Perioperative Management of Patients Receiving Anticoagulants - UpToDate PDF

19/10/2020 Perioperative management of patients receiving anticoagulants - UpToDate
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Perioperative management of patients receiving

anticoagulants
Authors: James D Douketis, MD, FRCPC, FACP, FCCP, Gregory YH Lip, MD, FRCPE, FESC, FACC
Section Editor: Lawrence LK Leung, MD
Deputy Editor: Jennifer S Tirnauer, MD
All topics are updated as new evidence becomes available and our peer review process is complete.
Literature review current through: Sep 2020. | This topic last updated: Aug 08, 2019.
INTRODUCTION
The management of anticoagulation in patients undergoing surgical procedures is

challenging because interrupting anticoagulation for a procedure transiently increases the
risk of thromboembolism. At the same time, surgery and invasive procedures have
associated bleeding risks that are increased by the anticoagulant(s) administered for
thromboembolism prevention. If the patient bleeds from the procedure, their anticoagulant
may need to be discontinued for a longer period, resulting in a longer period of increased
thromboembolic risk. A balance between reducing the risk of thromboembolism and
preventing excessive bleeding must be reached for each patient.
Additional issues relate to the specific anticoagulant used. For those taking a vitamin K
antagonist (eg, warfarin), it takes several days until the anticoagulant effect is reduced and
then reestablished perioperatively; the risks and benefits of "bridging" with a shorter acting
agent, such as heparin, during this time are unclear. The newer direct oral anticoagulants
(eg, direct thrombin inhibitor dabigatran, factor Xa inhibitors rivaroxaban, apixaban,
edoxaban) have shorter half-lives, making them easier to discontinue and resume rapidly,
but the direct factor Xa inhibitors lack an approved drug-specific antidote, which raises
concerns about treatment of bleeding and management of patients who require an urgent
surgery or invasive procedure.
Our approach to managing ongoing anticoagulation in patients undergoing surgery or an

invasive procedure is discussed here. Additional details regarding the use of specific
anticoagulants and antiplatelet agents are presented separately.
● Vitamin K antagonists – (See "Warfarin and other VKAs: Dosing and adverse effects".)
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● Heparins – (See "Heparin and LMW heparin: Dosing and adverse effects".)
● Direct thrombin inhibitors and direct factor Xa inhibitors – (See "Direct oral
anticoagulants (DOACs) and parenteral direct-acting anticoagulants: Dosing and adverse
effects".)
● Antiplatelet agents – (See "Perioperative medication management", section on
'Medications affecting hemostasis'.)
Specific recommendations for individuals with prosthetic heart valves are discussed
separately. (See "Antithrombotic therapy for prosthetic heart valves: Management of
bleeding and invasive procedures".)
Perioperative venous thromboembolism prevention in patients not receiving ongoing

anticoagulation is also discussed separately. (See "Prevention of venous thromboembolic
disease in adult nonorthopedic surgical patients".)
OVERVIEW OF OUR APPROACH
General approach — Interruption of anticoagulation temporarily increases thromboembolic

risk, and continuing anticoagulation increases the risk of bleeding associated with invasive
procedures; both of these outcomes adversely affect mortality [1-6]. Our approach to
perioperative management of anticoagulation takes into account these risks, along with
specific features of the anticoagulant the patient is taking [7].
Of note, much of our approach is based on expert opinion; thrombotic and bleeding risks
may vary depending on individual circumstances, and data from randomized trials or well-
designed observational studies are not available to guide practice in many settings. In
addition, the best surrogate for complete resolution of anticoagulant effect is not always
known or available for the newer direct oral anticoagulants. Thus, this approach should be
used as clinical guidance and should not substitute for clinician judgment in decisions about
perioperative anticoagulant management for individual patients.
Our approach to decision making is outlined as follows; this is presented in an interactive

format on the Thrombosis Canada website:
● Estimate thromboembolic risk – A higher thromboembolic risk increases the

importance of minimizing the interval without anticoagulation ( table 1). We estimate
thromboembolic risk for patients with atrial fibrillation based on age and comorbidities.
For those with a recent deep vein thrombosis or pulmonary embolism, we estimate the
risk based on the interval since diagnosis.
If thromboembolic risk is transiently increased (eg, recent stroke, recent pulmonary

embolism), we prefer to delay surgery until the risk returns to baseline, if possible. (See
'Estimating thromboembolic risk' below.)
For patients with more than one condition that predisposes to thromboembolism, the
condition with the highest thromboembolic risk takes precedence.
● Estimate bleeding risk – A higher bleeding risk confers a greater need for perioperative
hemostasis, and hence a longer period of anticoagulant interruption. Bleeding risk is
dominated by the type and urgency of surgery; some patient comorbidities also
contribute. Procedures with a low bleeding risk (eg, dental extractions, minor skin
surgery) often can be performed without interruption of anticoagulation. (See
'Estimating procedural bleeding risk' below and 'Deciding whether to interrupt
anticoagulation' below.)
● Determine the timing of anticoagulant interruption – The timing of anticoagulant

interruption depends on the specific agent the patient is receiving. As examples,
warfarin requires earlier discontinuation than the shorter-acting direct oral
anticoagulants (eg, dabigatran, rivaroxaban, apixaban, edoxaban) ( table 2).
Additional considerations may be required individuals with reduced renal and/or hepatic
function. (See 'Timing of anticoagulant interruption' below.)
● Determine whether to use bridging anticoagulation – For most patients, we do not

