REVIEW

CURRENT
OPINION New antithrombotic agents in the ambulatory
setting
Neville M. Gibbs, William M. Weightman, and Stephen A. Watts

Purpose of review
Many patients presenting for surgical or other procedures in an ambulatory setting are taking new
antiplatelet or anticoagulant agents. This review assesses how the novel features of these new agents affect
the management of antithrombotic therapy in the ambulatory setting.
Recent findings
There have been very few studies investigating the relative risks of continuing or ceasing new
antithrombotic agents. Recent reviews indicate that the new antithrombotic agents offer greater efficacy or
ease of administration but are more difficult to monitor or reverse. They emphasize the importance of
assessing the bleeding risk of the procedure, the thrombotic risk if the agent is ceased, and patient factors
that increase the likelihood of bleeding. The timing of cessation of the agent, if required, depends on its
pharmacokinetics and patients bleeding risks. Patients at high risk of thrombotic complications may require
bridging therapy. Once agreed upon, the perioperative plan should be made clear to all involved.
Summary
As there are few clinical studies to guide management, clinicians must make rational decisions in relation
to continuing or ceasing new antithrombotic agents. This requires knowledge of their pharmacokinetics,
and a careful multidisciplinary assessment of the relative thrombotic and bleeding risks in individual
patients.
Keywords
ambulatory, antiplatelet, bleeding, novel anticoagulant, thrombosis

INTRODUCTION Should we proceed with the procedure or should

The limitations and unacceptably high incidence of
treatment failures with older antiplatelet agents
have led to the development of newer more potent
agents, which are being used as dual therapy for the
prevention of coronary or carotid stent thrombosis
and secondary prevention in patients with previous
acute coronary syndrome (ACS) or arterial throm-
bosis [13]. At the same time, new direct acting oral
anticoagulants have been introduced for prophy-
laxis against deep venous thrombosis (DVT) for
certain surgical procedures, as well as for the treat-
ment of DVT and the prevention of venous throm-
boembolism (VTE) in patients with nonvalvular
atrial fibrillation [49]. Many patients who are being
considered for ambulatory procedures may be tak-
ing one or more of these agents. When faced with
such patients, the clinicians involved in their care
must make several important decisions that could
impact the safety of the patient or the success for the
surgical outcome. These decisions include, but are
not limited to:
it be postponed to a safer time? Should the anti-
thrombotic agent, whether it is antiplatelet or anti-
coagulant, be continued during the perioperative
period? If not, how long prior to the procedure
should it be ceased and is bridging therapy required?
When is it safe to restart these agents postprocedure?
Can the antithrombotic actions be reversed? Does
laboratory or point of care monitoring help in
decision-making? Should regional techniques be
avoided? What are the special considerations in
the ambulatory setting?
Most of these questions have received consider-
able attention in relation to older antithrombotic
Department of Anaesthesia, Sir Charles Gairdner Hospital, Nedlands,
Western Australia, Australia
Correspondence to Dr Neville M. Gibbs, Department of Anaesthesia,
Sir Charles Gairdner Hospital, Hospital Avenue, Nedlands WA 6009,
Australia. Tel: +61 419903325; e-mail: Neville.gibbs@uwa.edu.au
Curr Opin Anesthesiol 2014, 27:589596
DOI:10.1097/ACO.0000000000000127

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 Ambulatory anesthesia
KEY POINTS

Newer antithrombotic drugs have advantages in
relation to potency, reliability, or ease of
administration, but are more difficult to monitor and
reverse, increasing the adverse implications of residual
drug levels.

The management principles are the same as for older
agents, although the safe preoperative and
postoperative drug-free intervals may differ.

The safe preoperative and postoperative drug-free
periods are influenced not only by the
pharmacokinetics of the new agent, but also by
surgical bleeding risks, and patient factors that affect
bleeding risks, including renal function.

The shorter duration of action of novel direct acting
anticoagulants may reduce the requirement for
bridging therapy.

