differently with respect to cross-reac- ivity with digoxin metabolites, digitoxin, and digitoxin ietabolites. The. ACS assay again had the least analog or setabolite.
?linical
42:3
Chemistry
173-379
(1996) -
Effect of antibody specificity on results of selected digoxin immunoassays among various clinical groups ‘3
PR.kDLP KIVIN
lYe
examined
(Abbott
Stratus
29
applied
digoxin-free
sonspecific nented
iVe observed tmong
the
ailure
patients,
ord
DLIF
and
the
tssays
also
ACS
behaved
ivity
with
digoxin
ietabolites.
had
g/L
for
the
surgery
and
from
three
DLIF.
The
discrepancies
(defined of only
results
reactive
factors
SD
1DEXING
digoxin-like
ThRMS:
tonitoring.
drug
immunoreactive
metabolism
#{149} methods
factors
.
sess
digoxin the
measurements
impact
of
are
individual
currently patient
the
only
physiology
way and
to
drug
Ciba
Depts.
edicine,
of
2
Medicine,
September
I, 1995;
02032.
Box 357110, WA
Seattle,
of Seattle,
correspondence.
MA
Seattle,
Laboratories,
of Pathology for
E. Walpole,
of Washington,
Clinical
‘Laboratory Received
Laborator’,
University
‘Northwest *Author
Diagnostics,
Corning
WA
Seattle,
and
‘Medicine,
School
of
98195. 98133. WA
98104.
accepted
November
28,
they often
373
the
purpose
Stratus
IT#{174}, and
Ciba
interference
from
from
patients
with
some
digoxin
least
two
patterns when
patients.
Tangentially, for
on most
significant
discrepancy
ACS”
Digoxin,
groups
three
methods
we also
were
compared
samples
and
digoxin
with be
sub-
respect of
to
serious
therapy.
three
automated Baxter-Dade
with
respect
to
samples
(b) cross-reactivity We
report
concentrations applied
that
at
were
to digoxmn-free
the results
to observe
its
and
DLIF
in digoxin-free
analogs.
digoxin
and
different
can
Corning
apparent
useful
of digoxin TDxFLx,
the
frequently
newborns,
to compare
and
with
these
obviously,
clinical
be
Since
DLIF
patients
are
patients, towards
was
prep-
from
populations
Abbott
of
specimens.
anti-digoxin
might
[9-11].
study
immunoa digitalis-like
DLIF
failure
metabolites
digoxin-positive
patient
circulating
endogenous
these
have
systems,
of selected
detected
false-
with
management
of our
immunoassay
with
giving
on specimens
discrepancy,
relevance
potentially
specificities
successful
free
cross-react
digoxin-like
therapy
in
to assay clinical
results
renal
in
may
cross-react
patients
show
Such
for
digoxin
sults
1995.
e.g.,
other.
assays
Fax 206-548-6189.
digoxin
failure
(a)
I
in which
to
antibodies is circulated
and
to
The
the
unrelated
developed
endogenous
desirable, different
concern
itself,
no digoxin.
hepatic
has
specificity
of increased
exhibit
digoxin
hypothesized
frequently
reasons First,
digoxmn
metabolites
false-positive
assays
The erum
Finally,
(DLIF),
severe
each
drug
comparison
a trend
digoxmn
[8].
received
stances,
Second,
digoxmn
than
incidence
groups
and
good
of substances
[4-6].
to increase
[9-13],
monitoring
3-5%.
forms,
giving
have
the
3
positive
greatest
well
of
affinity
who or
sets
is
immuno-
is surrounded. with
of the
therapy
specific
are several
test
cross-react
Third,
greater
structure
digitoxin
bias
[7].
arations,
analog agreed
a mean
compared)
three
free
There this
cases
However,
monitoring of the
descriptions
nevertheless
in attempts
of results
[1-3].
with
failure.
for
which
for some
heart
composition
applied with
KENNY2,*
administered
congestive and
reagent
digoxin
where
and
being
and
A.
measurements
abounds
bound
and
the
least
methods
with
liver
of digoxin
design
ambiguity that
FERRERI,
MARGARET
and such
system the
commercial
to cross-reac-
the
had
of by the
digoxin
significant Of
on the fate
literature
showed
patients,
respect
again The
pairs
had
digitoxin,
assay
each
assay
assay
with
and
assays
interference
specimens,
digoxin
assay
to newborns
interference.
