REVIEW

CURRENT
OPINION Acute coagulopathy in pediatric trauma
Pamela M. Choi and Adam M. Vogel

Purpose of review
To summarize our current understanding of the pathophysiology, diagnosis, and management of acute
traumatic coagulopathy in children.
Recent findings
Traumatic coagulopathy is a complex process that leads to global dysfunction of the endogenous
coagulation system and results in worse outcomes and increased mortality. Although the cause is
multifactorial, it is common in severely injured patients and is driven by significant tissue injury and
hypoperfusion. Viscoelastic coagulation tests have been established as a rapid and reliable method to
assess traumatic coagulopathy. Additionally, massive transfusion protocols have improved outcomes in
adults, but limited studies in pediatrics have not shown any difference in mortality.
Summary
Prospective studies are needed to determine how to best diagnose and manage acute traumatic
coagulopathy in children.
Keywords
coagulopathy, resuscitation, thromboelastography, transfusion, trauma

INTRODUCTION results from the adult trauma literature. Despite

Trauma is a leading cause of morbidity and
mortality in children, and is a significant public
health concern [1]. Acute coagulopathy of trauma
is an ill-defined but well-described phenomenon of
multifactorial cause that is very common in severely
injured patients and is strongly associated with
increased morbidity and mortality [2–5,6 ]. The
&
identification and management of this coagulop-
athy is a critical component of the resuscitative
effort.
Although traumatic coagulopathy has been
established as an indicator of poor outcomes, many
questions remain regarding its pathophysiology,
diagnosis, and treatment. Unfortunately, the
majority of literature on this subject is a product
of the adult trauma population. Children are not
‘little adults’ and have unique and age-dependent
physiologic hemodynamic and hemostatic charac-
teristics that may make translating the results of
adult data on traumatic fluid resuscitation and
massive transfusion to children challenging. With
respect to hemostasis, pediatric patients exhibit age-
dependent variation in coagulation factor profiles
and function that has been termed ‘developmental
hemostasis’ [7]. Although a child’s coagulation
system is fully functional at birth, these variations
may lead to confusion when interpreting laboratory
these limitations, the adult literature forms the
backbone of our understanding of coagulopathy
of trauma and must be considered in order to pro-
vide a more complete discussion of coagulopathy in
pediatric trauma. The purpose of this review is to
describe the recent developments in our under-
standing of acute traumatic coagulopathy in both
adults and children, and how these developments
impact the management of critically ill pediatric
trauma patients.
EPIDEMIOLOGY AND SIGNIFICANCE
Acute traumatic coagulopathy is extremely com-
mon. One prospective single-center study found
that 56% of 45 adult trauma patients had coagul-
opathy within 25 min after injury, whereas another
Division of Pediatric Surgery, Department of Surgery, St Louis Children’s
Hospital, Washington University School of Medicine, St Louis, Missouri,
USA
Correspondence to Adam M. Vogel, MD, St Louis Children’s Hospital,
One Children’s Place, Suite 5S40, St Louis, MO 63110, USA. Tel: +1
314 454 6022; fax: +1 314 454 2442; e-mail: vogelam@wudosis.
wustl.edu
Curr Opin Pediatr 2014, 26:343–349
DOI:10.1097/MOP.0000000000000086

