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, Mild or subtle cobalamin deficiency is a relatively common phenomenon, probably far more frequent than the classical deficiency state with overt findings like megaloblastic anemia.' Anemia and macrocytosis are usually not evident and the blood count, being normal to start with, rarely changes significantly after treatment.2 "'' The bone marrow appearance is usually normal. This lack of or MCV values. Cobalamin therapy for 6 months did not significantly change neutrophil lobe averages in 35 subjects with mild deficiency, compared with 8 nondefkient 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.

Serum methylmalonic acid and total homocysteine in patients with suspected cobalamin deficiency: A clinical study based on gastrointestinal histopathological findings

“…In a subgroup of our patients in which peripheral blood smears were examined, the presence of 6-lobed neutrophils seemed to be a very insensitive, nonspecific sign of early cobalamin deficiency. In a recent study, similar results have been reported for neutrophil lobe average and presence of 5 or more lobes [31].…”

Evaluation of Macrocytic Anemias

“…All are designed to establish, as efficiently and economically as possible, what the cause of the anemia is and to institute appropriate treatment wherever possible. 7,51 …”

Laboratory Evaluation for Vitamin B12 Deficiency: The Case for Cascade Testing

“…This concurs with most reports in the literature stating that the presence of hypersegmented neutrophils on the peripheral blood smear is neither sensitive nor specific for this purpose. 15 However, careful review of a peripheral blood smear by a hematologist or hematopathologist may provide helpful clues regarding the underlying cause of a macrocytic anemia.…”