use bridging anticoagulation (use of a short-acting parenteral agent to reduce the
interval without anticoagulation), because it increases bleeding risk without reducing
the rate of thromboembolism. However, some patients on warfarin with an especially
high thromboembolic risk (eg, mechanical heart valve, recent stroke) may benefit from
bridging with heparin or low molecular weight (LMW) heparin. (See 'Bridging
anticoagulation' below.)
Example cases — The following examples illustrate our decision-making process using this
approach in general terms; importantly, management of every case must be individualized
based on the judgement of the treating clinicians:
● A 76-year-old female with non-valvular atrial fibrillation, hypertension, and prior stroke
three months ago, receiving warfarin, requires elective hip replacement with neuraxial
anesthesia; renal function is normal, and weight is 75 kg. This patient has a very high
thromboembolic risk ( table 1) and a high bleeding risk ( table 3).
• Omit warfarin for five days before the procedure (last dose on preoperative day
minus 6).
• Preoperative bridging with dose LMW heparin (eg, dalteparin, 100 units/kg [7500
units] subcutaneously twice daily) starting on preoperative day minus 3, with last
dose on the morning of day minus 1.
• Resume warfarin within 24 hours after surgery (usual dose).
• Postoperative low-dose LMW heparin for VTE prevention (eg, dalteparin 5000 units
subcutaneously once daily) within 24 hours after surgery until postoperative
bridging is started.
• Postoperative bridging on postoperative day 2 or 3, when hemostasis is secured (eg,
dalteparin, 100 units/kg [7500 units] subcutaneously twice daily; continue for at
least four to five days, until the INR is therapeutic.
● A 70-year-old male with non-valvular atrial fibrillation, diabetes, and hypertension

(CHA2DS2-VASc score = 3) receiving dabigatran who requires a colon resection for
cancer; renal function is normal. This patient has a moderate thrombotic risk ( table 1)
and a high bleeding risk ( table 3).
• Omit dabigatran for two days before the procedure (last dose of dabigatran on day
minus 3).
• No bridging.
• Resume dabigatran on day +2 or +3 after surgery, when patient is able to take
medication by mouth.
• Use prophylactic-dose LMW heparin for VTE prophylaxis for the first two to three
postoperative days.
● A 55-year-old male with an unprovoked deep vein thrombosis (DVT) four months ago,
receiving apixaban 5 mg twice daily, who requires a colonoscopy because of a personal
history of premalignant colorectal polyps; renal function is normal. This patient has a
high thrombotic risk ( table 1) and a low bleeding risk ( table 3).
• Omit apixaban for one day before the procedure (last dose of apixaban on day
minus 2).
• No bridging.
• Resume apixaban the day after the procedure, after at least 24 hours have elapsed
when hemostasis secured. If the patient requires polyp removal, delay resumption
of apixaban for one to two more days.
● A 68-year-old female with non-valvular atrial fibrillation, hypertension, and congestive

heart failure (CHA2DS2-VASc score = 4), receiving rivaroxaban 15 mg daily in the
morning, requires a dental cleaning and two dental extractions; creatinine clearance is
35 mL/min. This patient has a high thrombotic risk ( table 1) and a low bleeding risk (
table 3).
• Omit rivaroxaban on the day of the procedure.

• Use oral tranexamic acid mouthwash just before the procedure and two to three
times that day after the procedure.
• Resume rivaroxaban the day after the procedure, after at least 24 hours have
elapsed (assuming the dental extractions were uneventful).
ESTIMATING THROMBOEMBOLIC RISK
The major factors that increase thromboembolic risk are atrial fibrillation, prosthetic heart
valves, and recent venous or arterial thromboembolism (eg, within the preceding three
months).
Atrial fibrillation — Atrial fibrillation accounts for the highest percentage of patients for
whom perioperative anticoagulation questions arise. Importantly, patients with atrial
fibrillation are a heterogeneous group; risk can be further classified according to clinical
variables such as age, hypertension, congestive heart failure, diabetes, prior stroke, and
other vascular disease ( table 1) [2,8]. The CHA2DS2-VASc score ( table 4) (calculator 1),
which incorporates these variables, is discussed in detail separately; of note, use of risk
scores has not been prospectively validated in the perioperative setting. (See "Atrial
fibrillation: Risk of embolization".)
The magnitude of this issue was illustrated in three large trials: RE-LY (Randomized
Evaluation of Long-Term Anticoagulant Therapy), ROCKET AF (Rivaroxaban Once daily, oral
direct factor Xa inhibition Compared with vitamin K antagonism for prevention of stroke and
Embolism Trial in Atrial Fibrillation), and ARISTOTLE (Apixaban for Reduction in Stroke and
Other Thromboembolic Events in Atrial Fibrillation) [9-11]. These trials of each randomly
assigned 15,000 to 20,000 patients to warfarin versus another oral anticoagulant
(dabigatran, rivaroxaban, or apixaban, respectively). Surgical or other invasive procedures
were required in one-fourth of patients in RE-LY and one-third of patients in ROCKET AF and
ARISTOTLE.
● RE-LY (dabigatran versus warfarin) – Of the 4591 patients who underwent elective
procedures or surgery in the RE-LY trial, the perioperative thromboembolic risk was 1.2
percent, based on a composite endpoint of stroke, cardiovascular death, and pulmonary
embolus [9]. There were no differences in thromboembolic risk with dabigatran versus
warfarin, or with the high versus the low dabigatran dose. However, urgent surgery was
associated with a higher risk of ischemic stroke or systemic embolism than elective
surgery (warfarin: 1.8 versus 0.4 percent; dabigatran 150 mg twice daily: 1.4 versus 0.4
percent; dabigatran 110 mg twice daily: 2.8 versus 0.3 percent).
● ROCKET AF (rivaroxaban versus warfarin) – Of the 4692 anticoagulant interruptions in

this trial, 40 percent were for surgery or invasive procedures [11]. The thromboembolic
risk during anticoagulant interruption was similar for rivaroxaban and warfarin (0.3 and
0.4 percent).
● ARISTOTLE (apixaban versus warfarin) – During 9260 procedures performed on patients

in the ARISTOTLE trial, the perioperative thromboembolic risk was 0.57 percent for
warfarin and 0.35 percent for apixaban [10].
Bleeding risk in these trials and registries are presented below. (See 'Overview of whether to
interrupt' below.)
Prosthetic heart valve — The risks of thromboembolism and perioperative management of

patients with prosthetic heart valves are discussed separately. (See "Antithrombotic therapy
for prosthetic heart valves: Management of bleeding and invasive procedures", section on
'Management of antithrombotic therapy for invasive procedures' and "Diagnosis of
mechanical prosthetic valve thrombosis or obstruction".)
Recent thromboembolism — Thromboembolic risk is greater in the immediate period

