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12 World J Emerg Med, Vol 1, No 1, 2010 Maegele
INTRODUCTION
Trauma is the leading cause of death in persons aged
5 to 44 years
[1]
and accounts for approximately 10% of
all deaths in general.
[2]
Despite substantial improvement
in acute trauma care, uncontrolled haemorrhage is
responsible for over 50% of all trauma-related deaths
within the first 48 hours after admission.
[3]
These clinical
observations together with recent research resulted in a
new appreciation of the central role of coagulopathy in
acute trauma care. Current literature suggests that acute
traumatic coagulopathy (ATC) is multifactorial with certain
mechanisms being predominant whereas others manifest
only in specic clinical states
[4]
(Figure 1). To date, six key
initiators of coagulopathy in trauma have been described
as tissue trauma, shock, hemodilution, hypothermia,
acidemia, and inammation.
[4]
Most recently, Brohi et al
[5]

emphasized the role of hypoperfusion for the initiation
of ATC. As each abnormality itself may substantially
exacerbate the other, a downward spiral is initiated rapidly
and accelerates to death.
[6]
However, the adverse outcomes
from uncontrolled non-surgical hemorrhage and disturbed
hemostasis are not restricted to mortality only but also
include organ dysfunction and loss due to prolonged
hemorrhagic shock as well as the early termination of
Acute traumatic coagulopathy:
Incidence, risk stratication and therapeutic options
Marc Maegele
Department of Trauma and Orthopedic Surgery and Institute for Research in Operative Medicine (IFOM), University of
Witten/Herdecke, Cologne-Merheim Medical Center (CMMC), Ostmerheimerstr. 200, D-51109 Cologne, Germany
Corresponding Author: Marc Maegele, Email: Marc.Maegele@t-online.de
BACKGROUND: Uncontrolled hemorrhage is responsible for over 50% of all trauma-related
deaths within the first 48 hours after admission. Clinical observations together with recent research
resulted in an appreciation of the central role of coagulopathy in acute trauma care. A synopsis is
presented of different retrospective analyses based upon datasets from severe multiply injured patients
derived from the TR-DGU database (Trauma Registry of the Deutsche Gesellschaft fr Unfallchirurgie
(DGU)/ German Society of Trauma Surgery) with respect to frequency, risk stratication and therapeutic
options of acute traumatic coagulopathy (ATC).
METHODS: The synopsis of different analyses based upon the datasets from severe multiply
injured patients derived from the TR-DGU database and development/validation of a scoring system
(TASH-score = Trauma Associated Severe Hemorrhage) that allows an early and reliable estimation
for the probability of massive transfusion as a surrogate for life-threatening hemorrhage after severe
multiple injuries.
RESULTS: The high frequency of ATC upon emergency room admission is associated with
significant morbidity and mortality in multiply injured patients. The TASH-score is recognized as an
easy-to-calculate and valid scoring system to predict the individuals probability for massive transfusion
and thus ongoing life-threatening hemorrhage at a very early stage after severe multiple injuries.
CONCLUSION: An early aggressive management of ATC including a more balanced
administration of blood products to improve outcome is advocated.
KEY WORDS: Coagulopathy; Epidemiology; Management; Risk stratication;Trauma
World J Emerg Med 2010;1(1):12-21
Original Article
2010 World Journal of Emergency Medicine 2010 World Journal of Emergency Medicine
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13 World J Emerg Med, Vol 1, No 1, 2010
surgical procedures in order to save life.
[6]
Thus, early
recognition accompanied by adequate and aggressive
management of ATC would substantially reduce
mortality and improve outcomes in severely injured
patients.
[7]
A comprehensive review of the mechanisms
underlying ATC has been published.
[4]
The present study has three purposes. First, the
clinical impact of the problem is emphasized by
providing actual frequency rates of ATC upon emergency
room (ER) admission. Second, as early identification
of patients at risk for severe bleeding requiring massive
transfusion (MT) is rather difficult in the acute clinical
setting but may substantially influence therapeutic
strategies towards a more aggressive stabilization of
the disturbed hemostatic system, a simple scoring
system allowing an early and reliable estimation for the
probability of MT as a surrogate for life-threatening
hemorrhage after severe multiple injuries are presented.
Third, key issues are considered during acute care of
the bleeding trauma patient including novel approaches
towards a more balanced transfusion therapy.
METHODS
The data were collected from different analyses
of datasets from severe multiple injured patients
derived from the Trauma Registry of the Deutsche
Gesellschaft fr Unfallchirurgie (TR-DGU) database/
Arbeitsgemeinschaft Scoring of the German Society of
Trauma Surgery(DGU).
[8]
TR-DGU
The TR-DGU database/ Arbeitsgemeinschaft
Figure 1. Potential mechanisms underlying ATC. Besides dilutional
coagulopathy, hemorrhage may also induce shock followed by acidemia
and hypothermia, further triggering coagulopathy to form the so-called
"lethal triad". Trauma with shock, hypoperfusion and hypoxia can also
cause ATC associated with further consumption and hyperbrinolysis.
The clinical importance of inflammation for the development of ATC
has not yet been fully understood.
[4]
Scoring of the DGU
[8]
which was founded in 1993 is
run by a small steering group from different trauma
centers in Germany (Working Group on Polytrauma/
AG Polytrauma). It is a prospective, multicenter,
standardized and anonymous documentation of multiply
injured trauma patients at four consecutive post-
trauma stages from injury to hospital discharge: pre-
hospital phase; emergency room and initial surgery (until
