REVIEW

CURRENT
OPINION Coagulopathy in the surgical patient:
trauma-induced and drug-induced coagulopathies
Ruben Peralta a,b, Hassan Al Thani a, and Sandro Rizoli a

Purpose of review
Coagulopathy is the derangement of hemostasis that in surgical patients may result in excessive bleeding,
clotting or no measurable effect. The purpose of this review is to provide an overview of the most current
evidence and practical approach to trauma- and drug-induced coagulopathy in surgical patients.
Recent findings
Early identification and timely correction of coagulopathy in surgical patients with significant bleeding is
paramount to prevent death and other consequences of hemorrhage. Trauma-induced coagulopathy is
managed by protocols recommending fibrinogen replacement, FFP, platelets, TXA and frequent lab
monitorization including viscoelastic tests. For warfarin- or DOAC-induced coagulopathy, the management
follows similar principles plus drug reversal. Warfarin is diagnosed by prolonged international normalized
ratio and reversed by PCC or FFP. DOACs are inconsistently diagnosed by routine coagulation tests, and
reversed by a combination of TXA, PCC and specific antidotes (if available).
Summary
Despite different understandings of the pathophysiology, trauma- and drug-induced coagulopathies are
managed following similar protocols. In most of cases of significant surgical bleeding, timely and
protocolized approach to correct the coagulopathy is likely to improve patients’ outcome.
Keywords
bleeding, blood resuscitation, coagulopathy, surgery

INTRODUCTION generation or hypercoagulable states. Despite recent

Coagulopathy is any derangement of hemostasis. In
surgical patients, coagulopathy may lead to exces-
sive bleeding, thrombosis or be of no consequence.
Although previous generations of surgeons were
concerned mostly with inherited coagulopathies,
the 21st-century surgeons much more frequently
advances and growing understanding of the patho-
physiology, the many coagulation defects in TIC,
their temporal changes, multiple compensatory
pathways and iatrogenic interventions result in dif-
ferent interpretations of the mechanisms. There is
no single TIC pathway, implying that no single
&&

manage trauma-induced and drug-induced coagu- treatment exists either [1 ].

lopathies. This article provides an overview of
current approaches to the management of these
coagulopathies in surgical patients.
TRAUMA-INDUCED COAGULOPATHY
Trauma-induced coagulopathy (TIC) is common
and diagnosed in one of every four severely injured
patients. It is an intrinsic coagulopathy occurring
immediately after injury. TIC is often diagnosed
with excessive bleeding, where 3–4% of the patients
have massive bleeding requiring replacement of the
entire circulatory volume (or more) in hours. TIC
presents in different complex phenotypes that by
viscoelastic testing (VET) can be grouped as defects
in fibrinolysis (hyper or shutdown), thrombin
Surprisingly, there is some agreement on multi-
intervention principles for managing injured
patients with TIC, particularly, for massive bleeding
&&
(see European guidelines) [1 ]. The priority is to
control the sources of bleeding using surgery,
angio-embolization, tourniquets, pelvic binders
a
Department of Surgery, Trauma Surgery, Hamad General Hospital,
Doha, Qatar and bDepartment of Surgery, Universidad Nacional Pedro
Henriquez Urena, School of Medicine, Santo Domingo, Dominican
Republic
Correspondence to Sandro Rizoli, MD, PhD, FRCSC, FACS, Depart-
ment of Surgery, Trauma Surgery, Hamad General Hospital, PO Box
3050, Doha, Qatar. E-mail: srizoli@hamad.qa
Curr Opin Crit Care 2019, 25:668–674
DOI:10.1097/MCC.0000000000000676

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Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.