metabolites,
cross-reactivity.
etween
Stratus
cardiac
least
ACS
n digoxin-positive
with
results
to kidney
TDx
showed
the
digoxin
common
differently
The
setabolite
and
the
from
alone
Issays,
limited for
LAURANCE
and
arrhythmia
usefulness
from
associated
apparent
one
only one
ACS
immunoreactive
common
TDx
results;
assay
cohorts
of one
where
nterference;
lie Stratus
Corning
(b) drug-free serum supplemetabolites and analogs of digoxin.
samples:
where
metabolism cardiac
and
patterns
positive
blood,
12
digoxmn Baxter-
to (a) sera
digoxin-like
major
three
iigniflcant
in
endogenous
the
Ciba
LANDICHO,-
ZEBELMAN,5
assay,
ll
modification
DEL
M.
ARTHUR
automated
and
assay,
interference,
with
three
MALIK,
So&IL ROBY,2
Digoxin
without
patients or
(DLIF)
ctor
of
TDXFLX
Il#{174} Digoxin
assay)
)igoxin
Xu,2 V.
LEI PAUL
specificity
the
mmunoassays )ade
DATTA,1
HALVERSON,2
4
of the three
comparable
re-
374
Datta et al.:Digoxin
Materials TEST
immunoassays
and Methods
cence
digoxin,
used
digoxin
to evaluate
received
as
compounds
metabolites,
assay
a gift,
or
the structures
copy
(data
were and
not
The
a weighed
and
diluting
to
human
serum
drug-free been
CLINICAL
The
interference
serum
samples
mance
were
Center
or Harborview
Internal
obtained
Review
were
Board
(n
versions
ethanol,
by
or water with
donors
duplicate,
fresh
who
the
The
in
remaining by patient
and
medical
surgery were
with
measurable
numbers
(n
composition
review,
of
such
=
and
first
populations
were
confirmed
patients
studied
digoxin
antibody
ASSAY
SYSTEMS
digoxin
from
group
4.6%
(n
1. Mean
and
220)
for the
10%
and
assay;
and
tg/L
±
to
maximum
apparent
(e.g.,
The
trans-
Cortisol
indicated
in Table
systems
were
4.8%
(n
±
10.3%,
15) for
=
digoxin
(g.sg/L)
and
11%
±
assay;
ACS
specifications.
that
ments
quoted.
In the
first
the
analyses
phase for
and
(c) 0.8
the
ACS
were
“in
3.
.tgfL
±
provisiona
± 5.6%,
commercial
and
3.l(
assay.
Tht
accordin1
Quality-assurance
measured (total
was
measure
control”
and
was
for
the
done
measure-
and
was
ACS
the
0.1
II of our
by TDx,
genera
“master
curve’
calibrators
3.66
±
pure
respectively.
with
thc wa
of 0.5, 1.0
recovery The
p.gfL
digoxin
at concentrations assay
witi
0.4
schedule
When
Digoxin
study,
assay data
no
and
assa
and
was
lowest
100% limit
o:
gfL.
Digoxin
was
serum
108%,
two
on a weekly
protocol.
ACS
Digoxin
a six-point using
0.01
thereafter
calibration
100%,
with ±
ACS sensitivity,
by
of 0.69
.tg/L,
prototype
kit came
in drug-free 4.0
the
precision,
calibrated
designations
quality-control
229
assay
and
two-point
2.0,
study,
accuracy,
The
g/L)
supplemented
there
of the
evaluated
performance.
the
The
groups
/Lg/L
1.92 ,.tg/L
the
g/[ for th
and 3.0 .tg/L
CV
15) for
=
(fron
0.1
control sera pooh
12%
Stratus
and
were used and the assays were performed
Recalibration
1 and
used.
