REVIEW

CURRENT
OPINION Perioperative management of antiplatelet therapy in
noncardiac surgery
Daniela C. Filipescu a,b, Mihai G. Stefan b, Liana Valeanu a,c,
and Wanda M. Popescu d

Purpose of review
Perioperative management of antiplatelet agents (APAs) in the setting of noncardiac surgery is a
controversial topic of balancing bleeding versus thrombotic risks.
Recent findings
Recent data do not support a clear association between continuation or discontinuation of APAs and rates of
ischemic events, bleeding complications, and mortality up to 6 months after surgery. Clinical factors, such as
indication and urgency of the operation, time since stent placement, invasiveness of the procedure,
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preoperative cardiac optimization, underlying functional status, as well as perioperative control of supply–
demand mismatch and bleeding may be more responsible for adverse outcome than antiplatelet management.
Summary
Perioperative management of antiplatelet therapy (APT) should be individually tailored based on consensus
among the anesthesiologist, cardiologist, surgeon, and patient to minimize both ischemic/thrombotic and
bleeding risks. Where possible, surgery should be delayed for a minimum of 1 month but ideally for 3–6
months from the index cardiac event. If bleeding risk is acceptable, dual APT (DAPT) should be continued
perioperatively; otherwise P2Y12 inhibitor therapy should be discontinued for the minimum amount of time
possible and aspirin monotherapy continued. If bleeding risk is prohibitive, both aspirin and P2Y12
inhibitor therapy should be interrupted and bridging therapy may be considered in patients with high
thrombotic risk.
Keywords
antiplatelet therapy, bleeding, major adverse cardiovascular events

INTRODUCTION and pathways to inhibit their function. The main

Antiplatelet therapy (APT) is the cornerstone of phar-
macological treatment aimed at preventing arterial
thrombotic events and their recurrence. Perioperative
discontinuation of APT increases the risk of throm-
botic events, whereas continuation increases
the bleeding risk during and after the procedure
&&
[1,2 ]. Despite multidisciplinary collaborative efforts
documented in national/international guidelines,
recommendations, and algorithms, the optimal peri-
operative management of patients on APT is still a
&& && && &&
matter of debate [1,2 ,3 ,4,5 ,6,7 ]. The decision-
making process is complex and should be individually
tailored based on consensus among the anesthesiolo-
gist, cardiologist, surgeon, and patient to minimize
both ischemic/thrombotic risk and bleeding risk.
ANTIPLATELET AGENTS
Antiplatelet agents (APAs) include a diversity of
molecules which act on different platelet receptors
oral APAs used in prevention of atherothrombosis
are: acetylsalicylic acid (ASA), clopidogrel, prasugrel,
and ticagrelor. ASA irreversibly inhibits cyclooxy-
genase-1 and therefore thromboxane A2 synthesis.
Clopidogrel, prasugrel, and ticagrelor inhibit the
ADP pathway by blocking the P2Y12 platelet recep-
&&
tor [5 ]. Clopidogrel and prasugrel belong to the
a
Department of Anaesthesiology and Intensive Care Medicine, Carol
Davila University of Medicine and Pharmacy, bDepartment of Cardiac
Anaeshesia and Intensive Care II, cDepartment of Cardiac Anaeshesia
and Intensive Care I, Emergency Institute for Cardiovascular Diseases,
‘Prof. Dr C. C. Iliescu’, Bucharest, Romania and dThoracic and Vascular
Anesthesia Section, Yale School of Medicine, New Haven, Connecticut,
USA
Correspondence to Wanda M. Popescu, MD, Thoracic and Vascular
Anesthesia Section, Yale School of Medicine, 333 Cedar Street, TMP 3,
New Haven, CT 06520, USA. Tel: +1 203 785 2802;
e-mail: wanda.popescu@yale.edu
Curr Opin Anesthesiol 2020, 33:454–462
DOI:10.1097/ACO.0000000000000875

