REVIEW

C URRENT
OPINION Point-of-care, goal-directed management of
bleeding in trauma patients
Johannes Zipperle a, Felix C.F. Schmitt b and Herbert Schöchl a,c

Purpose of review
The purpose of this review is to consider the clinical value of point-of-care (POC) testing in coagulopathic
trauma patients with traumatic brain injury (TBI) and trauma-induced coagulopathy (TIC).
Recent findings
Patients suffering from severe TBI or TIC are at risk of developing pronounced haemostatic disorders.
Standard coagulation tests (SCTs) are insufficient to reflect the complexity of these coagulopathies. Recent
evidence has shown that viscoelastic tests (VETs) identify haemostatic disorders more rapidly and in more
detail than SCTs. Moreover, VET results can guide coagulation therapy, allowing individualised treatment,
which decreases transfusion requirements. However, the impact of VET on mortality remains uncertain. In
contrast to VETs, the clinical impact of POC platelet function testing is still unproven.
Summary
POC SCTs are not able to characterise the complexity of trauma-associated coagulopathy. VETs provide a
rapid estimation of underlying haemostatic disorders, thereby providing guidance for haemostatic therapy,
which impacts allogenic blood transfusion requirements. The value of POC platelet function testing to
identify platelet dysfunction and guide platelet transfusion is still uncertain.
Keywords
mortality, platelet function testing, point-of-care viscoelastic testing, traumatic brain injury, transfusion, trauma

INTRODUCTION many guidelines recommend viscoelastic tests (VETs)

Severe traumatic brain injury (TBI) and exsanguina-
tion remain the leading causes of early trauma-
related mortality [1]. Importantly, patients with
both types of injury are prone to develop significant
coagulopathy [2,3]. A meta-analysis demonstrated
that coagulopathy is evident in more than 30% of
patients with severe TBI [4]. A similar incidence of
haemostatic disorders has been reported in major
trauma patients [5,6]. Both TBI-related coagulop-
athy and trauma-induced coagulopathy (TIC) are
strongly associated with poor outcomes [4,7]. Coa-
gulopathy in severe TBI develops as a consequence
of the release of procoagulant tissue factor from the
damaged brain into the blood stream [3]. TIC is a
complex haemostatic disorder driven primarily by
shock-related hypoperfusion, endothelial damage,
activation of profibrinolytic pathways and tissue
trauma [2,8].
Early diagnosis of the underlying coagulation
disorder is essential. Standard coagulation tests
(SCTs), which are still widely used to diagnose coagul-
opathy in trauma, are unable to reflect the complexity
of these haemostatic abnormalities. Consequently,
to diagnose trauma-related coagulopathy [9–11].
Platelet dysfunction has been reported in both TBI
and major trauma and is also associated with unfav-
ourable outcomes [12–14]. However, the value of
point-of-care (POC) platelet function testing to iden-
tify platelet dysfunction and guide platelet transfusion
is a lot more uncertain, compared to VETs [15,16].
To prevent or correct coagulopathy and mini-
mise further blood loss, early and goal-directed hae-
mostatic interventions are recommended by current
guidelines [9–11]. Many trauma centres worldwide
have established ratio-driven massive transfusion
a
Ludwig Boltzmann Institute for Traumatology, the Research Centre in
Cooperation with AUVA, Vienna, bDepartment of Anaesthesiology, Hei-
delberg University Hospital, Heidelberg, Germany and cParacelsus
Medical University, Salzburg, Austria
Correspondence to Herbert Schöchl, MD, Ludwig Boltzmann Institute
for Traumatology, the Research Centre in Cooperation with AUVA,
Donaueschingenstrasse 13, 1200 Vienna, Austria.
E-mail: herbert.schoechl@medical-education.at
Curr Opin Crit Care 2023, 29:702–712
DOI:10.1097/MCC.0000000000001107

www.co-criticalcare.com Volume 29
Number 6
December 2023

Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.

 Point-of-care, goal-directed management of bleeding in trauma patients Zipperle et al.
KEY POINTS

Point-of-care (POC) standard coagulation tests do not
reflect the complexity of coagulopathy driven by
traumatic brain injury and trauma-
induced coagulopathy.

Viscoelastic tests (VETs) provide a comprehensive
overview of the whole coagulation process and can
rapidly identify underlying haemostatic disorders.

VET results allow for targeted haemostatic therapy
according to the needs of individual patients.

Several studies have revealed that VET-guided
transfusion management resulted in a reduction of
allogenic blood transfusion requirements.

The impact of VET on trauma-related mortality is
less clear.