The management of new antithrombotic agents in an
ambulatory setting requires careful patient selection,
detailed consultation between all clinicians involved,
and clear instructions and support for patients.
agents, including aspirin, dipyridamole, clopidog-
rel, and warfarin, and there are detailed review
&
articles and guidelines available [10,11,12 ,13]. This
article will focus on the newer agents in current use
that are administered via the oral route, as would be
expected in an ambulatory setting. Their pharma-
codynamics, pharmacokinetics, and clinical use will
be briefly outlined, and recent articles on the
implications of continuing or ceasing these agents
perioperatively will be summarized. The particular
concerns related to the perioperative management
of these agents in an ambulatory setting will be
discussed.
NEW ANTIPLATELET AGENTS
Prasugrel, like ticlopidine and clopidogrel, is a thie-
nopyridine derivative that acts irreversibly on the
P2Y12 receptor [13]. Its advantages over clopidogrel
include higher potency, and more rapid and con-
sistent clinical effect. Although it is absorbed as a
prodrug, only a single cytochrome P450 step is
required for conversion to its active metabolite,
and this is less affected by genetic variations or drug
interactions. Peak concentrations of its active
metabolite can be attained as soon as 30 min after
oral administration. About two-thirds is excreted via
the kidney and the remainder through the gut. Its
plasma half-life is about 7 h, although by irreversibly
binding to the P2Y12 receptor it affects individual
platelets for up to 10 days.
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As prasugrel is a more potent inhibitor of plate-
let aggregation than clopidogrel, it is more effica-
cious in the management of ACS and the prevention
of stent thrombosis and ischemic stroke. However, it
is associated with a higher risk of excessive bleeding,
both surgical and nonsurgical [9].
Ticagrelor is an orally active P2Y12 receptor
antagonist of a different class to the thienopyridines
[1,2,3]. It is a cyclopentyl-triazolo-pyrimidine
derivative. It is absorbed in its active form and
attains its peak effect within 24 h. It is excreted
by both the liver and the kidney with an elimination
half-life of about 7 h. Twice daily dosing is required.
As its action on the P2Y12 receptor is reversible, its
effects after cessation typically last only 2 to 3 days.
Although its advantage is a shorter duration of
clinical effect, its disadvantages, other than the risk
of bleeding, include the development of dyspnea.
This can occur in up to one-third of patients and is
occasionally severe [3].
Cangrelor is an intravenous P2Y12 receptor
antagonist of the same class as ticagrelor [1,2,3]. It
has a rapid onset and offset, which would make it an
attractive alternative to other longer acting anti-
platelet drugs. However, as it is an intravenous agent,
it is unlikely to be used by ambulatory patients.
Cilostazol is a phosphodiesterase inhibitor,
which like dipyridamole has both vasodilator and
antiplatelet actions [3]. Its side-effects are also similar
to those of dipyridamole. It is typically used to reduce
the symptoms of peripheral vascular disease, such as
intermittent claudication. It has a half-life of about
10 h and its effects on platelets are reversible. Its low
potency makes it unlikely to contribute to excessive
bleeding in the majority of patients.
NOVEL DIRECT ACTING ORAL
ANTICOAGULANTS
Dabigatran is a new oral direct thrombin inhibitor
[4,5,6,7]. It is administered as dabigatran etexilate,
which is converted by nonspecific esterases into
dabigatran, its active form. Unlike indirect throm-
bin inhibitors, it inactivates both fibrin-bound and
fibrin-free thrombin, increasing its efficacy. Its anti-
coagulant effect peaks about 90 min after oral
administration. As it does not undergo extensive
hepatic metabolism, it is less affected by many drug
interactions associated with warfarin, and unlike
ximelagatran, has low hepatotoxicity. It has an
elimination half-life of about 1214 h, which allows
once daily dosing. As it is excreted mainly by the
kidney, its elimination half-life is increased in
patients with renal dysfunction.
Rivaroxaban is a direct acting factor Xa inhibitor
with high bioavailability after oral administration
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 New antithrombotic agents in the ambulatory setting Gibbs et al.
[4,5,6,8]. Peak plasma levels are achieved about 3 h
after oral administration. It is not a prodrug and has
minimal drug interactions. It has an elimination
half-life of about 11 h, but its effects persist longer,
especially if taken with food, so once daily admin-
istration is possible. Two-thirds is eliminated via the
kidneys, and one-third by the liver. Like dabigatran,
its effects are prolonged in patients with renal dys-
function.
Apixaban is another orally active direct factor
Xa inhibitor with similar pharmacodynamics and
pharmacokinetics to rivaroxaban [4,5,6,8], but with
less dependence on renal elimination (about 25%),
which is one of its main advantages. Its disadvant-
age is the requirement for twice daily dosing.
SHOULD THE PROCEDURE BE
POSTPONED?
Withdrawal of antithrombotic therapy may be low
risk in many patients but hazardous in others,
&
depending on their baseline risk [11,12 ,13]. How-
ever, the baseline risk is not static and may fall as the
interval as the patients most recent thrombotic
event increases. Recent guidelines indicate that the
highest risk period is within 6 weeks of the insertion
of a bare metal stent, 3 months of a myocardial
infarction, stroke, ACS, or DVT, and 6 months of
&&
the insertion of a drug eluting stent [10,13,14 ].
The lowest risk period is after an interval of at
least 12 months. If a patient is scheduled for a non-
urgent procedure in a high-risk period, and would
require temporary cessation of antithrombotic
therapy because of bleeding risks, it would be safer
to postpone the procedure to a lower-risk period, if
possible.
SHOULD THE ANTITHROMBOTIC
MEDICATION BE CONTINUED OR
CEASED?
There have been several review articles that have
&& & &
addressed this question [14 ,1517,18 21 ,22,23],
& &
many focusing on specific subspecialties [20 ,21 ,
22,23]. All indicate that the decision to continue or
cease antithrombotic medication depends primarily
on the risks, and consequences of excessive bleeding
if the medication is continued. For the majority of
minor procedures, especially those undertaken in an
ambulatory setting, excessive surgical bleeding is
unlikely even if coagulation is impaired. For these
low-risk procedures (for example, most minor dental
or skin procedures, anterior chamber ocular pro-
cedures, and gastrointestinal endoscopy without
submucosal resection), continuation of the anti-
thrombotic or anticoagulant medication is the
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&& & &
most rational choice [14 ,1517,18 21 ,22,23]. In
contrast, if impaired coagulation would be associated
with an unacceptable risk of excessive surgical
bleeding, then the recommendation is to cease the
antithrombotic medication at a safe interval pre-
&& & &
operatively [14 ,1517,18 21 ,22,23]. Risk in this
setting refers to the consequences of excessive surgi-
cal bleeding rather than the incidence alone. The list
of procedures that are considered high risk for
bleeding varies between institutions, but will typi-
cally involve intracranial, spinal, cardiothoracic,
