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Review Article
Management of traumatic haemorrhage – the European
perspective
H. Sch€ochl,1 W. Voelckel2 and C. J. Schlimp3
1 Consultant, 2 Head of Department, Department of Anaesthesiology and Intensive Care, AUVA Trauma Centre,Salzburg, Austria3 Consultant, Ludwig Boltzmann Institute for Experimental and Clinical Traumatology, AUVA Research Centre,Vienna, Austria
SummaryTrauma-induced coagulopathy represents a life-threatening complication in severely injured patients. To avoid ex-
sanguination, rapid surgical bleeding control coupled with immediate and aggressive haemostatic treatment is man-
datory. In most trauma centres, coagulation therapy is established with transfusion of high volumes of fresh frozen
plasma. Due to logistic issues, only busy trauma facilities store pre-thawed plasma ready for immediate transfusion.
Thus, substantial time delays have been reported between the first unit of red blood cells transfused and the adminis-
tration of fresh frozen plasma. An alternative for rapid improvement of haemostatic capacity is purified coagulation
factor concentrates. They contain a well-defined concentration of coagulation proteins, carry a low risk for transfu-
sion-related lung injury and virus transmission, and are available for immediate use without the need for blood
group matching. In some European trauma centres, treatment algorithms have been developed for the administration
of coagulation factor concentrates based on visco-elastic test results..................................................................................................................................................................
Correspondence to: H. Sch€ochl; Email: [email protected]; Accepted: 9 September 2014
IntroductionExsanguination represents a significant cause of
Sch€ochl et al. | Coagulation factor concentrates in trauma in Europe Anaesthesia 2015, 70 (Suppl. 1), 102–107
immediate use [37–39]. Moreover, high volume plasma
transfusion may be accompanied by significant side
effects, such as acute lung injury, sepsis and multiple
organ failure [40].
Concept of goal-directed coagulationtherapy based on visco-elastic testresultsThe concept of individualised, goal-directed coagula-
tion therapy is based on the ability of visco-elastic tests
to rapidly diagnose the underlying coagulation disor-
der. Purified coagulation factor concentrates serve as
haemostatic components, which can be applied accord-
ing to the actual deficiencies of the patient. Compared
with FFP, coagulation factor concentrates have several
advantages: they can be stored in the emergency room;
they are available for immediate use; they contain a
well-defined concentration of coagulation proteins;
they do not require cross-matching before application;
and they carry only minimal risk of infection, transfu-
sion-associated cardiac overload and transfusion-
related acute lung injury. Essentially, three treatment
steps/options for different pathologies of TIC can be
addressed:
Inhibition of (hyper) fibrinolysis – improvementof clot stabilityHyperfibrinolysis is integral to major trauma. Recent
studies indicated that even low-grade fibrinolysis (> 3%)
detected by visco-elastic tests are associated with an
increased tendency to bleed, higher transfusion require-
ments, and higher mortality rate, compared with trauma
patients without any lysis [41–44]. Currently available
visco-elastic tests have inadequate sensitivity to detect
small increments in pro-fibrinolytic activation [45–47].
Thus, antifibrinolytic therapy should be initiated based
on pragmatic clinical aspects, such as pronounced
shock, hypothermia and substantial tissue trauma rather
than guided by visco-elastic tests (Figs. 1 and 2) [48].
Tranexamic acid allows sufficient and cost-effective
inhibition of fibrinolysis. Data derived from the Crash-
2 study indicated that, compared with placebo, early
application of tranexamic acid reduced the risk of death
in trauma patients by 1.5% (p = 0.0035) [49]. Notably,
a post-hoc analysis of the Crash-2 database discovered
that tranexamic acid administered beyond 3 h follow-
ing injury increased mortality [50]. Thus, early applica-
tion of tranexamic acid is recommended [51]. In
military emergency resuscitation, tranexamic acid
therapy resulted in a reduction in overall mortality
rates of 6.5% compared with the placebo group
(a)
(b)
(c)
(d)
Figure 1 Examples of ROTEM analyses of patientsadmitted to the emergency room. Panel a: normal RO-TEM results. Panel b: poor fibrin polymerisation: Sig-nificantly reduced FIBTEM A10 (6 mm) and reducedEXTEM A10 (36 mm); EXTEM CT is normal. Thisfinding may be an indication to increase fibrinogenconcentration. Panel c: thrombocytopenia: EXTEMA10 is diminished (< 41 mm) and FIBTEM A10 is inthe normal range. This can be interpreted as an indi-cation for platelet concentrates. Panel d: global severecoagulopathy: The CT and CFT in EXTEM are signifi-cantly extended and the A10 in both EXTEM(24 mm) and FIBTEM (4 mm) are massively reduced.A10 (20), clot amplitude after 10 (20) min runningtime; alpha, alpha angle; CFT, clot formation time; CT,clotting time; EXTEM, extrinsically activated test; FIB-TEM, fibrin polymerisation test (extrinsically activatedtest with additional inhibition of platelet componentby cytochalasin D); MCF, maximum clot firmness
gen concentration on hospital arrival is associated with
an increased risk of diffuse microvascular bleeding,
high hazard for massive transfusion, and is strongly
linked to higher mortality rates [53, 60]. Schlimp et al.
investigated 675 trauma patients and found that criti-
cally low fibrinogen (< 1.5 g.l�1) on admission to the
emergency room strongly correlated with shock severity
as determined by low base excess, low haemoglobin,
and high injury severity score [61]. Maintaining fibrin-
ogen levels appears to positively influence the mortality
of trauma patients. A retrospective study, including 252
massively transfused casualties, indicated that adminis-
tration of high total amounts of fibrinogen were associ-
ated with improved survival rates [62]. Morrison et al.
investigated the impact of fibrinogen-containing cryo-
precipitate in addition with tranexamic acid on survival
in severely injured combat casualties. Tranexamic acid
and cryoprecipitate were independently associated with
a similarly reduction in mortality, suggesting a central
role for fibrinogen in trauma-related bleeding [63].
