Trauma
Coagulation factor
concentrates in trauma
Many trauma patients exsanguinate due to uncontrolled
haemorrhage and coagulopathy and prompt surgical control of the
source of bleeding and rapid haemostatic therapy are crucial
Herbert Schöchl MD
AUVA Trauma Centre
Salzburg, Austria; Ludwig
Boltzmann Institute for
Experimental Clinical
and Traumatology, AUVA
Research Centre, Vienna,
Austria
Trauma is the leading cause of death in the first
four decades of life. 1 Many of these patients
exsanguinate due to uncontrolled haemorrhage
and trauma-induced coagulopathy (TIC). 2 TIC
occurs early after severe injury and is associated
with a substantial increase in blood loss, higher
transfusion requirements and an approximately
four-fold higher mortality compared with
non-coagulopathic patients. 3,4 Prompt surgical
control of the bleeding source and rapid
haemostatic therapy is crucial in order to
optimise outcome.
Data suggest that early transfusion of high
ratios of plasma and platelet concentrate (PC),
predominantly in a fixed 1:1:1 ratio with red
blood cells (RBCs), is associated with improved
outcome in patients with severe trauma-related
bleeding. 5,6 Some European trauma units have
established a more targeted approach to treat
coagulopathic trauma victims. The concept of
a goal-directed and individualised haemostatic
therapy is largely based on visco-elastic test
results and consists of purified coagulation factor
concentrates (CFCs). 6–9
A confounder of poor outcome
A variety of studies revealed that TIC is an
important confounder of poor outcome. TIC
occurs early after severe injury and is associated
with a substantial increase in bleeding rate,
transfusion requirements and a four-fold higher
mortality. 3,10 Exsanguination is potentially
avoidable by rapid surgical bleeding control.
Additionally it is crucial to achieve optimal
haemostatic conditions in order to avoid further
blood loss. Therefore, early haemostatic therapy
might also minimise allogeneic blood transfusion
requirements, potentially avoiding massive
transfusion and thereby improving outcomes.
The first coagulation factor reaching critical
low levels
In the course of severe bleeding, coagulation
factors do not decrease simultaneously. In major
trauma, fibrinogen reaches critical low levels
earlier than any other coagulation proteins and
has been identified as the primary coagulation
factor deficiency in severe bleeding. 11
Hypofibrinogenemia upon admission to the
emergency room (ER) is an independent predictor
of poor outcome and is strongly related to the
severity of shock. 12–14 Fibrinogen plays a central
role in both primary and secondary haemostasis;
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it is not only the precursor of fibrin but is also
fundamental in aggregating and linking
platelets. 15 Activated platelets express surface
glycoprotein IIb/IIIa receptors that have a high
affinity to fibrinogen. 15
Floccard et al16 collected blood samples of
trauma patients at the scene of accident and
found a median fibrinogen concentration of 1.2g/l
in patients with an Injury Severity Score (ISS) >40.
A further significant drop of fibrinogen was
observed before ER admission. In a prospective
observational study including 1122 trauma
patients, Hagemo et al showed that fibrinogen
<2.3g/l resulted in a substantial increase in 28-day
mortality. 12 Schlimp et al analysed data from 675
trauma patients upon ER admission and observed
that fibrinogen strongly correlated with shock
severity. Patients admitted to the ER with a base
deficit >6mmol/l showed fibrinogen levels <2.0g/l
in 81% and fibrinogen concentrations of <1.5g/l in
63% of the cases.17 McQuilten et al reported an
adjusted odds ratio of 3.28 (95% CI 1.17–6.28,
p<0.01) for mortality when fibrinogen was <1g/l
upon ER admission compared with patients with
fibrinogen levels between 2 and 4g/l.13
Fibrinogen supplementation
Based on these findings, current European
guidelines on management of major bleeding
in trauma recommend supplementation of
fibrinogen when plasma concentrations are in
the range of 1.5 to 2.0g/l,18 although there is
currently little evidence to directly support this
recommendation. 19
Fibrinogen supplementation may be achieved
through transfusion of large volumes of fresh
frozen plasma (FFP), cryoprecipitate or fibrinogen
concentrate. The fibrinogen content of FFP is
relatively low (~2.5g/l).20,21 If FFP is transfused in
a 1:1 ratio with RBCs, it is almost impossible to
keep fibrinogen concentration above a threshold
of >1.5g/l, particularly in massively transfused
patients.20 Rourke et al reported that FFP and PC
were not sufficient to maintain fibrinogen
concentration above the recommended level of
1.5g/l; albeit with RBCs and FFP transfused in 1:2
ratios. In particular, patients who received >10
RBC had low (<1.5g/l) fibrinogen concentrations.
Only additional supplementation of
cryoprecipitate resulted in maintenance of
fibrinogen concentrations >1.5g/l. 22
To rapidly increase plasma fibrinogen levels,
European guidelines recommend either