KEY POINTS
 Coagulopathy is common in surgical patients, and
surgeons are primarily responsible for managing
these patients.
 Despite contradictory understandings of the underlying
mechanisms, trauma-induced coagulopathy (TIC) is
managed according to broadly accepted principles.
 TIC management priority is to control source of
bleeding, diagnosis and correct the coagulopathy
according to protocols by restricting crystalloids, liberal
blood and blood product transfusion, tranexamic acid
and close monitorization (frequent labs).
 Drug-induced coagulopathy becoming ever more
common with increasing number and use of direct oral
anticoagulants (DOAC).
 Drug-induced coagulopathy and bleeding has similar
principles of management including protocols calling
for early diagnosis and timely reversal of coagulopathy
with antidotes (mostly unavailable for DOACS) and
FFP, PCC and tranexamic acid.
and more recently REBOA (resuscitative endovascu-
lar balloon occlusion of the aorta, Fig. 1) [2,3].
Volume repletion, correction/avoidance of acidosis,
hypothermia, hypocalcemia and coagulopathy are
done simultaneously, aggressively and from the
start of resuscitation. In massively bleeding patients,
however, these corrections will not be fully achieved
&&
until the bleeding sources are controlled [1 ,4–12].
More controversial are the principles of volume
resuscitation, blood component therapy (BCT),
goal-directed resuscitation and the early administra-
tion of tranexamic acid (TXA). Massive transfusion
protocols (MTP) are broadly used across the world,
despite significant regional variations (Fig. 2). MTP
provides fast access to blood and blood products
indicating the importance of blood component
therapy in modern resuscitation. In the USA,
numerous prehospital services routinely transfuse
plasma and/or red blood cells (RBC), whereas whole
blood is being studied. In Europe, Canada, Australia
and even Qatar 1 g of TXA is typically given to
bleeding patients by ambulance services.
Once in the hospital, the consensus is to follow
MTP for the most unstable bleeding patients while
restricting the infusion of crystalloids. Blood com-
ponents simultaneously replenish circulatory
volume and address coagulopathy. The growing
consensus is to move from ‘blind’ transfusion to
‘goal-directed’ resuscitation as soon as feasible,
which implies having purposeful strategies to
diagnose all coagulation defects in minutes of
hospital arrival. Static coagulation tests, such as
1070-5295 Copyright ß 2019 Wolters Kluwer Health, Inc. All rights reserved.
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Coagulopathy in surgical patients Peralta et al.
international normalized ratio (INR) and PTT con-
tinue to be of use despite inherent major limita-
tions, with a trend toward viscoelastic tests
[thromboelastography (TEG)/rotational thromboe-
lastometry (ROTEM)]. When done at bedside (as
point of care), TEG/ROTEM results are available in
minutes and can guide the clinician in the resusci-
&
tation process of severely injured patients [13 ].
Many trauma centers have created distinct TEG/
ROTEM-based algorithms [14]. Recent study by
&
Gonzalez et al. [15 ] demonstrated a survival benefit
for the TEG-based protocol used in Denver. Once
diagnosed, all discrete hemostatic defects are
directly targeted until correction, particularly in
bleeding patients. Fibrinogen concentrate and pro-
thrombin complex concentrate (PCC) are progres-
sively coming into use and investigation, whereas
recombinant factor VII has lost favor. The ROTEM-
based and PCC algorithms used at the authors’
institution is displayed in Figs. 3 and 4a and b.
Timing of the interventions is essential in deter-
mining the outcome of the bleeding patients [12].
Hemorrhage remains the most preventable cause of
death because of trauma. Another determinant of
outcome is maintaining a close and high-level mon-
itorization of the coagulation, from prehospital to
achieving hemostasis and correcting TIC. The rec-
ommendation to repeat coagulation tests every
30 min until patient stabilization is warranted.
Repeat tests include INR, platelet count, TEG or
ROTEM and fibrinogen levels. Fibrinogen, or coag-
ulation factor I, is not only essential to hemostasis
but also the first to drop to critical low levels after
trauma. Low fibrinogen on arrival to hospital is
associated with disproportional high rates of mor-
tality in trauma. Despite the lack of evidence, close
monitorization and correction of fibrinogen levels
to high normal levels (around 200 mg/dl) is recom-
mended. Fibrinogen is best replaced by fibrinogen
concentrate but most patients are still treated with
cryoprecipitate. Fresh frozen plasma (FFP) contains
small amounts of fibrinogen and should not be
the only product used to correct low fibrinogen in
&&
bleeding trauma patients [1 ].
In TIC, platelet dysfunction remains poorly
understood, in part because of significant technical
challenges to measure platelet function and to
interpret the result of the tests. Platelet function
tests are frequently unavailable off hours, require
specialized technicians and are affected by anemia,
which is common in injured patients. Most resusci-
tation algorithms advocate platelet transfusion
in TIC when platelet count drops below certain
thresholds (100 000 or 50 000/ml), history of anti-
platelet drug use, bleeding location (i.e. brain)
and severity.
www.co-criticalcare.com 669
The surgical patient

