E  The Open Mind

Pro–Con Debate: Viscoelastic Hemostatic Assays

Should Replace Fixed Ratio Massive Transfusion
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Protocols in Trauma
Kevin P. Blaine, MD, MPH, FASA,* and Roman Dudaryk, MD†
See Article, p 21

Major trauma patients at risk of traumatic coagulopathy are commonly treated with early clotting
factor replacement to maintain hemostasis and prevent microvascular bleeding. In the United
States, trauma transfusions are often dosed by empiric, low-ratio massive transfusion proto-
cols, which pair plasma and platelets in some ratio relative to the red cells, such as the “1:1:1”
combination of 1 units of red cells, 1 unit of plasma, and 1 donor’s worth of pooled platelets.
Empiric transfusion increases the rate of overtransfusion when unnecessary blood products are
administered based on a formula and not on at patient’s hemostatic profile. Viscoelastic hemo-
static assays (VHAs) are point-of-care hemostatic assays that provided detailed information
about abnormal clotting pathways. VHAs are used at many centers to better target hemostatic
therapies in trauma. This Pro/Con section will address whether VHA guidance should replace
empiric fixed ratio protocols in major trauma.  (Anesth Analg 2022;134:21–31)

GLOSSARY
ACT = activated clotting time; AUC = area under the curve; CA5 = clot amplitude at 5 min, an early pre-
dictor of the maximum clot firmness; CFT = clot formation time (ROTEM); CT = clotting time (ROTEM
and Quantra); DOAC = direct-acting oral anticoagulant; EXTEM = extrinsic pathway ROTEM; FCS =
fibrinogen contribution to clot stiffness (Quantra); FIBTEM = fibrinogen ROTEM; FP-24 = liquid
plasma frozen after 24 hours of collection; INR = international normalized ratio; INTEM = intrin-
sic pathway ROTEM; ISS = Injury Severity Score; iTACTIC = implementing Treatment Algorithms
for the Correction of Trauma-Induced Coagulopathy; K = kinetic time (TEG); LI = lysis index
(ROTEM); Ly30 = percent clot lysis at 30 minutes (TEG); MA = maximum amplitude (TEG); MCF
= maximum clot firmness (ROTEM); MTP = massive transfusion protocol; NSAID = nonsteroidal
anti-inflammatory drug; PBM = patient blood management; PCC = prothrombin complex concen-
trate; PCS = platelet contribution to clot stiffness (Quantra); PROPPR = Pragmatic Randomized
Optimal Platelet and Plasma Ratios; PT = prothrombin time; PTT = partial thromboplastin time;
R = reaction time (TEG); ROTEM = rotational thromboelastometry; rTEG = rapid TEG; TEG =
thrombelastography; TEG FF = TEG functional fibrinogen; VHA = viscoelastic hemostatic assay

H
emorrhage is the leading cause of preventable
death in major trauma1–4 and often requires
large volumes of blood products for resuscita-
tion and correction of coagulopathy.5,6 Both American
and European guidelines include recommendations
From the *Department of Anesthesiology and Perioperative Medicine,
Oregon Health & Science University, Portland, Oregon; and †Department of
Anesthesiology, Perioperative Medicine, and Pain Management, University
of Miami Health System/Ryder Trauma Center, Miami, Florida.
Accepted for publication July 12, 2021.
Funding: None.
The authors declare no conflicts of interest.
Reprints will not be available from the authors.
Address correspondence to Kevin P. Blaine, MD, MPH, FASA, Department
of Anesthesiology and Perioperative Medicine, Oregon Health & Science
University, 3181 SW Sam Jackson Park Rd, UH-2, Portland, OR 97230.
Address e-mail to blainek@ohsu.edu.
