Lecture Presented by Dr Manuel Quintana at the Egyptian African Critical Care Summit held at Cairo, egypt

2. Coagulopathy in
Servicio
de
Medicina
Intensiva
Grupo
de
Inves3gación
49.IdiPAZ
Hospital
Universitario
La
Paz-­‐Carlos
III.
Madrid.
TRAUMA PATIENTS
Dr. M. Quintana

3. 3
Charlas, estudios investigación y ayudas a congresos
• XXXX
• XXXX
• XXXX
Pertenencia a Sociedades Científicas
• Miembro de la Comisión de Transfusiones del HULP
• Miembro del Documento de Sevilla “Alternativas a la Transfusión”
• Miembro del Documento “Hemomas”
• Miembro de GIEMSA/ AWGE/NATA
• Socio ESCIM/SEMICYUC/SETS/SEMES/SOMIUCAM
Hospital
Universitario
La Paz.
Madrid
Facultad de
Medicina.
Universidad
Autónoma
de Madrid
| Declaración de conflicto de intereses
.
2017

4. • Dra MªJ Colomina/ BCN
• Dr F. Ariza/Cali
• Dr N. Suarez/ Madrid
• SEMICYUC Group of TyATSA
• CASTYM Group

5. “The
white
rabbit
wore
his
eyeglasses
—¿Where
do
I
start,
your
majesty?
—Start
from
the
biggining
—replied
the
king—.
Follow
un3l
you
get
to
the
end.
Then
stop.”
Alice's Adventures in Wonderland.
Lewis Carroll. 1865

6. What we know……

8. trauma = bleeding

9. • In 2020 it will be the second cause of dead in all group of ages.
• Most of the patients do not get transfusions (91%) only a few
need massive transfusion (3%).
• These received more than 71% of the RBC (18% not crossed)
• Bleeding could be the in hospital cause of death even up to 1/3 of
the patients who died, specially in the first 24h of admission
• Mortality from 39% to 57%
– Patients who recieve more than 10 RBC during their stay at the
ICU ( 2.6% of all trauma patients) have a 39% mortality
– Mortality of those who recieve more than 50 RBC whitin the
first 24h (0.6% of all trauma patients) have a 57% mortality
• Survival of the bleeding patients depends on the right tranfusion
treatment
• Just 1 patient can consume all the blood bank of a hospital

10. and what we learn about that……

11. Mortality
from
major
trauma
con2nues
to
be
a
worldwide
problem,
and
massive
haemorrhage
remains
a
major
cause
of
poten3ally
preventable
deaths.
Development
of
coagulopathy
further
increases
mortality
considerably,
and
coagulopathy
is
a
key
target
in
the
phase
of
bleeding.
The
concepts
of
‘damage
control
surgery’
(DCS)
and
‘damage
control
resuscita3on’
(DCR)
have
been
developed
during
the
past
10
years
to
ensure
early
control
of
bleeding
and
coagulopathy
in
order
to
reduce
morbidity
and
mortality
in
trauma
haemorrhage.
11
Norton
R,
Kobusingye
O.
Injuries.
N
Engl
J
Med
2013;
368:1723–1730.
Johansson
PI,
Stensballe
J,
Oliveri
R,
et
al.
How
I
treat
pa3ents
with
massive
hemorrhage.
Blood
2014;
124:3052–3058.
Holcomb
JB,
Jenkins
D,
Rhee
P,
et
al.
Damage
control
resuscita3on:
directly
addressing
the
early
coagulopathy
of
trauma.
J
Trauma
2007;
62:307–
310.
Shapiro
MB,
Jenkins
DH,
Schwab
CW,
et
al.
Damage
control:
collec3ve
review.
J
Trauma
2000;
49:969–978.

12. damage control hemostatic time!!!

13. Clinical issues
• Bleeding is the first cause of death in severe trauma 1
• Trauma associated coagulopathy at admission is related
with trauma severity and its mortality 2
• The right haemostatic treatment is fundamental in
prognosis, just below a right ventilation3
1Sauaia A et al. J trauma 1995; 38:185-193
2Brohi K et al. J Trauma 2003; 54:1127-1130
3MacLeod JB et al. J Trauma 2003; 55:39-44

14. Clinical
issues
• Primary
causes:
mechanic
injury
• Mechanic
organs
injury
• Mechanic
vessels
injury
• Secondary
causes:
coagulopathy
• Bleeding
associated
coagulopathy
• Trauma
associated
coagulopathy
Lynn M Bloodline Reviews 2001