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 Perioperative management of anti platelet therapy Filipescu et al.
KEY POINTS
 Surgery should be delayed at least for 1 month and
ideally for 3–6 months from a cardiac event.
 Aspirin indicated for secondary prevention of ischemic
events should be continued perioperatively, except in
high bleeding risk procedures (neurosurgery).
 DAPT could be continued perioperatively in patients
with high risk of thrombosis and low bleeding risk but
de-escalating from ticagrelor or prasugrel to
clopidogrel can further decrease the bleeding risk.
 In case of surgery with intermediate or high bleeding
risk, APAs should be discontinued for as short as
possible (i.e., aspirin and ticagrelor 3–5 days,
clopidogrel 5 days, and prasugrel 7 days) and be
resumed postoperatively as soon as hemostasis
is controlled.
 Individualized APT, using a web-based tool providing
real-time personalized risk prediction of thrombotic risk
or bleeding risk at 5 years with and without DAPT, is
more appropriate than a ‘one-size-fits all’ approach.
thienopyridine group, irreversibly blocking the
P2Y12 receptors. In contrast, ticagrelor, a cyclopen-
tyltriazolopyrimidine, is a reversible P2Y12 inhibi-
tor. The onset of action is faster for ASA and
ticagrelor as compared with prasugrel and clopidog-
rel; the latter need activation from a prodrug form
[8,9]. Clopidogrel has a more complicated and less
efficient metabolism which results in a wide inter-
individual variability. Due to the genetic polymor-
phism involved in the activation of clopidogrel, up
to 40% of patients are considered ‘poor responders’,
as they present with high platelet reactivity
during therapy [10]. Genetic variations also influ-
ence ASA effects, as 57% of patients may not opti-
mally respond to therapy [11,12].
As expected, the major adverse effect of APT is
bleeding. The lowest bleeding risk is seen with ASA,
while the highest one is seen with prasugrel. Dual
APT (DAPT) (ASA þ P2Y12 inhibitor) carries a higher
bleeding risk than monotherapy, but interindivid-
&&
ual variability is significant [2 ,5 ].
&&
CLINICAL USE OF ANTIPLATELET AGENTS
APAs are indicated for primary and secondary pre-
vention of atherothrombosis, as monotherapy (ASA
or P2Y12 inhibitor) or DAPT. The use of ASA in
individuals without cardiovascular disease (primary
prevention) is associated with a lower risk of cardio-
vascular events but an increased risk of major bleed-
&
ing [13 ]. Currently, primary prevention with ASA is
indicated only in patients 40–70 years of age who
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are of higher risk of atherosclerotic cardiovascular
disease but not at increased bleeding risk [14]. Older
patients exhibit an unfavorable risk–benefit profile
for ASA [15]. Also, the indication for ASA should be
& &
individualized in people with diabetes [16 ,17 ].
Secondary prevention with APT is recom-
mended in patients with stable coronary artery dis-
eases (SCAD), acute coronary syndromes (ACS), after
coronary artery bypass grafting or percutaneous cor-
onary interventions (PCIs), transcutaneous aortic
valve replacement, peripheral arterial disease
&
(PAD), carotid disease, and stroke [8,9,18 ]. In ACS
patients, DAPT using ticagrelor or prasugrel (rather
than clopidogrel) is indicated [4,7 ,18 ]. For
&& &
patients with SCAD undergoing PCI, DAPT with
clopidogrel is the therapy of choice [4,7 ,18 ].
&& &
DAPT is also indicated in some patients with recent
stroke [19]. However, in patients with prior strokes
or PAD, monotherapy with ASA or clopidogrel is
sufficient [9].
OPTIMAL DURATION OF ANTIPLATELET
THERAPY FOR SECONDARY PREVENTION
When indicated for secondary prevention, ASA signif-
icantly reduces the risk of subsequent cardiovascular
&&
events and is indicated as a lifelong therapy [3 ,8].
The optimal duration of DAPT remains a con-
troversial topic. Some differences exist between the
recommendations set forth by the American and the
&& &&
European societies [4,7 ,20 ]. In the setting of
SCAD, the American College of Cardiology/Ameri-
can Heart Association (ACC/AHA) guidelines recom-
mend 2 weeks of DAPT for patients undergoing
balloon angioplasty and 4 weeks for those undergo-
ing bare-metal stent (BMS) placement. In patients
with drug-eluting stents (DES), recent ACC/AHA
guidelines encourage shifting toward a shorter
DAPT regimen than previously recommended (from
12 to 6 months), which may be adapted (prolonged
or shortened) according to patient-specific risks of
ischemia/thrombosis and bleeding [4]. For patients
with high bleeding risk, the duration of DAPT can be
shortened to 3 months [4]. The efficacy and safety of
shorter durations of DAPT has been confirmed in
recent trials and meta-analyses [21,22].
However, the recent European guidelines no
longer consider the type of implanted stent as a
useful parameter for defining the duration of a
DAPT. The European recommendation is of 6-
month DAPT duration irrespective of the type of
&&
stent, for patients with SCAD [7 ]. Patients present-
ing with ACS represent a special category; irrespec-
tive of the type of intervention, both guidelines
recommend a 12-month DAPT duration as optimal
&& &&
[4,7 ,20 ].
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Anesthesia and medical disease
Different scores and tools have been developed
