Effect of antibody specificity on results of selected digoxin ... - CiteSeerX

1 downloads 0 Views 1MB Size Report
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

of

References

15.

RP. Clinical

Cardiol

16.

use of serum

digoxin

concentrations.

Am J

1992;39:767-75.

EC. Inaccuracies in digoxin Clin Biochem 1988:21:353-7. Godley Pi, Frohna PA, Horton MW, Reitmeyer Wi.

measurement. Karbowki

JA,

Marked

digoxin-like

enzyme

immunoreactive

immunoassay.

Thong

B, Soldin

anti-digoxin clonal

Lingwood

antibodies,

antibody Chem

that

factor

interference

Drug Intell Clin Pharm

Si,

and

CA.

Lack

of

preparation

recognizes

the

with

between

from

Altman

human

0G. two

Bova and

DuCharme

OW,

characterization

plasma.

Statistical

methods

S.

Harris

Proc NatI Acad

methods

of clinical

for

assessing

measurement.

of a new,

carbohydrate

of current specific,

moiety

and

controversies

[Review].

6. Pudek

MR, Seccombe DW, Humphries active substances and bile acids in the disease

[Letter].

Dasgupta instead

A, of total

Clin

Chem

Saldana

S,

digoxin

Chem

K. Digoxin-like immunoreof patients with liver

serum

1986:32:2005-6. Heimann

in patients

P.

Monitoring

free

digoxin

with

congestive

heart

failure

and high concentrations of digoxin-like immunoreactive substances. Clin Chem 1990;36:2121-3. 8. losefsohn M, Soldin SJ, Hicks JM. A dry-strip immunometric assay for digoxin on the Ames Seralyzer. Ther Drug Monit 1990:12: 201-5. 9. Valdes R Jr. Endogenous digoxin-like immunoreactive factors: impact implications

on

digoxin [Review].

measurements Clin

Chem

and

potential

Clerico

A,

Balzan

5,

cardiac

Del

CMG,

glycoside-like

Paci

A, Cocci

substances

F, Bertelli in

19.

Isolation adrenal

of cor-

or renal

Kerkez SA, Poston L, Wolfe CD, Quartero HW, Carabelli P, Petruckevitch A, et al. A longitudinal study of maternal digoxin-like immunoreactive substances in normotensive pregnancy and pregnancy-induced hypertension. Am J Obstet Gynecol 1990;162:

20.

Goto A, Yamada K, Yagi N, Hui C, Terano Y, Sugimoto as endogenous digitalis-like factor in animals [Letter]? 1992;38:161-2.

21.

Valdes R Jr, Graves SW. Protein binding of endogenous digoxin like immunoreactive factor in human serum and its variation with clinical condition. J Clin Endocrinol Metab 1985;60:1135-43.

1. Ouabain Clin Chem

22. Avendano

C, Alvarez iS, Sacristan JA, Adin i, Alsar Mi. Interference of digoxin-like immunoreactive substances with TDx Digoxin II assay in different patients. Ther Drug Monit 1991;13:523-7.

23.

physiological

A.

newborns,

Schlebusch H, Jarausch J, Domke I. Endogenous digoxin-like immunoreactive factors (DLIF) as measured by the CEDIA digoxin assay and a fluorescence polarization immunoassay. Wien KIm Wochenschr Suppl 1992;191:59-66. Kenny MA, Ahmad S. Malik S. Novel steroid glycosides useful as hypertensives and in the early detection of hypertension and in other assays and therapy. US AppI 520,175 (1990), PCT 1991.

1985;31:1525-32.

Shaikh IM, Lau BW, Siegfried BA, Valdes R Jr. digoxin-like immunoreactive factors from mammalian tex. J Biol Chem 1991:266: 13672-8.

agree-

Lancet

18.

poly-

of digoxin. Clin

Sci U S A

Naomi S. Graves 5, Lazarus M, Williams GH, Hollenberg NK. Variation in apparent serum digitalis-like factor levels with different digoxin antibodies. Am J Hypertens 1991;4:795-801.

1988:22:703-4. specificity

DW,

of a ouabain-

783-7.

an

1986:32:5-12.

10.

JM,

ment

MP,

17.

1985:31:1625-31.

5. 501dm SJ. Digoxin-issues

7.

Blaustein

Bland

Endogenous

2. Cook JD, Koch TR, Cook MS, Knoblock

Clin

F, et al. Identification

adults, pregnant women and patients with hypertension insufficiency. Drugs Exp Clin Res 1988:14:603-7.

1. Lewis

4.

JM,

Mandel

1986;i:307-10.

Center

specimens.

3.

Hamlyn

like compound 1991:88:6259-63.

Co.,

laboratory

at University

analyses

of the

Welicome

Chemistry

and

Two

by

24.

Miller ii, Straub RW, Valdes R Jr. Digoxin immunoassay with cross-reactivity of digoxmn metabolites proportional to their biological activity. Clin Chem 1994:40:1898-903.

Datta digoxin

P, Larsen

metabolites

F. Specificity

[Letter].

of

digoxmn

Clin Chem

immunoassays

1994:40:1348-9.

toward

Suggest Documents