15. • “baseline”
Coagulopathy
•
“associated”
Coagulopathy
•
“deriva1ve”
Coagulopathy
•
“added”
Coagulopathy
Coagulopathy
pathophysiology

16. • Defects
in
clot
strenght
due
to
fibrinogen
and
platelet
deficiency
• Defects
in
clot
stability
due
to
hyperfibrinolisis
and
FXIII
deficiency
• Delay
in
clot
forma3on
due
to
factors
deficiency
secondary
to
its
consume
Bleeding
associated
coagulopathy
pathophysiology
*Kozek-Langenecker S. Yearbook of Intensive care and Emergency Medicine 2007

17. What´s new……

18. • Coagulopathy appears early after injury, before fluid infusion at the scene.
• Coagulation factors and fibrinolysis are activated precociously
• Coagulopathy (more than bleeding) incidence is high
• Severity is related to injury and not to hypoperfusion

19. BLEEDING
CAUSES
IN
SEVERE
TRAUMA
Severe
Trauma
Coagulopathy
(Secondary)
Coagulopathy
(Primary)
• Consume
(IDC)
• Deple3on
• Acidosis
and
hypoperfusion
• Hypothermia
• Cristaloid
infusion
• Insufficient
blood
products
infusion
Promoters
Arch
surg/vol
143
(no.
8),
Aug
2008

20. Trauma associated coagulopathy is.. early, primary, acute and
related to traumatic shock worsen by fluid therapy, acidosis,
hypocalcemia, hypothermia...
• no concept uniformity
• no animals model validity developed
by now.
• retrospective, no controls
• All of them include classical mortality
trauma factors, but they dont study
coagulation factors, fibrinolysis,..

22. 22

23. Classically,
coagulopathy
had
a
late
origin
due
to
factors
deficiency
lost
by
bleeding
added
to
dilu3on
of
the
exis3ng
ones
by
fluids
infusion
Current
studies
report
that
coagulopathy
appears
very
early
and
even
a
third
of
the
pa3ents
already
have
it
by
admission,
even
before
fluid
infusion

24. 24

26. 26

27. Coagulopathy
• This group vary according to laboratory criteria used to its
diagnosis, showing to be less sensitive but more specific
the APTT than PT
(4) McLeod JB, Lynn M, McKenedy MG, Cohn SM, Murtha. Early coagulopathy predicts mortality in trauma. J Trauma.
2003;55: 39-44.

28. 28

30. Coagulation monitoring
¿how?
Experiences with quick thromboelastography could lead
us to a more efficient therapy with blood products and
haemostatic related pharmacology
Kashuk JL, Moore EE, Wohlauer M, Johnson JL, Pezold M, Lawrence J,et al. Initial experiences with point-of-care rapid
thrombelastography for management of life-threatening postinjury coagulopathy. Transfusion. 2011. Jul 25. doi: 10.1111/j.
1537-2995.2011.03264.x. [Epub ahead of print]

31. 31

33. “Everybody
talks
about
it,
nobody
understands
it”
JH
Levy,
2000

34. 34

35. 35
The
pathophysiology
of
coagulopathy
in
trauma
can
be
stra2fied
into
three
dis3nct
types
that
oRen
exist
in
varying
degrees,
as
single
en22es
in
the
less
sick
pa2ent
but
coexist
with
the
poten2al
to
amplify
in
the
bleeding
trauma
pa2ent:
• acute
trauma3c
coagulopathy
(ATC),
• coagulopathy
associated
with
the
lethal
(pentad?)
triad
• consump3ve
coagulopathy