admission to the intensive care unit (ICU)); ICU; and
outcome status at discharge and description of injuries and
procedures. The registry contains detailed information on
demographics, injury pattern, co-morbidities, pre- and in-
hospital management, time course, relevant laboratory
findings including data on transfusion, and outcome
of each individual. Through the 2006 data from a total
of 29 353 trauma victims have been input the registry,
approximately 3000 new cases are added each year. Since
the introduction of the on-line version of the registry
in 2002, the use of fresh frozen plasma (FFP) units is
routinely documented. Between 2002 and 2006, 17 935
patients have been input the registry. Currently, there are
140 hospitals affiliated with the registry, mostly from
Germany (n=90), of which 100 are actually contributing
data into the database. Contributing hospitals are mostly
level I trauma centers. The data are not dominated by
single trauma centers but this does not exclude potential
center effects due to different levels and strategies of
care. The TR-DGU is not an obligatory registry. The
participation is free of charge and data are contributed
on a voluntary basis. It is estimated that from the total
number of severe trauma cases in Germany, approximately
30% are covered by the registry. The trauma registry
is approved by the review board of the DGU and is in
compliance with the institutional requirements.
RESULTS
Frequency of ATC in multiple injuries upon
ER admission
A retrospective analysis using the TR-DGU database
was conducted to determine to what extent clinically
relevant coagulopathy has already been established upon
ER admission, and whether its presence was associated
with the amount of intravenous fluids administered
intravenously during the pre-hospital phase of care, with
the severity of injury, and with impaired outcome and
mortality.
[9]
Altogether 8 724 patients with complete data
sets were screened. Coagulopathy was defined by the
presence of abnormal coagulation parameters upon ER
arrival of the patient, i.e. prothrombin time test (Quick's
Trauma Hemorrhage
Rescusitation
Dilution Acidemia
Shock
ATC
Tissue
damage
Hypothermia
Hyper-
brinolysis
Consumption
Hypoperfusion
/Hypoxia
C
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Inammation
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14 World J Emerg Med, Vol 1, No 1, 2010 Maegele
value) <70% and/ or platelets <100.000/l.
[10]
In Germany,
the prothrombin time is preferentially reported and
documented as Quick's value in percentage (%; 70-130%
= normal
[10]
). A Quick's value of <70% is equivalent to a
prothrombin time ratio of approximately 1.4.
[11,12]
Acute traumatic coagulopathy upon ER admission
was present in 2 989 (34.2%) of all patients. Males were
more affected than females (72.5% vs. 27.5%) and in
96% the trauma mechanism was blunt. There was an
increasing frequency of coagulopathy with increasing
amounts of intravenous fluids administered during the
pre-hospital phase of care (Figure 2). The incidence of
ATC was also associated with the trauma load as reected
by injury severity scores (ISS). 2522 (84%) patients with
coagulopathy had an ISS more than or equal to 16 upon
hospital admission and the frequency of coagulopathy
increased with higher ISS scores (Figure 2). The presence
of acute ATC was associated with impaired outcome and
increased mortality. Of all patients with coagulopathy,
29% developed multi-organ failure (MOF) in their
later hospital stay. Early in-hospital mortality (<24 hr)
was 13% in patients with coagulopathy versus 1.5% in
patients without coagulopathy; the overall in-hospital
mortality totalled 28% versus 8.4% (P<0.001). Mortality
increased with injury severity but was generally higher
in patients with coagulopathy across all severity grades
studied. Figure 3 depicts mortality rates of patients with
and without coagulopathy with respect to their severity
of injury as reected by ISS.
ATC present on admission but independent of
injury severity
Recently Brohi et al
[5]
introduced the role of
hypoperfusion in the initiation of ATC by reporting their
results from a prospective cohort study of major trauma
patients (n=208) admitted to a single trauma center. In
this cohort, patients without tissue hypoperfusion were
not coagulopathic, irrespective of the amount of thrombin
generated. Prolonged partial thromboplastin and
prothrombin time was only observed with an increased
base decit (BD). An increasing BD was associated with
high soluble thrombomodulin and low protein C levels.
Low protein C levels were associated with prolonged
partial thromboplastin and prothrombin time as well
as hyperfibrinolysis with low levels of plasminogen
activator inhibitor-1 and high d-dimer levels. Longer
thrombomodulin time and low protein C level were
significantly associated with increased mortality, blood
transfusion requirements, acute renal injury, and reduced
ventilator-free days. These researchers concluded that
ATC occurs only in the presence of tissue hypoperfusion
and appears to occur without significant consumption
of coagulation factors. In an extension to this work, we
analysed Base excess (BE) levels from severe multiply
injured patients in respect to ATC frequencies upon ER
admission. Also in our datasets, the frequency of ATC
was strongly associated with BE level (Figure 4).
Figure 2. The incidence of ATC in subgroups according to ISS (4
subgroups) and intravenous uids administered during the pre-hospital
phase of care (5 subgroups). Each line represents a group of patients
with a similar ISS score, while each vertical group represents patients
who had received comparable amounts of intravenous uids during the
pre-hospital phase of care. Sample sizes for the groups ranged between
68 and 1439 patients.
i.v.uids administered pre-clinically (ml)
100
90
80
70
60
50
40
30
20
10
0
<1000 1000+ 2000+ 3000+ 4000+
P
a
t
i
e
n
t
s

