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\begin{document}

\title{Emergency Cardiac Surgery in Patients on Oral Anticoagulants and
Antiplatelet Medications}



\author[1]{Rami Akhrass}%
\author[1]{A. Marc Gillinov}%
\author[1]{Faisal Bakaeen}%
\author[1]{Deena Akras}%
\author[1]{Scott Cameron}%
\author[1]{Jay Bishop}%
\author[1]{Samir Kapadia}%
\author[2]{Lars Svensson}%
\affil[1]{Cleveland Clinic}%
\affil[2]{Cleveland Clinic Main Campus Hospital}%


\vspace{-1em}



  
  \date{May 22, 2024}


\begingroup
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\selectlanguage{english}
\begin{abstract}
Emergency surgery, blood transfusion, and reoperation for bleeding have
been associated with increased operative morbidity and mortality. The
recent increased use of direct oral anticoagulants and antiplatelet
medications have made the above more challenging. In addition,
cardiopulmonary bypass (CPB) with its associated hemodilution,
fibrinolysis and platelet consumption may exacerbate the pre-existing
coagulopathy and increase the risk of bleeding. Management decisions are
typically made on a case-by-case basis. Surgery is delayed when possible
and less invasive percutaneous options should be considered if feasible.
Attention is paid to exercising meticulous techniques, avoiding
excessive hypothermia and treating coexisting issues such as sepsis.
Ensuring a dry operative field upon entry by correcting the coagulopathy
with reversal agents is offset by the concern of potentially hindering
efforts to anticoagulate the patient (heparin resistance) in preparation
for CPB, in addition to possibly increasing the risk of thromboembolism.
Proper knowledge of the anticoagulants, their reversal agents, and the
usefulness of laboratory testing are all essential. Platelet transfusion
remains mainstay for antiplatelet medications. Four-factor prothrombin
complex concentrate is considered in patients on oral anticoagulants if
CPB needs to be instituted quickly. Specific reversal agents such as
idarucizumab and andexanet alfa can be considered if significant tissue
dissection is anticipated such as redo sternotomy, but are costly and
may lead to heparin resistance and anticoagulant rebound.%
\end{abstract}%



\sloppy


\textbf{Emergency Cardiac Surgery in Patients on}

\textbf{Oral Anticoagulants and Antiplatelet Medications}

\textbf{Rami Akhrass, MD,\textsuperscript{1} Marc Gillinov,
MD,\textsuperscript{1} Faisal Bakaeen, MD,\textsuperscript{1} Deena
Akras,\textsuperscript{1} Scott J. Cameron, MD,
PhD,\textsuperscript{2}Jay Bishop, MD,\textsuperscript{2} Samir Kapadia,
MD,\textsuperscript{2}and Lars Svensson, MD, PhD\textsuperscript{1}}

\textsuperscript{\textbf{1}} Department of Thoracic and Cardiovascular
Surgery, \textsuperscript{2}Department of Cardiovascular Medicine,
Heart, Vascular and Thoracic Institute, Cleveland Clinic, Cleveland.
Ohio.

Funding: There was no financial support for this study.

Disclosures: All authors declare no conflicts of interest except: Dr.
Bishop is on speaker bureau for Janssen and Dr. Gillinov is consultant
to Edwards Lifesciences, Medtronic, Abbott, CryoLife, AtriCure, Johnson
and Johnson, ClearFlow and has the right to equity from ClearFlow.

Word count: 3,398

Address for correspondence:

Rami Akhrass, MD

Department of Thoracic and Cardiovascular Surgery

Heart, Vascular and Thoracic Institute

9500 Euclid Avenue

Cleveland, Ohio 44195

akhrasr@ccf.org

\emph{Central Message:}

Emergency cardiac surgery in patients on oral anticoagulants and
antiplatelet medications is challenging. Knowledge of the anticoagulants
and their reversal agents with their limitations is essential.

