

2. Evaluate iron studies (serum iron, ferritin, TIBC, transferrin saturation) - iron deficiency is present in 62% of hypersegmentation cases without megaloblastic anemia. 2

3. Review the complete blood count:

   • Check hemoglobin and MCV - hypersegmentation may precede macrocytosis in early folate deficiency. 1
   • Assess for other cytopenias that might suggest myelodysplasia (though this is primarily a mouse model concern). 3

4. Consider clinical context:

   • Active infection, particularly CNS infections, can cause hypersegmentation. 4
   • Review specimen processing - cytocentrifugation artifacts are possible. 4

Critical Pitfalls to Avoid

• Do not dismiss neutrophil hypersegmentation when hemoglobin and MCV are normal - it can be the earliest sign of folate deficiency before anemia develops. 1

• Do not assume all hypersegmentation is megaloblastic - iron deficiency is a common alternative cause that requires different treatment. 2

• Do not overlook infection as a cause, particularly in patients with CSF specimens or severe bacterial infections. 4

• Always correlate with clinical presentation - hypersegmentation in isolation requires different interpretation than hypersegmentation with anemia and macrocytosis. 1, 2