Importantly, the combination of both tranexamic acid
and cryoprecipitate yielded the best survival rate.
The concentration of fibrinogen in both FFP and
solvent-detergent plasma varies between 2.0 and
2.9 g.l�1 [33, 34, 64]. Thus, large quantities of plasma
are required to sufficiently increase plasma fibrinogen
levels [65]. Clinical studies have revealed that transfu-
sion of red cells and FFP in a 1:2 ratio was insufficient
to preserve fibrinogen concentration in multiple trans-
fused recipients. Only additional supplementation with
cryoprecipitate resulted in maintenance of an adequate
fibrinogen content [60]. Consequently, the recent
European guidelines for massive trauma-related bleed-
ing recommend fibrinogen concentrate (3–4 g) or
cryoprecipitate (50 mg.kg�1) to restore appropriate
plasma fibrinogen levels [51]. According to our institu-
tional algorithm, fibrinogen concentrate should be
administered to bleeding patients if clot amplitude in
the FIBTEM assay after 10 min running time (A10) is
< 7 mm. We aim for an A10 target level of 10–12 mm
(Fig. 3) [66].
(a) (b)
Figure 2 ROTEM traces showing hyperfibrinolysis ina patient with severe trauma and shock on admissionto the emergency room. Note the typical spindle of theEXTEM, INTEM and FIBTEM tracing. The in vitroaddition of aprotinin (APTEM test: extrinsically acti-vated test with aprotinin) fully inhibits hyperfibrinoly-sis resulting in a stable clot. Coagulation therapy withtranexamic acid is indicated.
Sch€ochl et al. | Coagulation factor concentrates in trauma in Europe Anaesthesia 2015, 70 (Suppl. 1), 102–107
Improvement in thrombin generationThrombin is the central enzyme of the whole coagula-
tion process and is paramount to the structure and
quality of the clot [67]. Immediately after injury,
thrombin generation is up-regulated and, with the
exception of seriously injured patients, is not an initial
problem at the time of admission to the emergency
room [68, 69]. The diagnosis of compromised throm-
bin formation remains challenging. Neither prolonged
PT or aPTT, nor an extended clotting time in visco-
elastic tests, sufficiently portrays the magnitude of
thrombin generation [68, 70]. Indeed, Dunbar and
Chandler found that trauma patients with prolonged
PT (> 18 s), which is suggestive of TIC, had a three-
fold higher thrombin generation compared with indi-
viduals with normal PT (p = 0.01) [68].
A number of animal studies have indicated that
administration of prothrombin complex concentrate
increased thrombin generation and decreased blood
loss in trauma-related bleeding compared with placebo
and recombinant factor VIIa [71–73]. To improve
thrombin generation, prothrombin complex concen-
trate is increasingly used in many European trauma
centres [74–78]. According to the treatment algorithm
developed by our group (Fig. 4), thrombin generation
should be augmented only if the ROTEM shows pro-
longed clotting time (EXTEM CT) > 80 s [15]. This
threshold is chosen because the EXTEM CT exceeds
the upper limit of 80 s when the activity of coagulation
factors is decreased to < 35% [79]. It should be noted
that administration of fibrinogen concentrate might
also result in a shortening of the EXTEM CT below
the threshold of 80 s due to higher availability of sub-
strate for initial clot formation. Therefore, we do not
recommend administration of prothrombin complex
concentrate before normalisation of the FIBTEM A10.
In a retrospective study of severely injured patients
who received ≥ 5 units of red cells within 24 h,
favourable outcomes were reported after ROTEM-
guided haemostatic therapy with fibrinogen concen-
trate (median dose 6 g) and prothrombin complex
concentrate (median dose 1800 U). The observed mor-
tality was lower than predicted by the Revised Injury
(a) (b)
Figure 3 ROTEM analysis of major trauma patient(injury severity score 31) on admission to the emer-gency room. Panel a: significant reductions in EXTEMA10 (40 mm) and FIBTEM A10 (3 mm). Panel b: RO-TEM analysis following treatment with 5 g fibrinogenconcentrate. Note fibrinogen concentrate administra-tion resulted in a substantial improvement of clotamplitudes (A10, A20 and MCF) in both, EXTEM andFIBTEM and a normalisation of the EXTEM CT.
Figure 4 Treatment algorithm based on ROTEM testresults from AUVA Trauma Centre, Salzburg, Austria[84]. BGA, blood gas analysis; BW, body weight; CT,clotting time; FFP, fresh frozen plasma; ISS, injuryseverity score; ML, maximum lysis; PC, plateletconcentrate; PCC, prothrombin complex concentrate;TXA, tranexamic acid
Sch€ochl et al. | Coagulation factor concentrates in trauma in Europe Anaesthesia 2015, 70 (Suppl. 1), 102–107
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