Hypotensive (SBP<90), partial or non-responder to MTP

Arrest on arrival OR CPR <15min
+ good ECG rhythm OR
+ good heart activity on FAST Access common femoral artery

CxR possible aortic injury?

No REBOA YES No
No massive HTX

Activate REBOA PROTOCOL (involve IR + vascular surgery)

REBOA Zone I
YES FAST positive
Laparotomy & hybrid OR

No

REBOA Zone III YES Pelvic Xray fracture

No

Hybrid OR REBOA Zone I

FIGURE 1. Resuscitative endovascular balloon occlusion of the aorta algorithm for the management of massive bleeding in
severely injured patient with uncompressible torso trauma of the Hamad Trauma Center. A-line, arterial line; B/L, bilateral;
CXR, chest X-ray; HTX, hemothorax; IR, interventional radiology; MTP, massive transfusion protocol; OR, operating room;
REBOA, resuscitative endovascular balloon occlusion of the aorta.

TIC can be further aggravated if the patients
used anticoagulants and/or antiplatelet drugs
prior to injury, which will require specific manage-
ment. Drug-induced coagulopathies are addressed
next.
DRUG-INDUCED COAGULOPATHY:
VITAMIN K ANTAGONISTS
A common challenge to contemporary surgeons
is to manage anticoagulation drugs, which are
often prescribed for vitamin K antagonist (VTE)
prophylaxis, atrial fibrillation and acute coronary
syndrome. For elective planned operations, with-
holding the anticoagulants, bridging with alterna-
tive drugs and planning the surgery appropriately
are proven to reduce the perioperative risk of bleed-
ing. For some elective operations (i.e. knee/hip
arthroplasty, Caesarian section, spine, etc.) recent
studies suggest prophylactic TXA reduces blood loss
and transfusion requirements [16]. In cardiac sur-
gery, concerns over TXA increasing risk of seizure
have been raised.
The most frequent anticoagulant used world-
wide is warfarin, and other VKA. Fortunately, war-
farin is easy to detect by INR and VET (prolonged
R/TEG or CT/ROTEM) (Fig. 2), and most surgeons
are familiar with its reversal with vitamin K, FFP and
PCC [17,18]. Compared with FFP, PCC reversal is
associated to lower mortality, faster INR reduction
and less volume overload without increasing throm-
boembolic events [19], and thus, favored for urgent
reversal. PCC is commercially available as a four-
factor concentrate (Kcentra) and factor-activated
form (FEIBA). The PCC protocol used at the authors’
institution is in Fig. 4a and b.

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 Coagulopathy in surgical patients Peralta et al.

