The Differential Cell Count
Berend Houwen
Department of Pathology and Laboratory Medicine
Loma Linda University School of Medicine, Loma Linda, California
Laboratory Hematology 7:89-100
©2001 Carden Jennings Publishing Co., Ltd.
ABSTRACT
Differential cell counts have provided extensive data through more than a century of laboratory hematology. Routine bench morphology count continues to play a role in analyses of blood and other tissues such as bone marrow, but for many purposes it is being replaced by other technologies that provide greater precision and consistency. This discussion of the differential cell count traces the development of electronic analysis and looks at the recent impact of monoclonal antibody-based flow cytometry. The introduction of the extended differential count has led to a rapid increase in electronic analysis, with resultant increased accuracy, lower cost, and more efficient turn-around times. Moreover, the extended differential is leading to acquisition of effective data on complex specimens and is paving the way for new parameters in the field.
INTRODUCTION
Differential cell counts typically are considered enumerations
of the different white blood cell (WBC) types circulating
in the blood. However, differential counts can also apply
to other cell lineages such as red blood cells or to cells within
the same lineage but at different maturation levels. The
WBC differential count has become widely accepted and
used by clinicians, and is generally considered to yield clinically
useful information in health and disease.
As a laboratory test, the differential cell count is unlike
almost all other tests performed in the clinical laboratory. It
provides a pathology report on the morphological appearance
of blood cells and on the frequency in which they
appear, not in a descriptive manner but in a highly stylized,
quantitative format. It is called a "differential" count because
all enumerated cells are brought into a common mathematical
context, ie, a frequency distribution for the different cell
types present. The total number of cells counted may vary,
but in most clinical situations it is 100, and specific cell types
are commonly expressed as percentages of the total count.
Thus there is within this context a particular distribution of
cell types for healthy, normal individuals, and there are distribution patterns associated with disease states.
Over time the information derived from the WBC differential
count has become a cornerstone in laboratory hematology
and is widely used for screening, case finding, diagnosis,
and monitoring of hematologic and nonhematologic disorders.
It is used, for example, in diagnosis of bacterial or viral
infectious disease; evaluation of allergic conditions; diagnosis
and monitoring of malignant disease such as leukemia; and
staging of HIV infection. The WBC differential count is
often also used to monitor a patient's progress and/or
response to treatment. For example, a decrease in elevated
neutrophil counts in patients treated for (bacterial) infectious
disease is generally regarded as a positive response.
However, the test is not without its problems. The traditional
procedure for the differential WBC count by manual
microscopy is time consuming and labor intensive and is
therefore one of the most expensive routine tests in the clinical
hematology laboratory. Furthermore, the 100-cell differential
count is often criticized for its statistical shortcomings
because of its small sampling size. Despite these problems,
most clinicians consider the manual WBC differential count
effective, perhaps not as a direct decision-making tool, but more as a source of collateral information, like taking a patient's body temperature. The manual differential count thus shows a combination of poor statistical reliability, high expense, and definite clinical utility, making it a prime target for automation and alternate approaches. Those efforts date back to the 1960s, and to date continue to push the boundaries of differential cell counting.
Newer technologies have enabled WBC differential counts to be obtained electronically from automated analyzers, at much lower cost, with greater statistical reliability, often with greater overall accuracy, and with faster availability of results to the clinician. Moreover, these technologies have enabled laboratorians to measure cellular differentiation and to quantify cell types other than WBC, with sometimes surprising clinical utility as outcomes.
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