0.3,
imprecision
(b) 0.9
the
limits oi
assays
evident
Stratus,
the
replaced
for this
assay
commercialized the were
performance
and ACS
prerelease
Olgoxin
essentially
difference
formulation unchanged. between
assays
0:
Tin
materials. the
A tw
in nondigitalize
specimens). ACS
Stratus
n
Mean
Max
Mean
Max
Mean
Ma
11
0.04
0.37
0.03
0.15
0.01
0.0
0.19
0.41
0.05
0.17
0.01
0.0
20
0.38
0.58
0.12
0.41
0.02
0.0
Diabetics
17
0.05
0.34
0.18
0.53
0.06
0.2
Heart
16
0.02
0.13
0.38
0.53
0.01
0.0
Liver failure
28
0.06
0.23
0.08
0.32
0.01
0.0
Low albumin Newborn
19 20
0.08 0.39
0.52
0.00
0.00
0.03
0.2
0.50
0.13
0.40
0.00
0.0
Pregnancy
25
0.03
0.13
0.00
0.00
0.00
0.0
Renal
11
0.21
1.00
0.28
0.79
0.01
0.0
Transfusion
17
0.08
0.34
0.07
0.63
0.01
0.0
Transplant
37
0.08
0.32
0.08
0.53
0.06
0.2
Cord
therapy
(n
0.2,
±
assay;
for
.tg/L
(d) 0.63 2.9%
TDx
Category
±
manufacturers’
same
reports types
were
lower
digoxin
between-day
TDx
100)
=
tgfL
3.2
nominal
autopsy).
by published
patient
Autopsy
(n
to paramagnetic
applied to commercial
were:
=
6.9%
(0-5
laboratory
(e.g.,
shown
was
Abbott Labs. (Abbott Park, IL) TDxFLx Digoxin II assay incorporates an acidic surfactant pretreatment with a fluores-
Table
inserts)
ACS
(a) 0.8 g/L
study
chemilumi.
reported
and
for
Comin
monoclona]
conjugated
Stratus,
package
Ciba
ester-labeled
The
IL of ar
competing
is a two-reagent
digitoxin
digoxin methods
In phase immunoassay
the
respective
detection automated
and TDx,
100%,
DIGOXIN
assay
sensitivity
the
conjugate
acridinium
solid phase.
was
1.
Three
Digoxin
involving
particles as the
three
(Deerfield, detection
Results
(ACS
selected this with
interference. are
reagents;
j.tgfL
treatment
associated assay
ACS
concen-
to 3.73
or circumstance
digoxin
83)
=
drug
commercialized
of
patient
set (n
Digoxin
0.34
229)
sam-
assay
the
below.
The diagnosis
record
all from
Digoxin
sera
or hemodialysis),
They
ACS
from
MA)
for
Diagnostics fluorometric
to a glass fiber surface. The
system
instruments
to an
digoxin-positive
to evaluate described
Medical
according
The
ranged
patients.
determined
kits
specimens
nondigitalized
plant
assay
used
patients
or sets.
prototype
was
bound
(Walpole,
during
perfor-
of Washington The
phosphatase-labeled
±
instrument
Baxter
involves
digoxin, respectively. Typical
had
reassayed
The
assay
nescent
found.
Center
series
alkaline
their
mL/donor).
then
to compare
authorization.
108)
=
in these
assay).
Fig.
prepared
(350-600
University
in two
of all three
trations
used
Medical
to evaluate
second
data
were
healthy
was
from
collected
was used the
spectros-
indicated
from in
bombardment
resonance
SPECIMENS
clinical
ples
by fast atom solutions
the
dihydrodigi-
label.
H Digoxin
antibody
For
and
quantities
surveyed
when
laboratory.
concentration unit
analogs
commercially,
in methanol,
pools
for
were
quadruplicate
the
our
magnetic
test
substance
phiebotomized
Compounds
in
confirmed
shown).
available
(dihydrodigoxin
‘H nuclear
dissolving then
us
structural
digoxin
were
prepared by
spectrometry
and
specificity
prepared
toxin), mass
polarization
Stratus
COMPOUNDS
The
compared
blood
surgery
dialysis
8
Clinical
1.10
Chemistry
No.