Copyright © 2021 International Anesthesia Research Society
DOI: 10.1213/ANE.0000000000005709
for empiric, fixed ratio massive transfusion protocols
(MTPs).7–9 However, viscoelastic hemostatic assays
(VHAs) are increasingly available at many trauma
centers and offer readily available, patient-specific
coagulation data to guide trauma resuscitation. VHAs
might even replace ratio-based transfusions.10 The
following Pro-Con discussion addresses some argu-
ments in favor, and in opposition, to the replacement
of fixed ratio transfusions by VHA-guided MTPs.
BACKGROUND
Trauma patients with severe hemorrhagic shock are
at risk for developing trauma-induced coagulopa-
thy,5,11,12 a complex and multifactorial syndrome of
microvascular bleeding that cannot be controlled
surgically.11 Trauma-induced coagulopathy does not

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 VHAs in Massive Transfusion for Trauma
always correlate with abnormalities of conventional
laboratory parameters.13 For example, a patient on
chronic warfarin with an international normalized
ratio (INR) of 1.2 would be hemostatically normal
by standard laboratory definitions,14 while a trauma
patient (presumably not on warfarin) with an INR of
1.2 might have coagulopathic bleeding.15 The exact
molecular mechanisms underlying trauma coagu-
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lopathy remain to be characterized fully, with several
postulated pathways which are not mutually exclu-
sive: thrombomodulin and activated protein C,16–19
pathologic fibrinolysis,20–22 and endotheliopathy.23–26
There is consensus that coagulopathy treatment
requires prompt (within 1 hour) replacement of pro-
coagulant hemostatic mediators to preserve coagula-
tion and thrombogenesis.27
For this discussion, the “usual care” therapy for
hemorrhage in trauma implies fixed ratio, compo-
nent-based MTPs, such as the “1:1:1” or “1:1:2” (2
units of red cells, 1 unit of plasma, 1 donor’s worth
of platelet) concept. This notion hypothesizes that the
hemorrhaging trauma patient benefits from a com-
bination of blood products that approximates whole
blood (such as by alternating between administering
1 unit of red cells, 1 unit plasma, and 1 donor’s worth
of platelets or fraction of a platelet pool), which would
thereby correct any deficiency in clot mediators.28 In
the United States, fractionated blood products com-
monly include plasma, platelets, and cryoprecipi-
tate.29 Some European centers have more experience
with prothrombin complex concentrates (PCC) and
fractionated fibrinogen.30 When fractionated products
are used, this concept has been called reconstituted
blood31,32 or balanced resuscitation.31–34 A few centers
have experimented with cold-stored whole blood in
trauma,35 and rigorous outcome data are enthusiasti-
cally anticipated.
Generally, liberal blood product administration in
nonhemorrhage and nontrauma situations have not
been shown to improve outcomes36–38 and may even
harm some patients.36,37 Red cell transfusions do not
seem to improve oxygen carrying capacity39–41 and
storage conditions may worsen oxygen delivery.42–44
Plasma transfusions predispose patients to trans-
fusion-associated lung injury,45–47 and may worsen
coagulopathy by diluting some coagulation factors
and fibrinogen.48–50 Pooled platelets and cryoprecip-
itate are produced from multiple donors and expose
patients to a high antigen load with debatable effi-
cacy in the setting of hemorrhage.51–55
It remains uncertain whether trauma patients uni-
versally benefit from fixed ratio MTPs. Given the
lack of high-quality evidence to support ratio-based
transfusion, it may be time to consider alternative
approaches to diagnosing and treating coagulopathy
in trauma.
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PRO: VHAS SHOULD REPLACE FIXED
TRANSFUSION RATIOS IN MTPS IN TRAUMA TO
REDUCE OVERTRANSFUSION
Despite widespread adoption, the literature sup-
porting fixed ratio MTPs in trauma remains objec-
tively weak,56–59 lacking prospective data and reliant
on retrospective studies that are critically limited by
survivorship and selection biases.58–60 The Pragmatic,
Randomized Optimal Platelet and Plasma Ratios
(PROPPR) trial, often cited as the highest-level evi-
dence for fixed ratios, was nonetheless a negative
trial—“1:1:1” was not better than the modestly less
stringent “1:1:2” ratio for mortality or for 34 of 35
planned secondary end points.61 We lack rigorous
prospective data supporting ratio-based MTPs.