following a thromboembolic event and declines over time. Individuals with a recent
thromboembolic event are likely to benefit from delaying surgery, if possible. If emergency
surgery is required (eg, acute cholecystectomy), bridging anticoagulation may be used to
reduce the interval without an anticoagulant. (See 'Bridging anticoagulation' below.)
Venous — The perioperative risk of venous thromboembolism (VTE) is greatest in

individuals with an event (eg, deep vein thrombosis, pulmonary embolus) within the prior
three months and those with a history of VTE associated with a high-risk inherited
thrombophilia ( table 1). However, many patients with VTE do not require thrombophilia
testing, and we do not perform this testing specifically to evaluate perioperative thrombotic
risk in patients who otherwise do not warrant screening. Appropriate use of thrombophilia
screening is discussed separately. (See "Clinical presentation and diagnosis of the
nonpregnant adult with suspected deep vein thrombosis of the lower extremity".)
Individuals with cancer have a moderate risk, and those with an event more than one year
ago have a low risk of VTE complications.
Thus, patients who require surgery within the first three months following an episode of VTE
are likely to benefit from delaying elective surgery, even if the delay is only for a few weeks.
This approach is supported by data showing that the recurrence risk for individuals with a
recent VTE is highest within the initial three to four weeks and diminishes over the following
two months [12-14]. Without anticoagulation, the early risk of recurrent VTE was
approximately 50 percent; treatment with warfarin for one month reduced this risk to 8 to 10
percent, and after three months of warfarin therapy the risk declined to 4 to 5 percent [14-
16].
Arterial — The risk of recurrent arterial embolism from any cardiac source is

approximately 0.5 percent per day in the first month after an acute event [17]. The vast
majority of cases are due to atrial fibrillation; other less common cardiac sources include
paradoxical embolism, non-bacterial thrombotic endocarditis in a patient with malignancy,

dilated or poorly contractile left ventricle, or left ventricular aneurysm ( table 5) [18-20].
Thus, patients with a recent arterial embolism are likely to benefit from delaying elective
surgery, if such a delay is possible.
ESTIMATING PROCEDURAL BLEEDING RISK
The risk of bleeding is dominated by the type of surgery or invasive procedure. Patient
comorbidities (eg, older age, decreased renal function) and medications that affect
hemostasis (eg, aspirin) may also contribute [3,21,22].
As a general guideline, we divide procedures into high and low bleeding risk (two-day risk of
major bleeding 2 to 4 percent or 0 to 2 percent, respectively); examples of high bleeding risk
procedures include coronary artery bypass surgery, kidney biopsy, and any procedure lasting
>45 minutes; low bleeding risk procedures include cholecystectomy, carpal tunnel repair,
and abdominal hysterectomy ( table 3) [2]. Importantly, these categories do not substitute
for clinical judgement or consultation between the surgeon and other treating clinicians.
Neuraxial, intracranial, and cardiac procedures are especially concerning because the
location of potential bleeding increases the risk of serious complications. (See "Neuraxial
anesthesia/analgesia techniques in the patient receiving anticoagulant or antiplatelet
medication".)
Major bleeding is generally defined as bleeding that is fatal, involves a critical anatomic site
(eg, intracranial, pericardial), requires surgery to correct, lowers the hemoglobin by ≥2 g/dL,
or requires transfusion of ≥2 units packed red cells; however, there is heterogeneity in
definitions used by different clinicians [23].
The risks of some specific types of procedures are also discussed in detail separately in the
following topic reviews, along with management issues specific to those procedures:
● Neuraxial anesthesia – (see "Neuraxial anesthesia/analgesia techniques in the patient

receiving anticoagulant or antiplatelet medication")
● Gastrointestinal procedures – (see "Management of anticoagulants in patients

undergoing endoscopic procedures", section on 'Elective procedures')
● Percutaneous coronary intervention (eg, angioplasty, atherectomy, stenting) – (see

"Periprocedural management of antithrombotic therapy in patients receiving long-term
oral anticoagulation and undergoing percutaneous coronary intervention", section on
'Elective patients' and "Coronary artery disease patients requiring combined
anticoagulant and antiplatelet therapy", section on 'Prevention')
● Ophthalmologic procedures – (see "Diabetic retinopathy: Prevention and treatment",

section on 'Patients taking antiplatelet or anticoagulant medication' and "Age-related
macular degeneration: Treatment and prevention", section on 'Safety in patients taking
anticoagulants or antiplatelet drugs' and "Cataract in adults", section on 'Management
of antithrombotic agents')
Dental and cutaneous procedures are generally associated with a low risk of bleeding. (See
'Settings in which continuing the anticoagulant may be preferable' below.)
Patient factors can also contribute to bleeding risk; these patient-related risks can be
quantified using bleeding risk scores. An example is the HAS-BLED score (calculator 2), which
was used in the BNK Online Bridging Registry (BORDER), an observational registry that
assessed perioperative outcomes in outpatients undergoing invasive cardiac procedures (eg,
cardiac catheterization, pacemaker implantation, cardiac surgery) [24]. Nearly all of the
patients were receiving a vitamin K antagonist, which was interrupted for the procedure and
replaced with a bridging agent, usually a low molecular weight (LMW) heparin. There were
35 clinically relevant bleeding episodes during 1000 procedures (3.5 percent). A HAS-BLED
bleeding risk score ≥3 was the most predictive variable for bleeding (HR 11.8, 95% CI 5.6-
24.9). The HAS-BLED score assigns one point each for hypertension, abnormal renal or liver
function (two points for both), stroke, bleeding tendency, labile INRs, elderly age, and
antiplatelet drugs or alcohol ( table 6).
DECIDING WHETHER TO INTERRUPT ANTICOAGULATION
Overview of whether to interrupt — Once the thromboembolic and bleeding risks have

been estimated, a decision can be made about whether the anticoagulant should be
interrupted or continued. Data comparing the relative benefits of continuing anticoagulation
versus interrupting an anticoagulant are limited, and decisions that balance
thromboembolic and bleeding risks must be made on a case-by-case basis. No scoring
system can substitute for clinical judgment in this decision making.
● In general, the anticoagulant must be discontinued if the surgical bleeding risk is high.
Those at very high or high thromboembolic risk should limit the period without
anticoagulation to the shortest possible interval; in some cases this involves the use of a
bridging agent. (See 'Settings requiring anticoagulant interruption' below and 'Whether
to use bridging' below.)
● In contrast, individuals undergoing selected low bleeding risk surgery often can
continue their anticoagulant; in certain cases, continuation of the anticoagulant may
preferable. (See 'Settings in which continuing the anticoagulant may be preferable'
below.)
Practices to reduce bleeding and thromboembolic risks should be employed regardless of

