Neutrophil nuclear segmentation in mild cobalamin deficiency: Relation to metabolic tests of cobalamin status and observations on ethnic differences in neutrophil segmentation

Ralph Carmel, Ralph Green, Donald W. Jacobsen, George D. Qian

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29 Citations (Scopus)

Abstract

Neutrophil hypersegmentation is considered the most sensitive peripheral blood cell marker of cobalamin deficiency. However, its diagnostic value in the mild deficiency states that accompany most low cobalamin levels and its relation to metabolic tests of cobalamin status are unknown. The authors compared neutrophil lobe averages and percent neutrophils with 5 or more lobes (%5+ lobes) in 169 subjects with their mean corpuscular volume (MCV) and serum cobalamin, methylmalonic acid (MMA), homocysteine, and folate levels and, in 65 cases, with the deoxyuridine suppression test (dUST). Only 9 subjects had hypersegmentation by lobe average and 20 subjects by %5 + lobes. They were not more often cobalamin-deficient than subjects without hypersegmentation. Moreover, only one of 34 subjects with dUST results diagnostic for cobalamin deficiency had neutrophil hypersegmentation. Both indices of neutrophil segmentation in the 169 subjects correlated significantly with homocysteine levels. They also showed weak inverse correlation with cobalamin levels, but did not correlate with MMA, folate, or MCV values. Cobalamin therapy for 6 months did not significantly change neutrophil lobe averages in 35 subjects with mild deficiency, compared with 8 nondeficient controls, and only marginally improved the %5 + lobes. A surprising, incidental observation was that blacks had significantly greater neutrophil segmentation by both criteria than did whites and others. This difference was unrelated to cobalamin or folate status. Our results indicate that dUST abnormalities precede all morphologic changes of deficiency, including hypersegmentation. Although a tendency exists for neutrophil segmentation to increase very slightly as some serum values, especially homocysteine, start to worsen in mild cobalamin deficiency, the metabolic changes precede overt hypersegmentation. Neutrophil nuclear segmentation is insufficiently sensitive in relation to metabolic evidence of deficiency to be used as a clinical tool in the diagnosis of mild cobalamin deficiency.

Original languageEnglish (US)
Pages (from-to)57-63
Number of pages7
JournalAmerican Journal of Clinical Pathology
Volume106
Issue number1
StatePublished - Jul 1996
Externally publishedYes

Fingerprint

Vitamin B 12
Neutrophils
Deoxyuridine
Homocysteine
Folic Acid
Methylmalonic Acid
Erythrocyte Indices
Serum
Routine Diagnostic Tests
Blood Cells
Observation

Keywords

  • Blacks
  • Cobalamin deficiency
  • Deoxyuridine suppression
  • Homocysteine
  • Methylmalonic acid
  • Neutrophil

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

@article{813c08c2d8f9479981c8e3d72355e04b,
title = "Neutrophil nuclear segmentation in mild cobalamin deficiency: Relation to metabolic tests of cobalamin status and observations on ethnic differences in neutrophil segmentation",
abstract = "Neutrophil hypersegmentation is considered the most sensitive peripheral blood cell marker of cobalamin deficiency. However, its diagnostic value in the mild deficiency states that accompany most low cobalamin levels and its relation to metabolic tests of cobalamin status are unknown. The authors compared neutrophil lobe averages and percent neutrophils with 5 or more lobes ({\%}5+ lobes) in 169 subjects with their mean corpuscular volume (MCV) and serum cobalamin, methylmalonic acid (MMA), homocysteine, and folate levels and, in 65 cases, with the deoxyuridine suppression test (dUST). Only 9 subjects had hypersegmentation by lobe average and 20 subjects by {\%}5 + lobes. They were not more often cobalamin-deficient than subjects without hypersegmentation. Moreover, only one of 34 subjects with dUST results diagnostic for cobalamin deficiency had neutrophil hypersegmentation. Both indices of neutrophil segmentation in the 169 subjects correlated significantly with homocysteine levels. They also showed weak inverse correlation with cobalamin levels, but did not correlate with MMA, folate, or MCV values. Cobalamin therapy for 6 months did not significantly change neutrophil lobe averages in 35 subjects with mild deficiency, compared with 8 nondeficient controls, and only marginally improved the {\%}5 + lobes. A surprising, incidental observation was that blacks had significantly greater neutrophil segmentation by both criteria than did whites and others. This difference was unrelated to cobalamin or folate status. Our results indicate that dUST abnormalities precede all morphologic changes of deficiency, including hypersegmentation. Although a tendency exists for neutrophil segmentation to increase very slightly as some serum values, especially homocysteine, start to worsen in mild cobalamin deficiency, the metabolic changes precede overt hypersegmentation. Neutrophil nuclear segmentation is insufficiently sensitive in relation to metabolic evidence of deficiency to be used as a clinical tool in the diagnosis of mild cobalamin deficiency.",
keywords = "Blacks, Cobalamin deficiency, Deoxyuridine suppression, Homocysteine, Methylmalonic acid, Neutrophil",
author = "Ralph Carmel and Ralph Green and Jacobsen, {Donald W.} and Qian, {George D.}",
year = "1996",
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T1 - Neutrophil nuclear segmentation in mild cobalamin deficiency