MASSIVE TRANSFUSION PROTOCOL for Adults

MTP pack PRBC FFP Platelet TXA Fibrinogen Cryoprecipitate rFVIIa
every 30min units units units gram concentrate units μg/kg
gram
#1 6U O+ 6 AB 6 1g over 2-4g bolus
O- women 10min
<50y.
#2 (30mi n) 6 6 - 1g over Repeat dose if 7mg
8h serum levels 8mg i f >85kg
<200mg/dL
#3 (60mi n) 6 6 6 10
#4 (90mi n) 6 6 - 7mg
#5 (120mi n) 6 6 6
#6 (150mi n) 6 6 - 10 5mg
#7 (180mi n) 6 6 6
#8 (210mi n) 6 6 -
#9 (240mi n) 6 6 6 10

FIGURE 2. Massive transfusion protocol of the Hamad Medical Center. FFP, fresh frozen plasma; MTP, Massive Transfusion
Protocol; PRBC, packed red blood cells; rFVIIa, recombinant factor VIIa; TXA, tranexamic acid.

DRUG-INDUCED COAGULOPATHY: DIRECT betrixaban). Due to reliable pharmacokinetics, bio-

ORAL ANTICOAGULANTS availability not affected by diet or other drugs, lower
Direct oral anticoagulants (DOAC) are oral antico- risk of bleeding compared with warfarin and lab
agulants that directly inhibit thrombin (dabigatran) monitorization not required, they quickly became
or factor Xa (rivaroxaban, apixaban, endoxaban, the drug of choice for VTE prophylaxis/treatment

Massive hemorrhage = unstable/transient response

ABCDE + eFAST + IV IO lines

consider: pelvic binder
tourniquet
REBOA
surgery
CT EXTEM>80
acvate MTP (ext. 92151) give PCC 1.500IU or 4U FFP
2U RBC (trauma fridge) + 4gm fibrinogen
1gm TXA
2gm calcium + start rewarming FIBTEM A10/MCF ≤7 and EXTEM A10/MCF ≤45
consider: inotropes give 4gm fibrinogen or 10U cryo

ROTEM ML ≥15% give addional 1gm TXA

normal FIBTEM and EXTEM A10/MCF ≤45

ABG + rapid INR
give 1U platelets (pooled)
CBC, INR, fibrinogen
repeat Q30 min.

FIGURE 3. Rotational thromboelastometry-based coagulopathy algorithm of the Hamad Trauma Center. ABG, arterial blood
gases; CBC, complete blood count; eFAST, extended focused sonographic assessment in trauma; INR, international
normalized ratio; MTP, massive transfusion protocol; RBC, red blood cell; REBOA, resuscitative endovascular balloon
occlusion of the aorta; ROTEM, rotational thromboelastometry; TXA, tranexamic acid.

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The surgical patient

(a)
PCC use in Traumatic Hemorrhage
4F-PCC
Trauma, warfarin (VKA) or NOAC-associated factors II, VII, IX, X
traumatic hemorrhage If not available
consider rFVIIa 90μg/kg

Immediately Evaluate for other

Lab: INR, PTT, fibrinogen, CBC, plat count
give vitamin K 10mg IV stat
give 2U FFP stat
give 4-factor PCC (based INR/body weight)
discuss BP goals
coagulation abnormalities
if fibrinogen <100mg/dL = 4g fib or 10U cryo
if platelet count <100x109/L = 6U plat
if platelet dysfunction = 6U plat, DDAVP 0.3/kg IV
check platelet inhibition = verifynow® P2Y12 assay

INR≤1.4 Repeat INR at

Recheck INR
2, 6, 12 & 24h FEIBA®
INR≥1.5

2U FFP stat INR <4 4-6 >6

Repeat vitamin K Q12hh x2 factor IX U/kg BW 10 25 50
Repeat INR Q60min until ≤1.4 Max dose 1000 2500 5000

(b) PCC use in Traumatic Hemorrhage

4F-PCC
Trauma, warfarin (VKA) or NOAC-associated factors II, VII, IX, X + prot C + S + AT
traumatic hemorrhage If not available
consider rFVIIa 90μg/kg

Immediately Evaluate for other

Lab: INR, PTT, fibrinogen, CBC, plat count
give vitamin K 10mg IV stat
give 2U FFP stat
give 4-factor PCC (based INR/body weight)
discuss BP goals
coagulation abnormalities
if fibrinogen <100mg/dL = 4g fib or 10U cryo
if platelet count <100x109/L = 6U plat
if platelet dysfunction = 6U plat, DDAVP 0.3/kg IV
check platelet inhibition = verifynow® P2Y12 assay