whether the patient's anticoagulant is interrupted or continued. Examples include the
following:
● Agents that interfere with platelet function should be avoided for routine analgesia (eg,
nonsteroidal anti-inflammatory drugs [NSAIDs], aspirin) unless the benefit outweighs
the increased risk of bleeding, and routine perioperative use of aspirin should be
avoided due to an increased risk of bleeding and lack of benefit. By contrast, if these
agents are administered for a separate indication (eg, recent stroke, acute coronary
syndromes, implanted coronary stent) they can (and generally should) be continued
[25]. Issues associated with perioperative aspirin use are discussed in detail separately.
(See "Perioperative medication management", section on 'Medications affecting
hemostasis' and "Periprocedural management of antithrombotic therapy in patients
receiving long-term oral anticoagulation and undergoing percutaneous coronary
intervention".)
● For those not receiving an anticoagulant in the immediate postoperative period,

thromboprophylaxis to reduce the risk of venous thromboembolism should be used
when appropriate. (See "Prevention of venous thromboembolic disease in adult
nonorthopedic surgical patients".)
Settings requiring anticoagulant interruption — Individuals undergoing surgery with a

high risk of bleeding will require interruption of their usual anticoagulant perioperatively,
putting them at higher risk of thromboembolic complications related to their underlying
condition.
● If the very high risk of thromboembolism is transient (eg, ischemic stroke within the
previous month), attempts should be made to delay elective surgery, if possible, until
the thromboembolic risk has returned to baseline.
It may also be advisable to delay elective surgery in a patient with atrial fibrillation who
has had inadequate anticoagulation in the preceding month. This is based on the
observation that among patients with nonvalvular atrial fibrillation, over 85 percent of
thrombi resolve after four weeks of warfarin therapy [26]. (See "Atrial fibrillation: Risk of
embolization", section on 'Imaging predictors'.)
● Individuals with a temporarily very high or high thromboembolic risk in whom surgery
cannot be delayed (eg, potentially curative cancer surgery in a patient who just had an
acute VTE) should limit the interval without an anticoagulant to minimize the risk of
thromboembolism. This generally involves stopping the usual anticoagulant as close to
surgery as possible, restarting it as soon as possible, and using a bridging agent before
and/or after surgery while the usual anticoagulant is not therapeutic, especially for
those on warfarin. A temporary inferior vena cava filter may also be appropriate in
selected individuals (See 'Timing of anticoagulant interruption' below and 'Bridging
anticoagulation' below and 'Temporary vena cava filters' below.)
● For individuals with a chronically elevated thromboembolic risk, we often use bridging
anticoagulation to minimize the period when anticoagulation is not being used. (See
'Appropriate settings for bridging' below.)
● Individuals with a moderate thromboembolic risk generally can interrupt their

anticoagulant for surgery without bridging. The bleeding risk from bridging may
outweigh any potential benefit, especially in those with low-risk nonvalvular atrial
fibrillation [27,28].
Temporary vena cava filters — Placement of a temporary inferior vena caval (IVC) filter
indicated in patients with a recent (within the prior three to four weeks) acute VTE who
require interruption of anticoagulation for a surgery or major procedure in which it is
anticipated that therapeutic-dose anticoagulation will need to be delayed for more than 12
hours postoperatively. As an example, most patients who require surgery using general or
neuraxial anesthesia that must be performed within three to four weeks of an acute VTE
would require placement of an IVC filter. Further information about the placement of IVC
filters is presented separately. (See "Placement of vena cava filters and their complications".)
In contrast, patients who require temporary interruption of anticoagulation for a minor

procedure such as central venous catheter placement, which may be performed with
omission of one dose of an anticoagulant, would not require an IVC filter. Individuals with a
VTE more than four weeks prior to the intended surgery do not require placement of an IVC
filter, and other clinical situations such as prior perioperative VTE or high-risk thrombophilia
are not routine indications for perioperative placement of an IVC filter.
Settings in which continuing the anticoagulant may be preferable — For individuals

undergoing selected surgery that confers a low risk of bleeding (eg, cataract extraction) it
may be preferable for them to continue their anticoagulant, depending on patient factors
and the judgement of the treating clinician. Continuing the anticoagulant likely reduces the
risk of thromboembolism, and in some settings (eg, cardiac implantable electronic device) it
actually reduces the risk of bleeding as well. For those receiving warfarin or another vitamin
K antagonist, it is important to confirm that the INR is not above the therapeutic range at the
time of the procedure.
● Dental procedures – Dental procedures are generally considered to confer a low risk of
bleeding, and anticoagulation can be continued in most patients during these
procedures. The evidence for the safety of continuing anticoagulation comes from
patients receiving warfarin with an INR in the therapeutic range [29-35]. In the
ARISTOTLE trial, which included patients anticoagulated with warfarin versus apixaban
for atrial fibrillation, perioperative bleeding rates were approximately 1 percent in
patients undergoing dental and other low bleeding risk procedures. Bleeding can be
further reduced with the use of topical hemostatic agents (eg, tranexamic acid
mouthwash, used three to four times daily for one to two days) [8,34,36-39].
An exception is multiple tooth extractions, which we consider high bleeding risk. (See
'Settings requiring anticoagulant interruption' above.)
● Cutaneous procedures – Cutaneous procedures (eg, skin biopsy, tumor excision, bone
marrow biopsy) are also generally considered to confer a low risk of bleeding; the
potential for local control measures further reduces concerns about bleeding risk.
● Selected cardiac procedures – For certain cardiac procedures, there is evidence that
continuing anticoagulation is safe (and in some cases associated with better outcomes)
compared with stopping and restarting the anticoagulant.
• Cardiac implantable devices – We agree with a position document from the