The value of POC platelet testing is unproven so far
and is therefore not recommended by
current guidelines.
protocols of red blood cells (RBCs), fresh frozen
plasma (FFP) and platelet concentrates (PCs) applied
in predefined ratios of 1 : 1:1 or 2 : 1:1 [17]. In some
European trauma centres, haemostatic therapy is
primarily guided by VET results, which serve as
the basis for tailored haemostatic interventions
according to the actual needs of individual patients
[18–20]. Nevertheless, the optimal approach coping
with coagulopathy in severe trauma remains con-
troversial [21,22]. Moreover, the most appropriate
triggers to start and stop a massive transfusion pro-
tocol and the best strategy to avoid both coagulop-
athy and over-transfusion are still being debated
[23–26]. The aim of this narrative review is to pro-
vide a comprehensive overview of the current
understanding and value of POC testing in TBI
and major trauma patients.
STANDARD COAGULATION TESTS
The value of point-of-care standard
coagulation tests
The coagulation status of severely injured patients is
still broadly assessed using SCTs, such as prothrom-
bin time ratio (PTr), international normalised ratio
(INR), activated partial thromboplastin time (aPTT)
and functional fibrinogen. Interestingly, a variety of
studies still define TIC as an INR >1.2 [27,28 ,29].
&&
Davenport et al. reported a low agreement with
laboratory PTr and POC PTr in patients with TIC,
with 29% of the results being false negatives [30]. In
contrast, Beynon et al. described a high correlation
1070-5295 Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.
Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.
between conventional INR assessment and POC
testing. For an INR cutoff value >1.3, the authors
demonstrated a high sensitivity (100%) and specif-
icity (98.7%) [31]. However, the ability of whole-
blood POC devices to accurately characterise TBI-
associated coagulopathy or TIC is limited.
Fibrinogen plays an essential role in both pri-
mary and secondary haemostasis and is probably the
most important coagulation protein [32]. In severely
injured patients, fibrinogen is the first coagulation
factor to reach critically low levels [33]. Moreover,
hypofibrinogenemia upon ER admission is associ-
ated with higher bleeding rates, increased allogenic
blood transfusion demands and poor outcome [34–
37]. A critical fibrinogen level associated with a
tendency towards increased bleeding is assumed
to be in the range of <1.5 g/l [34,35]. Consequently,
current guidelines recommend early fibrinogen sub-
stitution, particularly when levels decline below
1.5 g/l [9].
Thus, early detection of hypofibrinogenemia in
coagulopathic trauma patients is crucial. A newly
developed handheld POC-device (qLabs FIB, Micro-
point Bioscience, Santa Clara, CA) allows for rapid
assessment of functional fibrinogen concentration
from a single drop of citrated whole blood. A recent
study demonstrated a very strong correlation
between the qLabs FIB and Clauss fibrinogen
(r ¼ 0.95). A fibrinogen level >2.0 g/l was detected
with a sensitivity of 100% and a specificity 93.5%
[38].
The limitations of standard coagulation tests
SCTs capture only pro-coagulant pathways, leaving
anticoagulatory activation pathways unrecognized.
Moreover, SCTs identify only the very early phase of
the coagulation process, with the measurement ter-
minating after only 5–7% of the total thrombin
amount has been generated [39]. Subsequent ampli-
fication and propagation phases, as described by the
‘cell-based coagulation model’, are left undetected
[40]. Moreover, cellular components, such as eryth-
rocytes and platelets, which are indispensable for
sufficient haemostasis, are eliminated during the
centrifugation process [40]. Therefore, the value of
SCTs in predicting bleeding or transfusion require-
ments is limited [41–44].
VISCOELASTIC TESTING METHODS
Viscoelastic testing (VET) methods enable a rapid
and comprehensive assessment of the entire coag-
ulation process, from the initiation of coagulation
to the clot formation velocity and the strength of
the clot as well as the stability of the formed clot
www.co-criticalcare.com 703
The surgical patient

[45]. VETs were developed as POC monitors and test
results are typically available within minutes. Gratz
et al. demonstrated in a prospective study of severe
TBI cases that VET results were available in a median
time of 38 min earlier than SCT results (P ¼ 0.037)
&
[46 ]. In contrast to SCTs, VETs are performed in
whole blood and therefore corpuscular elements are
&
preserved [30,46 ].
Moreover, VET parameters can serve as guidance
for individualised haemostatic therapy according to
the patient’s actual deficiencies, avoiding unneces-
sary and potentially harmful exposure to allogenic
blood components [47,48].
Applied technologies for viscoelastic tests
Depending on the employed methods, either the
cup (TEG 5000, ClotPro [Haemonetics Corpora-
tion, Braintree, MA, USA]) or the pin (ROTEM
[Werfen, Barcelona, Spain]) continuously rotates
at an angle of usually, 4.758 to the left and right.
The formation of initial fibrin strands between the
pin and the cup wall diminishes the rotation angle,
depending on the increasing clot strength, which is
graphically represented as a curve over time
[45,49,50]. (Fig. 1) With these technologies, vari-
ous coagulation-relevant parameters can be
extracted (Table 1).
The cartridge-based system used in TEG 6S and
Quantra (HemoSonics, LLC, Durham, NC, USA)
applies different methodologies. TEG 6s exposes
coagulating blood to vibration frequencies and
measures the resonance frequency caused by the
motion of the blood meniscus [51,52]. Quantra is
based on sonic estimation of elasticity via resonance
(SEER), applying ultrasound to monitor changes in
the viscoelastic properties of the clot [53–55]. The
increasing clot stiffness reduces the induced vibra-
tion and can also be graphically displayed as a curve
over time [49,56] (Fig. 1).
The development and introduction of fully
automated, cartridge-based test systems (TEG 6s,
ROTEM sigma and Quantra), in which blood sam-
ples are automatically processed and mixed with
different activators, as well as systems that signifi-
cantly simplify the pipetting process (ClotPro) facil-
itate the diagnostic procedure and have now largely
eliminated the risk of operational errors [49,53,57].

FIGURE 1. The applied methology of ROTEM, ClotPro, TEG 5000, TEG6s and Quantra. All devices measure the viscoelastic
properties of a forming clot in citrated whole blood at a standardised temperature of 378C. TEG 5000 and ClotPro use a
rotating cup and a stationary pin, while ROTEM uses a rotating pin and a stationary cup. TEG6s and Quantra measure the
vibration frequency of a forming clot using ultrasound.

704 www.co-criticalcare.com Volume 29
Number 6
December 2023

Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.

 Point-of-care, goal-directed management of bleeding in trauma patients Zipperle et al.

Table 1. Assays available for TEG, ROTEM /ClotPro and Quantra

Name Activator Information

Intrinsic assays
INTEM (ROTEM) Ellagic acid Intrinsic coagulation factors (XII, XI, IX, VIII), heparin-
IN-test (ClotPro) sensitive
CK (TEG) Kaolin
(Quantra)
Extrinsic assays
EXTEM (ROTEM) Tissue factor Extrinsic coagulation factors (VII), low heparin-sensitivity
EX-test (ClotPro)
CRT Rapid TEG Kaolin þ tissue factor
Fibrin polymerization assays
FIBTEM (ROTEM) Cytochalasin Strength of the fibrin clot. Allows for the differential
diagnosis of a reduced clot amplitude in global tests
FIB-test (ClotPro) Cytochalasin þ tirofiban
Functional Fibrinogen (TEG) abciximab
Fibrinogen Contribution, FCS (Quantra)
Heparinase-Assays
HEPTEM (ROTEM) Intrinsically-activated test þ Allows to diagnose or exclude heparin effects in
HEP-test (ClotPro) heparinase intrinsic assays
CKH (TEG)
Heparinase Clot Time, CTH (Quantra)
Lysis-Tests
APTEM (ROTEM) Extrinsically-activated test þ Allows for the evaluation of fibrinolytic therapy
AP-test (ClotPro) tranexamic acid
t-PA-test (ClotPro) Extrinsically-activated test þ t-PA Activation of fibrinolysis for the detection of
antifibrinolytic therapies or fibrinolytic shutdown
DOAK-Tests
RVV-Test (ClotPro) Russell’s viper venom Prolongation of CT indicates the presence of a FXa
inhibitor
Eca-Test (ClotPro) Ecarin Prolongation of CT indicates the presence of a direct
Thrombin inhibitor