major abdominal, head and neck cancer resection,
major joint replacement, and urological surgery
&& & &
[14 ,1517,18 21 ,22,23]. Most of these would be
undertaken in an inpatient setting. High-risk pro-
cedures, commonly undertaken in an ambulatory
setting, include many intraocular and strabismus
correction procedures, endoscopic resection of large
sessile polyps, insertion of implantable pacemakers
or cardiac-defibrillator devices, and extensive dental
clearances. Many procedures will fall between these
two categories and be considered intermediate risk
(for example, many ambulatory orthopedic pro-
cedures, hernia repairs, gynecological laparoscopic
surgery, and pain management procedures). For each
procedure, categorization of the bleeding risk is the
responsibility of the procedural clinician. It is recom-
mended that discussion and consultation occur well
in advance of the planned procedure and include
patients in decision-making by informing them of
the conflicting risks.
Different considerations apply to low-potency
agents such as aspirin, dipyridamole and cilostazol,
which are often continued irrespective of the
&&
slightly increased bleeding risk [3,14 ]. Most guide-
lines recommend continuing regular aspirin, except
for the highest risk surgical procedures.
There have been very few studies assessing risks
of cessation versus continuation of antithrombotic
agents, particularly for the new antithrombotic
agents. Assaad et al. [24], in a retrospective chart
review, found that thrombotic and bleeding com-
plication rates were similar in patients continuing or
ceasing antithrombotic medication prior to screen-
ing colonoscopies, but none of their patients were
taking newer antithrombotic agents. Takeuchi et al.
[25] found that antithrombotic medication was
associated with an increased bleeding risk after
endoscopic submucosal resections, but this occurred
mostly after the recommencement of the anti-
thrombotic medication postoperatively, and again
did not include novel agents. Holster et al. [26] in a
meta-analysis found that novel direct acting oral
anticoagulants were associated with an increased
risk of spontaneous gastrointestinal bleeding, but
they did not assess periprocedural bleeding risks.
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 Ambulatory anesthesia
HOW LONG PREOPERATIVELY SHOULD
NEW ANTITHROMBOTIC AGENTS BE
CEASED?
When ceasing potent antithrombotic medication,
the safe interval depends on both drug and patient
factors. Recommendations and guidelines about
&& & &
safe intervals vary [14 ,1517,18 21 ,22,23]. The
minimum recommended interval appears to be at
least three elimination half-lives. This would reduce
drug levels to about 12.5% of their therapeutic
level. For most agents this would require cessation
of the drug at least 1 day, and possibly 2 days
preoperatively. However, for irreversible agents
such as prasugrel, the time for new platelets to be
generated must be considered, increasing the mini-
mum interval to 57 days. For dabigatran, rivarox-
aban, and to a lesser extent apixaban, the patients
renal function must also be considered, allowing
double the minimum interval if renal function is
significantly impaired (for example, creatinine
clearance <50 ml/min).
Apart from drug pharmacokinetics, other factors
to consider include surgical and patient bleeding
risks. Patients undergoing high-risk procedures
and those with higher baseline bleeding risks
may require a longer preoperative interval. Higher
baseline bleeding risks include combinations of
antithrombotic medications, a previous history of
bleeding, known coagulation disorders, age more
than 65 years and hypertension. Table 1 provides
suggested recommendations on preoperative cessa-
tion intervals.
THROMBOTIC RISK IF ANTITHROMBOTIC
AGENTS ARE CEASED
The thrombotic risk depends not only on the indica-
tion for the antithrombotic therapy and the interval
as the last thrombotic or embolic event, but also
& &&
on patients comorbidities [10,11,12 ,13,14 ]. For
example, patients receiving anticoagulation for atrial
fibrillation would be considered high, intermediate,
or low risk on the basis of their CHADS2 score; high
risk more than 4; intermediate risk 3 to 4; low risk less
than 3 independent of a history of a thrombotic event
[4] [CHADS2 score (congestive heart failure 1,
hypertension 1, age >75 years 1, diabetes
mellitus 1, previous stroke or transient ischemic
attack 2)] [27]. Patients with a prothrombotic dis-
order or intercurrent malignancy are also at high risk.
A mechanical heart valve is also an independent
high-risk factor.
BRIDGING THERAPY
Bridging therapy should be considered only for
those patients at the highest risk of thrombotic
complications whose antithrombotic medication
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must be ceased because of an unacceptable risk of
&& &
surgical bleeding [14 ,1517,18 ]. The relatively
short duration of action of dabigatran, rivaroxaban,
and apixaban compared with warfarin may reduce
the need for bridging therapy. However, for certain
high-risk procedures bridging therapy with thera-
peutic doses of low-molecular-weight heparin
(LMWH) may be required. This may be possible in
an ambulatory setting if the outpatient adminis-
tration of LMWH can be safely arranged. As bridging
therapy is not without its own risks, the decision to
bridge must be made on an individual patient
basis, and must include consultation with the clini-
cian managing the patients long-term anticoagula-
tion and a hematologist, if necessary.
Unfortunately, LMWHs are an ineffective bridge
for antiplatelet agents [3]. Intravenous adminis-
tration of short acting agents, such as tirofiban,
may be required in an inpatient setting [17].
RECOMMENCING NEW ANTITHROMBOTIC
AGENTS POSTOPERATIVELY
The rapid onset and potency of the new antiplatelet
and new oral anticoagulant agents means that they
should not be recommenced until the risks of
surgical bleeding have returned to near baseline
&& &
values [14 ,1517,18 ]. This will depend on the
surgical procedure itself as well as on patients bleed-
ing risks. Patients without additional bleeding risks
(Table 1) undergoing a procedure with not more
than an intermediate risk of bleeding can recom-
mence antithrombotic medication 24 h postopera-
tively. However, patients with higher bleeding risks
should have antithrombotic medication withheld at
least 48 h, depending on their thrombotic risk.
These intervals do not necessarily apply to throm-
boprophylactic doses of LMWH.
LABORATORY MONITORING OF NEW
ANTITHROMBOTIC AGENTS
The assessment of antiplatelet agents is never simple
because of inherent wide interpatient variability,
the multiple pathways of activation, and the inter-
dependence between platelets and other aspects of
coagulation [28]. The point-of-care options for
monitoring the effect ADP antagonists include the
VerifyNow P2Y12 assay, and the ADP channels of
thrombelastograph platelet mapping and multi-
&
plate whole blood aggregometry [28,29 ,30,31].
However, although these tests might have moderate
sensitivity and specificity for the detection of these
agents, the responses are nonlinear. Moreover, the
relationship between abnormal values and bleeding
risks is unclear. For these reasons, making decisions
about bleeding risks should not be on the basis of the
results of these platelet function tests alone.
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 New antithrombotic agents in the ambulatory setting Gibbs et al.