European Heart Rhythm Association (EHRA) that states the majority of patients
undergoing implantation of a cardiac electronic device (eg, pacemaker, cardioverter-
defibrillator) should continue their anticoagulant perioperatively [40]. This is based
on data from the BRUISE CONTROL trial, which randomly assigned patients on
warfarin undergoing implantation of a cardiac implantable electronic device to
continuation of warfarin or heparin bridging, as well as other smaller trials [41]. This
trial found a lower risk of bleeding in patients who continued warfarin. Potential
explanations for the increased bleeding in the heparin bridging arm include
initiation of postprocedure bridging too early (eg, within 24 hours after the
procedure) or better identification of surgical bleeding sites that could be addressed
during the procedure in patients receiving continued warfarin.
An exception is a patient with a low risk of thromboembolic events, in whom

warfarin may be discontinued, or a patient receiving a direct oral anticoagulant, for
whom temporary discontinuation is likely to be appropriate; bridging
anticoagulation is not recommended in such individuals [40]. In an analysis of 611
patients from the RE-LY trial (dabigatran versus warfarin in atrial fibrillation) who
underwent implantable device surgery, pocket hematomas occurred at a similar
frequency in those who had interruption of dabigatran and those who had
interruption of warfarin without bridging [42]. It is not clear whether uninterrupted
dabigatran would be associated with lower risks of bleeding and/or thrombosis.
(See "Cardiac implantable electronic devices: Periprocedural complications".)
• Endovascular procedures and catheter ablation – Endovascular procedures

include a variety of venous and arterial interventions such as angioplasty, catheter
ablation, and atherectomy. In a meta-analysis of randomized trials involving over
20,000 patients undergoing these procedures, uninterrupted warfarin therapy was
associated with equivalent or lower rates of complications compared with
interruption of warfarin [43]. As an example, a benefit of warfarin continuation
rather than discontinuation with bridging was reported in the COMPARE trial, which
randomly assigned patients with atrial fibrillation undergoing catheter ablation to
continued warfarin or discontinuation of warfarin with bridging [44]. In this trial,
patients randomized to continue warfarin had a lower risk of stroke and less
bleeding.
We also agree with the EHRA position document statement that all patients
undergoing catheter ablation for atrial fibrillation should receive full anticoagulation
with heparin in addition to continuing their oral anticoagulant [40].
If a decision is made to discontinue the anticoagulant (eg, patient with renal insufficiency),
bridging is reserved for those with a high-very high thromboembolic risk, and not used for
those with a moderate thromboembolic risk. (See 'Appropriate settings for bridging' below.)
TIMING OF ANTICOAGULANT INTERRUPTION
If a decision has been made to interrupt the anticoagulant for surgery with high or
moderate bleeding risk, the agent should be stopped in sufficient time to allow
anticoagulation to resolve. For some agents, laboratory testing is a reliable indicator that the
anticoagulant effect has resolved after discontinuation (eg, warfarin); for others, well-
validated and easily accessible testing is not always available (eg, direct oral anticoagulants
[DOACs]). If a moderate or high bleeding risk surgery is required urgently or immediately,
reversal of the anticoagulant may also be required. (See 'Urgent/emergency invasive
procedure' below.)
Data to guide the timing of anticoagulant interruption are evolving, especially for DOACs,
and much of our practice is based on expert opinion and observational studies as we await
results from ongoing trials [45]. Risks of bleeding with neuraxial anesthesia and risks of
thrombosis in patients with prosthetic heart valves are especially concerning; these issues
are discussed in detail separately. (See "Neuraxial anesthesia/analgesia techniques in the
patient receiving anticoagulant or antiplatelet medication" and "Antithrombotic therapy for
surgical prosthetic heart valves and surgical valve repair: Indications".)
Typical durations of anticoagulant interruption are illustrated by the RE-LY trial, which
randomized individuals with nonvalvular atrial fibrillation to warfarin or dabigatran for
prevention of thromboembolism [9]. In this trial, nearly half of patients treated with
dabigatran had surgery within 48 hours of stopping the drug, whereas only approximately 1
in 10 patients treated with warfarin had surgery within 48 hours of drug discontinuation.
The incidence of thromboembolism was low (<1 percent), and bleeding rates were similar for
those receiving warfarin or either dabigatran dose. (See 'Atrial fibrillation' above.)
Warfarin — Warfarin blocks a vitamin K-dependent step in clotting factor production; it

impairs coagulation by preventing synthesis of factors II (prothrombin), VII, IX, and X.
Resolution of warfarin effect is determined by measurement of the prothrombin time (PT),
which is standardized across institutions using an international normalized ratio (INR).
● Discontinuation – If it has been determined that warfarin discontinuation is

appropriate, we typically omit warfarin for five days before elective surgery (ie, the last
dose of warfarin is given on day minus 6) and, when possible, check the PT/INR on the
day before surgery [8,14,46,47]. If the INR is >1.5, we administer low dose oral vitamin K
(eg, 1 to 2 mg) to hasten normalization of the PT/INR and recheck the following day. We
proceed with surgery when the INR is ≤1.4. An INR in the normal range is especially
important in patients undergoing surgery associated with a high bleeding risk (eg,
intracranial, spinal, urologic) or if neuraxial anesthesia is to be used. (See 'Estimating
procedural bleeding risk' above and 'Neuraxial anesthesia' below.)
This timing of warfarin discontinuation is based on the biological half-life of warfarin (36
to 42 hours) and the observed time for the PT/INR to return to normal after stopping
warfarin (eg, two to three days for the INR to fall to below 2.0; four to six days to
normalize) [46]. Normalization of the INR may take longer in patients receiving higher-
intensity anticoagulation (INR 2.5 to 3.5), and in elderly individuals [48]. Half-lives of
other vitamin K antagonists also differ (eg, 8 to 11 hours for acenocoumarol;
approximately four to six days for phenprocoumon [49]; approximately three days for
fluindione). (See "Warfarin and other VKAs: Dosing and adverse effects", section on
'Warfarin administration'.)
For a procedure that requires more rapid normalization of the INR, additional
interventions may be needed to actively reverse the anticoagulant. (See
'Urgent/emergency invasive procedure' below.)
This discontinuation schedule will produce a period of several days with subtherapeutic
anticoagulation. As an example, it is estimated that if warfarin is withheld for five days
before surgery and is restarted as soon as possible afterwards, patients would have a
subtherapeutic INR for approximately eight days (four days before and four days after
surgery) [14]. Thus, for patients at very high or high thromboembolic risk, bridging may
be appropriate.
● Use of bridging preoperatively – We generally reserve bridging for individuals