Balanced resuscitation with reconstituted blood
implies that transfusion of blood product combina-
tions approximates whole blood. The reality is that
cold-stored products differ substantially from freshly
exsanguinated blood. Donated red cells and plate-
lets are older62,63 and metabolically quiescent.40,63 In
plasma, clotting proteins do not equally survive the
freezing and thawing process. Plasma processing
typically destroys 30% to 50% of factors VIII and X.64
Fibrinogen especially demonstrates poor freezer-sta-
bility; thawed fresh frozen plasma contains fibrino-
gen concentrations of only 157 to 191 mg/dL.32 As
this concentration approximates the threshold of 150
to 200 mg/dL proposed for acquired hypofibrino-
genemia in trauma,7,65,66 plasma is unlikely to replace
fibrinogen and may even lower circulating levels in
some patients by dilution.66,67 Due to ex vivo protein
C activity after 6 hours at room temperature, thawed
plasma and liquid plasma frozen after 24 hours of
collection (FP-24) are depleted in factors V, VII, and
VIII.68 Factor V is concerning as it is the clotting factor
most commonly reduced in severe traumatic coagu-
lopathy.17,18,69,70 Reconstituted whole blood should
perhaps be considered “approximated whole blood,”
instead.
While fixed ratio MTPs in trauma lead  to liberal
transfusion habits, most other realms of periopera-
tive medicine have adopted more restrictive transfu-
sion practices. The patient blood management (PBM)
movement has sought to reduce the transfusion of
all blood products, while emphasizing preoperative
optimization, restrictive transfusion triggers, and
pharmacologic agents.71,72
Many PBM practices are useful in trauma care.
While preoperative optimization is generally unfea-
sible, transfusion-sparing techniques have already
been adopted. Examples include mechanical tam-
ponade and tourniquets,7,73–75 permissive hypoten-
sion,7,76–78 avoidance of hypothermia and acidosis,7,76,79
the early use (<3 hours of injury) of antifibrinolytic
ANESTHESIA & ANALGESIA
 E  The Open Mind
agents,7,76,79–81 early and aggressive calcium supple-
mentation,7,79 and cell-salvage devices.82 PCCs83–86 and
recombinant fibrinogen87 may also be used to rapidly
augment clotting proteins.
Perhaps the cornerstone of intraoperative PBM
is the tolerance of abnormal laboratory results.88
In many (nontrauma) operative scenarios, simply
delaying red cell transfusion until the hemoglobin
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reaches 7.0 g/dL,88,89 or the INR reaches 1.5,90 can
have a tremendous impact on the total amount of
blood that is transfused without increasing mortality.
In the setting of trauma, conventional laboratory
results are limited by slow reporting and inaccuracy.
While most clinicians expect a turnaround time of 20
minutes for stat laboratories drawn in the emergency
department (ED),91 one study reported a mean turn-
around of 45 minutes for an urgent prothrombin time
(PT)/INR result, with substantial variability between
sites; reporting delays >60 minutes were not uncom-
mon.91 In the hemorrhaging patient with acute hypo-
volemic anemia, the hemoglobin measurement may
take hours to reflect the circulating red cell mass.92
Although PT/INR cutoffs have been proposed to
diagnosis traumatic coagulopathy in some studies,
no formal threshold has been defined. INR cutoffs of
1.2 or 1.5 have been shown to yield too many false
positives without correlating with hemorrhage out-
comes.13 The partial thromboplastin time (PTT) and
activated clotting time (ACT) are insensitive markers
of mild and moderate coagulopathy, with sensitivities
estimated at only 50%.93,94 While more accurate, the
turnaround time for a gold standard complete blood
count (to obtain a platelet count) and Clauss fibrino-
gen assay can exceed 60 minutes or even 100 minutes
at some centers,95 outside the “Golden [One] Hour”
time limit for optimal resuscitation. Modern point-
of-care technologies allow for rapid measurement of
blood gases, lactate, and even coagulation times (eg,
the i-Stat Coagulation, Abbott Laboratories, Abbot
Park). Besides suffering from the same diagnostic
limitations as their laboratory-based counterparts,
point-of-care INR values are less accurate.96 Rapid
base deficit and serum lactate are loosely correlated
with hypoperfusion generally and do not diagnose
coagulopathy.92 In sum, traditional laboratory test-
ing has limited value in the diagnosis of traumatic
coagulopathy.