to stratify bleeding risk and thrombotic risk in the
setting of DAPT and help determine optimal dura-
&&
tion [7 ,8,23]. A free web-based tool was developed
to provide real-time personalized risk prediction of
ischemic or bleeding risk at 5 years [23].
In patients with PCI and high thrombotic risk, a
longer DAPT duration is determined by angio-
graphic and clinical factors [ACS, previous myocar-
dial infarction (MI), previous stent thrombosis,
decreased ejection fraction, chronic kidney disease,
&& && && &
and diabetes mellitus] [2 ,3 ,4,7 ,8,18 ]. Similarly,
patients at high bleeding risk (impaired renal func-
tion, diabetes mellitus, cancer, history of spontane-
ous bleeding, on concomitant coagulation altering
drugs, thrombocytopenic, low body weight, females
and elderly) may benefit from a shorter duration of
&&
DAPT [3 ,4,8,24]. As such, for patients at high
bleeding risk, the DAPT duration can be shortened
to 1 month (European guidelines, irrespective of
stent type) or 6 months for patients with ACS (both
&& &&
guidelines) [4,7 ,20 ].
In patients with high bleeding risk, alternatives
to standard duration DAPT have been developed. A
short-term DAPT course (1–3 months) can be fol-
&
lowed by monotherapy using ticagrelor [25,26 ].
Another option would be de-escalating therapy
1 month after PCI for ACS, from DAPT with potent
P2Y12 inhibitors to clopidogrel-based DAPT [27].
PERIOPERATIVE MANAGEMENT OF THE
ANTIPLATELET THERAPY
Management of APT in the perioperative period is
determined by answering several questions. First,
did the patient complete the optimal duration of
APT recommended? Second, what is the thrombotic
risk associated with temporary cessation of therapy
periprocedurally? Third, does the patient need to
interrupt ASA or DAPT for the proposed procedure –
what is the bleeding risk for different procedures?
Fourth, what are mitigating risk strategies in
patients undergoing nonelective procedures at
increased thrombotic risk?
Generally, the perioperative team needs to
weigh the consequences of delaying an invasive
procedure to optimize APT and find a balance
between the risks of thrombosis, perioperative
major adverse cardiovascular events (MACE) and
&
procedural bleeding [28 ,29].
PERIOPERATIVE THROMBOTIC RISK
Regardless of continuation or discontinuation of
APT, surgery causes a systemic inflammatory
response with activation of the coagulation system
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predisposing patients to thrombotic complications
&& &
[3 ,28 ,30]. Moreover, perioperative discontinua-
tion of long-term APT is associated with increased
risk of cardiovascular thrombotic events, with cata-
strophic consequences in patients recently treated
&& &&
with PCI [2 ,3 ].
Approximately 25% of stented patients require
noncardiac surgery (NCS) within 2 years after PCI
[31]. These patients are at a higher risk of periopera-
tive MACE as compared with those without stents
&
[28 ,31–33]. The risk depends on the individual
ischemic risk and is reportedly as high as 21% [34].
The highest risk is seen in the first month after
stenting [35]. Although there is a general consensus
on avoiding surgery early after PCI, NCS was reported
in one of every 29 patients with recent PCI, mandat-
ing for better timing of NCS after PCI [35].
When NCS is anticipated, PCIs with the lowest
thrombotic risk and the shortest DAPT requirements
should be utilized. When surgery is planned in the first
6 months after PCI, new-generation DES are safer than
old-DES or BMS. When surgery is planned 6 months
after PCI, the type of stent may be less relevant to the
thrombotic risk [32]. Significantly, PCI with DES opti-
mized for biocompatibility is safe and efficacious, even
with only 1 month of DAPT [36].
While planning surgery to optimize the dura-
tion of APT is recommended by multiple guidelines
[1,37,38], it is sometimes difficult to foresee who will
need early surgery. When preparation is not possi-
ble, other options include: procedure postpone-
ment, DAPT discontinuation after the mandatory
minimum period, perioperative continuation of
ASA with interruption of P2Y12 inhibitor for a short
duration, switching from potent APAs to clopidogrel
or bridging from irreversible to reversible P2Y12
&& && &&
inhibitors (Table 1) [1,2 ,3 ,5 ,6,27].
In patients post-PCI, elective NCS should be per-
&& &&
formed after full completion of DAPT [2 ,5 ,39], as
discussed above. Generally, both thrombotic risk
and bleeding risk are highest in the first month
after PCI. In this interval, scheduling NCS should
be discouraged, as DAPT should be continued
&& && &&
[2 ,4,5 ,7 ,8]. However, in patients with stents
implanted for ACS, the risk of events is much higher
in the first 3 months and remains high even 12–24
months after stenting [40]. The minimum DAPT
duration in this setting is 6 months, and optimally
12 months [4]. Generally, if major surgery is under-
taken within 6 months post-PCI, it is safer to perform
it in hospitals where catheterization laboratories are
&& && && &&
available 24/7 [2 ,5 ,7 ,20 ].
Nondeferrable surgery (emergent/urgent proce-
dures) should be performed in patients in
which the risk toward life-loss, organs-loss, or limb-
&&
loss is too high to justify postponing surgery [5 ]. For
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 Perioperative management of anti platelet therapy Filipescu et al.