w
i
t
h

c
o
a
g
u
l
o
p
a
t
h
y

(
%
)ISS 1-15
ISS 16-24
ISS 25-49
ISS 50-75
Figure 3. The mortality of patients with and without ATC on ER arrival
according to the severity of injury as reected by ISS.
ISS
80
60
40
20
0
0-15 16-24 25-49 50-75
M
o
r
t
a
l
i
t
y

(
%
)
No coagulopathy
Coagulopathy
Figure 4. Incidence of ATC as a function of BE on ER arrival.
BE
100
80
60
40
20
0
>-2 (-2)-(-4) (-4)-(-6) (-6)-(-8) (-8)-(-10) <-10
P
a
t
i
e
n
t
s

w
i
t
h

c
o
a
g
u
l
o
p
a
t
h
y

(
%
)
No coagulopathy
Coagulopathy
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15 World J Emerg Med, Vol 1, No 1, 2010
Variables Value Points
Hemoglobin (g/dl) <7 8
<9 6
<10 4
<11 3
<12 2
8
BE (mmol/l) <-10 4
<-6 3
<-2 1

3
Blood pressure
systol
(mmHg) <100 4
<120 1
4
Heart rate (bpm) >120 2 2
Free intraabdominal uid 3
(e.g. FAST)
Extremities
> clinically instable pelvic fracture 6
> clinically femur fracture/open/ 3
dislocated

6
Male 1 1
total 24
Figure 5. TASH-score. The TASH-score of 18 equals to a 50% risk for
massive transfusion (MT) after severe multiple injuries.
Figure 6. An example for the clinical application of the TASH-score to
identify patients at risk for MT.
A 36-year-old male motor cyclist
TBI 1
Lung contusion/hemopneumothrax left
pelvic fracture (instable)
Laboratory:
hemoglobin (g/dl) 6, 9
BE (mmol/l)-4, 5
Clinical examination:
HR
bpm
140
BP
systol
(mmHg) 85
FAST -
MT predicted:
>85%
TASH-score: A simple scoring system to
reliably predict the probability for massive
MT after severe multiple injuries
Lack of reliable early indicators for the individuals
risk for MT and thus persisting hemorrhage may result
in underestimation of or failure to detect early surgical
and coagulopathic bleeding, delayed intervention, and
impaired outcome. Recently, our group presented a
simple scoring system, i.e. the Trauma Associated Severe
Hemorrhage (TASH) Score, that may easily and quickly
(<15 minutes upon ER arrival) be applied in the ER to
identify patients at high risk for MT after severe multiple
injury.
[13]
Taken as a surrogate for severe ongoing
bleeding, calculation of TASH-score can substantially
impact strategies to control bleeding, to stabilize
coagulation, and to improve infrastructure and logistics
in acute trauma care.
To generate the score, potential clinical and
laboratory variables documented in the TR-DGU
database were subjected to uni-and multivariate logistic
regression analysis to predict the probability for MT
during early in-hospital resuscitation as a surrogate for
post-traumatic life-threatening hemorrhage. MT was
defined by a transfusion requirement of more than or
equal to 10 units of packed red blood cell concentrates
(pRBCs) between ER and ICU admission. Seven
independent variables were identied to be signicantly
correlated with an increasing probability for MT and
were incorporated into a risk score, the TASH-score
(Figure 5). Detailed information about model building
and validation has been published previously.
[13]
Increasing TASH-score is associated with an increased
probability for MT. A clinical example of its application
in acute clinical trauma care is demonstrated in Figure 6.
Current recommendations for coagulation
management in acute care following major
trauma
Early recognition together with adequate and
aggressive management of acute early coagulopathy
has been shown to reduce morbidity and mortality
[7]