Available reagents for viscoelastic tests
Various activators and/or inhibitors support the
differential diagnosis of a possible underlying coag-
ulation disorder. Table 2 summarises the currently
available assays with their respective activation
pathways for TEG, ROTEM, ClotPro and Quantra.
However, the existing reagents provided for the
different devices vary considerably in terms of acti-
vation pathways, composition, and concentration
[49,53]. Consequently, established algorithms can-
not simply be transferred from one device to
another without adjustments [53,58].
Viscoelastic test parameters
The parameters delivered by the available devices are,
in principle, comparable but termed slightly differ-
ently (Fig. 2).
The diagnostic value of clotting time and
r-time
The ROTEM/ClotPro and Quantra clotting time (CT)
and the TEG r-time (RT) represents the time that
elapses from the addition of an activator to the
blood sample until the achievement of a predefined
threshold [clot amplitude (CA) of 2 mm for TEG,
ROTEM and ClotPro]. The CT/RT is the first avail-
able parameter and is influenced by the activity of
coagulation factors and inhibitors, such as heparin,
vitamin K antagonists and direct oral anticoagu-
lants. It is often overlooked that CT/RT is, to a large
extent, also dependent on the concentration of
available fibrinogen. In scenarios of low fibrinogen,
a CA of 2 mm might be reached only with a sub-
stantial time delay. In an ex vivo study Gratz et al.
demonstrated, that up to a dilution of 95%, the
ROTEM CT was significantly shortened with the

1070-5295 Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved. www.co-criticalcare.com 705

Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.

The surgical patient
Table 2. Nomenclature and parameters of TEG, ROTEM /ClotPro and Quantra
Parameter TEG5000/TEG6s
Initiation of coagulation
Time until clot amplitude r-time (reaction time, min)
reaches 2 mm
Kinetics of clot formation
Time between 2 mm and k-time (kinetic time, min)
20 mm of amplitude of
the forming clot
Clot strength
Clot amplitude (CA) after CA 10 (clot amplitude after
5/10 min running time 10, mm)
Maximum strength of the MA (maximum amplitude,
clot (mm) mm)
Clot lysis LY30/60 (lysis index,
Magnitude of clot lysis at a reduction of amplitude at
certain time point 30/60 min after MA, %)
use of fibrinogen concentrate (FC), which provides
the main substrate for clot formation. In contrast,
prothrombin complex concentrate (PCC), which
augments thrombin generation, had only minor
effects on the CT [59]. Comparable findings have
been reported in trauma patients treated with these
coagulation factor concentrates [60]. Therefore, to
correctly interpret CT/RT, simultaneous measure-
ment with a fibrin polymerisation test, such as
FIBTEM/FIB-test, TEG functional fibrinogen test
(FF) or Quantra FCS-test is required. Only when
the fibrin polymerisation amplitude is almost
normal (suggestive of normo-fibrinogenemia) and
CT/RT is still prolonged, this might be considered as
a hint of altered thrombin generation, which could
be augmented by PCC or plasma [9,59].
Clot firmness
The maximum clot strength (ROTEM/ClotPro MCF,
TEG MA or clot stiffness Quantra) results from the
interaction of platelets, the fibrin network and acti-
vated FXIII. The CA can be determined after 5–10 min
(CA5/10) and correlates well with the final maximum
clot strength [61–63]. Reduced CA is strongly associ-
ated with bleeding tendency, transfusion require-
ments and mortality in trauma patients [30,64–67].
The significance of fibrin polymerisation
assays
Fibrin polymerisation assays, such as ROTEM-FIB-
TEM, ClotPro FIB-Test, TEG functional fibrinogen
(FF) test and Quantra fibrinogen contribution to clot
firmness (FSC) test, provide an early estimation of the
fibrinogen concentration of trauma patients [65,68–
70]. A reduced CA in the fibrin polymerisation assays
706 www.co-criticalcare.com
Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.
ROTEM/ClotPro Quantra
CT (clotting time, s) CT (clot time, s)
CFT (clot formation time, s)
CA 5/10 (clot amplitude
after 5/10, mm)
MCF (maximum clot CS (clot stiffness, hPa)
firmness, mm)
CL30/45/60 (clot lysis, CSL (clot stability to lysis, the difference
amplitude 30/60/45 min between clot stiffness changes with and
after CT, %) without TXA, %)
is indicative of hypofibrinogenemia [69,71,72]. Cyto-
chalasin D, which is applied in the ROTEM FIBTEM
assays, is a more potent inhibitor of platelet contri-
bution to clot strength compared to abciximab, a
glycoprotein (GP) IIb/IIIa inhibitor, which is used
for the FF test of TEG and the FSC of Quantra [49].
The ClotPro FIB-test uses both, cytochalasin D and
the GPIIb/IIIa inhibitor tirofiban, in order to inhibit
platelet contribution to clot firmness. As fewer pla-
telets are inhibited with abciximab, the reference
range for the FF-test is significantly higher than it
is with the FIBTEM-test. Therefore, the correlation
between FF-test and fibrinogen concentration,
according to the Clauss method, is lower compared
to the cytochalasin D assays and plasma fibrinogen
[70,71,73,74]. After fibrinogen administration, the
CA10 in the FIBTEM/FIB-Test should reach a target
value of >12 mm or >20 mm for TEG FF [71].
Reduced clot amplitude due to diminished
platelet contribution
A reduced CA in standard VETs, with preserved
clot amplitude in the fibrin polymerisation tests,
corresponds to thrombocytopenia. If the FIBTEM/
FIB-Test threshold is >10 mm/12 mm or the FF MA
in TEG >20 mm, and the CA10 in standard tests
remains <40 mm, this may indicate thrombocyto-
penia and should trigger the administration of pla-
telet concentrates in bleeding patients [71].
The impact of hyperfibrinolysis
The definition of hyperfibrinolysis varies among the
available devices. For ROTEM/ClotPro, a maximum
lysis >15% is defined as hyperfibrinolysis [75]. For
TEG hyperfibrinolysis is defined as a reduction >3%
Volume 29
Number 6
December 2023
 Point-of-care, goal-directed management of bleeding in trauma patients Zipperle et al.