Table 1. Perioperative management of antiplatelet therapy based on the thrombotic and hemorrhagic risks

Hemorrhagic risk
Low Intermediate High
Type of
surgery Thrombotic risk Aspirin P2Y12 inhibitors Aspirin P2Y12 inhibitors Aspirin P2Y12 inhibitors

Low Continue Discontinuea Continue Discontinuea Discontinue Discontinuea

Elective surgery Intermediate Postpone Postpone Postpone Postpone Postpone Postpone
and high surgeryb surgeryb surgeryb surgeryb surgeryb surgeryb
Nondeferrable Intermediate Continue Continue Continue Discontinuea Continue Discontinuea
surgery
High Continue Continue Continue Discontinuec Continue Discontinuec

a
Discontinue P2Y12 inhibitors as per guideline recommendations (see text) and resume postoperatively.
b
Postpone surgery until full dual antiplatelet therapy completed (minimum mandatory duration).
c
Discontinue oral P2Y12 inhibitors and consider bridging with iv short-acting antiplatelet agents.

emergency procedures in patients on DAPT post-PCI,
the 30 and 180-day mortality can be as high as 6 and
10%, respectively [41]. Urgent procedures are per-
formed in patients who are stable and can be deferred
&& &&
for 24 h or a few days [3 ,5 ]. During this time
period, partial recovery of platelet function can lead
to lower bleeding risk without increasing the risk
of MACE.
PERIOPERATIVE BLEEDING RISK IN
PATIENTS ON ANTIPLATELET THERAPY
Assessment of bleeding risk is another key compo-
nent of preoperative evaluation, both in the elective
and nonelective setting. Bleeding risk is highly
influenced by surgery type and can be divided into
high, intermediate and low risk, depending on the
possibility of achieving adequate hemostasis
&& &&
[3 ,5 ,6,24]. Moreover, the surgeon’s experience
&&
should always be taken into account [5 ,6]. Classi-
fication of surgeries based on bleeding risk is pre-
sented in Table 2.
Several years ago, the POISE-2 trial had brought
into question continuing ASA for NCS (higher risk of
major bleeding 4.6% on ASA versus 3.8% on no APT,
P < 0.04) in a cohort of more than 10 000 patients
[42]. However, in a subanalysis of POISE, ASA proved
to have a protective antithrombotic effect with no
increased risk of bleeding, in patients with prior PCI
&&
[43 ]. Moreover, recent evidence is pointing toward
low or negligible bleeding risk with perioperative
continuation of ASA in abdominal, lung, orthope-
dic, spine, or urologic surgery [44–51].
In contrast, P2Y12 inhibitor-related bleeding risk
is debated. Clopidogrel was associated with nonsig-
nificant increased postpolypectomy bleeding [52],