and key recommendations for coagulation management
in the acute phase after severe multiple injuries have
been published.
[14,15]
Besides, general recommendations
have been suggested for time management, monitoring,
di agnost i c procedures, surgi cal approaches for
bleeding control including damage control surgery
and embolization, and specific treatment strategies
to support coagulation. These include physiological
targets as well as the suggested use and dosing of blood-
products, pharmacological agents, and coagulation factor
replacement in the patient with acute bleeding trauma.
Table 1 shows the current European guidelines for the
management of bleeding following a major trauma.
[15]

A clinical strategy for blood volume replacement during
the rst 24 hours after injury is shown in Figure 7.
Variables Variable Points Score
<7 8
<9 6
Hemoglobin (mg/dl) <10 4
<11 3
<12 2
<-10 4
Base excess (mmol/L) <-6 3
<-2 1
Sytolic blood pressure (mmHg)
<100
<120
4
1
Heart rate (beats/min) >120 2
Free intraabdominal uid (e.g.by FAST) 3
Clinically instable pelvic fracture 6
Open or dislocated femur fracture 3
Male gender 1
TASH
(sum of score points)
=
Probability
for mass
transfusion
TASH P
1-8 <5%
9 6%
10 8%
11 11%
12 14%
13 18%
14 23%
15 29%
16 35%
17 43%
18 50%
19 57%
20 65%
21 71%
22 77%
23 82%
24+>85%
TASH Score
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16 World J Emerg Med, Vol 1, No 1, 2010 Maegele
Addressing an early and more balanced
transfusion therapy in massively bleeding
patients
Recent military experience suggests that the
early use of fresh frozen plasma (FFP) together with
packed red blood cell (pRBCs) concentration at a 1:1
ratio for casualties requiring MT (> 10 pRBC units/24
hr) is associated with improved outcome.
[7,16,17]
We
retrospectively reviewed the datasets from the TR-
DGU database for MT during the period of 2002 and
2006 to test the hypothesis whether an early aggressive
transfusion at a pRBC:FFP ratio of 1:1 between ER
arrival and ICU admission would be associated with
reduced mortality.
[18]
Altogether 713 patients were
identied for analysis and were divided into three groups
according to the pRBC to FFP ratio transfused during
immediate MT. One group had undergone MT with a
pRBC:FFP ratio of more than 1.1, one with a pRBC:FFP
ratio of 0.9-1.1 (1:1), and one with a pRBC:FFP ratio
of less than 0.9. The mortality rates of patients were
compared among the groups.
484/ 713 pat i ent s had undergone MT wi t h a
pRBC:FFP ratio of more than 1.1, 114 patients with
a pRBC:FFP ratio of 0.9-1.1 (1:1), and 115 patients
with a pRBC:FFP ratio of less than 0.9. There was no
statistical difference between the three groups in injury
characteristics and pathophysiological status at scene
and upon ER arrival, laboratory findings, frequency
of emergency interventions, and volume loading.
The mortality rates at less than 6 hours, less than 24
hours, and 30 days in the three study groups are shown
in Figure 8. 32.6% (158/484) of the patients with a
pRBC:FFP ratio of more than 11 died at the first 24
hours after ER admission; the 30-day mortality rate of
this group was 45.5% (220/484 patients). In contrast, the
acute (<24 hours) and 30-day mortality rates were lower
in patients who were transfused with a pRBC:FFP ratio
of 0.9-1.1 (1:1) but lowest in those who had undergone
MT with a pRBC:FFP ratio of <0.9. The acute (<24
hours) and 30-day mortality rates in this group were
11.3% (13/115 patients) and 24.3% (28/115 patients),
respectively (Figure 8). The less than 6 hours mortality
rates in the three groups were 24.6% (119/484 patients),
9.6% (11/114 patients), and 3.5% (4/115 patients).
DISCUSSION
The present study highlights the clinical relevance
of ATC by providing recent data on its actual high
frequency during acute trauma care, by suggesting a
stratification tool to early identify patients at high risk
for MT representing a surrogate for severe ongoing
bleeding, and by providing current treatment strategies
including novel approaches towards a more aggressive
and a more balanced transfusion therapy. Early evidence
suggests that the recognition accompanied by adequate
and aggressive management of acute early coagulopathy
would substantially reduce mortality and improve
outcome in severely injured patients.
[7]
ATC in one of four patients upon ER arrival has
recently been identified to be associated with negative
Figure 7. Clinical strategy for blood volume replacement during
the first 24 hours after injury including triggering values for the
administration of specific blood components. Recent studies
have suggested a more aggressive coagulation management with
different components administered early and in a balanced ratio.
Antifibrinolytic agents (e.g. tranexamic acid, -aminocaproic acid)
should be considered in the treatment of the bleeding trauma patient
but should be stopped once the bleeding is adequately controlled. PCC
should be used for the emergency reversal of vitamin-K-dependent
oral anticoagulants only; there is no place for the use of AT III in the
treatment of the bleeding trauma patient. FFP:fresh frozen plasma;
Fg: fibrinogen; Hb:haemoglobin; Hct:hematocrit; Plts:platelets;
pRBC:packed red blood cells; PT:prothrombin time; aPTT:activated
partial thromboplastin time; rFVIIA:recombinant factor VIIa;
TBI:traumatic brain injury (adopted/modied from
[14]
)
Blood volume replacement
rFVIIa
Platelets
Fibrinogen
FFPa
pRBC
Colloids
Crystalloids
0 0.5 1.0 1.5 2.0 2.5 3.0
Persisting bleeding despite
attempts to control bleeding
and best-practice use of
blood components
Plts < 50 10
9
/l
(Plts < 100 10
9
/l in severely bleeding
mulple injury and TBI)
Figure 8. Mortality rates for patients transfused at different pRBC:FFP
ratios during acute care. Early (< 6-hour and < 24-hour) and 30-day
mortality rates in percent (%) for patients transfused at a pRBC:FFP
ratio of > 1:1, a pRBC:FFP ratio of 0.9-1.1 (1:1), and a pRBC:FFP ratio
of < 0.9 during immediate care.
Transfusion ratios
50
40
30
20
10
0
pRBC: FFP > 1.1 pRBC: FFP 0.9-1.1 pRBC: FFP < 0.9
M
o
r
t
a
l
i
t
y