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 Surgery
KEY POINTS
 Traumatic coagulopathy is a complex process of
multifactorial cause that is commonly seen in critically ill
patients, especially in those with acidosis, shock,
severe injuries, and traumatic brain injury, and is
independently associated with mortality.
 The benefits of viscoelastic coagulation tests such as
thromboelastography are its point-of-care availability
and the ability to convey rapid and reliable data that
aids in goal-directed hemostatic resuscitation.
 Massive transfusion protocols with high ratios of plasma
and platelets to packed red blood cells have improved
outcomes in adult trauma patients; however, further
prospective trials are needed in the
pediatric population.
study found that 77% of 102 pediatric patients had
abnormal prothrombin time (PT) or partial throm-
boplastin time (PTT) levels upon arrival at the hos-
&
pital [6 ,8]. A 10-year retrospective review of 803
pediatric trauma patients found that 37.9% of those
admitted to the ICU had coagulopathy [defined as
an International Normalization Ratio (INR)
1.2]
&
[9 ].
Several adult studies have identified the risk
factors for acute traumatic coagulopathy, including
penetrating injury, traumatic brain injury (TBI),
&&
injury severity, and shock [4,10 ]. Similar risk fac-
tors are seen in the pediatric population. A review of
200 pediatric patients from a European trauma regis-
try showed that coagulopathy was present in 44% of
&
patients with severe isolated TBI [11 ]. Similarly, a
single-center retrospective review showed that coa-
gulopathy is present in 42% of children presenting
with severe TBI [12]. Injury Severity Score (ISS),
hypotension, acidosis, and nonaccidental trauma
were also associated with coagulopathy in pediatric
& &
trauma [5,6 ,9 ].
Traumatic coagulopathy is an independent pre-
dictor of mortality. Coagulopathic (defined as
admission INR >1.5) adult patients in a combat
hospital were found to have an increased mortality
rate of 24%, compared with 4% in noncoagulo-
pathic patients, and had an increased relative risk
of death of 5.4 [4]. Coagulopathy is also associated
with higher transfusion requirements, greater inci-
dence of multiorgan dysfunction syndrome, and
longer ICU and hospital length of stay as well as a
&&
four-fold increase in mortality [10 ].
A review of 744 pediatric combat casualties with
early coagulopathy (defined as admission INR >1.5)
had a mortality rate of 22% compared with 3.9% in
those who did not have an early coagulopathy [5].
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Studies in civilian trauma centers have found similar
results. In a 10-year retrospective review of pediatric
trauma patients, a direct relationship was found
between mortality rate and initial INR, as mortality
reached nearly 70% in those with an admission INR
greater than 1.8. Another study found a similar
relationship between increased PT and mortality,
and also found that 96% of all deaths occurred in
pediatric trauma patients with abnormal coagulation
studies on presentation to the emergency depart-
&
ment [6 ]. Coagulopathy was also found to be inde-
pendently associated with longer ventilator days as
& &
well as longer ICU and hospital length of stay [6 ,9 ].
PATHOPHYSIOLOGY OF TRAUMATIC
COAGULOPATHY
The pathophysiology of acute traumatic coagulop-
athy is a result of an imbalance between procoagulant
factors, anticoagulant factors, platelets, endothelial
&&
components, and fibrinolysis [13 ]. Hemorrhage
and tissue damage are the initiating factors for the
coagulation cascade and thrombin formation, but are
also believed to be the causative factors behind
trauma-induced coagulopathy. Tissue injury results
in the exposure of collagen as well as tissue factor to
initiate the intrinsic and extrinsic pathways, result-
ing in the consumption of factors (Fig. 1). However,
traumatic coagulopathy does not occur with tissue
injury alone [15] and requires hypoperfusion.
Hypoperfusion stimulates the endothelium to
release thrombomodulin, which interacts with
thrombin to activate protein C [16]. Activated
protein C inactivates factors V and VIII, leading to
hypocoagulation, and consumes plasminogen acti-
vator inhibitor-1 (PAI-1), which is an antagonist of
tissue-type PAI-1 (t-PA). The resulting increase in t-
PA leads to hyperfibrinolysis [16,17]. This is evident
clinically as fibrinogen concentrations decrease
after injury [18,19]. A review of pediatric trauma
patients requiring transfusions found hypofibrino-
genemia in 52% [6 ].
&
Hemorrhagic shock results in an increased intra-
vascular osmotic pressure and a shift of fluid into the
intravascular space. This physiologic dilution of
coagulation factors results in a net reduction in
&&
coagulation activity [10 ]. An iatrogenic dilution
may also be caused by overadministration of fluids
in the acute treatment of trauma.
Tissue hypoperfusion also leads to metabolic
acidosis, which contributes to coagulopathy by
decreasing the rate of coagulation factor biochemical
reactions. An acidosis of a pH of 7.2 decreases the
coagulation factor and complex activity by 50% [14].
Animal models of hemorrhagic shock have also
shown that resuscitation with normal saline worsens
Volume 26  Number 3  June 2014
 Acute coagulopathy in pediatric trauma Choi and Vogel