T2 - Relation to metabolic tests of cobalamin status and observations on ethnic differences in neutrophil segmentation

AU - Carmel, Ralph

AU - Green, Ralph

AU - Jacobsen, Donald W.

AU - Qian, George D.

PY - 1996/7

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N2 - Neutrophil hypersegmentation is considered the most sensitive peripheral blood cell marker of cobalamin deficiency. However, its diagnostic value in the mild deficiency states that accompany most low cobalamin levels and its relation to metabolic tests of cobalamin status are unknown. The authors compared neutrophil lobe averages and percent neutrophils with 5 or more lobes (%5+ lobes) in 169 subjects with their mean corpuscular volume (MCV) and serum cobalamin, methylmalonic acid (MMA), homocysteine, and folate levels and, in 65 cases, with the deoxyuridine suppression test (dUST). Only 9 subjects had hypersegmentation by lobe average and 20 subjects by %5 + lobes. They were not more often cobalamin-deficient than subjects without hypersegmentation. Moreover, only one of 34 subjects with dUST results diagnostic for cobalamin deficiency had neutrophil hypersegmentation. Both indices of neutrophil segmentation in the 169 subjects correlated significantly with homocysteine levels. They also showed weak inverse correlation with cobalamin levels, but did not correlate with MMA, folate, or MCV values. Cobalamin therapy for 6 months did not significantly change neutrophil lobe averages in 35 subjects with mild deficiency, compared with 8 nondeficient controls, and only marginally improved the %5 + lobes. A surprising, incidental observation was that blacks had significantly greater neutrophil segmentation by both criteria than did whites and others. This difference was unrelated to cobalamin or folate status. Our results indicate that dUST abnormalities precede all morphologic changes of deficiency, including hypersegmentation. Although a tendency exists for neutrophil segmentation to increase very slightly as some serum values, especially homocysteine, start to worsen in mild cobalamin deficiency, the metabolic changes precede overt hypersegmentation. Neutrophil nuclear segmentation is insufficiently sensitive in relation to metabolic evidence of deficiency to be used as a clinical tool in the diagnosis of mild cobalamin deficiency.

AB - Neutrophil hypersegmentation is considered the most sensitive peripheral blood cell marker of cobalamin deficiency. However, its diagnostic value in the mild deficiency states that accompany most low cobalamin levels and its relation to metabolic tests of cobalamin status are unknown. The authors compared neutrophil lobe averages and percent neutrophils with 5 or more lobes (%5+ lobes) in 169 subjects with their mean corpuscular volume (MCV) and serum cobalamin, methylmalonic acid (MMA), homocysteine, and folate levels and, in 65 cases, with the deoxyuridine suppression test (dUST). Only 9 subjects had hypersegmentation by lobe average and 20 subjects by %5 + lobes. They were not more often cobalamin-deficient than subjects without hypersegmentation. Moreover, only one of 34 subjects with dUST results diagnostic for cobalamin deficiency had neutrophil hypersegmentation. Both indices of neutrophil segmentation in the 169 subjects correlated significantly with homocysteine levels. They also showed weak inverse correlation with cobalamin levels, but did not correlate with MMA, folate, or MCV values. Cobalamin therapy for 6 months did not significantly change neutrophil lobe averages in 35 subjects with mild deficiency, compared with 8 nondeficient controls, and only marginally improved the %5 + lobes. A surprising, incidental observation was that blacks had significantly greater neutrophil segmentation by both criteria than did whites and others. This difference was unrelated to cobalamin or folate status. Our results indicate that dUST abnormalities precede all morphologic changes of deficiency, including hypersegmentation. Although a tendency exists for neutrophil segmentation to increase very slightly as some serum values, especially homocysteine, start to worsen in mild cobalamin deficiency, the metabolic changes precede overt hypersegmentation. Neutrophil nuclear segmentation is insufficiently sensitive in relation to metabolic evidence of deficiency to be used as a clinical tool in the diagnosis of mild cobalamin deficiency.

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