(
P
a
t
i
e
n
t
s

i
n

%
)
<6-hour mortality
<24-hour mortality
30-day mortality
Fg 1.0 g/l
Hct 21-24% (Hb-target 7-9 g/dl)
PT, aPTT > 1.5 normal
?
?
www.wjem.org
17 World J Emerg Med, Vol 1, No 1, 2010
outcome.
[19,20]
Our data from the TR-DGU database
revealed an incidence rate of 34.2%
[9]
and that the
presence of ATC was associated with the amount of
intravenous fluids administered during the pre-hospital
care and the severity of injury.
Current literature suggests that ATC is multifactorial
but t her e ar e cer t ai n mechani sms l i kel y t o be
predominant while others are likely to manifest under
specific circumstances only.
[4]
A recent review of
mechanisms of ATC
[4]
proposed 6 key initiators in
such patients: tissue trauma, shock, hemodilution,
hypot hermi a, aci demi a, and i nfl ammat i on, wi t h
tissue trauma being the initiator and shock being the
principal driver. In our datasets, the frequency of ATC
was strongly associated with BE levels. Persisting
shock leads to intravenous therapy and subsequent
hemodilution that exacerbates the already established
hemostatic disorder. The aggravation of the established
Recommendations Grade
1 The time elapsed between injury and operation should be minimized for patients in need of urgent surgical bleeding control 1 A
2 The extent of traumatic hemorrhage should be clinically assessed using a grading system such as that established by the American College of
Surgeons
1 C
3 Hyperventilation or excessive postive end-expiratory pressure should not be used when ventilating severely hypovolaemic trauma patients 2 C
4 Patient in hemorrhagic shock and an identied source of bleeding should ungergo an immediate bleeding control procedure unless initial
resuscitation is sucessful
1 B
5 Patients presenting with hemorrhagic shock and an unidentied source of bleeding should undergo immediate further assessment 1 B
6 Early focused assessment with sonography for trauma (FAST) should be used for the detection of free uid in patients with suspected torso
trauma
1 B
7 Patients with signicant free intraabdominal uid according to sonography (FAST) and hemodynamic instability should undergo urgent
surgery
1 C
8 Hemodynamically stable patients with suspected head, chest, and/or abdominal bleeding after high-energy injuries should undergo
assessment via computed tomography
1 C
9 Single hematocrit (Hct) measurements should not be used as an isolated laboratory marker for bleeding 1 B
10 Serum lactate measurement should be used as a sensitive test to estimate and monitor the extent of bleeding and shock 1 B
11 Base decit should be used as a sensitive test to estimate and monitor the extent of bleeding and shock 1 C
12 Patients with pelvic ring disruption in hemorrhagic shock should undergo immediate pelvic ring closure and stabilization 1 B
13 Patients with ongoing hemodynamic instability despite adequate pelvic ring stabilization should receive early angiographic embolization/
surgical bleeding control
1 B
14 Early bleeding control should be achieved by packing, direct surgical bleeding control, and the use of local hemostatic procedures. In the
exsanguinating patient, aortic cross-clamping may be employed as an adjunct to achieve bleeding control
1 C
15 Damage control surgery should be employed in the severely injured patient presenting with deep hemorrhagic shock, ongoing bleeding, and
coagulopathy. Additional factors to trigger damage control are hypothermia, acidosis, inaccessible major anatomic injury, time-consuming
procedures, concomitant major injury outside the abdomen
1 C
16 The target systolic blood pressure should be 80 to 100 mmHg until major bleeding has been stopped in the initial phase following trauma
without brain injury
2 C
17 Crystalloids should be applied initially to treat the bleeding trauma patient. Colloids may be added within the prescribed limits for each