36. 36
ACUTE
TRAUMATIC
COAGULOPATHY
–
ATC-­‐

37. 37
Acute
coagulopathy
of
trauma
(ATC)
and
shock
(ACoTS),
is
observed
in
25–35%
of
trauma
pa3ents
at
hospital
arrival,
associated
with
significant
2ssue
injury,
shock
and
increased
mortality.
ATC
is
a
hypocoagulable
condi3on
evidenced
by
increased
prothrombin
2me
and
by
prolonged
cloVng
2me
as
evaluated
by
viscoelas2c
haemosta2c
assays
(VHA).
An
important
cause
of
this
coagulopathy
is
the
endogenous
an3coagula3on
that
develops
to
balance
the
increasingly
more
procoagulant
vasculature,
represented
by
the
systemically
injured
endothelium
.
MacLeod
JB,
Lynn
M,
McKenney
MG,
et
al.
Early
coagulopathy
predicts
mortality
in
trauma.
J
Trauma
2003;
55:39–44.
Brohi
K,
Singh
J,
Heron
M,
et
al.
Acute
trauma2c
coagulopathy.
J
Trauma
2003;
54:1127–1130.
Co_on
BA,
Faz
G,
Hatch
QM,
et
al.
Rapid
thrombelastography
delivers
real2me
results
that
predict
transfusion
within
1
h
of
admission.
J
Trauma
2011;
71:407–417.
Davenport
R,
Manson
J,
De’ath
H,
et
al.
Func2onal
defini2on
and
characteriza2on
of
acute
trauma2c
coagulopathy.
Crit
Care
Med
2011;
39:2652–2658.
Ostrowski
SR,
Sorensen
AM,
Larsen
CF,
et
al.
Thrombelastography
and
biomarker
profiles
in
acute
coagulopathy
of
trauma:
a
prospec2ve
study.
Scand
J
Trauma
Resusc
Emerg
Med
2011;
19:64.
Johansson
PI,
Stensballe
J,
Rasmussen
LS,
et
al.
A
high
admission
syndecan-­‐
1
level,
a
marker
of
endothelial
glycocalyx
degrada2on,
is
associated
with
inflamma2on,
protein
C
deple2on,
fibrinolysis,
and
increased
mortality
in
trauma
pa2ents.
Ann
Surg
2011;
254:194–200.
Johansson
PI,
Henriksen
HH,
Stensballe
J,
et
al.
Trauma2c
endotheliopathy:
a
prospec2ve
observa2onal
study
of
424
severely
injured
pa2ents.
Ann
Surg
2016.
[Epub
ahead
of
print]

38. 38
Causes
contribu3ng
to
endogenous
an3coagula3on
• auto-­‐hepariniza2on
• protein
C
ac2va2on
• hyperfibrinolysis
these
are
all
related
to
and
driven
by
the
state
of
the
endothelium

39. 39
• the
endothelial
glycocalyx,
consis2ng
of
a
thick
layer
of
proteoglycans
and
glycosaminoglycans,
becomes
shedded
secondary
to
the
endothelial
damage,
resul2ng
in
release
of
heparan
sulphate
and
similar
cons3tuents
with
heparin-­‐
like
ac3vity
to
the
circula3ng
blood
(auto-­‐hepariniza3on)
• Reduced
levels
of
protein
C,
a_ributed
to
increased
produc2on
of
ac2vated
protein
C,
contribu3ng
to
the
hypocoagulablity
observed.
• Increased
fibrinolysis,
the
most
potent
endogenous
an2coagula2on,
is
observed
in
pa2ents
with
extensive
and
widespread
endothelial
ac2va2on
and
damage
secondary
to
trauma,
leading
to
enhanced
release
of
2ssue-­‐type
plasminogen
ac2vator
(tPA)
from
the
Weibel-­‐Palade
bodies
of
the
endothelial
cells,
inducing
premature
resolu2on
of
the
formed
clot.
endogenous anticoagulation
Kashuk
JL,
Moore
EE,
Sawyer
M,
et
al.
Primary
fibrinolysis
is
integral
in
the
pathogenesisoRheacutecoagulopathyoRrauma.AnnSurg2010;252:434–442.
Co_on
BA,
Harvin
JA,
Kostousouv
V.
Hyperfibrinolysis
at
admission
is
an
uncommon
but
highly
lethal
event
associated
with
shock
and
prehospital
fluid
administra2on.
J
Trauma
Acute
Care
Surg
2012;
73:365–370

40. 40
Hyperfibrinolysis
is
an
important
cause
of
severe
haemorrhage
and
occurs
in
severely
injured
pa3ents
correla3ng
with
poor
outcome

41. 41
COAGULOPATHY
IN
THE
LETHAL
TRIAD

42. 42

43. Hipotermia
Hipocalcemia
Acidosis
Hipotermia
Hipoperfusión/Acidosis
Hipocalcemia
Hiperglicemia
Hipoxia
Coagulopatía
Cortesia Dr JN Carreño

44. 44

45. 45
The
lethal
triad
is
frequently
observed
in
pa3ents
with
massive
haemorrhage
and
encompasses
acidosis,
hypothermia
and
coagulopathy
associated
with
high
mortality.