42,
3, 1996
375
A 0.60
0.90
0.50
0.40
0.70
3 O
3 0.30 0.50
-c C a a
5
0.20
a
0.30
a
>
digitoxosides
interference,
for
and
interference
dose,
respectively).
for the monodigi-
in
Datta
376
Table
et al.: Digoxin
digoxin
Apparent
+2.0 .1.5 +1.0
conca
and
conca
TDx
Stratus
ACS
Digoxigenin 0.5 (1.28)
added
0.9 (1.15)
0.8 (1.02)
0.1 (0.13)
1.0
(2.56)
2.1 (2.69)
1.6 (2.05)
0.1 (0.13)
2.0
(5.12)
3.7
3.9
0.1 (0.13)
4.0
(10.23)
4.2 (5.38)
Digoxigenin
(4.74)
(5.00)
7.2 (9.23)
0.2
1.0
(0.26)
monodigitoxoside
(1.92)
1.0 (1.28)
1.2 (1.54)
0.8
(1.02)
2.5 5.0
(4.8) (9.6)
2.5 (3.20) 5.4 (6.91)
3.2 (4.10) 5.7 (7.30)
1.7
(2.18)
(192)
11.2
Digoxigenin 1.0 2.5
(1.54) (3.84)
5.0
(7.68)
(14.30)
(14.08)
6.8 (8.71)
1.5 (1.92) 4.1 (5.25)
1.5 (1.92)
11.0
of ACS
2.5
2.0
and Stratus
(pg/LI
.2.0 03+1.5
3.2 (4.10)
bisdigitoxoside
0.0
1.3 (1.66) 3.3 (4.23) 7.9 (10.12)
(15.36)
1.5
Mean
1.0
10.0
compared
.2.5
2. SpecificIty of three automated dlgoxin assays towards digoxin metaboiltes and analogs.
Compound
10.0
immunoassays
12.8
3.2
14.0
x
(4.10)
6.3 (8.07)
7.0 (8.96)
(16.39)
(I)
10.3
(17.93)
-ao
(13.19)
#{149}25 0.0
Dihydrodigoxin
(0.13)
0.4
05
1.0
0.1 (0.13)
0.5
(0.64)
0.1
(0.51)
1.0
(1.28)
0.1 (0.13)
0.5 (0.64)
0.1 (0.13)
2.0
(2.56)
0.3
0.4
0.1 (0.13)
4.0
(5.11)
0.3 (0.38)
0.7 (0.90)
0.2
2.0
1.5
2.5
Mean of TDx and Stratus
3.0
3.5
(pg/LI
0.5
(0.65)
0.1 (0.13)
0.3
0.1 (0.13)
Comparison of 83 serum digoxin concentrations measured b Stratus and ACS immunoassays (top) and by Stratus and TDx immunoassays (bottom) according to the method of Bland and Altman (14], plotting the difference between the results by each method and the mean of the methods.
1.0
(1.31)
0.1 (0.13)
0.3 (0.38)
0.1 (0.13)
Mean
2.0 4.0
(2.61) (5.23)
0.3 (0.38) 0.5 (0.64)
0.4 (0.61) 0.6 (0.77)
0.1 (0.13)
SD). The dotted
0.1
(0.38)
(0.51)
Fig.
(0.13)
Digitoxin (0.38)
2.
bias:
tions
(1.34) (2.67)
0.1 (0.13) 0.3 (0.38)
0.4 (0.51) 0.3 (0.38)
2.0
(5.34)
0.5
0.4
4.0
(10.68)
0.8 (1.02)
(0.64)
(0.13) 0.1 (0.13) 0.1 (0.13)
(0.51)
0.1 (0.13)
0.4 (0.51)
of the
the was
ACS
minus
Stratus
(5%)
with
(0.65)
0.2 (0.26)
0.3 (0.38)
0.1 (0.13)
1.0
(1.30)
0.2 (0.26)
0.3 (0.38)
0.0
2.0
(2.61)
0.2
0.3
0.1 (0.13)
4.0
(5.22)
0.2 (0.26)
0.1 (0.13)
0.0
0.1
0.1
0.1 (0.13) 0.1 (0.13)
mg from
0.1 (0.13)
assays,
0.1 (0.13)
an intercept
but
(0.0)
1.0
(1.71)
(0.13)
0.1
(0.13)
2.0
(3.42)
0.1
4.0
(6.84)
0.0 (0.0)
a
pg/L
(0.13)
0.2
(0.13)
(0.26)
0.3
(0.38)
0.1 (0.13)
no
digoxin. assay
(0.0)
[14].
