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Heparin-induced thrombocytopenia in the critically ill: interpreting the 4Ts test in a randomized trial.
[heparin-induced thrombocytopenia]
Thrombocytopenia
occurs
in
20
%
to
45
%
of
critically
ill
medical-surgical
patients
.
The
4
Ts
heparin-induced
thrombocytopenia
(
HIT
)
score
(
with
4
domains
:
Thrombocytopenia
,
Timing
of
thrombocytopenia
,
Thrombosis
and
oTher
reason
[
s
]
for
thrombocytopenia
)
might
reliably
identify
patients
at
low
risk
for
HIT
.
Interobserver
agreement
on
4
Ts
scoring
is
uncertain
in
this
setting
.
To
evaluate
whether
a
published
clinical
prediction
rule
(
the
"
4
Ts
score
"
)
reliably
rules
out
HIT
in
"
low
-risk
"
intensive
care
unit
(
ICU
)
patients
as
assessed
by
research
coordinators
(
who
prospectively
scored
)
and
2
adjudicators
(
who
scored
retrospectively
)
during
an
international
heparin
thromboprophylaxis
trial
(
PROTECT
,
NCT
00182143
)
.
Of
3746
medical-surgical
ICU
patients
in
PROTECT
,
794
met
the
enrollment
criteria
for
this
HIT
substudy
.
Enrollment
was
predicated
on
one
of
the
following
occurring
in
ICU
:
platelets
less
than
50
×
10
(
9
)
/
L
,
platelets
decreased
to
50
%
of
ICU
admission
value
(
if
admission
value
<
100
×
10
(
9
)
/
L
)
,
any
venous
thrombosis
,
or
if
HIT
was
otherwise
clinically
suspected
.
Independently
,
4
Ts
scores
were
completed
in
real
time
by
research
coordinators
blinded
to
study
drug
and
laboratory
HIT
results
,
and
retrospectively
by
2
adjudicators
blinded
to
study
drug
,
laboratory
HIT
results
,
and
research
coordinators
'
scores
;
the
adjudicators
arrived
at
consensus
in
all
cases
.
Of
the
763
patients
,
474
had
a
central
or
local
laboratory
HIT
test
performed
and
had
4
Ts
scoring
by
adjudicators
;
432
were
scored
by
trained
research
coordinators
.
Heparin-induced
thrombocytopenia
was
defined
by
a
centrally
performed
positive
serotonin
release
assay
(
SRA
)
.
Of
the
474
patients
with
central
adjudication
,
407
(
85
.
9
%
)
had
a
4
Ts
score
of
3
or
lower
,
conferring
a
low
pretest
probability
(
PTP
)
of
HIT
;
of
these
,
6
(
1
.
5
%
[
95
%
confidence
interval
,
0
.
7
%
-
3
.
2
%
)
had
a
positive
SRA
.
Fifty
-
nine
(
12
.
4
%
)
had
a
moderate
PTP
(
4
Ts
score
of
4
-
5
)
;
of
these
,
4
(
6
.
8
%
)
had
a
positive
SRA
.
Eight
patients
had
a
high
PTP
(
4
Ts
score
of
≥
6
)
;
of
these
,
1
(
12
.
5
%
)
had
a
positive
SRA
.
Raw
agreement
between
research
coordinators
and
central
adjudication
on
each
domain
of
the
4
Ts
score
and
low
,
intermediate
,
and
high
PTP
was
good
.
However
,
chance-corrected
agreement
was
variable
between
adjudicators
(
weighted
κ
values
of
0
.
31
-
0
.
93
)
and
between
the
adjudicator
consensus
and
research
coordinators
(
weighted
κ
values
of
0
.
13
and
0
.
78
)
.
Post
hoc
review
of
the
6
SRA-
positive
cases
with
an
adjudicated
low
PTP
demonstrated
that
their
scores
would
have
been
increased
if
the
adjudicators
had
had
additional
information
on
heparin
exposure
prior
to
ICU
admission
.
In
general
,
the
fourth
domain
of
4
Ts
(
oTher
causes
of
thrombocytopenia
)
generated
the
most
disagreement
.
Real-time
4
Ts
scoring
by
research
coordinators
at
the
time
of
testing
for
HIT
was
not
consistent
with
4
Ts
scores
obtained
by
central
adjudicators
.
The
results
of
this
comprehensive
HIT
testing
highlight
the
need
for
further
research
to
improve
the
assessment
of
PTP
scoring
of
HIT
for
critically
ill
patients
.
Diseases
Validation
Diseases presenting
"central adjudication"
symptom
heparin-induced thrombocytopenia
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