concentrate or placebo. Plasma fibrinogen
concentrations remained higher in the fibrinogen
concentrate group up to 12h after admission.
Mortality and thromboembolic complications
were similar between groups. 31
potentially counteract low platelet counts, by
increasing overall clot firmness. 29 Velik-Salcher et
al investigated the effect of fibrinogen
concentrate transfusion on blood loss in a
thrombocytopenic swine model (target platelet
count < 30,000/µl). Transfusion of fibrinogen
concentrate (250mg/kg body weight) resulted
in lower blood loss and improved survival rate
compared with transfusion of 2U of PC. 29 In
situations where platelet count is low or platelet
function is compromised and PCs are not
available, high fibrinogen supplementation might
be considered as a treatment option. 30
Thrombin generation is initially not
deficient in major trauma
Compromised thrombin generation does not
appear an initial problem in the early stages of
TIC. 32,33 Therefore thrombin-generating
coagulation factors such as prothrombin complex
concentrate (PCC) are not advocated as first-line
therapy in trauma. 34 Importantly, prolonged
standard coagulation tests such as international
normalised ratio (INR), prothrombin time (PT),
activated partial thromboplastin time, ROTEM
clotting time or TEG r- and k-time do not
sufficiently reflect impaired thrombin production.
For example, Dunbar and Chandler reported 15
trauma patients with prolonged PT and INR
suggestive of TIC. Even though PT was >18 sec
and INR was >1.5, thrombin generation was
three-fold higher compared with controls
(p=0.01). 32
Fibrinogen supplementation
Nascimento et al randomised 50 hypotensive
adult trauma patients to either 6g fibrinogen
In severe bleeding trauma
patients, fibrinogen is the
first coagulation factor that
reaches critical low levels
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
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
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