\emph{Central picture:}

Oral anticoagulants and antiplatelet medications with their reversal
agents

\emph{Keywords:}

Direct oral
anticoagulants-antiplatelets-bleeding-transfusion-coagulopathy-emergency
cardiac surgery.

\emph{1. Introduction:}

Bleeding is a major concern in cardiac surgery with possibly requiring
blood transfusions and re-exploration, both identified as independent
risk factors for increased perioperative morbidity and mortality,
especially when intervening in an emergency
setting.\textsuperscript{1--4} The risk of bleeding is amplified in
patients on oral anticoagulants and antiplatelet medications that have
become a cornerstone in the treatment of conditions, such as strokes,
coronary artery disease (CAD), atrial fibrillation (AF), peripheral
vascular disease, and deep venous thrombosis (DVT).\textsuperscript{5,6}

Over 6-million patients are on anticoagulants and this number is
expected to rise to 12-million in 2030, mainly due to the aging
population with an increased prevalence of AF, and to the earlier
diagnosis of occult AF with use of implantable loop
recorders.\textsuperscript{5,7} Direct oral anticoagulants (DOACs), such
as direct thrombin inhibitor (dabigatran) and direct factor Xa
inhibitors (rivaroxaban, apixaban, edoxaban, betrixaban), have become
first-line choices in the treatment and prevention of thromboembolism as
well as stroke prophylaxis in patients with
AF.\textsuperscript{6}Randomized trials have demonstrated the
superiority of dabigatran (RE-LY trial) and apixaban (ARISTOTLE trial)
over the traditionally used vitamin-K antagonists (VKAs) in
thromboembolic stroke prevention.\textsuperscript{8,9} In addition,
DOACs have several other advantages including, rapid onset in their
action limiting the need for bridging, less drug-drug and drug-food
interactions, and easier use with reduction of blood level monitoring.

Anticoagulants also include antiplatelet medications, such as aspirin
(ASA) and the P2Y\textsubscript{12} receptor antagonists (clopidogrel,
ticagrelor and prasugrel), used for the treatment of CAD, acute coronary
syndrome (ACS) and following percutaneous coronary interventions (PCI).
Patients frequently receive dual antiplatelet medications consisting of
ASA and a P2Y\textsubscript{12} receptor antagonist, shown to improve
survival and reduce in-stent thrombosis.\textsuperscript{10}

The above landscape has made operating on patients receiving oral
anticoagulants and antiplatelet medications inevitable and an
unfortunate reality. We sought to review available literature with
regards to guidelines on management of patients receiving above
medications who require emergency cardiac operations. Informed consent
and institutional review board approval were not required and were
waived for the purpose of this study.

\emph{2. Value and limitations of laboratory testing:}

Examination of the patient's coagulation and hematological profiles is
critical; however; treatment options hinge upon proper knowledge of the
usefulness of various laboratory testing available. Normal laboratory
values are usually reassuring but may not always translate into clinical
hemostasis. It is helpful to know the mechanism of action of the drug at
hand and its effect on the coagulation cascade to develop an
understanding of the true value and usefulness of various blood tests
(Figure 1). For example, the international normalized ratio (INR) was
developed to monitor VKAs and has limited value in
DOACs.\textsuperscript{11}

The degree of anticoagulation and drug levels are of paramount
importance in determining the course of action. Typically, the
anticoagulant washes out after 5 half-lives have elapsed, taking into
account the patient's underlying renal and hepatic functions
(Table1).\textsuperscript{12} Main advantages of DOACs include their
rapid onset of action (Cmax in most cases is 1-4 hours) and short
half-lives (9-15 hours, with the exception of betrixiban of 37 hours).
In addition, the pharmacodynamic effect of this class of anticoagulants
is even shorter, unlike warfarin that has a much longer pharmacodynamic,
compared to its pharmacokinetic, half-life. Thus, urgent reversal of
DOAC agents may not always be necessary; however, in emergency cases,
monitoring of DOAC levels might be helpful, with several important
considerations to take note of when evaluating laboratory values:

\textbf{-Prothrombin time (PT)} : There is little correlation between PT
level and DOACs.\textsuperscript{11,13} PT is more reliable with higher
dabigatran levels.\textsuperscript{13}

\textbf{-Thrombin time (TT):} A normal TT virtually excludes clinically
relevant dabigatran levels; however, subtherapeutic levels of dabigatran
may prolong TT and is most useful as a quantitative
tool.\textsuperscript{11}

\textbf{-Dilute thrombin time (dTT):} measured by hemocolt, correlates
well with dabigatran levels and decreases the sensitivity of TT test by
diluting the patient's sample with normal plasma.\textsuperscript{14}

\textbf{-Liquid chromatography} or \textbf{(Tandem mass spectrometry)} :
is the gold standard for assessing DOAC concentration; however, there is
minimal clinical outcome data and the test may not be widely available
in clinical settings.\textsuperscript{11,15}

\textbf{-Ecarin Clotting Time:} This clotting assay uses ecarin derived
from the saw-scaled viper and is used to measure the activity of direct
thrombin inhibitors such as dabigatran. This test relies on both the
prothrombin and fibrinogen in the patient's sample and if abnormal can
result in issues with interpretation. The \textbf{Ecarin Chromogenic
Assay} is independent of variability in prothrombin and/or fibrinogen
levels and is not influenced by VKA.\textsuperscript{16}

\textbf{-Anti-Xa activity} : The absence of anti-factor Xa activity
excludes any clinically significant drug levels, but the test may not be
widely available.\textsuperscript{17}

\textbf{-Thromboelastography (TEG) or Rotational thromboelastometry
(ROTEM)} : Thrombin is generated in the TEG or ROTEM sample cups and may
produce a false normal test despite the presence of clinical
coagulopathy. TEG and ROTEM may not detect platelet defect due to ASA,
dipyridamole or P2Y\textsubscript{12} receptor antagonists. A
dose-dependent increase in ROTEM clotting time was noted for DOACs and
low levels of edoxaban, rivaroxaban or dabigatran only poorly impacted
ROTEM tests. Apixaban had only a low effect even at high
concentrations.\textsuperscript{18}

-\textbf{Quantra QPlus} : A novel point-of-care platform that uses
ultrasonic pulses to characterize dynamic changes in viscoelastic
properties of a blood sample during coagulation. In a prospective study,
the Quantra predicted clinical need for platelet transfusion but not for
fresh frozen plasma (FFP).\textsuperscript{19}

\emph{3. Management:}

Several recommendations can be made concerning the acute management of
coagulopathy in patients undergoing emergent cardiac surgical
intervention depending on the anticoagulant and are summarized in (Table
2).

1-Activated oral charcoal is given if DOAC was last ingested within 2-4
hours.

2-Vitamin K (5-10 mg IV) is administered for VKA reversal; however, its
effect may be too slow for emergent surgery.\textsuperscript{20}

3-Non-specific prohemostatic agents can be used including four-factor
prothrombin complex concentrate (4F-PCC) with a recommended dose of
25-50 IU/kg. Four-factor PCC was found to be close to 70\% effective in
achieving hemostasis in patients with major
bleeding.\textsuperscript{21,22} In a review by Goldstein et
al\textbf{,} 4F-PCC was superior to FFP for rapid INR reversal and
effective hemostasis in patients requiring VKA reversal for urgent
surgical procedures (most were non-cardiac).\textsuperscript{23} One
study reported 40 patients on oral VKA, mainly for AF, who underwent
urgent cardiac surgery and were randomized to FFP and PCC. Patients
received, pre cardiopulmonary bypass (CPB), either 2 units of FFP or
half of the calculated PCC dose. Post-bypass, they received 2 more units
of FFP or the second half of PCC dose. It was noted that reversal with
PCC was faster and bleeding was less compared to
FFP.\textsuperscript{24}

4- Three-factor PCC has less concentration of factor VII compared to 4F-
PCC and can be used for reversal of VKA. Both 4F-PCC and 3F-PCC do not
require large volumes to be administered, an advantage in patients with
heart failure and fluid overload.