Contact activation (intrinsic) pathway Tissue factor (extrinsic) pathway

Damaged surface Trauma

XII XIIa VIIa VII

XI XIa Tissue factor

IX IXa VIIa-tissue factor complex

VIII VIIIa

X X

Activated protein C
Xa
Protein S V Va

Protein C + thrombomodulin Xa/Va prothrombinase-complex

Prothrombin (II) Thrombin (II)

Fibrinogen (I) Fibrin (Ia)

t-PA
PAI-1
Plasminogen Plasmin

Fibrin degradation Cross linked

products fibrin clot
(d-dimers)

FIGURE 1. Coagulation cascade and impairments caused by acidemia. Boxed figures represent factors and complexes in
which activity is significantly decreased by acidemia. Dashed lines represent inhibition of reactions. Adapted and modified
from [14]. PAI-1, plasminogen activator inhibitor-1; tPA, tissue-type PAI-1.

acidosis by contributing to a nonanion gap metabolic complex disequilibrium of traumatic coagulopathy

acidosis over lactated Ringer’s, which is pH neutral
[20]. Animals treated with normal saline were also
more coagulopathic with greater overall blood loss
than those treated with lactated Ringer’s [21]. Hypo-
thermia, caused by shock, exposure, and large
volume resuscitation, also exacerbates coagulopathy
by a similar mechanism. For every 18C drop in
temperature, clotting activity is slowed by approxi-
&&
mately 5% [10 ].
Although platelet counts are mildly reduced by
trauma, they do not fall to levels that would be
expected to significantly contribute to coagulop-
&&
athy [13 ,22]. However, platelet function as deter-
mined by viscoelastic monitoring was found to be
significantly impaired in trauma patients [23]. Pro-
spective data has shown that platelet dysfunction is
an independent predictor of mortality despite reas-
suring platelet counts [24].
DETECTION OF COAGULOPATHY
The majority of research conducted on traumatic
coagulopathy is based on conventional coagulation
tests (CCTs) such as PT, INR, or PTT. However, these
CCTs have come under scrutiny as they were origin-
ally designed for the management of hemophilias as
well as to guide anticoagulation therapy. CCTs have
been shown not to adequately characterize the
[25–27]. A recent prospective study showed that INR
values did not adequately reflect coagulopathy in
stable adult trauma and surgical patients [28]. These
tests also require more time to process before results
&
are available [2,29 ].
Goal-directed hemostatic resuscitation utiliz-
ing near real-time assessment of hemostasis and
coagulopathy along with massive transfusion pro-
tocols (MTPs) has gained widespread acceptance in
the management of coagulopathic adult trauma
patients [30–33]. Thromboelastography (TEG), a
point-of-care measure of hemostasis that evaluates
the global viscoelastic mechanical properties of
whole blood, has been shown to be an accurate
measure of the acute coagulopathy of trauma [2,34].
The two most commonly used assays are TEG
and rotational thromboelastometry (ROTEM). In
TEG, a small sample of whole blood is pipetted
into a cuvette and activated with a reagent (most
commonly kaolin). The sample is placed into the
thromboelastograph machine, in which the cuvette
oscillates. A pin suspended in the blood sample
transduces the viscoelastic mechanical properties
into a graphical tracing, and computational algor-
ithms generate individual data points. In ROTEM,
&
the pin oscillates instead of the cuvette [35 ]. Rapid
TEG (rTEG) uses tissue factor in addition to accel-
erate activation of the clotting cascade and has been