FIGURE 2. The viscoelastic test parameters of ROTEM, ClotPro (a) and TEG 5000/TEG6s (b). Both devices deliver
comparable parameters in seconds and mm, but they are labelled differently. Quantra uses hPa and different terms (c).

of the maximum clot amplitude 30 or 60 min after
reaching the MA (LY30/60). [76] Cotton et al.
observed that a LY30 >3% was associated with a
strong increase in mortality in major trauma
patients [77]. Existing hyperfibrinolysis with typical
‘diamond of death’ formation in VET is rare and is
associated with very high mortality rates in trauma
patients [77–79]. It is essential to note that the
absence of lysis signs in VETs does not rule out
profibrinolytic activation [75]. A ‘0-line’ in the fibrin

1070-5295 Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved. www.co-criticalcare.com 707

Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.

The surgical patient
FIGURE 2. Continued.
polymerisation assays is also a strong indicator of
hyperfibrinolysis [80]. So far, there is no evidence
that a ‘positive’ control applying a fibrinolysis
inhibitor (APTEM/AP test) provides any additional
diagnostic information.
A generalized step-wise treatment algorithm
according to VET findings is outlined in Fig. 3.
The effect of viscoelastic test on allogenic
blood transfusion
Many, although not all, studies have demonstrated
that treatment algorithms based on VET resulted in
reduced transfusion requirements in TIC [20,29,81–
86]. Two studies in trauma patients that compared
transfusion requirements before and after imple-
mentation of a TEG-guided resuscitation protocol
reported significantly lower RBCs and FFP transfu-
sion rates [82,83]. In a retrospective study, David
et al. reported that fewer patients treated according
to ROTEM test results received massive transfusions
compared to patients treated based on SCT results
(15% vs. 42%, P < 0.01). No significant difference
was observed in mortality rates [86]. ‘The reversal of
trauma-induced coagulopathy study’ (RETIC)
included trauma patients with established TIC
according to predefined ROTEM criteria (FIBTEM
A10 < 9 mm or EXTEM CT > 90 s) [20]. Coagulo-
pathic patients received either FFP (15 ml/kg body
weight) or fibrinogen concentrate and/or pro-
thrombin complex concentrate guided by ROTEM
708 www.co-criticalcare.com
Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.
parameters. Patients in the FFP group received
massive transfusions significantly more often than
patients in the ROTEM-guided group (30% vs. 12%;
P ¼ 0.042), but mortality rates were similar in the
two groups [20].
The effect of viscoelastic test on mortality
Only a few studies have reported survival benefits
when VETs have been applied [81,87,88]. In a retro-
spective study of 3320 patients, Lammers et al. dem-
onstrated a significant reduction in mortality with
the implementation of VETs in the management of
military trauma (VET group 7.3% vs. non-VET group
13.1%; P ¼ 0.001) [87]. Cochran et al. reported data
from a prospective study of major trauma patients one
year pre and one-year postimplementation of a TEG6s-
driven transfusion algorithm. Both at 24 h (13% vs.
5%; P ¼ 0.006) and at 30 days (25% vs. 11%; P ¼ 0.002),
mortality was significantly lower in the post-TEG
group. However, no difference in the number or ratio
of transfused blood products was observed [88].
In a prospective randomised controlled trial,
Gonzalez et al. compared a goal-directed haemostatic
resuscitation concept based on TEG test results with a
transfusion protocol guided by SCTs [81]. A signifi-
cantly lower 28-day mortality in the VET group was
found compared to the SCT-guided group (19.6% vs.
36.4%, P ¼ 0.049). The ‘implementing Treatment
Algorithms for the Correction of Trauma-
Induced Coagulopathy trial (iTACTIC) prospectively
Volume 29
Number 6
December 2023
 Point-of-care, goal-directed management of bleeding in trauma patients Zipperle et al.

FIGURE 3. Visco-elastic test algorithm for coagulopathic trauma resuscitation. Adapted from Inaba et al. [48]. CT, clotting
time; CA, clot amplitude; EX-test, extrinsically activated test; FC, fibrinogen concentrate; FIB-Test, fibrin polymerization test;
MCF, maximum clot firmness; PCC, prothrombin complex concentrate.

randomised coagulopathic trauma patients with The limitations of viscoelastic testing

established TIC to a VET-guided haemostatic therapy
group using ROTEM or TEG 5000 or to a group in
which SCTs were used as a guidance for coagulation
&&
management [28 ]. Both groups initially received a
fixed 1 : 1:1 ratio of RBCs, plasma, and platelets prior
to randomisation. After every transfusion of 4 U of
RBCs, coagulation analyses were performed and, on
top of the fixed ratio transfusion protocol, additional
haemostatic treatments were applied based on VET or
SCT results. A similar 28-day mortality rate and com-
parable transfusion requirements were observed.
However, in the predefined subgroup of patients with
severe TBI, a significant reduction in mortality in the
VET-guided group was demonstrated (P ¼ 0.016). An
important criticism of the study is that only 28.7% of
the recruited patients were coagulopathic according
methods
VET methods cannot adequately represent all
aspects of coagulation disorders. Deficiencies of
the von Willebrand factor (vWF) or factor XIII can-
not be detected by VETs. So far, only TEG provides
assays which allow to assess platelet dysfunctions
(TEG PM). Despite sound evidence, auto-heparin-
isation has been suggested as one potential driver
of TIC, and TEG has been considered as an option
to diagnose this phenomenon [92]. However, a
comparison between INTEM-CT, which should
be prolonged in the presence of heparin-like
substances, and HEPTEM-CT, which contains
heparin-inactivating heparinase, was not able to
demonstrate any differences in major trauma
patients prone to auto-heparinisation [93 ].
&

to accepted definitions and that all patients received

blood products in a fixed 1 : 1:1 ratio; thus, no indi-
vidualised coagulation therapy was applied [28 ].
&&
For patients with isolated TBI, the evidence for
improved outcomes with the application of VETs is
&&
less clear [28 ,89]. In a small before and after study
including patients with severe TBI, platelet trans-
fusion guided by TEG Platelet-Mapping (TEG PM)
was associated with improved survival rates [90].
However, others reported only limited effects of
TEG PM directed platelet transfusion on outcome
after major TBI [91].
PLATELET DYSFUNCTION IN TRAUMA
The value of platelet function testing in
trauma
In both, severe TBI and TIC, platelet dysfunction is
strongly associated with poor clinical outcomes
[12,13,94–98]. The precise mechanisms behind
trauma-related platelet inhibition are still not fully
understood. Despite this fact, the impact of platelet
function testing as an additive and helpful diagnostic

1070-5295 Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved. www.co-criticalcare.com 709

Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.