VHAs have emerged as a solution to the challenge
of laboratory diagnosis and treatment-monitoring of
trauma-induced coagulopathy. VHAs been used in
trauma since the 1990s.97 Older VHA platforms, like
the TEG 5000 (Haemonetics Corporation) and ROTEM
Delta (Instrumentation Laboratory), are gradually
being replaced by the new generation of cartridge-
based units, including the TEG 6S (Haemonetics), the
ROTEMsigma (Instrumentation Laboratory), and the
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Hemosonics Quantra (Hemosonics). Cartridge-based
devices offer more measurement consistency, faster
results, and greater point-of-care ease of use. Hence,
VHAs have emerged as an ideal compromise that
recognize the complex pathological bleeding states in
major trauma, while reducing excessive fractionated
blood products.
The blood-sparing effect of VHAs is well recog-
nized. Meta-analyses, although predominantly from
studies in cardiac surgery, have consistently shown
that VHAs lead to less blood product use, with great-
est reductions for plasma (typically ~50% reduction)
and platelets (typically ~25% reduction). These meta-
analyses have shown little or no effect on blood loss,
cryoprecipitate use, or antifibrinolytic therapies.98–103
Admittedly, VHAs have not been shown consistently
to improve mortality,98–100,103 especially when com-
pared to usual care or clinician judgment,101 although
neither has reduced transfusion rates been shown
to worsen survival. VHAs are an intervention that
increases the value of care by reducing resource con-
sumption without worsening patient outcomes.
Most VHAs are whole blood assays. Unlike tradi-
tional clotting times (like the PT) which use purified
plasma, VHAs simultaneously measure multiple clot-
ting axes, and return useful data.12,104 For example,
thrombin generation is correlated with the latency
period between reagent activation and the initiation of
a fibrin clot; this can be measured as the reaction time
(R) for TEG, or the clotting time (CT) for ROTEM and
Quantra. The standard 4-channel ROTEM offers the
option to separate both the intrinsic pathway (INTEM)
and extrinsic pathway (EXTEM) CT,105 providing
additional information as to which clotting pathways
are deficient. Admittedly, the rarity of isolated factor
VII deficits in trauma70,106 and the extremely rapid
kinetics of tissue factor reagents107 limits the EXTEM
CT for guiding plasma transfusion,12 though the same
challenge is present for the PT/INR. VHAs using con-
tact activator agonists are thus preferred in trauma to
diagnose deficient clotting factors.12
While not helpful to diagnose clotting factor defi-
ciencies, tissue factor VHAs (like the EXTEM or the
Rapid TEG) are nonetheless important adjuncts that
facilitate reporting the remaining VHA parameters
without the need to wait for slower, contact activa-
tor results108–110 (Table  1). One of the most helpful
results in trauma is the estimate of total clot strength:
the TEG MA, ROTEM MCF, and Quantra PCS, which
are thought to approximate platelet count (with some
contribution from fibrinogen).111,112 These parameters
do not differ between tissue factor and contact activa-
tor agonists.110 While the gold standard measurement
remains the standard platelet count, with area under
the curves (AUCs) for maximum amplitude (MA) and
maximum clot firmness (MCF) generally reported
 VHAs in Massive Transfusion for Trauma
Table 1. Example of a VHA Interpretation Algorithm, From the iTACTIC Trial126
Treatment
Clotting factor replacement (4 units of plasma)
Fibrinogen supplementation (4 g equivalent, either
cryoprecipitate or fibrinogen concentrate)
Platelet transfusion (1 platelet pool)
Tranexamic acid (1 g)
Abbreviations: ACT, activated clotting time; CA5, clot amplitude at 5 min, an early predictor of the maximum clot firmness; CT, clotting time; EXTEM, extrinsic
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pathway ROTEM; FIBTEM, fibrinogen ROTEM; ITACTIC, implementing Transfusion Algorithms for the Correction of Trauma-induced Coagulopathy; LI, lysis index;
Ly30, percent clot lysis at 30 min; MA, maximum amplitude; TEG FF, TEG functional fibrinogen; rTEG, rapid TEG; VHA, viscoelastic hemostatic assay; TEG, throm-
belastography; ROTEM, rotational thromboelastometry.
