1. PEDIATRIC
SEVERE
TRAUMATIC
BRAIN
INURY:
HYPO
OR
HYPERCOAGULABLE
STATE?
Arun
Saini
MD1,
Elizabeth
Rourke
BS1,
Jose
Pineda
MD1,
MaUhew
A.
Borgman
MD2,
Andrew
P
Cap
MD3,
Philip
C.
Spinella
MD,
FCCM1,3
1
Division
of
CriEcal
Care
Medicine,
Department
of
Pediatrics,
Washington
University
School
of
Medicine;
St
Louis,
MO,
2
San
Antonio
Military
Medical
Center,
Fort
Sam
Houston,
TX
3US
Army
InsEtute
of
Surgical
Research,
Fort
Sam
Houston,
TX
Philip
C
Spinella
Email:
Spinella_P@kids.wustl.edu
Arun
Saini
Email:
arunsaini0369@gmail.com
Elizabeth
Rourke
Email:
Rourke_L@kids.wustl.edu
Contact
We
would
like
to
acknowledge
Lori
Barganier
RN,
Tina
Day,
Barb
Miller
BSN
and
Maraya
Camazine
for
paEent
recruitment
and
data
gathering.
Acknowledgement
IntroducXon
Design:
Single
center
prospecEve
observaEonal
cohort
study.
Subjects:
Children
≤
18
years
of
age
admired
with
sTBI
(Glasgow
Coma
Scale
≤
8
at
admission)
from
June
2012
to
January
2014.
Data:
We
collected
paEent
demographics
(age,
race,
gender,
weight),
injury
severity
score
(ISS),
clinical
data
(fluid
resuscitaEon,
blood
products
transfused,
medicaEons,
intracranial
pressure
[ICP]
and
surgical
procedure
performed
in
the
first
five
days),
prothrombin
Eme
[PT],
internaEonal
normalized
raEo
[INR],
acEvated
parEal
thromboplasEn
Eme
[aPTT],
and
TEG-­‐PM,
and
outcome
data
(ICU
mortality,
ICU
length
of
stay
and
a
measure
of
adapEve/daily
life
funcEoning
[WeeFIM
scale]
at
hospital
discharge).
TEG-­‐PM
was
done
daily
for
up
to
5
days
while
in
the
ICU.
DefiniXons:
• Hypocoagulable
platelet
count
<130,000
per
cumm
INR
>1.2
aPTT
>36
seconds
TEG(R)
>10
minutes
OR
TEG
(G)
<5
• Hypercoagulable
platelet
count
>
440,000
per
cumm
TEG(R)
<5
minutes
OR
TEG
(G)
>11
• Divergent:
Hypocoagulable
on
a
standard
coagulaXon
test
and
hypercoagulable
on
a
TEG
parameter.
• WeeFIM
scoring:
PaEents
were
evaluated
using
a
standardized
assessment
that
measures
independence
in
acEviEes
of
self
care,
sphincter
control,
transfers,
locomoEon,
communicaEon
and
social
cogniEon.
Using
normaEve
data,
funcEonal
independence
at
discharge
was
classified
as
poor,
moderate
or
good.
The
paEents
scores
will
group
them
into
one
of
three
categories:
Poor
funcEonal
independence,
a
WeeFIM
score
<
70,
moderate
funcEonal
independence,
a
WeeFIM
score
between
71-­‐84,
or
good
funcEonal
independence
with
a
WeeFIM
score
>85.
• StaXsXcal
analysis:
DescripEve
data
were
presented
as
median
and
interquarEle
range
or
percent.
Non-­‐normal
distributed
repeated
measures
were
compared
by
using
Friedman
test.
• The
small
sample
size
limits
power
to
compare
related
samples
and
to
assess
associaEon
between
coagulaEon
variables
and
outcomes.
• We
did
not
perform
thrombin
generaEon
tests
and
other
platelet
funcEon
assays
to
validate
TEG
vs
standard
coagulaEon
test
comparisons.
• The
goal
enrollment
for
this
study
is
30
sTBI
paEents
and
30
mild
to
moderate
TBI
paEents.
LimitaXons
• In
our
preliminary
data
in
children
with
sTBI,
we
found
a
very
high
frequency
of
divergent
results
between
standard
coagulaEon
tests
and
TEG-­‐PM
(specifically,
INR-­‐R
Eme).
• TEG-­‐PM
parameters
suggest
a
mixed
coagulopathic
state
with
increased
thrombin
generaEon
and
clot
strength
with
moderate
platelet
inhibiEon.
• Larger
prospecEve
studies
are
needed
to
determine
whether
standard
coagulaEon
tests
or
TEG-­‐PM
more
accurately
idenEfy
and
classify
coagulopathy
in
children
with
sTBI.