Table 2. Perioperative bleeding risk

Perioperative bleeding risk Blood transfusion requirement Type of procedure

Low Usually not required Peripheral, plastic, and general surgery biopsies
Easily achieved local hemostasis Minor orthopedic, otolaryngology, and general surgery
Endoscopic procedures
Breast surgery
Carotid and peripheral vascular surgery
Eye anterior chamber
Dental extraction and surgery
Intermediate May be required Major intrathoracic and intraperitoneal surgery
Potentially difficult to achieve local hemostasis; Cardiac surgery
risk of reintervention Open aorta surgery
Major orthopedic surgery
Otolaryngology
Urological surgery
Reconstructive surgery
High Usually required Intracranial neurosurgery
Difficult to achieve local hemostasis; possible Extensive thoracoabdominal dissection
bleeding in a closed space; impact on
mortality and surgery outcome

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Anesthesia and medical disease

but doubled the risk for reintervention due to major
bleeding, without reducing the risk of MACE or
mortality in patients who underwent cardiac and
NCS [53]. However, clopidogrel did not increase
blood loss in general surgery [54,55] and femoral
fractures [56,57].
Robust data on perioperative bleeding risk asso-
ciated with DAPT are lacking. In a large US database,
bleeding and transfusion were recorded in 32 and
21% of patients operated on in the first 6 months
after PCI, respectively [35]. Bleeding risks were high-
est when surgery was performed within 1 month of
PCI, with bleeding patients exhibiting a higher
perioperative mortality (7.9 versus 2.3%). In con-
trast, a meta-analysis of over 30 000 patients on APT
(ASA, clopidogrel, DAPT) at the time of NCS showed
no significant increase in the risk of reintervention
for bleeding. The authors concluded that in many
cases, APT can be safely continued perioperatively in
patients with important indications, such as recent
&&
PCI [58 ]. However, in the same study the risk of
transfusion increased in a stepwise manner depend-
ing on the degree of platelet inhibition (i.e.,
&&
ASA < clopidogrel < DAPT) [58 ]. Importantly,
patients who experience a bleeding episode are also
at higher risk of perioperative MACE [33].
WHICH ANTIPLATELET, WHEN AND HOW
LONG TO DISCONTINUE
PERIOPERATIVELY?
Based on the recent studies evaluating the benefits
and risks of ASA in prevention of perioperative
MACE, the current recommendations are that ASA
monotherapy should be discontinued preopera-
tively if prescribed for primary prevention
[42,59,60] (Fig. 1). If prescribed for secondary pre-
vention, guidelines recommend continuing ASA,
&&
unless bleeding risk is prohibitive [5 ]. Also, peri-
operative ASA may be more likely to benefit rather
than harm patients with prior PCI, and it should be
&& & &&
continued in this clinical scenario [43 ,61 ,62 ].
While most procedures can be safely performed
while on ASA monotherapy, a high bleeding risk
or neurosurgery require ASA discontinuation 3–5
&& &&
and 5–7 days prior, respectively [1,3 ,5 ,6,39]

Emergency
ASA Surgery ASA+ADP Inhibitors
PROCEED Did not complete DAPT
Completed Optimal
Primary Secondary
<2 wks PTCA* Duration DAPT
Prevention Prevention
<4 wks BMS*
< 6 mo BMS**
<3-6 mo DES*,**
<6-12 mo if s/p ACS*,**
Stable CAD, no PCI s/p PCI

Urgent Elective
DELAY
High Risk Surgery Surgery SURGERY
of Bleeding

Low Risk of High Risk Intermediate Risk

Bleeding of Bleeding of Bleeding

Stop ADP Inhibitors Stop ADP inhibitors

Stop ASA Continue Treatment continue ASA
and ASA

PROCEED WITH SURGERY Bridging Therapy

* ACC/AHA Guidelines
** ESC Guidelines

FIGURE 1. Algorithm for perioperative management of antiplatelet therapy in patients with coronary artery disease. ACS,
acute coronary syndrome; ADP, adenosine diphosphate; ASA, aspirin; BMS, bare-metal stents; CAD, coronary artery disease;
DAPT, dual antiplatelet therapy; DES, drug-eluting stent; PCI, percutaneous coronary intervention; PTCA, percutaneous
transluminal coronary angioplasty. Adapted with permission [9].