from 0.7 to 0.8,112–114 VHAs are reliable as indirect indi-
cators of thrombocytopenia. A single (industry-spon-
sored and authored) study reported an AUC of 89.5%
for thrombocytopenia using the Quantra PCS,115
which may prove more reliable. VHAs measurements
including the TEG Ly30 and ROTEM LI can esti-
mate fibrinolysis and potentially identify the hyper-
fibrinolytic phenotype in trauma.12 There is no other
point-of-care test for fibrinolysis. The recognition of
hypofibrinogenemia by the measures of clot forma-
tion kinetics (kinetic time [K] for TEG, clot formation
time [CFT] for ROTEM, alpha angle for both, fibrino-
gen contribution to clot stiffness [FCS] for Quantra) is
less certain in trauma than in cardiac surgery,113,116,117
although specialized VHA assays including the TEG
Functional Fibrinogen and ROTEM FIBTEM have the
potential to improve diagnosis.118 Such diverse infor-
mation is helpful to target blood product therapies.
Critics occasionally point out that VHA clotting
times can be slow to provide useful information.
Abnormal clotting times (beyond the reference limit)
are reported as longer than traditional clotting assays.
To register an abnormal result, the user must wait >10
minutes (or >600 seconds) for a TEG R, >204 seconds
for an INTEM CT, and >164 seconds for a Quantra CT,
while only >40 seconds for a PTT and >14 seconds
for a PT. These limits are deceptive because they do
not include specimen processing. The centrifuge time
alone will add 15 to 20 minutes to the conventional PT
or PTT.119,120 Cartridge-based VHAs systems can ini-
tiate analysis within moments, thus avoiding transit,
processing, and reporting delays. Furthermore, when
real-time remote display software is used, clinicians
can view the developing VHA tracing while the test
is still in progress, providing instantaneous (albiet
incomplete) results automatically. To initiate hemo-
static therapies within 1 hour, VHAs are thus the
only platform that can consistently return laboratory
results fast enough to inform treatment.
With a personalized clotting profile, VHAs may
reduce blood transfusions by guiding treatment
toward only those pathways that are disordered.
Providers can thereby avoid unnecessary transfusion,
such as (for example) by withholding plasma from
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TEG ROTEM
rTEG MA ≥65 mm, and rTEG ACT >120 s EXTEM CA5 ≥40 mm, and EXTEM CT >80 s
TEG FF MA <20 mm FIBTEM CA5 <10 mm
rTEG MA minus TEG FF MA <45 mm EXTEM CA5 minus FIBTEM CA5 <30 mm
Ly30 >10% LI30 <85%
a thrombocytopenic patient without clotting factor
deficiencies. Thus, there is no need to transfuse large
volumes of blood products expectantly, according to
a fixed ratio recipe. VHAs may not reduce blood loss
or improve mortality, but nor do they worsen these
outcomes, and they undeniably reduce transfusions,
which is a benefit by itself. The time has come for
VHAs to replace fixed ratio algorithms in MTPs in
trauma.
