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
22
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
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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; 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 al 16 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