considered at very high or high risk of thromboembolism (eg, recent stroke, mechanical
heart valve, CHA2DS2-VASc score of 7 or 8 ( table 4) (calculator 1), CHADS2 score of 5 or
6) if they require interruption of warfarin. In these cases, the bridging agent (eg,
therapeutic dose subcutaneous low molecular weight [LMW] heparin) is started three
days before surgery. (See 'Bridging anticoagulation' below.)
A bridging agent may also be appropriate if there is a prolonged period during which
the patient cannot take oral medications (eg, postoperative ileus).
● Restarting warfarin and postoperative bridging – We resume warfarin 12 to 24 hours

after surgery, typically the evening of the day of surgery or the evening of the day after
surgery, assuming there were no unexpected surgical issues that would increase
bleeding risk and the patient is taking adequate oral fluids [8]. We use the same dose
the patient was receiving preoperatively.
After warfarin is restarted in the perioperative setting, it takes 5 to 10 days to attain a

full anticoagulant effect as measured by an INR above 2.0. Thus, we generally treat
individuals at very high risk and some individuals with a high risk of thromboembolism
with a heparin bridging agent during this period. (See 'Bridging anticoagulation' below.)
Dabigatran — Dabigatran is a direct thrombin inhibitor; it reversibly blocks the enzymatic

function of thrombin in converting fibrinogen to fibrin (factor IIa).
● Discontinuation – Dabigatran can be omitted for two to three days before a surgical
procedure in patients with normal or mildly impaired renal function (ie, creatinine
clearance >50 mL/minute), and two to four days before the procedure in those with
more severe renal insufficiency (eg, creatinine clearance between 30 and 50 mL/minute),
with the longer intervals used for higher bleeding risk procedures and the shorter
interval for surgeries with less bleeding risk.
As an example, in a patient on dabigatran with a creatinine clearance >50 mL/min

undergoing a high bleeding risk procedure, the patient will skip four doses of
dabigatran (no drug on surgical day minus 2 and day minus 1) and no drug on the day
of surgery ( table 2). In dabigatran-treated patients with a creatinine clearance 30 to
50 mL/min undergoing a high bleeding risk procedure such as neuraxial anesthesia, a
longer interval for interruption is required. (See 'Neuraxial anesthesia' below.)
The last preoperative day on which dabigatran is administered can be more closely
estimated based on the elimination half-life of dabigatran, which varies according to
renal function (eg, 12 to 14 hours in patients with normal renal function) [2,50-53]. A
protocol incorporating bleeding risk and creatinine clearance was tested in a
prospective cohort of 541 dabigatran-treated patients undergoing surgery and was

found to be effective in minimizing bleeding and thrombotic complications [53].
Unlike the PT/INR for warfarin, routine coagulation tests have not been validated for
ensuring that dabigatran effect has resolved. A normal or near-normal aPTT may be
used in selected patients to evaluate whether dabigatran has been adequately cleared
from the circulation prior to surgery (eg, patients at high risk of surgical bleeding) (
table 7). Importantly, the reliability of aPTT testing may depend on the specific assay
used; if available, a diluted plasma thrombin time may be preferable [51,54,55]. (See
"Direct oral anticoagulants (DOACs) and parenteral direct-acting anticoagulants: Dosing
and adverse effects", section on 'Dabigatran' and "Clinical use of coagulation tests".)
● Use of bridging – In general, the rapid offset and onset of dabigatran activity obviates
the need for bridging anticoagulation. We reserve bridging anticoagulation for selected
individuals who are at very high risk for postoperative thromboembolism and require
extended interruption of dabigatran. Examples include postoperative bridging in
patients who are unable to take oral medications postoperatively due to intestinal ileus
from gastrointestinal surgery. (See 'Bridging anticoagulation' below.)
● Restarting dabigatran – Dabigatran should be resumed postoperatively when

hemostasis has been achieved, at the same dose the patient was receiving
preoperatively. Since dabigatran has a rapid onset of action, with peak effects occurring
two to three hours after intake, caution should be used in patients who have had major
surgery or other procedures associated with a high bleeding risk.
We often delay resumption of dabigatran for two to three days after high bleeding risk
procedures and, if needed, administer a lower dabigatran dose for the initial two to
three postoperative days (eg, 110 mg once daily) or use prophylactic dose LMW heparin
for this period. We generally restart dabigatran one day after low bleeding risk surgery
(if it was interrupted) and two to three days after high bleeding risk surgery.
Rivaroxaban — Rivaroxaban is a direct factor Xa inhibitor; it reversibly blocks the enzymatic

function of factor Xa in converting prothrombin to thrombin.
● Discontinuation – Rivaroxaban can be omitted for approximately two to three days