5-Antifibrinolytic agents such as aminocaproic acid and tranexamic acid
are frequently used even in elective cases. They exert their effect by
inhibiting plasminogen activators and to a lesser degree through
antiplasmin activity, thereby minimizing the untoward effects of
fibrinolysis seen with CPB and challenging an already attenuated
hematologic profile.\textsuperscript{25}

6-Two specific DOAC reversal agents (antidotes) have been approved by
the US Food and Drug administration (FDA): idarucizumab for reversal of
dabigatran and andexanet alfa for reversal of apixaban, edoxaban and
rivaroxaban.\textsuperscript{26} Dosing is typically based on predicted
concentration of the anticoagulant depending on its dose and last time
of ingestion.

Idarucizumab was studied in patients with dabigatran--associated
bleeding (REVERSE-AD trial). Most common sites of bleeding were
gastrointestinal and intracranial. Median time to achieve hemostasis was
2.5 hours and there was no correlation with drug levels. None underwent
CPB and several patients suffered thromboembolic events, 50\% of which
occurred within 5 days.\textsuperscript{27} In a multicenter experience
in Spain, Idarucizumab was used in 56 heart transplant patients, 7.5\%
required reoperations for bleeding and 66\% were transfused with blood
products.\textsuperscript{28}

The use of andexanet alfa (a recombinant modified factor Xa protein) as
an antidote was reported on 352 patients on factor Xa inhibitors who had
major bleeding (64\% intracranial and 26\% gastrointestinal). It
markedly reduced anti-factor Xa activity with good or excellent
hemostatic effects in 82\% patients.\textsuperscript{29} In one
prospective study of 66 patients on factor Xa inhibitors and presenting
with major bleeding, reversal was effective in 68\%, ineffective in 32\%
and 8\% suffered a major thromboembolic event.\textsuperscript{30}

These drugs are costly and have a short half-life that may result in
anticoagulant rebound when infusion is stopped. On the other hand,
specifically andexanet alfa, can bind to heparin-antithrombin complexes
precluding therapeutic activated clotting time (ACT) necessary for CPB
(heparin resistance) and should be used with
caution.\textsuperscript{31--33} It is worthwhile reporting on a
potential promising universal antidote (ciraparantag) to all DOACs that
binds to the anticoagulants via noncovalent hydrogen bonds, but is still
under investigation and not available for commercial
use\textsuperscript{34} (Table 3).

7-Hemodialysis (HD) is thought not to be very beneficial with regards to
urgent reversal as most DOACs, including rivaroxaban and apixaban, are
highly protein bound. Although edoxaban is relatively low protein bound,
it is not well cleared by HD. Betrixiban is 60\% protein bound, but
there is paucity of data demonstrating the effectiveness of dialysis in
clearing the drug. Dabigatran is 35\% protein bound and HD has been
proposed as a possible treatment strategy in patients with major
bleeding. Published reports have shown that 4-hours of HD can reduce the
plasma concentration of dabigatran by up to 68\%, with a recent
meta-analysis suggesting HD may be of some benefit in patients requiring
urgent reversal.\textsuperscript{35}

8-Antiplatelet medications: Aspirin irreversibly acetylates a serine
residue of cyclooxygenase 1, which ultimately decreases the synthesis
and release of the platelet-activating molecule thromboxane A2
(TxA\textsubscript{2}). The aspirin effect is permanent and lasts for
the lifespan of the circulating platelet (7-10
days).\textsuperscript{36} In was noted that there was no increased risk
of mortality or bleeding among patients undergoing coronary artery
bypass grafting (CABG) perioperatively taking ASA compared with placebo,
but it was associated with increased transfusion
requirements.\textsuperscript{37,38} Oral P2Y\textsubscript{12} receptor
antagonists, such as clopidogrel\textbf{,} prasugrel and ticagrelor, can
be more problematic given their more potent antiplatelet effect. Like
aspirin, the thienopyridine P2Y\textsubscript{12} receptor antagonists
clopidogrel and prasugrel covalently modify the receptor and the
antiplatelet effect lasts for the lifespan of the platelet. Ticagrelor;
however, is a non-thienopyridine P2Y\textsubscript{12} receptor
antagonist and its antiplatelet effect lasts for approximately 4 days.
In patients undergoing urgent CABG with prior ticagrelor administration,
serial platelet aggregometry revealed a return to normal platelet
function within 3-days.\textsuperscript{39}