INR≤1.4 Repeat INR at

Recheck INR
2, 6, 12 & 24h Kcentra®
INR≥1.5

2U FFP stat INR <4 4-6 >6

Repeat vitamin K Q12h x2 factor IX U/kg BW 25 35 50
Repeat INR Q60min until ≤1.4 Max dose 2500 3500 5000

FIGURE 4. Prothrombin complex concentrate algorithm of the Hamad Trauma Center. (a) KCENTRA. (b) FEIBA (factor eight
inhibitor bypassing activity).

and are supplanting warfarin. Modern surgeons fre-
quently operate on patients who use DOACs regularly.
One of the major challenges in acute surgical
cases and traumas, is to know whether the patient is
on DOACs. If the patient is able to inform the time
of the last dose, anticoagulation can be considered
fully resolved after five half-lives have elapsed. For
example, dabigatran’s half-life is 12–17 h, thus its
anticoagulation is resolved 2.5–3.5 days after the
last dose.
Routine coagulation tests can help determine if
DOAC anticoagulant effect is present. Thus, INR,
PTT, thrombin time (if dabigatran) and antifactor
Xa activity (if Xa inhibitors) should be done in
patients suspected of taking DOACs who are bleed-
ing, require urgent surgery or invasive procedure
&
[20 ,21–23]. Prolonged INR, PTT and increased anti-
factor Xa activity indicate the presence of antico-
agulants, but not the magnitude (for INR and PTT)
of their effect. Normal INR and PTT do not rule out