Table 1. New antithrombotic agents; advantages, disadvantages, and recommended preprocedure interval between cessation
and invasive procedures
Time to adequate offset
of clinical effect:
recommended interval for
patients with intermediate
surgical bleeding risk, low
Advantages versus older patient bleeding risk, and
New Agent agents Disadvantages normal renal function
Time to adequate offset
of clinical effect:
recommended interval
for patients with high
surgical bleeding riska,
high patient bleeding
riskb or impaired renal
function

Prasugrel Higher potency and more consistent Higher bleeding risk 57 days 710 days
effect than clopidogrel
Ticagrelor Higher potency and more consistent Higher bleeding risk 2 to 3 days 35 days
effect than clopidogrel
Short duration and reversible action Dyspnea side-effects in
up to 33%
Cilostazol Vasodilatory and antiplatelet effects May worsen heart failure 1 to 2 days 1 to 2 days
with greater efficacy than Associated with headaches
dipyridamole
Dabigatran Effective orally Higher bleeding risk than 1 to 2 days 24 days
warfarin
Once daily dosing No specific reversal agent
Less-drug interactions than warfarin Specialized monitoring test
required
Anticoagulant monitoring not Prolonged with renal
required dysfunction
Rivaroxaban Effective orally Higher bleeding risk than 1 to 2 days 24 days
warfarin
Once daily dosing No specific reversal agent
Low-drug interactions Standard coagulation tests
unreliable
Anticoagulant monitoring not Effect prolonged with renal
required dysfunction
Apixaban Effective orally Higher bleeding risk than 1 to 2 days 24 days
warfarin
Once daily dosing No specific reversal agent
Less-drug interactions No established coagulation
test
Anticoagulant monitoring Effect prolonged with renal
not required dysfunction