The
(1 SD); (bottom)
p.g/L
=
digoxin
showed
discrepant
a second the
r
pg/L
2.5 pg/L
dose,
TDx
Stratus
>
respectively).
was reversed between being
ACS
18% be
from
the
apparent
methods
for
patient
groups
specimen cortisol
digoxin 229
o serie sam
frequently
conditions
to
interfere
content) showed
are
digoxin
detected by any of the three assays (i.e.,mean
digoxin
2.0
digoxmn
configuration
Altman-type
and
in the
each. bias
between
digoxin-positive (ACS
and
within
for
four samples
inaccuracy
was analyzed
paired
samples),
patient, drawn The
at 2.5
the
endogenous
assay
biases
(12 8%,
(128%,
to specimens
three
ACS
and Stratus, the order of interference
Stratus
(1
pg/L
(without
SD
significant, just three sera gave discrepant (3%
g/L
values
the
values
0.9786.
between
of Stratus,
j.tg/L (SE
=
as >3
of the
statistics
of 0.05
0.3
0.5
read had
TDx
Stratus
and
ACS
0.0
j.gfL,
respec-
digoxin values
samples,
mean
ACS, respec-
had a high percentage with three values >0.3
of
g/L
0 and 0.3
p.gJL for nearly
in each group. Fig. 1E shows
the results for
gave negative
the Stratus method than
assay
method’s
the
specificity
16). Both
=
the ACS
results for this group’s
had
the
diabetes 0.34,
13 apparent sensitivity
DLIF
and sera,
measure-
limit.
1. i.e.,
tion
the
free
mea-
in Fig. 1A. deterthe
of 0.21
in the TDx the
was 0.8
a similar
on 28 specimens
and
respectively. assay
maximum
g/L
scattergram from
digoxin-
liver
seen
of
TDx
were
renal
and
and
newborn
these
sets,
TDx
>>Stratus
artifact.
and
blood
care
renal
use of very specific assays had
distribu-
infant
assays
patterns
>>ACS.
samples. collected
phenomenon heart
The
the assay with
throughout
the
period
cohort
from cord
In both
pattern
essentially from of study likely
to represent
the blood
expected.
less seems
on sera
in intensive
of the
specimens
is reproducible-i.e., surgery
assays
interference read
was The
cohorts.
differed
theoretically
ACS
Observations
but
similarity
40 specimens,
pattern
newborns
other
The was
two
by the three
to each
digoxin-
Intereference
in these
digoxin-free
pattern.
on the
interference
patients.
measurements
similar
assays
a DLIF
failure
from
patient
totaling
The
had
Stratus
and
likewise liver
and the
of
of digoxin
cord
that
least (total
specificity among
by the
by all three
patients
those
distribution
patients
the
cohorts
assay (the other two
in the ACS
measurements
to in the
from
DLIF
difference in DLIF
be explained
digoxin
the latter was
three different patterns of interference among
failure
common
Of the three automated ACS,
and
associated
with respect to the assays affected. The
of digoxin
in all these
(TDx
could
immunoas-
metabolites
commonly
all 12 of the digoxin-free
also found
DLIF,
by only
of DLIF. Stratus, and
antibody
these cohorts
and
digoxin
digoxin
rabbit antibodies).
the
interference in half averages
We
found
sera of patient groups
the three assays polyclonal
of three
commonly
229 patients) tested. The
0.0,
among
appropriately
and
analogs, assaying
affected among
0.0,
in Fig.
methods, g/L),
some
with a high frequency
interference
sensitivity
patients
examined
(0.32,
present. Digoxin
group
have
assays tested, TDx,
detected
some
lB shows
For
the Stratus method
greater
monoclonai
DLIF
as 1.0 g/L 0.0
among
value
sample
corresponding 0.3
test cord
of 60%
samples
blood
were
ACS
Twelve
results are 0.02, 0.12, and 0.38 pgfL,
a pancreas
two were
graphically
Stratus
as high
the
Discussion
A
Stratus
the
were
showed with
TDx
patient
0.4
=
value
specimens, the
ments
renal failure patients without
this cohort
other methods
whereas
group
says towards
difference
the lower limit of assay
at or below
CS assay. The f the
from
results
were
igoxin therapy, are plotted together in a scattergram 1 11 specimens
(the
and
significant
digoxin
blood
cord
each)
20
=
magnitude
frequency
cord
patients.