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DOAC-induced anticoagulation. Antifactor Xa
activity can be calibrated to a specific anticoagulant,
and thus used to monitor treatment response. For
dabigatran, a normal thrombin time (TT) eliminates
the possibility of dabigatran effect whereas absence
of antifactor Xa activity eliminates presence of any
anti-Xa anticoagulant effect. Viscoelastic tests do
not have a role in managing DOAC-induced coagul-
opathy. Other disadvantages of DOAC include cost,
newness and consequently the lack of experience in
its use by many clinicians. Literature is only
now emerging on the real risk of DOAC-induced
anticoagulation for injured patients. Recent study
analyzing data from the State of Michigan, demon-
strated that antiplatelet medications and/or warfa-
rin are associated with increased risk of mortality
after injury, but not DOACs [24].
The management of major bleeding induced by
DOACs includes the principles discussed under TIC,
plus:
(1) removal of any residual drug in the gastrointes-
tinal (GI) tract with activated charcoal (if taken
within minutes) and/or hemodialysis (for dabi-
gatran only),
(2) TXA administration,
(3) activated PCC (for dabigatran), four-factor inac-
tivated PCC (for Xa inhibitors) [21,25,26],
(4) specific antidotes (andexanet alfa for Xa inhib-
itors, idarucizumab for dabigatran) [25,26].
POSTOPERATIVE THROMBOSIS
It is well established that surgical patients are at
high-risk of VTE (venous thromboembolic events)
because of the underlying surgical disease (i.e.
trauma, cancer, etc.), prolonged bed immobiliza-
tion, surgical trauma, age and inflammation among
others. Unless contra-indicated, most surgical
patients receive both mechanical and pharmaco-
logic VTE prophylaxis [27].
CONCLUSION
The knowledge and role of the surgeon in managing
coagulopathic patients has tremendously evolved
over the last decade. Despite the advantages of
involving coagulation specialists, contemporary
surgeons are primarily responsible for the manage-
ment of both trauma-induced and drug-induced
coagulopathies, which are common causes of exces-
sive surgical bleeding.
In both trauma-induced and drug-induced coa-
gulopathy, the primary goal is to stop the hemor-
rhage while simultaneously correcting hemostasis
and other derangements, such as hypovolemia,
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Coagulopathy in surgical patients Peralta et al.
acidosis and hypothermia. TIC is managed with
early transfusion of blood components guided by
protocols. Most MTPs recommend FFP, fibrinogen
(cryoprecipitate or concentrate) and platelets,
whereas routine TXA is used in many parts of the
world but the USA. Timely interventions and mon-
itorization of hemostasis (i.e. frequent lab tests) are
also commonly used.
The principles of management of drug-induced
coagulopathy are similar to TIC, particularly when
massive bleeding exists. Warfarin and VKA are iden-
tified by abnormally prolonged INR and treated
with PCC or FFP. Evidence points to PCC being
superior to FFP in many instances.
DOACs act by direct inhibition of thrombin or
factor Xa. Lack of clinical experience, routine lab
tests and reversal agents are challenges to managing
bleeding in injured patients taking DOACs or requir-
ing emergent surgery. For such patients, the man-
agement options include administering TXA, PCC
and if available, specific antidotes (i.e. andexanet
alfa for Xa inhibitors or idarucizumab for dabiga-
tran). High index of suspicion and expertise from
involving multidisciplinary teams are the best
approach to these difficult patients.
Acknowledgements
None.
Financial support and sponsorship
None.
Conflicts of interest
S.R. has received honoraria and travel support from
Instrumentation Laboratory SpA, Werfen Company.
The remaining authors have no conflict of interest.
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. Spanh DF, Bouillon B, Cerny V, et al. The European guideline on management
&& bleeding and coagulopathy following trauma: fifth edition. Critical Care 2019;
23:98.
Outstanding work. Multidisciplinary, evidence-based and consensus guidelines to
managing trauma-induced bleeding and coagulopathy. Practical, designed to
standardized care. Arguably the best guidelines in the world for managing TIC.
2. Brenner M, Bulger EM, Perina DG, et al. Joint statement from the American
College of Surgeons Committee on Trauma (ACS COT) and the American
College of Emergency Physicians (ACEP) regarding the clinical use of
Resuscitative Endovascular Balloon Occlusion of the Aorta (REBOA). Trauma
Surg Acute Care Open 2018; 3:e000172.
3. Henry R, Matsushima K, Henry RN. Who would have benefitted from the
prehospital use of Resuscitative Endovascular Balloon Occlusion of the Aorta
(REBOA)? An Autopsy Study. J Am Coll Surg 2019. Jun 5 S1072-
7515(19)30365-5.