a
High-risk procedures include, but are not limited to, intracranial, spinal, cardiothoracic, major abdominal, head and neck cancer resection, major joint
replacement, and urological surgery; intraocular (excluding cataract) and strabismus correction procedures, endoscopic resection of large sessile polyps, insertion
of implantable pacemakers or cardio-defibrillator devices, and extensive dental clearances.
b
A history of bleeding complications, known as coagulation disorders, age more than 65 years, hypertension, liver or renal impairment, combinations of
antithrombotic and/or anticoagulant drugs.
&& & &
Reproduced from [14 ,1517,18 ,19 ].

The more predictable pharmacokinetics and
pharmacokinetics of the novel anticoagulants, dabi-
gatran, rivaroxaban, and apixaban make regular
monitoring and dose adjustment unnecessary. How-
ever, the effect of these agents on standard coagu-
&&
lation tests is less predictable [4,11,14 ,32,33 ]. If
required, the most reliable test for the assessment
of rivaroxaban and apixaban is antifactor Xa
activity; the prothrombin time (PT) may be sensitive
only to high doses or peak effects and is highly
reagent dependent. Similarly, the effects on the
activated partial thromboplastin time (aPTT) may
be minimal and variable. Monitoring dabigatran
is even more difficult; it does not alter anti-Xa
levels and its effects on the PT and aPTT are variable
and nonlinear. The thrombin clotting time can be
&
used for detecting its presence but not for a quanti-
tative assessment. The most sensitive test is the
ecarin clotting time. Again, the lack of data on
the relationship between these test results and
bleeding risks indicates that they should be used
as a guide only for urgent situations, and not as a