The surgical patient
tool for detection of platelet dysfunction has not
been conclusively demonstrated so far. Moreover,
the predictive value of POC platelet function testing
for perioperative bleeding and potential transfusion
requirements is poor [15,16,99–101]. To date, ther-
apy algorithms based on platelet function testing
have not produced convincing results [100,101].
Consequently, the current European guidelines on
managing major bleeding and coagulopathy follow-
ing trauma now advise against the routine use of POC
platelet function tests [9].
The limitations of point-of-care platelet
testing
Unlike VET methods, there is no accepted ‘gold
standard’ for POC platelet function testing. Both
the technological implementation and the applied
platelet agonists differ considerably between POC
platelet function analysers [102,103]. Importantly,
the available POC devices were primarily devel-
oped to assess the impact of platelet function inhib-
itors, such as aspirin or ADP antagonists, on
thrombocytes rather than to detect potential
bleeding due to trauma-induced platelet dysfunc-
tion [100]. Except for the Platelet Function Ana-
lyzer 100/200, only static measurement methods
are used. The shear forces, which are essential for
platelet activation, are therefore mostly not taken
into account [103]. Significant variability between
and within the applied tests has also been observed,
and the superiority of one POC device over another
has not been confirmed so far [103]. The wide-
spread use of platelet function testing in trauma
outside platelet inhibitor intake must be viewed
critically [104].
CONCLUSION
The value of POC SCTs such as PTr or INR in trauma
patients is largely unproven, and while data on
whole blood fibrinogen measurements are promis-
ing, no such data have been reported to date in
trauma patients. POC VETs are capable of character-
ising haemostatic deficiency and might serve as the
basis for individualised haemostatic intervention.
POC platelet function testing has not been stand-
ardised, and the impact on patient outcomes
remains to be elucidated.
Acknowledgements
None.
Financial support and sponsorship
None.
710 www.co-criticalcare.com
Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.
Conflicts of interest
J.Z. reports no conflicts of interest. HS has received
honoraria for participating in advisory board meetings
with Bayer Healthcare, Boehringer Ingelheim, Alexion
and Octapharm. He has also received speaker fees from
CSL Behring, Haemonetics, Bristol-Myers Squibb, Stago
and Vifor. FCFS has received research support from CSL
Behring and Philips, as well as speaker honorarium from
CSL Behring, LFB and AstraZeneca; he also acts as a
consultant on an advisory board for CSL Behring.
REFERENCES AND RECOMMENDED
READING
Papers of particular interest, published within the annual period of review, have
been highlighted as:
& of special interest
&& of outstanding interest
1. Oyeniyi BT, Fox EE, Scerbo M, et al. Trends in 1029 trauma deaths at a level 1
trauma center: impact of a bleeding control bundle of care. Injury 2017; 48:5–12.
2. Moore EE, Moore HB, Kornblith LZ, et al. Trauma-induced coagulopathy. Nat
Rev Dis Primers 2021; 7:30.
3. Maegele M, Schöchl H, Menovsky T, et al. Coagulopathy and haemorrhagic
progression in traumatic brain injury: advances in mechanisms, diagnosis,
and management. Lancet Neurol 2017; 16:630–647.
4. Harhangi BS, Kompanje EJ, Leebeek FW, Maas AI. Coagulation disorders
after traumatic brain injury. Acta Neurochir (Wien) 2008; 150:165–175;
discussion 175.
5. MacLeod JB, Lynn M, McKenney MG, et al. Early coagulopathy predicts
mortality in trauma. J Trauma 2003; 55:39–44.
6. Khan S, Brohi K, Chana M, et al. Hemostatic resuscitation is neither hemo-
static nor resuscitative in trauma hemorrhage. J Trauma Acute Care Surg
2014; 76:561–567; discussion 567–68.
7. Brohi K, Singh J, Heron M, Coats T. Acute traumatic coagulopathy. J Trauma
2003; 54:1127–1130.
8. Duque P, Calvo A, Lockie C, Schöchl H. Pathophysiology of trauma-induced
coagulopathy. Transfus Med Rev 2021; 35:80–86.
9. Rossaint R, Afshari A, Bouillon B, et al. The European guideline on manage-
ment of major bleeding and coagulopathy following trauma: sixth edition. Crit
Care 2023; 27:80.
10. Wiegele M, Schöchl H, Haushofer A, et al. Diagnostic and therapeutic
approach in adult patients with traumatic brain injury receiving oral antic-
oagulant therapy: an Austrian interdisciplinary consensus statement. Crit
Care 2019; 23:62.
11. Bugaev N, Como JJ, Golani G, et al. Thromboelastography and rotational
thromboelastometry in bleeding patients with coagulopathy: Practice man-
agement guideline from the Eastern Association for the Surgery of Trauma. J
Trauma Acute Care Surg 2020; 89:999–1017.
12. Vulliamy P, Kornblith LZ, Kutcher ME, et al. Alterations in platelet behavior
after major trauma: adaptive or maladaptive? Platelets 2021; 32:295–304.
13. Riojas CM, Ekaney ML, Ross SW, et al. Platelet dysfunction after traumatic
brain injury: a review. J Neurotrauma 2021; 38:819–829.
14. Davis PK, Musunuru H, Walsh M, et al. Platelet dysfunction is an early marker
for traumatic brain injury-induced coagulopathy. Neurocrit Care 2013;
18:201–208.
15. Stettler GR, Moore EE, Moore HB, et al. Platelet adenosine diphosphate
receptor inhibition provides no advantage in predicting need for platelet
transfusion or massive transfusion. Surgery 2017; 162:1286–1294.
16. Pommer P, Oberladst€atter D, Schlimp CJ, et al. Multiplate platelet function
testing upon emergency room admission fails to provide useful information in
major trauma patients not on platelet inhibitors. J Clin Med 2022; 11:2578.
17. Holcomb JB, Tilley BC, Baraniuk S, et al. Transfusion of plasma, platelets, and
red blood cells in a 1:1:1 vs a 1:1:2 ratio and mortality in patients with severe
trauma: the PROPPR randomized clinical trial. JAMA 2015; 313:471–482.