CON: VHAS ARE INACCURATE AND MISLEADING,
AND SHOULD NOT REPLACE FIXED RATIO
TRANSFUSIONS
The enthusiasm around VHA use in trauma relies on
the accuracy of these assays to measure procoagulant
pathways, though correlation with any gold standard
measurements and with clinical outcomes has been
lacking. Even if VHAs reduce transfusions, if the
tests are inaccurate or misleading, they should be not
codified into transfusion protocols. There are other,
safer ways to reduce transfusions, such as provider
education.
The clinical performance of VHAs in trauma has
been unimpressive. We have already discussed the
lack of a mortality benefit in meta-analyses. Among
all the small trials included in these analyses, there
is only 1 study121 that has suggested a mortality ben-
efit for VHA-guided protocols in trauma. The statis-
tical effect in this industry-supported trial was small
(P = .049) and the fragility index (the number of sur-
viving patients who would have had to die to over-
turn the statistical result) was <1, which (combined
with 11 patients excluded from analysis and 8 patients
from the control arm that actually followed the exper-
imental protocol) strongly suggests that the trial
result could not be replicated and so should not be
relied on as the sole evidence to justify VHA use. The
recent, much anticipated, implementing Transfusion
Algorithms for the Correction of Trauma-Induced
Coaguloapthy (iTACTIC) (Viscoelastic Haemostatic
Assay Augmented Protocols for Major Trauma
Haemorrhage) randomized trial of VHA-guided
trauma transfusion protocols versus fixed ratio pro-
tocols modified by conventional coagulation testing
ANESTHESIA & ANALGESIA
 E  The Open Mind
showed no difference in clinical outcomes.122 While
there was no difference in total blood product use, the
VHA arm saw higher transfusion rates for platelets
and cryoprecipitate, a finding which has been reported
in other studies of VHAs in trauma123 and suggests
that the VHAs may only reduce unnecessary plasma
use when compared to 1:1:1 controls. Secondary anal-
yses of VHA data from iTACTIC have not yet been
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published, but one potential explanation for VHA’s
lack of effect is their poor sensitivity for coagulopathy
in trauma. VHA results are frequently “normal,” even
when coagulopathic bleeding is evident. One study of
major trauma patients found that 29% of MTPs were
activated in patients with normal VHA results, and
that VHAs were normal even in most patients (66.7%)
with exceptionally severe trauma (Injury Severity
Score [ISS] >30).124 In the PROPPR trial (which used
TEG), while the incidence of major hemorrhage (>10
units of red cells in 24 hours) was 36.8%, prolonged
R times were seen in just 2.6%, and shortened MA in
15.0%, of patients at ED presentation.125 VHAs exhibit
an unacceptably high false-negative rate.
Studies examining the diagnostic utility of VHAs
commonly use INR and PTT cutoffs as a control or
standard test for coagulopathy.126–128 Such study
designs should be disregarded from this discus-
sion; if any other laboratory test were truly a “gold
standard,” then (by definition) those tests should be
used instead of VHAs. Comparisons to clinical out-
comes, including blood transfused, blood loss, or
mortality, are less commonly reported, but show low
sensitivity and high specificity.126,129 For traumatic
hemorrhage and massive transfusion in particular,
sensitivity estimates range from ~30% to 70% (>90%
would be preferred), while specificity range ~80% to
100%.69,126,128,130,131 Although thrombin generation can
be impaired by deficiencies of most clotting factors,
R and CT results are more sensitive to reductions in
some factors (eg, VIII and IX) than others (like V or
X),106,132 such that 2 patients in need of factor replace-
ment may have different R and CT results depending
on the relative levels of individual factors, ensuring
that some coagulopathies will be missed. VHAs can-
not be counted on to catch all patients in need for
hemostatic therapies.