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 Surgery
found to be the most rapid coagulation study avail-
able, as meaningful results may be available within
5–15 min as opposed to CCTs, which take approxi-
mately 30–48 min [34,36].
The TEG tracing provides information regarding
multiple aspects of the coagulation cascade (Fig. 2).
The r-value or activated clotting time (in rTEG) is the
time between test initiation and fibrin formation
(representative of clotting factor function). The
k-time is indicative of hypofibrinogenemia or
platelet deficiency. The a-angle is the rate of clot
formation and decreases with hypofibrinogenemia
or platelet deficiency. The maximal amplitude (MA)
represents the platelet contribution to clot strength,
whereas the percentage of clot lysis at 30 min (LY30)
represents fibrinolysis. Detailed reviews of viscoelas-
tic monitoring have been previously published
& & & &
[26–28,29 ,30–34,35 ,36,37 ,38 ].
In adults, TEG values have been shown to be
rapidly available, to correlate with CCTs, and to be
predictive of early blood cell, plasma, and platelet
& &
transfusion [29 ,34,37 ]. TEG values are also useful
in predicting substantial bleeding and the need for
massive transfusion, and are independent predictors
of early mortality. Adult patients sustaining pene-
trating trauma who have received TEG-guided
resuscitation have been found to have decreased
mortality compared with those who received a
&
standardized MTP [38 ].
As mentioned earlier, hyperfibrinolysis has also
been determined to be a component of traumatic
coagulopathy. The clinical randomization of an
antifibrinolytic in significant hemorrhage study, a
large randomized controlled trial of adult trauma
patients with significant hemorrhage, established
Clot strength
LY30
MA
α Angle
Time
R K 30 min
ACT
Coagulation Fibrinolysis
FIGURE 2. Rapid TEG tracing. TEG, thromboelastography.
Data from Vogel et al. [35 ]. &
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the significance of fibrinolysis in coagulopathy as
treatment with tranexamic acid (a synthetic anti-
fibrinolytic agent) significantly reduced mortality
[39]. However, CCTs do not adequately reflect
fibrinolysis, although this is represented by the
LY30 value of TEG. Adult patients with abnormal
LY30 values have been associated with increased
injury severity, acidosis, increased transfusion, and
&
mortality [40,41 ].
In children, a recent retrospective study
reviewed the use of rTEG in 86 severely injured
pediatric patients. Admission rTEG values were
found to be predictive of the need for packed red
blood cells (PRBCs) and fresh frozen plasma (FFP)
transfusion within 6 h, life-saving interventions, as
&
well as increased odds of mortality [35 ]. Unfortu-
nately, a prospective evaluation of goal-directed
hemostatic resuscitation in traumatically injured
children at risk for acute coagulopathy of trauma
has not yet been performed.
RESUSCITATION
A timely, appropriate, and adequate hemodynamic
and hemostatic resuscitation is required to
minimize morbidity and mortality in critically ill
traumatically injured patients. The pathology of
traumatic coagulopathy implies that this resuscita-
tive effort should be directed to correct specific
impaired or depleted factors. The comprehensive
nature of viscoelastic monitoring tests such as TEG
allows a more specific goal-directed hemostatic
resuscitation. However, these tests have yet to
be adopted in many centers. Additionally, the
fact that infusion of crystalloid products or PRBCs
without co-infusion of platelets or FFP worsens
coagulopathy may further complicate resuscitative
&&
efforts [10 ].
With this in mind, the use of MTP has become
widespread in an effort to minimize coagulopathy,
as it allows the replacement of coagulation factors
and platelets early in the resuscitation process. A
retrospective review of adult combat patients who
received massive transfusions found that patients
who received a high ratio of FFP to PRBC (1 : 1.4)
were associated with the lowest mortality rate [42].
Another military study of 466 civilian trauma
patients also found increased survival in patients
with high plasma and platelet-to-PRBC transfusion
ratios (
1 : 2) as well as increased ICU, ventilator,
and hospital-free days [43]. This study ultimately
recommended a plasma : platelet : PRBC ratio of
1 : 1 : 1. Since then, research in the adult civilian
population has consistently shown improved out-
comes when plasma and platelets are transferred in
higher ratios with PRBCs [44–46].
Volume 26  Number 3  June 2014