4. Sommer N, Schn€ uriger B, Candinas D, et al. Massive transfusion protocols in
nontrauma patients: a systematic review and meta-analysis. J Trauma Acute
Care Surg 2019; 86:4.
www.co-criticalcare.com 673
The surgical patient
5. Shackelford SA, del Junco DJ. Prehospital blood product transfusion and
combat injury survival—reply. JAMA 2018; 319:1167–1168.
6. David J, Wey P, Peyrefitte S. Prehospital blood product transfusion and
combat injury survival. JAMA 2018; 319:1166–1167.
7. Sperry JL, Guyette FX, Brown JB, et al. Prehospital plasma during air medical
transport in trauma patients at risk for hemorrhagic shock. N Engl J Med 2018;
79:315–326.
8. Cannon JW. Prehospital damage-control resuscitation. N Engl J Med 2018;
379:387–388.
9. Weymouth W, Long B, Koyfman A, et al. Whole blood in trauma: a review for
emergency clinicians. J Emergency Med 2019; 56:491–498.
10. Pivalizza EG, Stephens CT, Sridhar S, et al. Whole blood for resuscitation
in adult civilian trauma in 2017: a narrative review. Anesth Analg 2018;
127:157–162.
11. Kaada SH, Apelseth TO, Hagen KG, et al. How do I get an emergency civilian
walking blood bank running? Transfusion 2019; 59(S2):1446–1452.
12. Chang R, Kerby JD, Kalkwarf KJ, et al., PROPPR Study Group. Earlier time to
hemostasis is associated with decreased mortality and rate of complications:
results from the Pragmatic Randomized Optimal Platelet and Plasma Ratio
trial. J Trauma Acute Care Surg 2019; 87:342–349.
13. Drumheller BC, Stein DM, Moore LJ, et al. Thromboelastography and rota-
& tional thromboelastometry for the surgical intensivist: a narrative review. J
Trauma Acute Care Surg 2019; 86:710–721.
Overview on the use of viscoelastic tests (VET) in surgical ICU, and their potential
to directly impact on patient care. The study brings out the lack of standards and
poor methodology of previous studies.
14. Wahlen BM, El-Menyar A, Peralta R, et al. World Academic Council of
Emergency Medicine Experience document: implementation of point-of-care
thromboelastography at an academic emergency and trauma center. J Emerg
Trauma Shock 2018; 11:265–270.
15. 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.
First randomized controlled trial indicating that viscoelastic-based resuscitation may
reduce mortality. It indicates the importance of early identification of the coagulation
defects that can then be directly targeted instead of blind resuscitation.
674 www.co-criticalcare.com
Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.
16. Yates J, Perelman I, Khair S, et al. Exclusion criteria and adverse events in
perioperative trials of tranexamic acid: a systematic review and meta-analysis.
Transfusion 2019; 59:806–824.
17. Younis M, Ray-Zack M, Haddad NN, et al. Prothrombin complex concentrate
reversal of coagulopathy in emergency general surgery patients. World J Surg
2018; 42:2383–2391.
18. Jehan F, Aziz H, Okeeffe TS, et al. The role of four-factor prothrombin complex
concentrates in coagulopathy of trauma: a propensity matched analysis. J
Trauma Acute Care Surg 2018; 85:18–23.
19. Chai-Adisaksopha C, Hillis C, Siegal DM, et al. Prothrombin complex con-
centrates versus fresh frozen plasma for warfarin reversal. A systematic review
and meta-analysis. Thromb Haemost 2016; 116:879–890.
20. Tomaselli GF, Mahaffey KW, Cuker A, et al. 2017 ACC Expert Consensus
& decision pathway on management of bleeding in patients on oral antic-
oagulants. J Am Coll Cardiol 2017; 70:3042–3067.
Comprehensive document from the American College of Cardiology on clinical
decision pathways to manage bleeding patients taking oral anticoagulants.
21. Sholzberg M, Xu Y. Coagulation test interpretation in a patient taking direct
oral anticoagulant therapy. JAMA 2018; 320:1485–1486.
22. Jabet A, Stepanian A, Golmard JL. Are screening tests reliable to
rule out direct oral anticoagulant plasma levels at various thresholds
(30, 50, or 100 ng/ml) in emergency situations? Chest 2018; 153:288–
290.
23. Samuelson BT, Cuker A, Siegal DM, et al. Laboratory assessment of the
anticoagulant activity of direct oral anticoagulants. Chest 2017; 151:
127–138.
24. LaDuke ZJ, Hetch JP, Cain-Nielsen AH, et al. Association of mortality among
trauma patients taking preinjury direct oral anticoagulants versus vitamin K
antagonists. Surgery 2019. [Epub ahead of print]
25. Levy JH, Douketis J, Weitz JI, et al. Reversal agents for nonvitamin K antagonist
oral anticoagulants. Nat Rev Cardiol 2018; 15:273–281.
26. Cuker A, Burnett A, Triller D, et al. Reversal of direct oral anticoagulants:
guidance from the anticoagulation forum. Am J Hematol 2019; 94:697–
709.
27. Venclauskas Linas, Llau Juan V, Jenny J-Y, et al., for the ESA VTE Guidelines
Task Force. European guidelines on perioperative venous thromboembolism
prophylaxis. Eur J Anaesthesiol 2018; 35:134–138.
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