before a procedure, with the longer interval for higher bleeding risk procedures and the
shorter interval for lower bleeding risk procedures ( table 2). Thus, for high bleeding
risk procedures, the patient will skip two doses of rivaroxaban, and not receive any
doses on surgical days minus 2, minus 1, or the day of surgery. These intervals are
based on an elimination half-life of 7 to 11 hours and apply to individuals with normal
renal function or mild renal insufficiency (eg, creatinine clearance >50 mL/minute), who
are likely to be receiving the 20 mg once daily dose; and to those with moderate renal
insufficiency (eg, creatinine clearance between 30 and 50 mL/minute), who are likely to
be receiving the 15 mg once daily dose.
Longer intervals for interruption may be required for situations in which the bleeding
risk is very high, such as neuraxial anesthesia. (See 'Neuraxial anesthesia' below.)
Rivaroxaban interacts with dual inhibitors of CYP-3A4 and P-glycoprotein (eg, systemic
ketoconazole, ritonavir); dose adjustment or substitution of heparin may be appropriate
if these dual CYP-3A4 and P-glycoprotein inhibitors are used perioperatively. Interactions
with drugs that inhibit only one of these enzymes do not seem to alter rivaroxaban
anticoagulant effect.
ensuring that the rivaroxaban anticoagulant effect has resolved. A normal or near-
normal anti-factor Xa activity level may be used in selected patients to evaluate whether
rivaroxaban has been adequately cleared from the circulation prior to surgery (eg,
patients at high risk of surgical bleeding) ( table 7) [2]. Of note, the reliability of anti-
factor Xa activity testing may depend on the specific assay used, and clinicians are
advised to speak with their clinical laboratory to determine whether this assay is
available at their institution and whether it has been validated for direct factor Xa
inhibitors.
● Use of bridging – In general, the rapid offset and onset of rivaroxaban obviates the
need for bridging anticoagulation. In rare cases bridging may be required, such as the
use of postoperative bridging in individuals who have a very high thromboembolic risk
and are unable to take oral medications postoperatively due to intestinal ileus from
gastrointestinal surgery. (See 'Bridging anticoagulation' below.)
● Restarting rivaroxaban – Rivaroxaban can be resumed postoperatively when

hemostasis has been achieved, at the same dose the patient was receiving
preoperatively. Since rivaroxaban has a rapid onset of action, caution should be used in
patients who have had major surgery or other procedures associated with a high
bleeding risk.
We often delay rivaroxaban for two to three days after high bleeding risk procedures
and, if needed, use prophylactic dose LMW heparin for this period. We generally restart
rivaroxaban one day after low bleeding risk surgery (if it was interrupted) and two to
three days after high bleeding risk surgery.
Apixaban — Apixaban is a direct factor Xa inhibitor; it reversibly blocks the enzymatic

● Discontinuation – Apixaban can be omitted for approximately two to three days before
a procedure, with the longer interval for higher bleeding risk procedures and the
risk procedures, the patient will skip four doses of apixaban, and not receive any doses
on surgical days minus 2, minus 1, or the day of surgery. These intervals are based on an
apixaban elimination half-life of 8 to 12 hours. These intervals apply to individuals with
normal renal function or mild renal insufficiency (eg, creatinine clearance >50
mL/minute), who are likely to be receiving the 5 mg twice daily dose; and to those with
moderate to severe renal insufficiency (eg, creatinine clearance between 30 and 50
mL/minute), who are likely to be receiving the 2.5 mg twice daily dose.
Longer intervals for interruption may be required for situations in which the bleeding
risk is very high, such as neuraxial anesthesia. (See 'Neuraxial anesthesia' below.)
ensuring that apixaban effect has resolved. A normal or near-normal anti-factor Xa
activity level may be used in selected patients to evaluate whether apixaban has been
adequately cleared from the circulation prior to surgery (eg, patients at high risk of
surgical bleeding) ( table 7). Of note, the reliability of anti-factor Xa activity testing may
depend on the specific assay used, and clinicians are advised to speak with their clinical
laboratory to determine whether this assay is available at their institution and whether it
has been validated for direct factor Xa inhibitors.
● Use of bridging – In general, the rapid offset and onset of apixaban obviates the need
for bridging anticoagulation. In rare cases, bridging may be required, such as the use of
postoperative bridging in individuals who have a very high thromboembolic risk and are
unable to take oral medications postoperatively due to intestinal ileus from
● Restarting apixaban – Apixaban can be resumed postoperatively when hemostasis has

been achieved, at the same dose the patient was receiving preoperatively. Since
apixaban has a rapid onset of action, caution should be used in patients who have had
major surgery or other procedures associated with a high bleeding risk.
We often delay apixaban for two to three days after high bleeding risk procedures, and
if needed use prophylactic dose LMW heparin for this period. We generally restart
apixaban one day after low bleeding risk surgery (if it was interrupted).
Edoxaban — Edoxaban is a direct factor Xa inhibitor; it reversibly blocks the enzymatic

● Discontinuation – Edoxaban can be omitted for approximately two to three days before
a procedure, with the longer interval for higher bleeding risk procedures and the
risk procedures, the patient will skip two doses of edoxaban, and not receive any doses
on surgical days minus 2, minus 1, or the day of surgery. These intervals are based on an
edoxaban elimination half-life of 10 to 14 hours. These intervals apply to individuals with
normal renal function or mild renal insufficiency (eg, creatinine clearance >50
mL/minute) and those with moderate renal insufficiency (eg, creatinine clearance
between 30 and 50 mL/minute), who are likely to be receiving the 60 mg once daily or
the 30 mg once daily doses, respectively.
Longer intervals for interruption may be considered for those undergoing major
surgery, neuraxial anesthesia or manipulation, or other situations in which complete
hemostatic function may be required. (See 'Neuraxial anesthesia' below.)
ensuring that edoxaban effect has resolved. A normal or near-normal anti-factor Xa
activity level may be used in selected patients to evaluate whether edoxaban has been
adequately cleared from the circulation prior to surgery (eg, patients at high risk of
surgical bleeding) ( table 7). Of note, the reliability of anti-factor Xa activity testing may
depend on the specific assay used, and clinicians are advised to speak with their clinical
laboratory to determine whether this assay is available at their institution and whether it
has been validated for direct factor Xa inhibitors.
● Use of bridging – In general, the rapid offset and onset of edoxaban obviates the need
for bridging anticoagulation. In rare cases, bridging may be required, such as the use of
postoperative bridging in individuals who have a very high thromboembolic risk and are
unable to take oral medications postoperatively due to intestinal ileus from
● Restarting edoxaban – Edoxaban can be resumed postoperatively when hemostasis has

been achieved, at the same dose the patient was receiving preoperatively. Since
edoxaban has a rapid onset of action, caution should be used in patients who have had
major surgery or other procedures associated with a high bleeding risk.
We often delay edoxaban for two to three days after high bleeding risk procedures, and
if needed use prophylactic dose LMW heparin for this period. We generally restart
edoxaban one day after low bleeding risk surgery (if it was interrupted).
BRIDGING ANTICOAGULATION
Bridging anticoagulation involves the administration of a short-acting anticoagulant,

