AJCP / Editorial
Erythrocyte Sedimentation Rate
Journey Verifying a New Method for an Imperfect Test
Jeannette Guarner, MD,1 Hannah K. Dolan, MT(ASCP),2 and Lisa Cole, MT(ASCP)2
From the 1Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA, and 2 Emory Healthcare, Atlanta, GA.
Am J Clin Pathol  October 2015;144:536-538
DOI: 10.1309/AJCPQO81BGTKTVJJ
The rate of sedimentation of blood-formed elements in
a predetermined amount of time, also known as the eryth-
rocyte sedimentation rate (ESR), is used around the world
by many clinicians in an effort to assess acute inflamma-
tory response. ESR results have been incorporated into
many practices and algorithms as a way to determine the
presence of active inflammation.1-4 However, ESR is a
phenomenon that is not well understood since aggrega-
tion, precipitation, and packing of RBCs are facilitated by
many plasma proteins, including fibrinogen and immuno-
globulins, and affected by the amount and shape of RBCs.5
Because this phenomenon lacks specificity, clinical chem-
ists and pathologists who direct clinical laboratories where
ESR is measured believe it is a very imperfect test. In
this editorial, we review how instrumentation in clinical
laboratories has progressed to make it easier, faster, less
hazardous, and more standardized to perform ESR, and
we describe the challenges clinical laboratories encounter
when verifying fundamentally different technologies that
measure the ESR phenomenon.
The ESR testing method was developed by R. S.
Fåhræus and A. V. A. Westergren. The original method
was first described in 1921, and modifications of the
original method have been selected as the reference stan-
dard by several agencies.6 In general, this method uses
blood that has been anticoagulated and diluted and then
placed in the Westergren-Katz tube, which has to stand
in a strictly vertical position in a rack for 1 hour at room
temperature. The result is the measurement in millimeters
of the distance erythrocytes have fallen. This method is
manual and has many preanalytical and analytical factors
that can alter results. In addition, as the person performing
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DOI: 10.1309/AJCPQO81BGTKTVJJ
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the method has to manipulate and pour blood into the
Westergren-Katz tube, the technique is considered to have
a high biohazard risk. Thus, many companies have looked
into using methods that are better suited to modern clinical
laboratories.
One of the methods accelerates turnaround time to
less than 30 minutes by using the Boycott phenomenon.7
For this method, the sample can be obtained directly (by
using the vacuum) or filled manually into shorter, rect-
angular, tapered tubes that are placed in an instrument
that maintains the temperature and holds them at an 18°
angle to the vertical. The height of the RBCs is measured
using light transmission after the tube has been in place
for 20 minutes, and a mathematical correction is applied
to make the measurement comparable to the Westergren
ESR. Authors have found both favorable and unfavorable
comparisons of the shorter method to the standard refer-
ence method.8,9 However, since we do not really know
what analytes are being measured with either technique,
why not use the method that offers advantages from the
laboratory standpoint, including less manipulation of the
specimen, smaller sample volume, and decreased turn-
around time?
A second alternative sedimentation rate method that
uses rheometry has also made it onto the market. Rheom-
etry measures the flow and deformation of materials under
applied forces and can be determined on a microscale using
optical techniques as the sample flows in a microcapillary.
When applying rheometry to determining the ESR, the
instrument uses anticoagulated blood that is sampled directly
from the tube from which it was drawn (usual tubes used
for other purposes in the laboratory), and multiple optical
© American Society for Clinical Pathology

140
120
Boycott Instrument
100
80
60
40
20
0
0 20 40 60 80 100 120
Rheometry Instrument
❚Figure 1❚ Comparison of 300 samples using the Boycott and
rheometry instruments.
measurements are obtained as the blood flows in the micro-
tube. The sedimentation curve obtained is transformed to
comparable Westergren values. Several publications have
presented good correlation of the results when comparing
these instruments with the reference method.10-13 Advan-
tages of instruments that use this technology include rapid
results, low imprecision, and performance that can be main-
tained in blood stored for 24 hours.
The International Council for Standardization in Haema-
tology recommends comparisons of new faster methods to
the reference method.6 However, if your laboratory is already
using one of the faster methods and you want to change to
another method, the capability to compare to the reference
method will be limited. In the following, we describe the sur-
prises encountered while verifying two rheometry instruments
to an instrument that uses the Boycott phenomenon:
1. The precision studies for the low level had a coefficient
of variation (CV) between 25% and 28%, although the ESR
results ranged from 2% to 5% in the rheometry instrument.
The high level showed a CV that ranged between 11% and
13%, with ESR values that ranged between 30% and 45%.
2. For the comparison, we used 300 patient samples that
ranged from a value of 1 to 130 with an intercept that was
less than 1 and an almost perfect slope (1 and 1.08). How-
ever, the dispersion was enormous ❚Figure 1❚. Taking the test
as normal vs abnormal, 83% of samples were concordant
(28% in the normal range and 55% in the abnormal range)
and 17% discordant.
3. We were able to verify the normal range for males
younger than 50 years (<15 mm) and people older than
50 years (<30 mm) with 20 samples each, but for females
younger than 50 years, we had to create a new normal range
for our population (<25 mm).
The amount of dispersion of the correlation results
prompted us to study correlation of results with other
© American Society for Clinical Pathology
AJCP / Editorial
laboratory values (WBC counts and C-reactive protein)
and clinical histories (rheumatologic/infectious disease or
malignancy). The review included those cases that would
have been within the normal range for one of the methods
and elevated for the other. There were a total of 50 cases,
but review of the medical record was possible only in 45.
There were 25 female patients with discrepant results; in
36%, the method using rheometry could be considered to
correlate better according to the medical history. Of the 20
male patients, 55% were considered to correlate better with
the method using rheometry. The average difference was
20 mm in female patients and 16 mm in male patients, and
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140
there were six patients with a difference above 30 mm, with
one reaching 97 mm. Of these six patients, the method using
rheometry was considered better in two patients. One patient
had a renal transplant and the WBC count was normal, and
the second had breast cancer with a normal WBC count
and C-reactive protein. The latter was the patient in whom
the difference between the sedimentation rates was 97 mm.
In the other four patients, the sedimentation rate using the
Boycott phenomenon was considered better; two patients
had active infections, one had a renal neoplasia, and the last
patient had rheumatoid arthritis and scleroderma. In sum-
mary, although there are discordant cases when correlating
with other laboratory and clinical parameters, one method
does not seem to be better than the other.
We have had no clinical complaints after we imple-
mented the ESR that uses rheometry. Technologists are
pleased with the new instruments since these are less labor
intensive. However, the verification process was labor inten-
sive, with comparison studies that needed a large amount of
subjects and review of medical records of discrepant results,
in addition to having to establish a new normal range for a
specific population.
In this era where health care systems are pressed for
better utilization, clinicians continue to use tests that were
invented in the early 20th century and that measure phenom-
ena that are obscure and have many variables, such as the
ESR. Verification of disparate methods for a phenomenon
that is not due to one specific analyte can prove challenging
and may require added clinical correlations in addition to the
usual verification steps.
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© American Society for Clinical Pathology