18. Kaserer A, Casutt M, Sprengel K, et al. Comparison of two different
coagulation algorithms on the use of allogenic blood products and coagula-
tion factors in severely injured trauma patients: a retrospective, multicentre,
observational study. Scand J Trauma Resusc Emerg Med 2018; 26:4.
19. Schöchl H, Nienaber U, Hofer G, et al. Goal-directed coagulation manage-
ment of major trauma patients using thromboelastometry (ROTEM)-guided
administration of fibrinogen concentrate and prothrombin complex concen-
trate. Crit Care 2010; 14:R55.
20. Innerhofer P, Fries D, Mittermayr M, et al. Reversal of trauma-induced
coagulopathy using first-line coagulation factor concentrates or fresh frozen
plasma (RETIC): a single-centre, parallel-group, open-label, randomised trial.
Lancet Haematol 2017; 4:e258–e271.
Volume 29
Number 6
December 2023
 Point-of-care, goal-directed management of bleeding in trauma patients Zipperle et al.
21. Khan S, Davenport R, Raza I, et al. Damage control resuscitation using blood
component therapy in standard doses has a limited effect on coagulopathy
during trauma hemorrhage. Intensive Care Med 2015; 41:239–247.
22. Bougl e A, Harrois A, Duranteau J. Resuscitative strategies in traumatic
hemorrhagic shock. Ann Intensive Care 2013; 3:1.
23. McQuilten ZK, Flint AW, Green L, et al. Epidemiology of massive transfusion –
a common intervention in need of a definition. Transfus Med Rev 2021;
35:73–79.
24. Meneses E, Boneva D, McKenney M, Elkbuli A. Massive transfusion protocol
in adult trauma population. Am J Emerg Med 2020; 38:2661–2666.
25. Barmparas G, Huang R, Lee WG, et al. Overtransfusion of packed red blood
cells during massive transfusion activation: a potential quality metric for
trauma resuscitation. Trauma Surg Acute Care Open 2022; 7:e000896.
26. Thau MR, Liu T, Sathe NA, et al. Association of trauma molecular endotypes
with differential response to transfusion resuscitation strategies. JAMA Surg
2023; 158:728–736.
27. Frith D, Goslings JC, Gaarder C, et al. Definition and drivers of acute
traumatic coagulopathy: clinical and experimental investigations. J Thromb
Haemost 2010; 8:1919–1925.
28. Baksaas-Aasen K, Gall LS, Stensballe J, et al. Viscoelastic haemostatic assay
&& augmented protocols for major trauma haemorrhage (ITACTIC): a rando-
mized, controlled trial. Intensive Care Med 2021; 47:49–59.
This is the largest study so far comparing coagulation management protocols
based on SCTs and VETs. Survival benefits could be demonstrated only for TBI
patients whose treatment is based on VTRs.
29. Prat NJ, Meyer AD, Ingalls NK, et al. Rotational thromboelastometry sig-
nificantly optimizes transfusion practices for damage control resuscitation in
combat casualties. J Trauma Acute Care Surg 2017; 83:373–380.
30. Davenport R, Manson J, De’Ath H, et al. Functional definition and character-
ization of acute traumatic coagulopathy. Crit Care Med 2011; 39:2652–2658.
31. Beynon C, Erk AG, Potzy A, et al. Point of care coagulometry in prehospital
emergency care: an observational study. Scand J Trauma Resusc Emerg
Med 2015; 23:58.
32. Mosesson MW. Fibrinogen and fibrin structure and functions. J Thromb
Haemost 2005; 3:1894–1904.
33. Floccard B, Rugeri L, Faure A, et al. Early coagulopathy in trauma patients: an
on-scene and hospital admission study. Injury 2012; 43:26–32.
34. McQuilten ZK, Wood EM, Bailey M, et al. Fibrinogen is an independent
predictor of mortality in major trauma patients: a five-year statewide cohort
study. Injury 2017; 48:1074–1081.
35. Hagemo JS, Stanworth S, Juffermans NP, et al. Prevalence, predictors and
outcome of hypofibrinogenaemia in trauma: a multicentre observational
study. Crit Care 2014; 18:R52.
36. Curry N, Rourke C, Davenport R, et al. Early cryoprecipitate for major
haemorrhage in trauma: a randomised controlled feasibility trial. Br J Anaesth
2015; 115:76–83.
37. Rourke C, Curry N, Khan S, et al. Fibrinogen levels during trauma hemor-
rhage, response to replacement therapy, and association with patient out-
comes. J Thromb Haemost 2012; 10:1342–1351.
38. Sanfilippo S, Buisson L, Rouabehi H, et al. The qLabs1 FIB system, a novel
point-of-care technology for a rapid and accurate quantification of functional
fibrinogen concentration from a single drop of citrated whole blood. Thromb
Res 2023; 226:159–164.
39. Mann KG, Brummel K, Butenas S. What is all that thrombin for? J Thromb
Haemost 2003; 1:1504–1514.
40. Hoffman M, Monroe DM 3rd. A cell-based model of hemostasis. Thromb
Haemost 2001; 85:958–965.
41. Haas T, Fries D, Tanaka KA, et al. Usefulness of standard plasma coagulation
tests in the management of perioperative coagulopathic bleeding: is there
any evidence? Br J Anaesth 2015; 114:217–224.
42. Levy JH, Szlam F, Wolberg AS, Winkler A. Clinical use of the activated partial
thromboplastin time and prothrombin time for screening: a review of the
literature and current guidelines for testing. Clin Lab Med 2014; 34:453–477.
43. Chee YL, Crawford JC, Watson HG, Greaves M. Guidelines on the assess-
ment of bleeding risk prior to surgery or invasive procedures. British Com-
mittee for Standards in Haematology. Br J Haematol 2008; 140:496–504.
44. Holcomb JB, Minei KM, Scerbo ML, et al. Admission rapid thrombelasto-
graphy can replace conventional coagulation tests in the emergency depart-
ment: experience with 1974 consecutive trauma patients. Ann Surg 2012;
256:476–486.
45. Schöchl H, Voelckel W, Grassetto A, Schlimp CJ. Practical application of
point-of-care coagulation testing to guide treatment decisions in trauma.
J Trauma Acute Care Surg 2013; 74:1587–1598.
46. Gratz J, G€ uting H, Thorn S, et al. Protocolised thromboelastometric-guided
& haemostatic management in patients with traumatic brain injury: a pilot study.
Anaesthesia 2019; 74:883–890.
This is a prospective randomised controlled study comparing the availability of
SCTs and VETs in TBI patients. VET results were available significantly sooner than