A related problem is the lack of a clinically defined
reference range. The manufacturer’s suggested
VHA reference ranges are based on the distribution
within a normal population133 and reflect healthy
patients under ideal conditions. These ideal condi-
tions include venous blood drawn by a 21-gauge (or
larger) needle under minimal tourniquet pressure
that is incubated for 30 minutes in a citrated tube,134
all of which may be impossible during trauma. It is
a mistake to assume that values outside the reference
range constitute pathology. For example, according to
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the World Health Organization,135 a hemoglobin level
of 11.0 g/dL is anemic for adults; however, few prac-
titioners today would aggressively treat that value
with transfusion. For coagulation, there is good rea-
son to suspect that the variation for VHA results in
the healthy, hemostatically competent human popu-
lation does not necessarily match the manufactur-
ers’ suggested range.114,136–138 For example, race,139,140
sex,138–141 age,138,142 pregnancy,139,140,143 type of collection
tube,134,138 alcohol intoxication,141,144–146 physical activ-
ity,147 health status,139,148–152 and operator116 all affect the
results in healthy adults. Site-specific reference ranges
are commonly broader than manufacturer ranges136,137
and the adoption of wider ranges alone results in
less transfusion136,137,153,154 with the consequence of
even lower sensitivity. For VHAs, it remains uncer-
tain which threshold values predict coagulopathy, or
indeed if those clinically significant values are compa-
rable across different patients or situations (including
trauma). Expanded reference ranges will only worsen
VHA sensitivity by creating more normal results.
Except for unfractionated heparin, VHAs fail to
detect therapeutic anticoagulation.155–161 VHAs are
insensitive to warfarin anticoagulation.159,161,162 Direct
thrombin inhibitors prolong R and CT (though not
necessarily beyond the manufacturer’s upper refer-
ence limit),155 but with a paradoxical prolongation
of MA and MCF that complicates interpretation.160
While blood fully anticoagulated by Xa inhibitors can
prolong R and CT relative to a patient’s baseline, only
rarely will anti-Xa action alone be sufficient to increase
those times outside the reference range,155,161,163 and so
VHAs cannot be relied on identify trauma patients
anticoagulated with direct-acting anticoagulants.
Future VHA modifications (eg, by using ecarin or
dilute tissue factor agonists) may yet improve diag-
nostic accuracy for DOACs.164
Standard VHAs do not detect antiplatelet agents.12
There is interest in the specialized TEG Platelet
Mapping assay (Haemonetics) in trauma patients.165
Currently, Platelet Mapping does not hold a US Food
and Drug Administration indication to diagnose plate-
let dysfunction; Platelet Mapping is approved only to
inform the dose antiplatelet agents only in patients
with a known baseline MA.166 There is wide variation
in the Platelet Mapping results for normal (untreated)
humans that encompasses all values from 0 to 100%
“inhibition,” such that a true diagnostic range cannot
be defined.167 Even insignificant levels of nonsteroidal
anti-inflammatory drugs (NSAIDs)168 and common
genetic polymorphisms169 can confound results in
patients with normal platelet counts.170 In trauma, the
ability of Platelet Mapping to detect microvascular
bleeding has been disappointing. One study showed
that Platelet Mapping actually increased transfusions
with no improvement in hemostasis or mortality.165
 VHAs in Massive Transfusion for Trauma
VHAs are not unique in their inability to detect func-
tional platelet disorders. At present, outside of a few
specialized centers, there is no reliable blood test to
detect most common antiplatelet agents in trauma
patients without a previously known medication
history.
Since VHAs cannot be relied on to provide compa-
rable and meaningful results, they should not take the
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place of usual care in massive transfusion. VHAs are
insensitive and inaccurate tests that are biased toward
negative results, and so miss many clinical coagulop-
athies. Protocolized adherence to a VHA algorithm is
therefore likely to under-treat hemorrhaging patients.