46. 46
• Hypothermia-­‐induced
coagulopathy
is
atributed
to
platelet
dysfunc3on,
reduced
coagula3on
factor
ac3vity
and,
in
the
most
extreme,
induc3on
of
fibrinolysis.
• Acidosis
is
oRen
induced
by
hypoperfusion
and
to
some
extent
excess
administra3on
of
ionic
chloride,
that
is
NaCl,
during
resuscita2on.
• Acidosis
impairs
almost
all
essen2al
parts
of
the
haemosta2c
process
resul2ng
in,
for
example,
a
change
in
platelet
structure
and
shape
and
reduced
ac2vity
of
coagula2on
factor
complexes
on
the
cell
surface,
ul2mately
resul3ng
in
impaired
thrombin
genera3on.
Duchesne
JC,
McSwain
NE
Jr,
Co_on
BA,
et
al.
Damage
control
resuscita2on:
the
new
face
of
damage
control.
J
Trauma
2010;
69:976–990.
DjaldeV
M,
Fishman
P,
Bessler
H,
et
al.
pH-­‐induced
platelet
ultrastructural
altera2ons.
A
possible
mechanism
for
impaired
platelet
aggrega2on.
Arch
Surg
1979;
114:707–710.
Mar2ni
WZ,
Dubick
MA,
Pusateri
AE,
et
al.
Does
bicarbonate
correct
coagula2on
func2on
impaired
by
acidosis
in
swine?
J
Trauma
2006;
61:99–106.
Mar2ni
WZ,
Holcomb
JB.
Acidosis
and
coagulopathy:
the
differen2al
effects
on
fibrinogen
synthesis
and
breakdown
in
pigs.
Ann
Surg
2007;
246:831–835.

47. 47
Both
hypothermia
and
acidosis
impair
fibrinogen
availability
as
hypothermia
inhibits
fibrinogen
synthesis
and
acidosis
accelerates
fibrinogen
degrada3on,
leading
to
hypofibrinogenemia.

48. 48
CONSUMPTIVE
COAGULOPATHY

49. 49
Tissue
injury
induces
an
immediate
ac3va3on
of
the
coagula3on
system
through
exposure
of
2ssue
factor
and
other
2ssue
or
intracellular
components,
which
promotes
excessive
thrombin
genera3on.
To
protect
the
organism
against
intravascular
thrombin
by
excess
fibrin
forma2on,
the
ini3al
coagula3on
ac3va3on
is
followed
by
enhanced
plasminogen
ac3va3on
and
fibrinoly3c
ac3vity,
and
to
prevent
rebleeding
by
fibrinolysis,
the
plasminogen
ac2vator
inhibitor
(PAI)-­‐1
level
increases
progressively
in
the
hours
and
days
hereaRer.
Drake
TA,
Cheng
J,
Chang
A,
et
al.
Expression
of
3ssue
factor,
thrombomodulin,
and
E-­‐selec3n
in
baboons
with
lethal
Escherichia
coli
sepsis.
Am
J
Pathol
1993;
142:1458–1470.

50. 50
Importantly,
extensive
3ssue
injury
and
accompanying
shock
induces
widespread
endothelial
injury,
resul3ng
in
a
prothrombo3c
state
of
the
microvasculature
that
further
promotes
coagula2on
factor
and
platelet
consump2on,
ul3mately
leading
to
coagulopathy
and
further
risk
of
haemorrhage
Occasionally,
the
normal
an2coagulant
and
fibrinoly2c
control
mechanisms
fail
to
restrict
the
haemosta3c
ac3vity
to
the
area
of
3ssue
damage
resul3ng
in
disseminated
intravascular
coagula3on
(DIC).
Drake
TA,
Cheng
J,
Chang
A,
et
al.
Expression
of
3ssue
factor,
thrombomodulin,
and
E-­‐selec3n
in
baboons
with
lethal
Escherichia
coli
sepsis.
Am
J
Pathol
1993;
142:1458–1470.

51. 51
• Another
important
driver
of
consump3ve
coagulopathy
is
the
accompanying
inflammatory
response,
which
by
inducing
2ssue
factor
expression
on
various
cells
supports
a
viscous
cycle
of
reciprocal
ac3va3on
of
the
coagula3on
system.
A
cri3cal
driver
of
consump3ve
coagulopathy
is
sympathoadrenal
overac3va3on.
Gando
S,
Sawamura
A,
Hayakawa
M.
Trauma,
shock,
and
disseminated
intravascular
coagula3on:
lessons
from
the
classical
literature.
Ann
Surg
2011;
254:10–19.
Levi
M,
van
der
PT.
Inflamma3on
and
coagula3on.
Crit
Care
Med
2010;
38:S26–S34.