solution
2 C
18 Measures to reduce heat loss and warm the hypothermic patient should be applied early in order to achieve and maintain normothermia 1 C
19 A target Hb of 7 to 9 g/dl should be achieved and maintained 1 C
20 Patients with massive bleeding or significant bleeding complicated by coagulopathy [PT (prothrombin time) or aPTT (activated partial
thromboplastin time) more than 1.5 times control] should be treated with thawed fresh frozen plasma (FFP). The initial recommended dose is
10 to 15 ml/kg, but further doses may be required
1 C
21 Platelets should be administered to maintain a platelet count > 5010
9
/l
Maintainance of a platelet count > 10010
9
/l in patients with multiple trauma who are severely bleeding or have traumatic brain injury is suggested
An initial dose of 4 to 8 platelet concentrates or one aphaeresis pack is suggested
1 C
2 C
2 C
22 Fibrinogen concentrate or cryoprecipitate should be administered if signicant bleeding is accompanied by plasma brinogen levels < 1g/l.
An initial brinogen concentrate dose of 3-4 g or 50 mg/kg of cryoprecipitate is suggested, equivalent to 15-20 units in a 70-kg adult. Further
dosing should be according to lab values
1 C
23 Antibrinolytic agents should be considered and suggested dosages are tranexamic acid (trans-4-aminomethylcyclohexane-1-carboxylic
acid) 10-15 mg/kg followed by an infusion of 1-5 mg/kg per hour, e-aminocaproic acid 100-150 mg/kg followed by 15 mg/kg per
hour, or (after a test dose) aprotinin 2 million kallikrein inhibitory units (KIU) immediately followed by 500,000 KIU/hour in an
intravenous infusion. Antibrinolytic therapy should be stopped once the bleeding has been adequately controlled
2 C
24 The use of recombinant activated coagulation factor VII (rFVIIa) should be considered if major bleeding in blunt trauma persists despite
standard attempts to control bleeding and best-practice use of blood components. An initial dose of 200 mg/kg followed by two doses of 100
mg/kg at 1 and 3 hours after the rst dose is suggested
2 C
25 PCC should be used according to the manufacturers instructions and only for the emergency reversal of vitamin K-dependent oral
anticoagulants
1 C
26 The use of antithrombin III (AT III) in the treatment of the bleeding trauma patient is not recommended 1 C
Table 1. Synopsis of the current European guidelines for the management of bleeding after major trauma (adopted/modied from)
[15]
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18 World J Emerg Med, Vol 1, No 1, 2010 Maegele
coagulopathy is further triggered by hypothermia and
acidemia if hemorrhage remains unchecked.
In general, trauma patients with ATC are at high risk
to develop organ dysfunction and failure with prolonged
ICU and overall hospital stay as well as increased
mortality.
[19-23]
Some studies reported an up to 4-fold
increase in mortality if coagulopathy is present upon
ER arrival after severe multiple injuries.
[19,20]
MacLeod
et al
[20]
reported coagulation abnormalities early after
trauma to represent independent predictors of mortality
even in the presence of other risk factors. Our data from
the TR-DGU database presented here confirm these
ndings.
Although there is an increasing body of evidence for
the frequency of ATC upon ER arrival, the identification
of patients with active ongoing bleeding requiring MT is
still unsatisfactory. Substantial problems include i.) the
unavailability of global parameters within the very early in-
hospital phase, i.e. PT and aPTT are usually not available
until 30-40 minutes upon admission, and ii.) if available,
their potential physiologic values.
[19,24]
Second, surgical
relevant bleeding due to thoracic and/or retroperitoneal
or intraperitoneal organ injury is difficult to detect
and often requires time-consuming diagnostics.
[25]

