Page 37 - Williams Hematology ( PDFDrive )

14 Part I: Clinical Evaluation of the Patient Chapter 2: Examination of Blood Cells 15

samples, in abnormal samples, the spun hematocrit may be spuriously although because this parameter is affected by both hypochromia
elevated (up to 6 percent in microcytosis). The hemoglobin determina- and microcytosis, it is as least sensitive as the MCV in detecting iron-
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tion now is preferred to the hematocrit, because it is measured directly deficiency states. Another advantage of the MCH is the consistency
and is the best indicator of the oxygen-carrying capacity of the blood. across different analyzer types, as it is derived from two of the most
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accurately measured parameters: hemoglobin and red cell count. The
Measurement of Hemoglobin MCHC is not used much diagnostically, and is primarily useful for quality
Hemoglobin is intensely colored, and this property has been used in control purposes, such as detecting sample turbidity. These red cell indi-
methods for estimating its concentration in blood. Erythrocytes con- ces are average quantities and, therefore, may not detect abnormalities
tain a mixture of hemoglobin, oxyhemoglobin, carboxyhemoglobin, in blood with mixed-cell populations. In situations such as sideroblas-
methemoglobin, and minor amounts of other forms of hemoglobin. To tic anemia, recently transfused patients, patients with severe pernicious
determine hemoglobin concentration in the blood, red cells are lysed anemia with red cell fragmentation, and folate plus iron deficiency, both
and hemoglobin variants are converted to the stable compound cyan- large and small red cells are present, diminishing the value of the MCV.
methemoglobin for quantification by absorption at 540 nm. All forms of Red Cell Distribution Width The RDW is an estimate of the vari-
hemoglobin are readily converted to cyanmethemoglobin except sulfhe- ance in volume within the population of red cells, expressed as 1 SD of
moglobin, which is rarely present in significant amounts. In automated red cell volume measurements divided by the MCV. Instrument man-
blood cell counters, hemoglobin is usually measured by a modified ufacturers calculate RDW using different algorithms, so that reference
cyanmethemoglobin or an alternate lauryl sulphate method. In prac- ranges vary according to analyzer model. The RDW can be used in
tice, the major interference with this measurement is chylomicronemia, the laboratory as a flag to select those samples that should have man-
but newer instruments identify and minimize this interference. Nonin- ual review of blood films for red cell morphology. More significantly, a
vasive transcutaneous monitoring of total hemoglobin concentration, large literature has now developed around the evidence that the RDW
as well as methemoglobin and carboxyhemoglobin, using multiwave- is a biomarker predicting morbidity and mortality in a broad variety
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length pulse oximetry has become available. Although these instru- of clinical settings, such as angina/myocardial infarction, heart fail-
ments offer the opportunity to track hemoglobin concentration trends ure, trauma, pneumonia, sepsis, intensive care treatment, renal and
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in patients subject to blood loss and fluid shifts, it is not yet clear that liver disease, and in the general population. Most of these studies
they have sufficient precision to guide transfusion decisions. 21,22 Such are retrospective, observational, or cohort-based studies, often using
hemoglobin measurements may be unreliable under conditions of databases of routinely collected data gathered for other purposes, but
peripheral circulatory hypoperfusion. prospectively designed studies have arrived at similar conclusions. 37,38
The hemoglobin level varies with age (Table 2–1). Chapter 7 dis- The RDW retains its association with poor clinical outcomes whether
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cusses changes in hemoglobin in the neonatal period. After the first or not anemia is present, and it adds predictive power to more estab-
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week or two of extrauterine life, the hemoglobin falls from levels of lished predictive risk models. RDW may be a surrogate for systemic
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approximately 17 g/dL to levels of approximately 12 g/dL by 2 months of inflammation and/or oxidative stress, but the predictive value of RDW
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age. Thereafter, the levels remain relatively constant throughout the first is independent of other inflammatory markers, suggesting that this
year of life. Any child with a hemoglobin level below 11 g/dL should be biomarker is tracking other mechanistic processes as well. Identification
considered anemic. Chapter 8 discusses changes in hemoglobin con- of physiologic mechanisms linking RDW to adverse clinical outcomes
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centration with pregnancy and Chap. 9 discusses changes in hemoglo- will be important in using this predictive biomarker to inform thera-
bin levels in older persons. peutic decisions. 34
Standard Red Cell Indices Reticulocyte Count and RNA Content
The size and hemoglobin content of erythrocytes (red cell indices), The reticulocyte is a newly released anucleate red cell that enters the
based on population averages, have traditionally been used to assist in blood with residual detectable amounts of RNA (Chaps. 31 and 32).
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the differential diagnosis of anemia. A variety of newer indices based The number of reticulocytes in a volume of blood permits an estimate
on size and hemoglobinization characteristics of red cell subpopulations of marrow erythrocyte production and is thus useful in evaluating the
are discussed in the section “Novel Red Cell and Reticulocyte Indices”. pathogenesis of anemia by distinguishing inadequate production from
Mean Cell Volume Automated blood counters measure the MCV accelerated destruction (Chap. 32). The manual method for enumerat-
directly by either electrical impedance or light scatter measurements ing reticulocytes by placing a sample of blood in a tube containing new
of individual red cells. The MCV has been used to guide the diagnos- methylene blue and preparing a blood film to enumerate the propor-
tic workup in patients with anemia; for example, testing patients with tion of cells that show blue beaded precipitates (residual ribosomes) has
microcytic anemia for iron deficiency or thalassemia, and those with largely been replaced by automated methods, which are incorporated
macrocytic anemia for folate or vitamin B deficiency. This approach into high-volume hematology analyzers. Reticulocytes are identified
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has practical value, but also limitations ; for instance, MCV may be by direct fluorescence measurement after staining with RNA-binding
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normal in some older patients with pernicious anemia, or in advanced dyes or light scatter measurements to detect staining if nonfluorescent
pernicious anemia with severe red cell fragmentation, while one-third RNA-binding dyes are used. Various proprietary combinations of light
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of older patients have an elevated MCV without an evident cause. scatter and other parameters are used to minimize interferences such
Mathematical manipulations of various red cell indices take advantage as nucleated red cells, nuclear remnants (Howell-Jolly bodies), malaria
of the trend toward relatively more severe microcytosis than hypochro- parasites, or platelet clumps.
mia in thalassemia trait versus iron-deficiency anemia to assist in Automated reticulocyte counts are typically reported in absolute
the differential diagnosis of these disorders, particularly in high- numbers (reticulocytes per μL or per L of blood), obviating the need to
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prevalence populations where laboratory resources are limited, but correct for a reduced red cell count (anemia), if present. However, one
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their usefulness has been questioned. 31 may still consider the effect of elevated erythropoietin levels secondary
Mean Cell Hemoglobin The MCH, the amount of hemoglobin to severe anemia, which results in premature release of reticulocytes
per red cell, increases or decreases in parallel with the red cell volume persisting in the circulation for more than the usual 1 day, correspond-
(i.e., MCV) and generally provides similar diagnostic information, ingly inflating estimates of daily marrow reticulocyte production based

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