Until VHAs can be made more accurate, they should
not replace fixed ratio MTPS and their use in trauma
should remain adjunctive only.
KNOWLEDGE GAPS AND DIRECTIONS FOR
FUTURE RESEARCH
VHAs have been enthusiastically adopted into
trauma practice based on clinical experience rather
than evidence that they improve outcomes, with
the important exception of reduced blood product
use. Blood-sparing is an important objective and
well-supported, and perhaps should be consid-
ered as a primary outcome in future clinical trials.
Conversely, VHA results are extremely variable in
healthy patients, and evidence-based treatment
cutoffs need to be empirically derived. At least
VHAs have not been shown to worsen care over
fixed ratio MTPs.
Further investigation of optimal fixed ratio MTPs
is also much needed. The “1:1:1” paradigm entered
wide clinical practice with weak scientific support.
The only well-designed prospective trial (PROPPR)
did not answer the question  of efficacy. A state of
equipoise about transfusion ratios remains. There is
an ongoing need for prospective studies of different
transfusion strategies in trauma.
Table 2. Summary of Pro and Con Arguments
Pro Con
There are limited high-quality data There is no evidence that
that fixed ratio MTPs improve VHAs are superior to fixed
outcomes over other treatment ratio MTPs
options (eg, 1:1:1 vs 1:1:2, PCCs)
VHAs produce equivalent outcomes The manufacturer reference
to fixed ratio MTPs ranges are not defined by
clinical end points
VHAs reduce blood product use When clinical end points are
without worsening outcomes considered, VHAs under-
diagnose coagulopathy
VHAs provide useable data quickly VHAs cannot detect or screen-
ing for most anticoagulants
and antiplatelet agents
Abbreviations: MTP, massive transfusion protocol; PCC, prothrombin complex
concentrate; VHA, viscoelastic hemostatic assay.
26   
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It is appropriate as well to continue studying
the role of VHAs (if any) in trauma resuscitation.
Conceptually, a laboratory assay that can rapidly
identify specific hemostatic treatments simultane-
ously is very appealing, but our current VHAs are
insufficiently accurate. Serious, potentially disquali-
fying, limitations need to be considered when inter-
preting VHA results. In particular, the lack of a clearly
defined reference range and clinical benefit in trauma
(beyond blood-sparing) is a testament to need for
ongoing prospective research in this area. For exam-
ple, VHA modifications that improve selectively for
some assays might be compelling. VHA reagents
could be added to include dilute agonists, ecarin,
factor-selective agonists (eg, snake venoms), or selec-
tive pathway inhibitors (eg, antifibrinolytics). Future
VHA platforms might process samples by (for exam-
ple) titrating to the patient’s serum calcium or pH, or
by filtering red cells to analyze just the platelet-rich
plasma fraction. Finally, it is not clear that VHAs are
even the correct platform. Novel coagulation tests, yet
to be developed, may hold even greater sensitivity for
coagulopathy of trauma.
CONCLUSIONS
Empiric, fixed ratio MTPs have been adopted widely
for use in trauma hemorrhage, but VHAs are now
available as adjuncts for MTPs and might be con-
sidered to replace ratio-based transfusions. The Pro
argument is that VHAs reduce transfusions without
increasing adverse clinical outcomes. The Con argu-
ment is that VHAs are still unreliable and inaccu-
rate to diagnosis traumatic coagulopathy (Table  2).
Clinicians and researchers should expect the science
of trauma resuscitation to continue evolving, espe-
cially if future diagnostics and hemostatic therapies
become available. E
DISCLOSURES
Name: Kevin P. Blaine, MD, MPH, FASA.
Contribution: This author helped research the material, write
and edit the manuscript, and approve the final draft.
Name: Roman Dudaryk, MD.
Contribution: This author helped research the material, write
and edit the manuscript, and approve the final draft.
This manuscript was handled by: Richard P. Dutton, MD.
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