(n
whereas
TDx
One
concentrations
reagents
results
assays
shown
when
three
failure
registered
(relative
re-
distrib-
are
of sensitivity.
apparent
and
renal
cases,
heart surgery patients (n
We
ACS results
specificity
of patients with
an
digoxin.
of specimens
(0.34
with respect to patterns of endogenous
o relative numbers
the limit
as 0.6 g/L
digoxmn
(0.63
p.g/L);
in which
also
the antibody
of
assays
newborns
assay
having
methods,
of similar
TDx
samples had
as high
the TDx
respectively.
groups,
lower
TDx
digoxin-free
of patients.
in the
For
ACS
all
newborn
TDx
0.1
= =
.tg/L,
0.0
significant,
explore
ssay systems
and
six of these
more
data
groups
respectively).
apparent
Stratus
and
Similar
high
>Stratus
Stratus,
j.tg/L)
diabetes ACS
Eight
g/L
a higher
Stratus
by the
was
in
18 newborn
g/L.
the
its
TDx
for
results
insignificant values in both groups
assay
transfusion
assay
of blood), one sample
assays.
and
TDx
digoxin,
and
Results
jgfL,
had
TDx,
and
and
respectively)
tively. Although
measured
had
and
the
0.0
=
j.g/L)
sample
0.0
=
g/L the
.0 j.g/L
hese
patient
TDx patient
amples
0.0
=
ACS units
ACS
transplant
transplant
ransplant nd
organ
j.g/L;
0.53
and
at
Stratus, and TDx
both
TDx
assay and
concentrations
gfL,
DLIF
90%,
digoxin
sets,
six samples
and three
for
30%
In
1 or more
ACS
=
Stratus);
with
for the three methods:
.tg/L, for
pattern,
seen and
in each cohort, it registered between
TDx
Digoxin
and
by the
to that blood
blood
nine
(cortisol concentration in the
ACS
tively).This pattern is also reflected by the mean
each
0.52
jLg/L
the
Stratus
more (the
samples.
digoxin
0.30
=
the
to the
receiving
and
similar
D for cord
only
apparent
groups,
results
0.0
concentrations
these
significant
other
jLgIL were
assays
digoxin
respect
g/L
(0.37
ones.
25) had detectable
=
of
the
registered
In these
registered
included four
significant
affected
ACS
apparent
0.l
single
values
were
amounts
statistically
Two
cortisol therapy or
bias with
were
only
ACS
however,
in the
higher
on
(n
method.
cohort
and
showed
females
had
0.00
to the 28 digoxin-free
any
in each
Stratus
samples. than
by
distribution.
0.06
liver failure group
pregnant
0.04 -0.04
groups
in addition
low albumin,
respectively);
eight
3). The
concentration
autopsy
seen
these
samples
of the
digoxin
-
-0.12
(Table
digoxin-positive None
of
-
group,
>0,
by
DLIF
0.14
therapy
values
showed
reportahle
8
Cortisol
In this
again read close to 0.0 .tg/L for all the patients, but the other
or without
Stratus
42,
free
ACS
groups.
Mean Category
Chemistry
was
nothing different indicate to be an a third
378
Datta
separate
distribution,
other;
in
this
interference
dissimilar
group than
Our
results
the
the
on
do
examples
of nonspecific
not
insufficient
of 0.1
greater
of
blood.
endogenous
DLIF
Avendano
version
reflect
previously
or cord
in
with the TDx
equivalents)
has been
that liver
It is possible
observed
newborns,
across
assay,
The
for
they
be identified
ACS
measured
severe
100%
assay
ing sample
composition
number
pattern
TDx
and
metab-
are the
that
and
in all three
in the
infer failure,
as an
interference
1991
a current
the
suggested
number
on
samples
possibility cardenolides
their
would
drug interference
or
state
is needed
latter two
results
differences
process are
If these
assays,
patients,
alternative
physiological study
digoxmn.