Unlike adults, children are better able to tolerate
blood loss because of their substantial physiologic
reserve. As such, the needs of massive transfusion
are believed to be different than in adults [47].
Compared with the adult literature, there is limited
data on the use of MTP in pediatric trauma. A single-
center prospective study compared pediatric patient
outcomes before and after MTP was initiated. The
MTP was designed with a goal FFP : PRBC ratio of
1 : 1. Although MTP patients received twice the ratio
of platelets compared with the pre-MTP cohort, the
actual ratio MTP patients received was 1 : 1.8.
Additionally, there were no differences in overall
&
mortality [48 ].
Another single-center prospective study in chil-
dren described the use of an MTP with a 1 : 1 : 1 ratio
of PRBC, FFP, and platelets with broad therapeutic
goals of maintaining platelets greater than 50 000/
ml, hemoglobin greater than 10 mg/dl, and normal-
ization of PT, PTT, fibrinogen, and fibrin degra-
dation products. The MTP group was likely to be
more severely injured and consumed a higher over-
all amount of blood products. The non-MTP group
had a higher thromboembolic complication rate;
however, there were no differences in mortality.
The cohort included 55 patients and the investi-
gators noted that the actual ratio of FFP to PRBC was
1 : 3. This ratio was presumably the result of a delay
in obtaining thawed FFP compared with the more
readily available rapidly warmed PRBCs. As such,
there was actually no difference in the FFP-to-PRBC
ratio in the MTP group and the non-MTP group [47].
A recent retrospective review examined the
impact of blood product ratios in pediatric trauma
patients requiring massive transfusions, defined as
greater than 50% total blood volume within 24 h of
admission. Over a 7-year study period, 105 massive
transfusion patients were identified. Ultimately, the
ratios of FFP to PRBC and platelets to PRBC were not
found to impact mortality. In other words, high
ratios of plasma and platelets were not found to
increase survival. However, as a retrospective study,
patients received a wide range of ratios as trans-
fusions were determined by physician choice rather
than protocol. Additionally, all patients who died
suffered from severe head trauma, and so these
deaths were secondary to brain injury rather than
&
hemorrhage [49 ].
Adult studies have shown that factor VII has
decreased blood product requirement without dem-
onstrating any change in mortality [50–53]. In
pediatrics, factor VII has been found to be well
tolerated [54,55] and has resulted in decreased hem-
orrhage in cardiac surgery patients with preexisting
congenital coagulopathies [56,57]. The use of factor
VII in pediatric trauma patients has been limited to a
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Acute coagulopathy in pediatric trauma Choi and Vogel
few case reports of cerebral injury, in which admin-
istration of factor VII corrected the coagulopathy
fast enough to proceed with invasive neurosurgical
procedures [58,59]. A case report of a 5-year-old
boy with a grade 4 liver injury and right common
hepatic artery laceration also describes successful
TEG-guided resuscitation, including factor VII
administration, which resulted in discharge of the
patient from the hospital within 13 days [60].
CONCLUSION
Traumatic coagulopathy is the result of severe injury
and hemorrhage, and is an independent indicator of
poor outcomes. The use of viscoelastic monitoring
such as TEG offers a promising new diagnostic
modality, but its ability to improve the outcomes
in pediatric trauma has not yet been proven.
Additionally, although MTP have decreased mor-
tality in adults, the same benefits have not been
shown in children. Incorporating ‘real-time’ visco-
elastic hemostatic monitoring into MTP in a hybrid
resuscitation model may represent an optimal
treatment paradigm for managing coagulopathic,
critically ill trauma patients. Given the limitations
of present research on traumatic coagulopathy in
the pediatric population, prospective studies are
needed to better determine the guidelines for diag-
nosis and management.
Acknowledgements
None.
Conflicts of interest
There are no conflicts of interest.
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