The intraoperative use of Cytosorb adsorption, previously used in septic
patients, was tested in Europe on 55 patients who were on ticagrelor or
rivaroxaban and required emergency cardiac surgery, mostly CABG. The
Cytosorb adsorpter is included in the CPB circuit between the oxygenator
and the venous reservoir. The filter is made of biocompatible porous
beads capable of removing substances based on pore capture and surface
adsorption. It was effective in reducing bleeding complications with the
majority of patients not requiring transfusions and none required
re-exploration (compared to 37.5\% in the non-Cytosorb
group).\textsuperscript{40} The FDA has issued an Emergency Use
Authorization for the use of Cytosorb to treat COVID-19 patients and
respiratory failure; however, further testing to corroborate the
findings in the European study and determine its effect on other
substrates such as albumin and antibiotics will be important.

\emph{4. Discussion:}

The deleterious effects of blood transfusions are well documented and
calls have been made to restrict their use. In a study of greater than
18,000 patients at The Cleveland Clinic over 10-years, it was noted that
transfusions and reoperations for bleeding were independently associated
with increased risk of morbidity and mortality (8.5\% vs
1.8\%).\textsuperscript{2} Similarly, others showed a higher mortality
(14.2\% vs 3.4\%) in patients requiring re-exploration compared to the
rest, and the amount of packed red blood cells (pRBC) was associated
with an incremental increased risk (0.25\% for each unit
transfused).\textsuperscript{41} In another study of almost 5,400
patients, those who required re-exploration for bleeding had a twofold
mortality increase in early postoperative period, as well as an overall
mortality increase beyond 90 days.\textsuperscript{42} In addition, a
meta-analysis review of observational studies showed that preoperative
exposure to clopidogrel was associated with increased risk of death,
blood loss, transfusions and reoperations.\textsuperscript{44} An
individualized strategy for clopidogrel suspension was suggested in
patients undergoing CABG following ACS, guided by platelet function
testing, which significantly reduced postoperative bleeding and blood
use.\textsuperscript{45}

A review of 528,686 CABG patients, from the Society of Thoracic Surgery
(STS) database, revealed that patients requiring emergent surgery or
were on antiplatelet medications within 24-hours before the operation
had a significantly higher rate of re-exploration for bleeding, with an
increased risk-adjusted mortality of 5.9\% compared to 2.0\% for
others.\textsuperscript{43} Likewise, a meta-analysis of 557,923
patients found emergency surgery and preoperative aspirin use were among
the risk factors resulting in higher rate of re-exploration with an
increased risk of mortality and major morbidity.\textsuperscript{1} In a
separate study, it was noted that patients who received clopidogrel
prior to urgent CABG had a higher rate of re-exploration and blood
transfusions.\textsuperscript{47} Finally, an international prospective
study of patients undergoing urgent CABG on antithrombotic agents
(ACUITY trial) noted that transfusions of [?] 4 units pRBC was an
independent mortality risk factor for up to one year post
surgery.\textsuperscript{46}

The decision process is easier in patients for whom surgery can be done
semielectively or at least delayed for adequate anticoagulant washout,
as per the guidelines set forth by the STS.\textsuperscript{48} Patients
with high risk for thromboembolism can be bridged on short half-life
medications such as heparin that can be quickly reversed. Patients with
multi-vessel CAD on anticoagulants presenting with ST-elevation
myocardial infarction (STEMI) would undergo PCI of the culprit vessel
and surgical revascularization delayed until adequate anticoagulant
washout.