DLIF
that the
disease
patterns
digoxin for
we were
surgery
far,
was
that
false-positive
digoxin
antibodies.
methodological
Thus
the
such
to consider the [20] identified
fingerprints
cardiac
[19], and
on
three
is unlikely
set of digoxin
of impaired
antibody,
work, it may be useful former. Goto et al.
human
or metabolites
on
j.gfL
are a group
or analogs
results
100%,
significant
can
renal
described
investigators in
false-positive
study,
showed
[17].
specimens
by
instance,
These
in
in their
in conditions
reported For
a single
profiles there
or prematurity
of antigens
Because
be that
DLIF
responses
term
fluid,
cohorts
of
digoxin-positive)
interDLIF
252
immunochemical could
circulates
other
that
systems.
conclusion
for the
In contrast, the ACS
the
amniotic
include
incidence in
demonstrated
one
from
disThat
population.
concentrations
altered
among
account
patient
study this,
in sera
ouabain
groups.
seven
found
of
digoxin
among
[18]
could
been
patients, newborns,
differ-
nondigitalized,
or neonates,
to the digoxin
family
organism.
assays
groups
(e.g.,
DLIF)
in antigenicity
five digoxin
of
al.
[13]
21%,
women
all
coined
isomer
in our
present
with
pregnant
DLIF
results on cord blood
patterns
for characterizing et
did not
these
compared
They
DLIF
in this
and
cohorts.
patient has
From
to the same
than
by
with
a somewhat
blood.
Schlebusch fetuses
They
explanation
endogenous
found cord
with
women,
subjects.
from
of interference They
by
be
failure,
fingerprinting”
A study
can
sera
hepatic
umbilical
con-
is caused
interference
groups where
or
are
used
surgery
structural
the
proteins
ouabain.
a major
et al. came
The
Another
detected
antibodies
failure, or heart
probably
investigated. assay
patient
profile
“immunochemical their
is being
renal
for
of pregnancy
[21].
Naomi
anti-
here
to serum
with
in concentrations
among
strongly
is not
tivity
estrogens,
proteins
and Graves of the
ouabain
the of
anti-digoxin
methods.
be
our
appropriate.
reported
not
None
with In
incidence
cortisol,
of these
would
et al. [17],
an identical
with
binds
cross-reactivity in
of variations
of binding
by Valdes
at delivery.
low
(e.g.,
different
DLIF with
the
DLIF
possibility
Naomi
showed
serum
of probable
different
data
ent
latter
data
among
the
only
[16].
is therefore
results
all,
association
be hypertensive
by steroids
improved
possibility
original
is associated
they
detected
questioned
group
testosterone), the
the
because
tributions
concentrations been
hypertension,
caused
fingerprinting
each more
since at
or DLIF
been
would
of pregnancy
progesterone,
distribution
but
pregnancy
to
have
compared
DLIF
historically
has
with
nonspecificity
sistent
[15],
in the
DLIF
body
has
and to
inconclusive,
noise
DLIF
two
seems
immunoassays
assays.
a DLIF
of women
observed
other
are
baseline
pregnancy
institution,
ACS
women
pregnancy
hypertension
the assay
and
represent
to register.
third-trimester
DLIF
TDx
pregnant
probably
to
Stratus
et al.: Digoxin
th
in thes
metabolites
higher
in the
This
possibility assay,
consistently Digoxin of error
o
polyclon
with
is sup the
leas
yielded
th
metabolit in immuno
Clinical
In conclusion, ACS
of
assay
towards
had
digoxin
DLIF
the
three
better
digoxin
specificity
metabolites
interference
and
with
methods,
than
the
analogs,
digoxin-free
the
two
Chemistry
and
was
11.
monoclonal
polyclonal
42,
assays
less subject
to
12.
specimens.
No.
379
3, 1996
Schoner W. Endogenous digitalis-like factors. Clin Exp Hypertens A 1992:14:767-814. Tymiak AA, Norman JA, Bolgar M, DiDonato GC, Lee H, Parker WL, et al. Physicochemical characterization of a ouabain isomer isolated
from
bovine
hypothalamus.
Proc
NatI
Acad
Sci
U S A
1993:90:8189-93. 13.
The
reagents
used
in this
Ciba
Coming
Diagnostics
test
compounds
were
study
were
Corp.,
E. Walpole,
gifts
from
Research
Triangle
Park,
technical
assistance
of the Clinical
Harborview who
Medical
the
provided MA.
Burroughs
We
Center
with
assisted
NC.
generously
gratefully
acknowledge
and
the staffs
Medical
with
the
14.
at
collection
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