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(Fig. 1). In patients naı̈ve to APT, ASA should not be
initiated preoperatively to reduce the risk of
perioperative MACE.
European guidelines suggest that NCS can be
safely performed while on monotherapy (ASA, clo-
pidogrel) after stent implantation [39]. However, in
patients scheduled for intermediate bleeding risk
surgery, it is better to switch the P2Y12 inhibitor
to ASA, 7 days before the intervention to allow P2Y12
&&
receptor function recovery [5 ].
For patients on DAPT, the perioperative bleed-
ing risk is increased and medication management
should be done according to the urgency of the
procedure and pharmacokinetic profiles of the APAs
&& &&
[33,41,58 ,63 ]. The timing of P2Y12 inhibitors
discontinuation before surgery depends on their
potency, platelet turnover, and platelet function
recovery. However, full hemostatic competence is
not always necessary and shorter APT discontinua-
tion intervals are acceptable in clinical practice.
It is generally recommended to discontinue tica-
grelor, clopidogrel, and prasugrel at least 3–5, 5, and
&&
7 days before surgery, respectively [1,2 ,3 ,4,5 ,6].
&&
For intracranial neurosurgery, 2 more days are added
for every agent, as full platelet function recovery is
&&
required [2 ]. These recommendations rely mainly
on expert opinion. The paucity of relevant data is
reflected by recent systematic reviews and meta-
analyses which did not find a clear association
between continuation or discontinuation of APT
and rates of MACE, bleeding complications and
mortality up to 6 months after surgery
&&
[30,34,64 ]. Clinical factors other than periopera-
tive APT management, such as indication and
urgency of operation, time since stent placement,
invasiveness of the procedure, preoperative cardiac
optimization, and underlying functional status may
be more responsible for MACE and bleeding out-
comes. The lack of protection by perioperative APT
is supported by recent publications, which docu-
mented a high incidence of perioperative adverse
events even in patients who continued APT
& &&
[28 ,63 ]. More importantly, major bleeding events
(MBE) can induce MACE, due to a delay in APT
&
resumption [28 ]. In contrast, others found that
withholding APT for more than 7 days before elec-
tive NCS heightens the risk of net adverse clinical
events (ischemic or bleeding), while continuing APT
does not increase the risk of MBE [42]. These con-
flicting results point to the fact that it is unclear
whether perioperative continuation of APT protects
against MACE. Coupled with the data that shows
perioperative MI being mostly related to plaque
rupture and less to thrombotic events, avoiding
supply–demand mismatch, including optimal
bleeding control, may be a more effective strategy
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Perioperative management of anti platelet therapy Filipescu et al.
for prevention of MACE than perioperative mainte-
nance of APT [65].
In nonelective surgery occurring within 1 month
after stent implantation, patients may benefit from
a bridging strategy (Fig. 1). The oral irreversible
P2Y12 receptor inhibitors can be stopped for 5–7
days before surgery and substituted with an intrave-
nous, short-acting APA (cangrelor, tirofiban, eptifi-
batide). Intravenous therapy is initiated within 72 h
of discontinuation of the oral agent and maintained
until 1–6 h before surgery (depending on the intra-
venous agent used). Resumption of the oral P2Y12
inhibitors should occur as soon as possible postop-
&& &&
eratively [3 ,4,5 ,8]. These ‘off-label’ strategies are
not well studied and the risks of bleeding or stent
thrombosis may persist [66]. Therefore, ‘bridging
therapies’ are not supported by the ACC/AHA guide-
lines. Bridging APT with heparin (either unfractio-
nated or low-molecular-weight heparin) or NSAIDs
&&
is not recommended [5 ,67].
&&
ROLE OF PLATELET FUNCTION TESTS
Knowing the variability of platelet response to APAs,
guiding the duration of their discontinuation
according to the results of a platelet functional test
&& &&
(PFT) is attractive [2 ,5 ]. Several point-of-care
(POC) devices to identify platelet dysfunction
induced by APAs were developed, but different tests
capture different aspects of platelet function and are
therefore not interchangeable in the assessment of
platelet reactivity [68–72]. Furthermore, the hemo-
static safety threshold guaranteeing the absence of
perioperative risk of bleeding related to any residual
effects of APT has not been established and there are
not enough data to support timing of invasive pro-
cedures based on the of level of platelet inhibition
&& &&
[2 ,5 ].
Due to the lack of high-quality studies, recent
guidelines do not support the use of POC-PFT in
patients on APT undergoing PCI, cardiac and NCS,