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 Ambulatory anesthesia
routine quantitative assessment of residual drug
effects.
REGIONAL ANESTHESIA IN PATIENTS
TAKING NEW ANTITHROMBOTIC AGENTS
The risks of central neuraxial blocks in patients
receiving new antiplatelet agents can only be
extrapolated from the risks associated with older
agents, as there is little information on their specific
risks. In a recent review, Horlocker [34] recommends
at least a 57-day interval for clopidogrel and
&&
710 days for prasugrel. Benzon et al. [35 ] recom-
mend at least 7 days for prasugrel and 5 days for
ticagrelor. These intervals apply also to the removal
of an epidural catheter. Once a catheter is removed,
at least a 6 h interval is required prior to recommenc-
ing prasugrel or ticagrelor, although a 24 h interval
may be more appropriate.
&&
Benzon et al. [35 ] also review the safety of
regional techniques in patients receiving novel oral
anticoagulants. They recommend an interval of six
half-lives after cessation of dabigatran, rivaroxaban,
or apixaban before considering a neuraxial block
(including the removal of an epidural catheter),
with a 2448 h interval before recommencement
postoperatively, unless patients have a very high
thrombotic risk, in which case shorter intervals
could be considered.
A pragmatic approach is to classify central neu-
&&
raxial procedures as high risk themselves [14 ],
and to avoid them unless patients have ceased their
antithrombotic medication a similar interval pre-
operatively as required for their procedure (Table 1).
This should also apply to invasive or deep nerve
blocks (for example, psoas compartment, proximal
sciatic, infraclavicular, paravertebral). In contrast,
selected peripheral nerve blocks are low risk and
could be performed despite continuation of
antithrombotic medication.
TREATMENT OF EXCESSIVE BLEEDING IN
PATIENTS RECEIVING NEW
ANTITHROMBOTIC AGENTS
There are no specific reversal strategies for anti-
platelet or direct acting anticoagulant drugs
&& &&
[14 ,17,34,35 ,3638]. Therefore, the decision to
continue these agents during the perioperative
period should be made only for those patients hav-
ing procedures associated with low risks of surgical
bleeding. If reversal is required because of un-
expected severe surgical bleeding, or there is a bleed-
ing complication, only nonspecific strategies are
available, which should be used alongside general
hemostatic and if necessary resuscitative measures.
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Platelet transfusion may be effective in patients
receiving prasugrel or ticagrelor so long as there
have been at least two plasma elimination half-lives
since last ingestion. For rivaroxaban and apixaban,
prothrombin complex concentrates may be effec-
tive. For dabigatran, the limited options include
oral-activated charcoal to reduce absorption and
possibly hemodiaysis or hemofiltration to enhance
clearance. For severe uncontrolled bleeding
recombinant FVIIa should be considered.
SPECIAL CONSIDERATIONS IN THE
AMBULATORY SETTING
In an ambulatory setting, it is not always possible for
the anesthesiologist who assesses the patient pre-
operatively to provide the patients care on the day
of the procedure. Therefore, there should be general
agreement at an institutional level on the categor-
ization of risk and management of ambulatory
patients, including the criteria for postponement
and inpatient management, and the need for further
investigation or consultation. This is particularly
important in relation to antithrombotic therapy.
The process should ensure that all clinicians
involved in the care of the patient are aware of
the decisions made for individual patients. The
patient must have clear understandable written
instructions with a mechanism to obtain further
advice and support if required, both preoperatively
and postoperatively.
CONCLUSION
The management of antithrombotic agents in the
ambulatory setting requires a careful assessment of
the patients thrombotic and bleeding risks and
the bleeding risks of the planned procedure. The
optimal balance of risks requires a multidisciplinary
approach. This may involve postponement of elec-
tive procedures to a period of lower thrombotic risk.
The decision to continue or cease new antithrom-
botic agents depends mainly on the risks of surgical
bleeding. For procedures with a low surgical bleed-
ing risk, continuation of antithrombotic medication
may be the preferred option. If antithrombotic
agents are to be ceased preoperatively the well-
tolerated drug-free interval will depend on pharma-
cokinetics of the drug, the surgical bleeding risks,
and patient factors that increase the bleeding risk.
Bridging therapy may be required for patients who
have a high risk of both thrombotic and bleeding
complications. Figure 1 suggests a pathway by
which these conflicting risks can be considered
and minimized. The effects of the newer antiplatelet
and anticoagulant drugs are difficult to monitor and
Volume 27
Number 6
December 2014
 New antithrombotic agents in the ambulatory setting Gibbs et al.

Low risk of surgical Intermediate or high risk

bleeding of surgical bleeding

Postpone if
Low/intermediate possible to a High risk of
risk of thrombosis thrombosis or
or embolism lower risk embolism
category
Postponement
not possible

Cease novel anticoagulant Cease novel anticoagulant or

or antiplatelet agent* at the antiplatelet agent* at the
recommended interval recommended interval
Continue
preoperatively (Table 1) preoperatively (Table 1)
antithrombotic
taking into account patient taking into account patient
treatment
bleeding risk factors bleeding risk factors
irrespective of
Recommence within 2448 h Consider bridging therapy
risk of
postoperatively depending Recommence within 2448 h
thrombosis or
on patient and surgical postoperatively depending on
embolism
bleeding risk factors patient and surgical bleeding
risk factors

FIGURE 1. A suggested pathway to balance thrombotic and bleeding risks in patients taking new antithrombotic agents in an
ambulatory setting. Categorization of procedures into low, intermediate, and high risk of surgical bleeding is the responsibility
of the surgeon or proceduralist involved. The recommended intervals are those suggested in Table 1. Patients in the shaded
area are unlikely to be suitable for management in an ambulatory setting. It is possible that less potent antiplatelet agents
such as aspirin should be continued. Antithrombotic medication should not be ceased without consultation with the patients
cardiologist, neurologist, or hematologist or continued without consultation with the surgeon or proceduralist.