52. 52
This
occurs
in
response
to
excessive
3ssue
injury
and
shock/
hypoxia,
leading
to
release
of
catecholamines
in
concentra2ons
that
are
directly
toxic
for
the
endothelium,
ul2mately
resul2ng
in
further
endothelial
damage
and
downstream
coagulopathy.
Catecholamines
are
potent
ac3vators
of
platelets
and
promote
coagula3on
factor
release
and
ac3va3on
Makhmudov
RM,
Mamedov
Y,
Dolgov
VV,
et
al.
Catecholamine-­‐mediated
injury
to
endothelium
in
rabbit
perfused
aorta:
a
quan3ta3ve
analysis
by
scanning
electron
microscopy.
Cor
Vasa
1985;
27:456–463.
Cannon
WB.
A
considera3on
of
possible
toxic
and
nervous
factors
in
the
produc3on
of
trauma3c
shock.
Ann
Surg
1934;
100:704–713.

53. and what´s about dilution……

54. 54
Coagulopathy
secondary
to
dilu3on
of
coagula3on
factors
and
platelets
is
also
an
important
part
of
the
lethal
triad
and
dilu2onal
coagulopathy
is
further
aggravated
when
synthe3c
colloids
are
administered.
Hydroxyethyl
starch
(HES)
causes
an
efflux
of
plasma
proteins
from
the
blood
to
the
inters22al
space,
reduces
the
plasma
concentra2on
of
coagula2on
factor
VIII
and
von
Willebrand
factor,
inhibits
platelet
func2on
and
interferes
with
the
interac2on
between
ac2vated
FXIII
and
fibrin
polymers
-­‐>This
may
contribute
to
the
increased
bleeding
and
mortality
of
HES
administra3on
in
bleeding
trauma
Be
careful
with
the
quan1ty
and
the
moment
of
administra3on!!!!

55. 55
Administra3on
of
blood
products
also
contributes
significantly
to
coagulopathy
in
massive
bleeding
and
the
‘best’
haemosta2c
capacity
possible
to
accomplish
with
administra2on
of
balanced
RBCs,
plasma
and
platelets
(1
:
1
:
1)
results
in
a
haematocrit
around
30%,
a
coagula2on
factor
concentra2on
60%
and
a
platelet
count
of
80
109
/l,
……
which
is
far
below
normal
concentra3ons

56. We know the problm… but
what´s about the solution?

58. Bleeding
Management
First:
STOP
THE
BLEEDING
Second:
Transfusion
Third:
Coagulophaty
Treatment

59. 59

60. • Defects
in
clot
strenght
due
to
fibrinogen
and
platelet
deficiency
• Defects
in
clot
stability
due
to
hyperfibrinolisis
and
FXIII
deficiency
• Delay
in
clot
forma3on
due
to
factors
deficiency
secondary
to
its
consume
Bleeding
associated
coagulopathy
pathophysiology
*Kozek-Langenecker S. Yearbook of Intensive care and Emergency Medicine 2007

61. Coagulophaty
Treatment
physiopathological
objec3ves
• Trombin
(genera2on)
• (Func2onal)
fibrinogen
• (Func2onal)
Platelets
• (Modula2on
of
)
fibrinolysis
61

62. What do you need to take
home?

63. DCR:
main
components
• Haemosta3c
resuscita3on
–
early
use
of
blood
products
to
avoid
further
coagulopathy
in
respect
to
fluids
and
dilu2on.
• Permissive
hypotensive
resuscita3on
to
decrease
bleeding
and
support
bleeding
control.
• Regaining
homeostasis
and
avoid
further
coagulopathy
related
to
hypothermia,
acidosis
and
electrolyte
disturbances
(hypocalcemia,hyperkaliemia);
hypoxia
and
hyperglicemia
63

64. Key
points
• Coagulopathy
is
a
key
target
for
diagnosis
and
aggressive
treatment
in
the
bleeding
phase.
• Haemosta3c
resuscita3on
aims
to
control
coagulopathy
early
and
consistently
in
bleeding
trauma
pa3ents.
64

65. 65
• trauma
pa3ents
present
with
an
inherent
risk
of
coagulopathy
• concurrent
with
the
rapidity
of
changes
in
the
haemosta3c
system
during
massive
bleeding
• the
importance
of
rapid
diagnosis
and
therapy
cannot
be
stressed
enough
• think
in
lethal
pentad
• use
prohemosta3c
with
head

66. Thank you for your attention
MQ
manuel.quintana@uam.es