for therapy optimization or to treat perioperative
&&
bleeding [1,2 ,4,73,74]. However, recent data sug-
gest that personalized DAPT on the basis of bedside
genotyping for CYP2C19 carrier and phenotyping
based on POC-PFT is feasible and proves to be cost-
effective [75–77].
RESUMING ANTIPLATELET THERAPY
AFTER SURGERY
Since the most critical period for the development of
ischemic complications is the postoperative phase,
APT should be resumed as soon as possible
&& &&
[1,2 ,5 ]. ASA, if discontinued, should be resumed,
if possible, the same day of the intervention and
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Anesthesia and medical disease
P2Y12 inhibitors within 24–72 h after surgery
&& &&
[1,2 ,5 ]. However, restarting any APA less than
2 days postoperatively was associated with bleeding
and mandates close monitoring [41]. The timing of
the resumption of APT may be deferred in cases of
clinically relevant bleeding complications, while
the patient is kept under clinical and electrocar-
diographic surveillance to detect MACE [8]. No clear
data have been published regarding the use of a
loading dose when resuming oral P2Y12 inhibitors
&&
after surgery [1,3 ,76–78]. Usually, the same P2Y12
&&
inhibitor is resumed [2 ]. Switching to clopidogrel
may be considered, as it has a lower risk of bleeding
complications compared with prasugrel and ticagre-
&&
lor [3 ,8]. In this case, a loading dose of clopidogrel
should be given [8].
CONTROLLING ANTIPLATELET THERAPY-
INDUCED PERIOPERATIVE BLEEDING
Although the management of perioperative bleed-
ing during APT is addressed by several guidelines,
in practice it is difficult to differentiate between
APT-induced versus surgical or other cause of
&&
perioperative hemorrhage [1,5 ,74]. To stop bleed-
ing without increasing the thrombotic risk, the
treatment needs to be individualized and devel-
oped in collaboration with the surgeon and cardi-
ologist.
Although platelet transfusion seems to be the
logical approach for patients on APT bleeding peri-
operatively, there is limited evidence supporting
this therapy. Studies in patients with intracerebral
hemorrhage (ICH) while on APT and treated
with platelet transfusion have shown mixed
results [79–81]. Furthermore, in traumatic brain
injury patients, platelet transfusion significantly
improved platelet function but was not associated
with improved outcomes [82]. However, platelet
transfusion given before cranial decompressive sur-
gery was partially effective in patients on clopidog-
rel and is still indicated in patients with ICH who
have been treated with APAs and will undergo neu-
rosurgery [74,83]. These contradictory results on
the efficacy of platelet transfusion in reversing
the APT effects can be related to recent ingestion
of APAs, which inactivate newly transfused plate-
lets, platelet storage, and group incompatibilities
[74,80–82,84–86].
Potential antiplatelet reversal therapies include
desmopressin, tranexamic acid, recombinant acti-
vated coagulation factor VII and fibrinogen, but no
clear recommendations can be made for periopera-
&&
tive bleeding [5 ,73,87]. Ticagrelor reversal with a
monoclonal antibody or by extracorporeal adsorp-
tion also shows promise [84,88,89].
460 www.co-anesthesiology.com
Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.
RESUMPTION OF ANTIPLATELET
THERAPY AFTER BLEEDING
After controlling bleeding, the APT should be
resumed considering both the clinical indication
and the APA used and the relevance of bleeding
and its risk of relapse [8]. Therapies with less bleeding
risk include downgrading the DAPT from prasugrel or
ticagrelor to clopidogrel with ASA, decreased dosages
of P2Y12, or switching from DAPT to monotherapy
with prasugrel or ticagrelor at standard dosages. All
these options seem to be reasonable approaches, yet
lack safety and effectiveness data [8].
CONCLUSION
The risk/benefit ratio of an invasive procedure sched-
uled on patients on APT should be systematically
assessed by a multidisciplinary team, including sur-
geons, anesthesiologists, and cardiologists, especially
in high-risk patients. Where possible, the surgery
should be delayed for a minimum of 1 month but
ideally for 3–6 months from the index cardiac event.
If the procedural bleeding risk is acceptable, DAPT
should be continued perioperatively. Otherwise
P2Y12 inhibitor therapy should be discontinued for
as short a duration as possible and ASA monotherapy
continued. If bleeding risk is prohibitive (neurosur-
gery), both ASA and P2Y12 inhibitor therapy should
be interrupted and bridging therapy may be consid-
ered in patients with high thrombotic risk.
Acknowledgements
None.
Financial support and sponsorship
None.
Conflicts of interest
D.C.F. – speaker bureau fee from Werfen. M.G.S., L.V.,
W.M.P., – none.
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