5. Jacomella V, Corti N, Husmann M. Novel anticoagulants in the therapy of

reverse, so when required, safe preoperative inter-
vals should be ensured. Particular care should be
undertaken in the ambulatory setting to ensure that
all those caring for the patient take part in decision-
making, and that the patients receive appropriate
advice and support to follow all perioperative
instructions.
Acknowledgements
None.
Conflicts of interest
There are no conflicts 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. Garg VP, Halperin JL. Novel antiplatelet and anticoagulant agents in the
cardiac care unit. Cardiol Clin 2013; 31:533544.
2. Shimada YJ, Giugliano RP. Emerging antithrombotic drugs for acute coronary
syndrome. Expert Opin Emerg Drugs 2013; 18:307318.
3. Hall R, Mazer CD. Antiplatelet drugs: a review of their pharmacology and
management in the perioperative period. Anesth Analg 2011; 112:292318.
4. Harder S, Graff J. Novel oral anticoagulants: clinical pharmacology, indica-
tions and practical considerations. Eur J Clin Pharmacol 2013; 69:1617
1633.
peripheral arterial and coronary artery disease. Curr Opin Pharmacol 2013;
13:294300.
6. Steinberg BA, Piccini JP. Anticoagulation in atrial fibrillation. Br Med J 2014;
348:g2116.
7. Augustides JGT. Advances in anticoagulation: focus on dabigatran, an oral
direct thrombin inhibitor. J Cardiothor Vasc Anesth 2011; 25:1208
1212.
8. Augustides JGT. Breakthroughs in anticoagulation: advent of the oral direct
factor Xa inhibitors. J Cardiothor Vasc Anesth 2012; 26:740745.
9. Bassand J-P. Current antithrombotic agents for acute coronary syndromes:
focus on bleeding risk. Int J Cardiol 2013; 163:518.
10. Douketis JD, Spyropoulos AC, Spencer FA, et al. Perioperative management
of antithrombotic therapy. Chest 2012; 141:e326Se350S.
11. Ortel TL. Perioperative management of patients on chronic antithrombotic
therapy. Blood 2012; 120:46994705.
12. Philip I, Berroeta C, Leblanc I. Perioperative challenges of atrial fibrillation.
& Curr Opin Anesthesiol 2014; 27:344352.
This review covers the thrombotic risks in patients with atrial fibrillation and
provides a guide to perioperative anticoagulation management.
13. Nicolaides A, Fareed J, Kakkar AK, et al. Periprocedural management of
antithrombotic therapy and use of bridging anticoagulation. Clin Appl Thromb
Hemost 2013; 19:221225.
14. Baron TH, Kamath PS, McBane RD. Management of antithrombotic therapy in
&& patients undergoing invasive procedures. N Engl J Med 2013; 368:2113
2124.
This detailed review covers warfarin, novel anticoagulant, and antiplatelet manage-
ment in the perioperative period, with risk assessment and guidelines for cessation,
monitoring, bridging, and reversal.
15. Spyropoulos AC, Douketis JD. How I treat anticoagulated patients under-
going an elective procedure or surgery. Blood 2012; 120:29542962.
16. Ferrandis R, Castillo J, de Andres J, et al. The perioperative management of
new direct oral anticoagulants: a question without answers. Thromb Haemost
2013; 110:515522.
17. Schlitt A, Jambor C, Spannagl M, et al. The perioperative management of
treatment with anticoagulants and platelet aggregation inhibitors. Dtsch
Arztebl Int 2013; 110:525532.

0952-7907 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins www.co-anesthesiology.com 595