However, it is inevitable that surgeons will be confronted where
emergency surgery is needed for patients on anticoagulants. Examples
would be a patient with ACS where PCI in not possible due to coronary
anatomy or lack of expertise, or a patient with an aortic dissection,
where the risk of bleeding is further aggravated by coagulopathy induced
by hypothermia and circulatory arrest, resulting in platelet dysfunction
and reduced activity of clotting factors.\textsuperscript{49} Other
examples include endocarditis and sepsis, where underlying issues, such
as dilution, hemolytic anemia and disseminated intravascular
coagulopathy (DIC) worsen the coagulopathy. In addition, CPB creates its
own insults of endothelial activation, fibrinolysis, and consumption of
platelets and coagulation factors, all aggravating an already attenuated
hematological profile.\textsuperscript{50}

Several documents and guidelines have been established with regards to
treatment of patients on oral anticoagulants presenting with an acute
bleed, or in the perioperative setting of emergency surgeries, mainly
non-cardiac, where correction of the coagulopathy typically takes place
before the incision is made.\textsuperscript{20,51} Cardiac surgery
patients, on the other hand, present a unique challenge, especially in
an emergency setting, where answers to some of the following questions
may shed some light on the dilemma and aggressiveness in attempting to
correct an underlying coagulopathy:

1-Does the preoperative administration of reversal agents hamper
subsequent heparinization and achievement of therapeutic ACT needed for
CPB? If so, when is the best time to administer, pre or post pump? While
a normal coagulation profile is initially desirable to ensure a dry
entry and minimize blood loss, the patient will paradoxically require
full anticoagulation shortly thereafter for initiation of CPB.
Therefore, it is paramount that any treatment modalities instituted to
correct the coagulopathy do not interfere with the ability to fully and
rapidly anticoagulate with heparin in preparation for CPB. Reports have
emerged on the difficulty of adequately anticoagulating patients with
heparin required for CPB or even during endovascular repair procedures
following the administration of andexanet alfa that has led to heparin
resistance.\textsuperscript{33} This is due to the binding of andexanet
alfa to heparin-antithrombin complexes preventing them from exerting
their anticoagulant function. Higher doses of heparin or antithrombin
supplementation maybe required to achieve therapeutic
anticoagulation.\textsuperscript{31,32}

Therefore, pre CPB administration of specific reversal antidotes in a
situation of primary sternotomy for emergency CABG, where minimal tissue
dissection is anticipated, heparin resistance might be problematic if
quick initiation of CPB is needed. On the other hand, redo-sternotomy
cases require meticulous tissue dissection and a ``dryer'' operative
field, where pre CPB correction of underlying coagulopathy would be
desirable. Surgical judgment will dictate the need of full or partial
correction of coagulopathy depending on the anticipated amount of
dissection, realizing that heparin resistance may become an issue later
on.

2-What is the risk of thromboembolism? Attention is generally directed
towards avoiding bleeding, but discussion is not complete without noting
the risk of thromboembolism secondary to anticoagulant
interruption.\textsuperscript{8,9} Postoperative bleeding will require
longer delay in the resumption of the anticoagulant with the potential
of increased postoperative thromboembolic risk. While achieving near
normal lab values is desirable, the reversal agents may have the
unwanted effect of causing thrombosis, and their impact on improving
outcomes is not well established.\textsuperscript{24,30} However, the
thromboembolic rate with PCC treatment was noted to be comparable with
that of anticoagulation discontinuation without reversal. While the
studies examining the reversal agents were prospective, they were
open-labeled and lacked a control group.\textsuperscript{22,27} The
timing of postoperative anticoagulant resumption should be based on the
bleeding vs thrombotic risk according to the CHA2DS2-VASc
Score.\textsuperscript{34}

3-Is postoperative anticoagulation needed, as in cases with mechanical
valves or post pump assist devices? These patients present additional
challenges, where aggressive correction of coagulopathy may lead to
valve or device circuit thrombosis. The use of heparin-bonded tubing as
well as biological rather than mechanical valves should be considered.
Surgical judgment and patient's clinical condition will have to dictate
proper course of action. For example, slight increase in chest tube
drainage can be tolerated, and aggressive correction of lab values if
patients are not bleeding is probably unnecessary and should be avoided.