Therefore, significant hemorrhage and coagulopathy
may be underestimated or even missed during early
resuscitation.
[20,26]
The awareness and recognition of
a patient with a substantial bleeding problem and in
potential need for MT at a very early stage after arrival
would also be supportive in providing adequate logistics
and infrastructure in tight collaboration with the local
blood product supplier.
The TASH-score published previously by our
group
[13]
is again recognized as an easy-to-calculate and
valid scoring system to predict the individuals probability
for MT and thus ongoing life-threatening hemorrhage at a
very early stage after severe multiple injuries. All variables
necessary to calculate the score are available within
the first 15 minutes upon ER arrival. Furthermore, the
variables are easily obtained not only in advanced trauma
centers but also in less sophisticated facilities. The TASH-
score was developed and validated in corresponding
subsets on the basis of 6 044 severely injured patients
from the TR-DGU database, and increasing TASH-scores
equally corresponded to the increased probability for
MT. To date, several predictive algorithms for MT have
been suggested.
[13,27-29]
In comparing score performance
reflected by ROC values, our TASH-score to date
performed best with an area under the ROC curve of
0.892.
[13]
The score could be supportive in clinical
decision-making for i.) early operative intervention
in case of surgical bleeding, or ii.) early initiation of
effective coagulation management. The score could also
be employed in stratifying patients for trials of blood
substitutes or other interventions, and in quantifying
the success of such trials. One potential limitation of
the TASH-score may be related to the fact that both
development and validation of the score were performed
on datasets from almost entirely blunt trauma patients
(> 95%). It may be possible that the assumptions based
upon datasets from those patients may not be appropriate
for the penetrating trauma population.
The better understanding of the potential initiators
and mechanisms that are responsible for the development
of ATC has already led to some redirection in the
management of bleeding patients after trauma with an
emphasis on the early restoration of hemostasis. In this
context, the concept of damage control resuscitation has
been introduced
[30]
along with corresponding guidelines
and recommendations to support coagulation in the acute
phase after severe multiple injuries.
[14,15]
The current
concepts and recommendations are based upon available
strategies to aggressively correct ATC, to limit the
duration of exposure to shock and hypoperfusion, and
to reduce hemodilution, hypothermia and acidemia. The
clinical role of inflammatory processes associated with
ATC has not yet been fully elucidated.
A novel therapeutic approach includes the early
administration of high-dose fresh frozen plasma to
massively transfused trauma patients.
[7]
Since pRBCs
also result in hemodilution and reduction of clotting
ability,
[31-34]
mathematical modelling
[35,36]
as well as early
clinical data
[7,18,30,37]
suggest that blood components should
be administered in a xed red blood cell: plasma: platelet
ratio of 1:1:1 in order to avoid dilution and to substitute
blood loss with a composition physiologically as similar
as whole blood. In accordance, analysis of the data from
the TR-DGU database in this study indicated a clear
association between pRBC:FFP transfusion ratio and
mortality after early aggressive FFP administration.
[18]
The author is aware of the fact that the registry data
like prospective observational studies share similar
limitations in the comparability of therapeutic subgroups.
Therefore, the observed associations do not necessarily
represent causality. In addition, the retrospective nature
of the present analyses eliminates the ability to determine
whether the noted transfusion results reflect a proactive
versus a reactive intervention. This, in turn, may be a
limiting factor for assessing the role of transfusion in
mitigating organ dysfunction.
www.wjem.org
19 World J Emerg Med, Vol 1, No 1, 2010
There has been quite some discussion in the past
on the potential gain attributed to early aggressive
transfusion therapy. For data interpretation, additional
information on treatment strategies used to control
bleeding in the acute phase after trauma need to
be considered as a delay in care could be a major
determinant for increased transfusion requirement and
outcome. This information, for example, includes the
introduction of focused abdominal sonography for trauma
(FAST),
[38,39]
the whole-body computed tomography
[40-43]