Copyright Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
 Ambulatory anesthesia
18. Armstrong MJ, Gronseth G, Anderson DC, et al. Summary of evidence-based
& guideline: periprocedural management of antithrombotic medications in patie-
nts with ischemic cerebrovascular disease. Neurology 2013; 80:20652069.
This review covers thrombotic risk assessment in patients with cerebrovascular
disease and includes guidelines for perioperative anticoagulation management.
19. Abraham NS, Castillo DL. Novel anticoagulants: bleeding risk and manage-
& ment strategies. Curr Opin Gastroenterol 2013; 29:676683.
This review covers bleeding risk assessment in patients undergoing endoscopic
gastrointestinal procedures and includes guidelines for perioperative anticoagula-
tion management.
20. Bonhomme F, Hafezi F, Boehlen F, Habre W. Management of antithrombotic
& therapies in patients scheduled for eye surgery. Eur J Anaesthesiol 2013;
30:449454.
This review covers bleeding risk assessment in patients undergoing ophthalmo-
logical procedures and includes guidelines for perioperative anticoagulation
management.
21. Becker DE. Antithrombotic drugs: pharmacology and implications for dental
& practice. Anesth Prog 2013; 60:7280.
This review covers bleeding risk assessment in patients undergoing dental proce-
dures and includes guidelines for perioperative anticoagulation management.
22. Callahan S, Goldsberry A, Kim G, Yoo S. The management of antithrombotic
medication in skin surgery. Dermatol Surg 2012; 38:14171426.
23. Manchikanti L, Falco FJ, Benyamin RM, et al. Assessment of bleeding risk of
interventional techniques: a best evidence synthesis of practice patterns and
perioperative management of anticoagulant and antithrombotic therapy. Pain
Physician 2013; 16:SE261SE318.
24. Assaad B, Sesi VK, Figari R, et al. Antithrombotic management of stroke
patients before colonoscopy. J Stroke Cerebrovasc Dis 2013; 22:733736.
25. Takeuchi T, Ota K, Harada S, et al. The postoperative bleeding rate and its risk
factors in patients on antithrombotic therapy who undergo gastric endoscopic
submucosal dissection. BMC Gastroenterol 2013; 13:136144.
26. Holster IL, Valkhoff VE, Kuipers EJ, Tjwa ETTL. New oral anticoagulants
increase risk for gastrointestinal bleeding: a systematic review and meta-
analysis. Gastroenterology 2013; 145:105112.
27. Gage BF, Waterman AD, Shannon W, et al. Validation of clinical classification
schemes for predicting stroke: results from the National Registry of Atrial
Fibrillation. JAMA 2001; 285:28642870.
596 www.co-anesthesiology.com
Copyright Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
28. Gibbs NM. Point-of-care assessment of antiplatelet agents in the peri-
operative period: a review. Anaesth Intensive Care 2009; 37:354
369.
29. Gorog DA, Fuster V. Platelet function tests in clinical cardiology. Unfulfilled
& expectations. J Am Coll Cardiol 2013; 61:21152129.
This review provides an up-to-date summary of the currently available options for
monitoring the effects of antiplatelet agents.
30. Sinhal AR, Aylward PE. New antiplatelet agents and the role of platelet
function testing in acute coronary syndromes. Clin Ther 2013; 35:1064
1068.
31. Comin J, Kallmes DF. Platelet-function testing in patients undergoing neuro-
vascular procedures: caught between a rock and a hard place. Am J
Neuroradiol 2012; 34:730734.
32. Eby C. Novel anticoagulants and laboratory testing. Int J Lab Hematol 2013;
35:262268.
33. Garcia D, Barrett YC, Ramacciotti E, Weitz JI. Laboratory assessment of the
& anticoagulant effects of the next generation of oral anticoagulants. J Thromb
Haemost 2013; 11:245252.
This review covers the options and limitations of monitoring direct acting anti-
coagulant agents.
34. Horlocker TT. Regional anaesthesia in the patient receiving antithrombotic
and antiplatelet therapy. Br J Anaesth 2011; 107:i96i106.
35. Benzon HT, Avram MJ, Green D, Bonow RO. New oral anticoagulants and
&& regional anaesthesia. Br J Anaesth 2013; 111:i96i113.
This review covers the bleeding risks associated with regional anesthetic tech-
niques and discusses guidelines for both antiplatelet and anticoagulant therapy,
including novel anticoagulants. There is also a detailed review of monitoring and
reversal strategies.
36. Makris M, Van Veen JJ, Tait CR, et al. Guideline on the management of
bleeding in patients on antithrombotic agents. Br J Haematol 2013; 160:35
46.
37. Gordon JL, Fabian TC, Lee MD, Dugdale M. Anticoagulant and antiplatelet
medications encountered in emergency surgery patients: a review of reversal
strategies. J Trauma Acute Care Surg 2013; 75:475486.
38. Fawole A. Practical management of bleeding due to the anticoagulants
dabigatran, rivaroxaban, and apixaban. Cleve Clin J Med 2013; 80:443
451.
Volume 27
Number 6
December 2014