SCT results.
47. Schöchl H, Nienaber U, Maegele M, et al. Transfusion in trauma: thromboe-
lastometry-guided coagulation factor concentrate-based therapy versus
standard fresh frozen plasma-based therapy. Crit Care 2011; 15:R83.
1070-5295 Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.
Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.
48. Inaba K, Rizoli S, Veigas PV, et al. 2014 Consensus conference on viscoe-
lastic test-based transfusion guidelines for early trauma resuscitation: Report
of the panel. J Trauma Acute Care Surg 2015; 78:1220–1229.
49. Ziegler B, Voelckel W, Zipperle J, et al. Comparison between the new fully
automated viscoelastic coagulation analysers TEG 6 s and ROTEM Sigma in
trauma patients: a prospective observational study. Eur J Anaesthesiol 2019;
36:834–842.
50. Oberladst€atter D, Voelckel W, Schlimp C, et al. A prospective observational
study of the rapid detection of clinically-relevant plasma direct oral antic-
oagulant levels following acute traumatic injury. Anaesthesia 2021;
76:373–380.
51. Lee MY, Jang S, Park CJ, Cho YU. Establishing reference range and
assessing precision performance of the TEG6 s system; verification of
TEG6 s to introduce to clinical laboratory. Clin Lab 2022; 68.
52. Zipperle J, Ziegler B, Schöchl H, et al. Operability of a resonance-based
viscoelastic haemostatic analyzer in the high-vibration environment of air
medical transport. J Clin Med 2022; 11:3630.
53. Volod O, Bunch CM, Zackariya N, et al. Viscoelastic hemostatic assays: a
primer on legacy and new generation devices. J Clin Med 2022; 11:860.
54. Volod O, Viola F. The Quantra system: system description and protocols for
measurements. Methods Mol Biol 2023; 2663:743–761.
55. Michelson EA, Cripps MW, Ray B, et al. Initial clinical experience with the
Quantra QStat System in adult trauma patients. Trauma Surg Acute Care
Open 2020; 5:e000581.
56. Rossetto A, Wohlgemut JM, Brohi K, Davenport R. Sonorheometry versus
rotational thromboelastometry in trauma: a comparison of diagnostic and
prognostic performance. J Thromb Haemost 2023; 21:2114–2125.
57. Neal MD, Moore EE, Walsh M, et al. A comparison between the TEG 6 s and
TEG 5000 analyzers to assess coagulation in trauma patients. J Trauma
Acute Care Surg 2020; 88:279–285.
58. Hagemo JS, Næss PA, Johansson P, et al. Evaluation of TEG(1) and RoTEM
(1) inter-changeability in trauma patients. Injury 2013; 44:600–605.
59. Gratz J, Schlimp CJ, Honickel M, et al. Sufficient thrombin generation despite
95% hemodilution: an in vitro experimental study. J Clin Med 2020; 9:3805.
60. Ponschab M, Voelckel W, Pavelka M, et al. Effect of coagulation factor
concentrate administration on ROTEM1 parameters in major trauma. Scand
J Trauma Resusc Emerg Med 2015; 23:84.
61. Meyer AS, Meyer MA, Sørensen AM, et al. Thrombelastography and rota-
tional thromboelastometry early amplitudes in 182 trauma patients with
clinical suspicion of severe injury. J Trauma Acute Care Surg 2014;
76:682–690.
62. Woolley T, Midwinter M, Spencer P, et al. Utility of interim ROTEM(j) values
of clot strength, A5 and A10, in predicting final assessment of coagulation
status in severely injured battle patients. Injury 2013; 44:593–599.
63. Vigstedt M, Baksaas-Aasen K, Henriksen HH, et al. Thrombelastography
(TEG(1) 6 s) early amplitudes predict maximum amplitude in severely injured
trauma patients. Scand J Clin Lab Invest 2022; 82:508–512.
64. Plotkin AJ, Wade CE, Jenkins DH, et al. A reduction in clot formation rate
and strength assessed by thrombelastography is indicative of transfusion
requirements in patients with penetrating injuries. J Trauma 2008; 64:
S64–S68.
65. Schöchl H, Cotton B, Inaba K, et al. FIBTEM provides early prediction of
massive transfusion in trauma. Crit Care 2011; 15:R265.
66. Schöchl H, Solomon C, Traintinger S, et al. Thromboelastometric (ROTEM)
findings in patients suffering from isolated severe traumatic brain injury.
J Neurotrauma 2011; 28:2033–2041.
67. Nystrup KB, Windeløv NA, Thomsen AB, Johansson PI. Reduced clot
strength upon admission, evaluated by thrombelastography (TEG), in trauma
patients is independently associated with increased 30-day mortality. Scand
J Trauma Resusc Emerg Med 2011; 19:52.
68. Infanger L, Dibiasi C, Schaden E, et al. Comparison of the new viscoelastic
coagulation analyzer ClotPro1 with ROTEM1 delta and conventional
coagulation tests in critically ill patients with COVID-19. Front Med (Lau-
sanne) 2021; 8:777145.
69. Harr JN, Moore EE, Ghasabyan A, et al. Functional fibrinogen assay indicates
that fibrinogen is critical in correcting abnormal clot strength following
trauma. Shock 2013; 39:45–49.
70. Demailly Z, Wurtz V, Barbay V, et al. Point-of-care viscoelastic hemostatic
assays in cardiac surgery patients: comparison of Thromboelastography 6S,
Thromboelastometry Sigma, and Quantra. J Cardiothorac Vasc Anesth
2023; 37:948–955.
71. Baksaas-Aasen K, Van Dieren S, Balvers K, et al. Data-driven development
of ROTEM and TEG algorithms for the management of trauma hemor-
rhage: a prospective observational multicenter study. Ann Surg 2019;
270:1178–1185.
72. Schöchl H, Voelckel W, Schlimp CJ. Management of traumatic haemor-
rhage—the European perspective. Anaesthesia 2015; 70(Suppl 1):102–
107; e35–7.
73. Schlimp CJ, Solomon C, Ranucci M, et al. The effectiveness of different
functional fibrinogen polymerization assays in eliminating platelet contribu-
tion to clot strength in thromboelastometry. Anesth Analg 2014;
118:269–276.
www.co-criticalcare.com 711
The surgical patient
74. Peng HT, Nascimento B, Tien H, et al. A comparative study of viscoelastic
hemostatic assays and conventional coagulation tests in trauma patients
receiving fibrinogen concentrate. Clin Chim Acta 2019; 495:253–262.
75. Raza I, Davenport R, Rourke C, et al. The incidence and magnitude of
fibrinolytic activation in trauma patients. J Thromb Haemost 2013;
11:307–314.