Conclusions
Variables n= 16
Age in years 13.5 (10.7-16.2)
Male gender (%) 12 (75)
Weight in kilograms 62 (50-70)
Isolated TBI (%) 6 (37.5)
GCS at admission 5 (3-6)
ISS at admission 29 (17-42)
AIS Head/Neck 4 (4-5)
ICP > 20 cmH2O at anytime during length of stay 12 (75)
Surgical procedure 12 (75)
Mortality (%) 1 (6)
Length of mechanical ventilation in days 5.5 (1.7-13)
Length of ICU stay in days 14 (11.7-19)
WeeFIM score at hospital discharge 81.5 (80-90.8)
Coagulopathy
aGer
severe
traumaEc
brain
injury
(sTBI)
occurs
frequently
and
is
independently
associated
with
worse
outcome.
Reduced
clot
strength
measured
by
Thromboelastography
with
Platelet
Mapping
(TEG-­‐PM),
has
been
associated
with
increased
mortality
in
adults.
No
studies
describing
viscoelasEc
measures
of
hemostasis
over
Eme
and
their
associaEon
with
outcomes
have
been
reported
in
children
with
sTBI.
Our
primary
objecXve
was
• To
determine
if
TEG
parameters
correlate
with
standard
coagulaEon
tesEng
in
children
with
severe
TBI.
Our
secondary
objecXve
was
• To
determine
if
any
coagulaEon
measure
is
associated
with
neurological
outcomes
in
children
with
severe
TBI.
We
hypothesized
that,
1.)
TEG
parameters
would
not
correlate
with
standard
coagulaEon
measures,
and
2.)
paEents
with
hypo
or
hypercoagulable
states
would
be
at
increased
risk
for
worse
neurological
outcome.
• 16
children
with
sTBI
were
enrolled
• 12.5%
of
paEents
had
poor
(WeeFIM
<
70),
50
%
of
paEents
had
moderate
(WeeFIM
71-­‐84),
37.5%
paEents
had
good
funcEonal
independence
measure
(WeeFIM
>85)
at
hospital
discharge.
• We
found
divergent
results
between
INR
and
R
Xme
in
58%
paXents
on
admission,
83%
day
1,
75
%
day
2,
and
75%
day
3
in
simultaneously
drawn
samples.
• There
was
a
poor
correlaEon
between
INR
and
R
Eme
(R2=
0.038,
p=0.21)
(Figure
1).
• Platelet
count
(PC)
and
G
value
results
were
divergent
(PC
≤
130
per
1000
mm3
and
G
value
≥
11)
only
in
10
%
of
samples.
However,
there
was
poor
correlaEon
between
platelet
count
and
G
value
(R2
=0.02,
p=0.75)
(Figure
1).
• On
Day
3,
most
paXents
are
hypercoagulable
by
TEG
R
results
vs
hypocoagulable
by
INR/PTT
standards.
• Over
5
days,
TEG
G
indicates
increasing
clot
strength
despite
decreasing
platelet
count
(Figure
2).
• There
was
increased
ADP-­‐mediated
platelet
inhibiEon
at
admission,
that
had
its
nadir
at
3
days
(Figure
2).
Table
1.
Study
cohort
characterisXcs.
Methods
and
Materials
• 62%
(8/13)
of
Plasma
and
PC
transfusions
occurred
when
TEG
results
indicated
a
hypercoagulable
state,
(Table
2).
• Total
of
8
(50%)
paEents
were
transfused
blood
products
in
the
first
5
days
(pRBC
0
cc/kg
(0-­‐10),
FFP
0
(0-­‐9.75),
platelet
concentrate
0
(0-­‐3.75)),
(Table
2).
• No
clinical
and
coagulaXon
variable
was
found
to
be
associated
with
the
neurological
outcome.
Patient
Time
Point
Product
INR
or PCc
TEG R
or G
Result
2 6 Hr FFPa 1.14 3.2 Dd
2 Day 2 FFP 2.08 4.5 D
3 6 Hr FFP 1.53 3.4 D
4 Day 2 PCb 151 6 -
6 Day 2 FFP 1.6 4.2 D
8 Day 4 PC 116 9.5 -
11 6 Hr FFP 1.43 3.1 D
12 6 Hr FFP 1.56 4 D
12 6 Hr PC 105 8.6 -
12 Day 1 PC 120 8.7 -
17 Day 2 FFP 1.42 4.4 D
17 Day 1 PC 94 9.3 -
17 Day 2 PC 114 11.3 D
Figure
1:
Divergent
results
of
standard
coagulaXon
tests
and
TEG®.
Table
2:
Coag
parameters
prior
to
transfusion.
a
fresh
frozen
plasma,
b
platelet
concentrate,c
platelet
count
1000per
mm3
d
divergent
results
Disclosures:
• ParEal
funding
support
by
NaEonal
InsEtutes
of
Health
(U54
HL112303)
Results
Results
Figure
2:
Trend
of
coagulaXon
parameters.
*=
p<0.05
O=
Outlier
Figure
3:
Trend
of
platelet
inhibiXon.
*=
p<0.05
O=
Outlier