Trauma
Augmentation of thrombin
generation
To increase thrombin generation, PCCs
and activated recombinant factor VII
(rFVIIa) have been studied in trauma-
related bleeding. 6,8,35–37 Two randomised
controlled studies failed to show
a survival benefit in trauma patients
receiving rFVIIa. 35,36
PCC preparations can be formulated
with either three factors (FII, FIX, FX) or
four factors (FII, FVII, FIX, FX). 38 Beyond
emergency reversal of vitamin K
antagonists, data on PCC use in trauma
are limited and prospective trials have not
yet been performed. 39–44
The European guidelines on
management of major bleeding and
coagulopathy following trauma
recommend administration of PCC
primarily for the emergency reversal of
vitamin K-dependent oral anticoagulation
and for treatment of Xa inhibitors. 18 In
bleeding trauma patients with thrombo-
elastometric signs of delayed initiation of
the coagulation process, PCC can be
considered. 18
Josef et al compared PCC
administration in coagulopathic (INR
>1.5) trauma patients with pelvic and
lower extremity fractures with patients
who were treated with FFP. Patients who
received PCC had faster correction of INR
and shorter time to surgical intervention
compared with patients who received
FFP. PCC therapy was also associated
“In severe bleeding
trauma patients,
fibrinogen is the first
coagulation factor
that reaches critical
low levels”
with lower overall blood product
requirements (p=0.02) and lower
transfusion costs (p=0.0001). 37
Trauma patients on vitamin K
antagonists and direct oral
anticoagulants
In another study, the same group
reported 45 trauma patients, 85% on
warfarin, who received 51 doses of PCC.
PCC application resulted in a rapid
correction in INR and reduction in blood
product transfusion. 39 Majeed et al
reported 84 bleeding patients under
rivaroxaban or apixaban who received
PCC at a median dose of 2000U for the
reversal. Intracranial haemorrhage was
the most common bleeding event,
followed by gastrointestinal bleeding.
PCCs were assessed as effective in 69.1%
of patients. 45
Currently, there are no studies
published on the effectiveness of PCC
in trauma patients on direct oral
anticoagulants (DOACs). 46 However, our
experiences with major trauma patients
on DOACs revealed that high doses of
PCC (50U/kg body weight) are necessary
to control bleeding.
Risk of thromboembolic events
Joseph et al reported an incidence of
thromboembolic events in the range of
6% after PCC administration in a
heterogeneous group of trauma patients. 47
Our group has shown that PCC
administration resulted in a substantial
and prolonged increase in endogenous
thrombin generation compared with
patients who received no coagulation
therapy or fibrinogen concentrate only. 48
PCCs are potent pro-coagulants and, as
such, the possibility of associated
thromboembolic complications should
be c onsidered carefully. 49 Robust safety
data related to PCC use in TIC are still
lacking.
Studies on the use of coagulation
factor concentrates in trauma
Data showing that fibrinogen
supplementation improves survival
in trauma patients are still limited. In
a retrospective study the administration
of fibrinogen concentrate along with PCC
(4 factor concentrate) resulted in
favourable survival rates compared with
those predicted by both the trauma injury
severity score and the revised injury
severity classification score. 6 Innerhofer
et al compared FFP transfusion versus
coagulation factor concentrate (fibrinogen
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