76. Ives C, Inaba K, Branco BC, et al. Hyperfibrinolysis elicited via thromboelasto-
graphy predicts mortality in trauma. J Am Coll Surg 2012; 215:496–502.
77. Cotton BA, Harvin JA, Kostousouv V, et al. Hyperfibrinolysis at admission is
an uncommon but highly lethal event associated with shock and prehospital
fluid administration. J Trauma Acute Care Surg 2012; 73:365–370; dis-
cussion 370.
78. Schöchl H, Frietsch T, Pavelka M, Jambor C. Hyperfibrinolysis after major
trauma: differential diagnosis of lysis patterns and prognostic value of
thrombelastometry. J Trauma 2009; 67:125–131.
79. Moore EE, Moore HB, Thomas SG, et al. Serial ‘death diamond’ TEGs are a
bedside indicator of futile resuscitation during massive transfusion. J Trauma
Acute Care Surg 2023; 95:e19–e21.
80. Wang IJ, Park SW, Bae BK, et al. FIBTEM improves the sensitivity of
hyperfibrinolysis detection in severe trauma patients: a retrospective study
using thromboelastometry. Sci Rep 2020; 10:6980.
81. Gonzalez E, Moore EE, Moore HB, et al. Goal-directed hemostatic resuscita-
tion of trauma-induced coagulopathy: a pragmatic randomized clinical trial
comparing a viscoelastic assay to conventional coagulation Assays. Ann
Surg 2016; 263:1051–1059.
82. Mohamed M, Majeske K, Sachwani GR, et al. The impact of early throm-
boelastography directed therapy in trauma resuscitation. Scand J Trauma
Resusc Emerg Med 2017; 25:99.
83. Unruh M, Reyes J, Helmer SD, Haan JM. An evaluation of blood product
utilization rates with massive transfusion protocol: before and after throm-
boelastography (TEG) use in trauma. Am J Surg 2019; 218:1175–1180.
84. Zhu Z, Yu Y, Hong K, et al. Utility of viscoelastic hemostatic assay to guide
hemostatic resuscitation in trauma patients: a systematic review. World J
Emerg Surg 2022; 17:48.
85. Wang H, Robinson RD, Phillips JL, et al. Traumatic abdominal solid organ
injury patients might benefit from thromboelastography-guided blood com-
ponent therapy. J Clin Med Res 2017; 9:433–438.
86. David JS, James A, Orion M, et al. Thromboelastometry-guided haemostatic
resuscitation in severely injured patients: a propensity score-matched study.
Crit Care 2023; 27:141.
87. Lammers DT, Marenco CW, Morte KR, et al. Viscoelastic testing in combat
resuscitation: Is it time for a new standard? J Trauma Acute Care Surg 2020;
89:145–152.
88. Cochrane C, Chinna S, Um JY, et al. Site-of-care viscoelastic assay in major
trauma improves outcomes and is cost neutral compared with standard
coagulation tests. Diagnostics (Basel) 2020; 10:486.
89. Cannon JW, Dias JD, Kumar MA, et al. Use of thromboelastography in the
evaluation and management of patients with traumatic brain injury: a sys-
tematic review and meta-analysis. Crit Care Explor 2021; 3:e0526.
712 www.co-criticalcare.com
Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.
90. Furay E, Daley M, Teixeira PG, et al. Goal-directed platelet transfusions
correct platelet dysfunction and may improve survival in patients with severe
traumatic brain injury. J Trauma Acute Care Surg 2018; 85:881–887.
91. Guillotte AR, Herbert JP, Madsen R, et al. Effects of platelet dysfunction and
platelet transfusion on outcomes in traumatic brain injury patients. Brain Inj
2018; 32:1849–1857.
92. Ostrowski SR, Johansson PI. Endothelial glycocalyx degradation induces
endogenous heparinization in patients with severe injury and early traumatic
coagulopathy. J Trauma Acute Care Surg 2012; 73:60–66.
93. Zipperle J, Oberladst€atter D, Weichselbaum N, et al. Thromboelastometry
& fails to detect autoheparinization after major trauma and hemorrhagic shock.
J Trauma Acute Care Surg 2022; 92:535–541.
This study challenges the role of ‘auto-heparinization’ in TIC. Moreover, this
phenomenon cannot be detected by ROTEM parameters.
94. Sirajuddin S, Valdez C, DePalma L, et al. Inhibition of platelet function is
common following even minor injury. J Trauma Acute Care Surg 2016;
81:328–332.
95. Solomon C, Traintinger S, Ziegler B, et al. Platelet function following trauma.
A multiple electrode aggregometry study. Thromb Haemost 2011;
106:322–330.
96. Verni CC, Davila A Jr, Balian S, et al. Platelet dysfunction during trauma
involves diverse signaling pathways and an inhibitory activity in patient-
derived plasma. J Trauma Acute Care Surg 2019; 86:250–259.
97. Vulliamy P, Gillespie S, Armstrong PC, et al. Histone H4 induces platelet
ballooning and microparticle release during trauma hemorrhage. Proc Natl
Acad Sci USA 2019; 116:17444–17449.
98. Castellino FJ, Chapman MP, Donahue DL, et al. Traumatic brain injury causes
platelet adenosine diphosphate and arachidonic acid receptor inhibition
independent of hemorrhagic shock in humans and rats. J Trauma Acute
Care Surg 2014; 76:1169–1176.
99. Kvint S, Gutierrez A, Venezia A, et al. Application of a TEG-platelet mapping
algorithm to guide reversal of antiplatelet agents in adults with mild-to-
moderate traumatic brain injury: an observational pilot study. Neurocrit Care
2022; 37:638–648.
100. Schriner JB, George MJ, Cardenas JC, et al. Platelet function in trauma: is
current technology in function testing missing the mark in injured patients?
Shock 2022; 58:1–13.
101. Tantry US, Hartmann J, Neal MD, et al. The role of viscoelastic testing in
assessing peri-interventional platelet function and coagulation. Platelets
2022; 33:520–530.
102. Connelly CR, Yonge JD, McCully SP, et al. Assessment of three point-of-care
platelet function assays in adult trauma patients. J Surg Res 2017;
212:260–269.
103. George MJ, Burchfield J, MacFarlane B, et al. Multiplate and TEG platelet
mapping in a population of severely injured trauma patients. Transfus Med
2018; 28:224–230.
104. Bolliger D, Lance MD, Siegemund M. Point-of-care platelet function monitor-
ing: implications for patients with platelet inhibitors in cardiac surgery.
J Cardiothorac Vasc Anesth 2021; 35:1049–1059.
Volume 29
Number 6
December 2023