4-Was the underlying indication for preoperative anticoagulation
addressed at the time of surgery? An example would be concomitant MAZE
and left atrial appendage (LAA) clipping for preexisting AF (STS Class I
recommendation, evidence level A and B), where the risk of future
postoperative embolization may be reduced such that the coagulopathy can
be corrected and the need for postoperative anticoagulation avoided or
at least delayed.\textsuperscript{52}

Proposals in the literature on management of the cardiac surgical
patient on anticoagulants in the acute setting are mainly based on
expert opinion and extrapolation from non-emergent cardiac or emergent
non-cardiac guidelines, rather than from controlled trials. Proper
knowledge of mechanism of action of the anticoagulants and the
effectiveness as well as potential limitations of available reversal
agents is important. These agents are costly and may lead to heparin
resistance that could preclude timely institution of CPB; therefore,
their judicious use is essential. Decision is typically made on a
case-by-case basis considering product availability, local hospital
policies and overall patient's clinical condition. The development of
hospital and system-wide strategies that promote a multidisciplinary
approach utilizing evidence-based clinical practices ensures appropriate
and judicious use of these important resources.

\emph{5. Conclusion:}

Currently, there are no randomized trials or well-designed observational
studies that could direct the treatment of the difficult subset of
patients on oral anticoagulants or antiplatelet medications requiring
emergent cardiac surgery. In addition, the best metrics for complete
resolution of anticoagulant effect in not always known or available for
the newer DOACs. Therefore, at the present time only general
recommendations can be made and used as guiding principles based on
expert opinion that include the following:

\begin{enumerate}
\tightlist
\item
  Consider less invasive alternatives to surgery, such as PCI for ACS.
\item
  Delay surgery when possible.
\item
  Treat coexisting issues such as sepsis.
\item
  Avoid excessive hypothermia.
\item
  Exercise meticulous surgical techniques.
\item
  Correct underlying coagulopathy. Four-factor PPC can be used in
  patients on VKAs or DOACs, especially if CPB needs to be instituted
  quickly.
\item
  Specific reversal agents such as idarucizumab and andexanet alfa can
  be considered in cases where significant tissue dissection is
  anticipated such as redo sternotomy; however, this may lead to heparin
  resistance and anticoagulant rebound.
\item
  Cytosorb adsorption may be promising for patients on antiplatelet
  medications; otherwise, platelet transfusion might be necessary.
\end{enumerate}

Patients on oral anticoagulants and antiplatelet medications requiring
emergency cardiac surgery present unique and formidable treatment
challenges. Benefits and risks of delaying or proceeding with surgical
intervention should be carefully weighed, through an individualized
heart-team approach. Treatment paradigms described above along with
specific institutional guidelines, algorithms and policies for urgent
reversal of anticoagulants are all helpful and should be developed to
ensure best possible outcomes.

\emph{Abbreviations:}

ACS: acute coronary syndrome

ACT: activated clotting time

AF: atrial fibrillation

CABG: coronary artery bypass grafting

CAD: coronary artery disease

CPB: cardiopulmonary bypass

DOAC: direct oral anticoagulation

FFP: fresh frozen plasma

INR: international normalized ratio

VKA: vitamin-K antagonist

PCC: prothrombin complex concentrate

PCI: percutaneous coronary intervention

pRBC: packed red blood cell

STS: society of thoracic surgery

\emph{References:}

1. Biancari F, Mikkola R, Heikkinen J, Lahtinen J, Airaksinen KEJ,
Juvonen T. Estimating the risk of complications related to
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