for prompt detection of bleeding, and the early use of
interventional radiology
[44]
and surgical techniques such
as damage control surgery
[6,45,46]
to control hemorrhage.
Within the 1999-2005 TR-DGU database the time
to completed radiography including chest and pelvic
x-ray and FAST could be substantially reduced from 25
minutes (1999) to 15 minutes (2005).
[47]
Simultaneously,
the use of whole-body computed tomography more
than tripled from 1999 to 2005 while the rate of damage
limiting orthopedic interventions for femur fractures in
multiply injured patients increased to 53%.
[47]
The faster
diagnostics translated into faster referral to both operation
rooms for bleeding control in case of hemorrhagic shock
and intensive care unit when no surgical intervention was
necessary. The data from the same registry between 1993
and 2005 showed that the mortality decreased from 22.8%
to 18.7%
[47]
as the percentage of patients requiring blood
transfusion including massive transfusion and the number
of blood concentrates transfused decreased.
[48]
Detailed
information on the potential relationship of transfusion
volume with surgical treatment is not available from the
TR-DGU. There is no blood substitution during the pre-
hospital phase of care among the hospitals or medical
centers afliated with the registry.
Despite the issues mentioned above, several
expert s have meanwhi l e revi sed t hei r pre-ICU
transfusion protocol emphasizing the early use of
FFP in a pRBC:FFP ratio of 1:1.
[7,16]
This approach
has recently been extended to the transfusion of an
increased fibrinogen:pRBC ratio which was shown to
be independently associated with improved survival
to hospital discharge in patients with combat-related
trauma requiring MT, primarily by decreasing death
from hemorrhage.
[49]
By using a pro-active approach
for an early balanced transfusion therapy in massively
bl eedi ng pat i ent s, Johannson and col l eagues
[50]

introduced an acute transfusion package consisting of
five units of pRBC, five unites of FFP, and two unites
of PC (platelet concentration). A similar approach with
a pre-defined ratio of the different blood products but
based upon a validated guideline extended by timing of
laboratory tests and a sound logistic protocol is urged
by other authors.
[51,52]
However, further prospective studies
are necessary to further elucidate this more balanced
transfusion approach including the potential role of
platelets and other therapeutic components.
Although key recommendations and guidelines
for the management of bleeding following the major
trauma have been issued,
[14,15]
the clinical management
of ATC shows substantial differences in the speciality of
physicians responsible for trauma management decisions.
A recent qualitative international survey of clinical
practice among senior physicians responsible for the
treatment of patients with multiple injuries highlighted
the variabilities of existing clinical practices around the
world.
[53]
While blood loss, temperature, pH, platelets,
prothrombin time/INR/activated partial thromboplastin
time, and overall clinical assessment were the most
common criteria for the assessment of coagulopathy, the
management of hypothermia, acidosis, blood products,
and adjuvant therapy showed a considerable amount
of regional as well as institutional variability. Forty-
five percent of the respondents claimed to follow a MT
protocol in their institution, 19% reported inconsistent
use, and 34% did not use a protocol at all for massive
transfusion. Interestingly, only very few MT protocols
specifically addressed the key issues recommended
by the current guidelines. The results from this survey
should draw more attention to the need for a more
common definition of ATC and more standardized
clinical protocols to ensure optimum patient care in
the acute phase after severe multiple injuries.
[53]
These
protocols should be based upon state-of-the art guidelines
and recommendations being subject to updating and
revision as important new evidence becomes available.
In conclusion, there is a high frequency of ATC
upon ER admission which is associated with signicant
morbidity and mortality in multiply injured patients.
The TASH-score is recognized as an easy-to-calculate
and valid scoring system to predict the individuals
probability for massive transfusion and thus ongoing life-
threatening hemorrhage at a very early stage after severe
multiple injuries. An early aggressive management of
ATC including a more balanced administration of blood
products to favor improved outcome should be proven in
a well-controlled clinical trial.
Funding: None
Ethical approval: The TR-DGU is approved by the review board of
www.wjem.org
20 World J Emerg Med, Vol 1, No 1, 2010 Maegele
the DGU and is in compliance with the institutional requirements.
Competing interest: There are no conicts of interest associated
with this article.
Contributors: Marc Maegele proposed the study and wrote the
paper. TR-DGU and TR-DGU afliated centers contributed to the
study.
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Received February 4, 2010
Accepted after April 25, 2010