typically a low molecular weight (LMW) heparin, during the interruption of a longer-acting
agent, typically warfarin. There are no data on using the newer direct oral anticoagulants
(eg, direct thrombin inhibitors, direct factor Xa inhibitors) as bridging agents; further, the
direct factor Xa inhibitor agents lack a specific reversal strategy should bleeding occur. Thus,
we use LMW heparin or unfractionated heparin when bridging is required. (See 'Heparin
product and dose' below.)
Appropriate settings for bridging
Whether to use bridging — The intent of bridging is to minimize the time the patient is
not anticoagulated, thereby minimizing the risk for perioperative thromboembolism.
However, this needs to be balanced with the importance of mitigating the risk of
postoperative bleeding. A slight delay in resumption of postoperative anticoagulation is
preferable to premature initiation of postoperative bridging that results in bleeding, which
ultimately will lengthen the period without an anticoagulant and thus increase
thromboembolic risk.
The clinician needs to decide whether bridging is appropriate and, if so, whether the benefit
applies preoperatively, postoperatively, or both.
Bridging anticoagulation may be appropriate in patients who will have a very high
thromboembolic risk with prolonged interruption of their anticoagulant (generally a vitamin
K antagonist [VKA]). Individual patient comorbidities that increase bleeding risk may also
need to be considered because an increased postoperative bleeding risk may be a reason to
avoid bridging. We suggest the use of bridging in individuals taking warfarin for one of the
following conditions [1]:
● Embolic stroke or systemic embolic event within the previous three months
● Mechanical mitral valve (see "Antithrombotic therapy for prosthetic heart valves:
Management of bleeding and invasive procedures", section on 'Our approach')
● Mechanical aortic valve and additional stroke risk factors (see "Antithrombotic therapy
for prosthetic heart valves: Management of bleeding and invasive procedures", section
on 'Our approach')
● Atrial fibrillation and very high risk of stroke (eg, CHADS2 score of 5 or 6, stroke or
systemic embolism within the previous 12 weeks, concomitant rheumatic valvular heart
disease with mitral stenosis)
● Venous thromboembolism (VTE) within the previous three months (preoperative and
postoperative bridging) (see 'When to bridge: Preoperative, postoperative, or both'
below)
● Recent coronary stenting (eg, within the previous 12 weeks) (see "Periprocedural
management of antithrombotic therapy in patients receiving long-term oral
anticoagulation and undergoing percutaneous coronary intervention")
● Previous thromboembolism during interruption of chronic anticoagulation
For most other patients on warfarin with atrial fibrillation (ie, for most individuals not
included in the list of examples above), we suggest not using bridging anticoagulation.
However, this approach is largely based on our experience. Many of these populations such
as individuals with valvular atrial fibrillation (or associated with mitral valvular heart disease)
have not been addressed in large trials, and there may be cases in which the clinician who
best knows the patient may have greater concerns about thrombosis and may decide that
bridging is appropriate. We feel more strongly about avoiding bridging the lower the
patient's baseline thromboembolic risk (eg, lower CHADS2 or CHA2DS2-VASc score ( table 8
)) and the higher the risk of bleeding. This practice is supported by the BRIDGE trial (Bridging
Anticoagulation in Patients who Require Temporary Interruption of Warfarin Therapy for an
Elective Invasive Procedure or Surgery), which randomly assigned 1884 patients with atrial
fibrillation who required interruption of warfarin for an invasive procedure to receive
bridging anticoagulation with the LMW heparin dalteparin versus placebo [56]. The
incidence of arterial thromboembolic events 30 days after the procedure was similar in those
who received dalteparin or placebo (0.3 versus 0.4 percent). The incidence of major bleeding
(a secondary outcome) was higher in those who received dalteparin (3.2 versus 1.3 percent),
although none of the bleeds were fatal. Patients were excluded from the trial if they had a
mechanical heart valve, or a recent (within previous 12 weeks) stroke, embolism, or transient
ischemic attack.
Results of a randomized trial comparing postoperative bridging versus no bridging in

patients with a mechanical heart valve (PERIOP-2), where all patients receive preoperative
bridging, are eagerly awaited [6,57].
Additional evidence to support our practice comes from a systematic review and meta-
analysis of 34 studies in patients undergoing elective surgery or procedures [58]. All of the
studies were observational except for one randomized trial in patients undergoing dental
extraction. Bridging was used in 7118 patients; most received LMW heparin, at several dose
levels. The large range of heparin doses and inclusion of procedures with varied bleeding
risks led to a high degree of heterogeneity. There was no significant difference in the rate of
thromboembolism in patients who received bridging compared with patients who did not
(odds ratio [OR]: 0.80; 95% CI 0.42-1.54). Bridging was associated with a threefold increase in
major bleeding compared with no bridging (OR: 3.60; 95% CI 1.52-8.50); full-dose heparin
was associated with an increase in overall bleeding compared with lower heparin doses (OR:
2.28; 95% CI 1.27-4.08) (see 'Heparin product and dose' below). Bridging versus no bridging
did not affect major outcomes in patients who required a major procedure during
participation in large anticoagulation trials for atrial fibrillation, including the RE-LY (warfarin
versus dabigatran), ROCKET-AF (warfarin versus rivaroxaban), and ARISTOTLE (warfarin
versus apixaban) trials [9-11]. In the RE-LY trial patients receiving warfarin had more
thromboembolic events associated with bridging than with non-use of bridging (1.8 versus
0.3 percent); patients who received bridging also had a higher risk of major bleeding
(warfarin: 6.8 percent with bridging, 1.6 percent without; dabigatran: 6.5 percent with
bridging, 1.8 percent without) [59].
Additional "real world" data comes from the ORBIT-AF and Dresden registries. ORBIT-AF
(Outcomes Registry for Better Informed Treatment of Atrial Fibrillation) is a community-
based registry of outpatients with atrial fibrillation receiving any oral anticoagulant; in this
study, 2200 of 7372 individuals (30 percent) had interruption of anticoagulation for a
procedure [60]. Bridging was used in 24 percent of these interruptions, especially in patients
with a history of stroke or a mechanical heart valve and/or receiving warfarin; bleeding
events were more common in individuals who received bridging compared with those who
did not receive bridging (5.0 versus 1.3 percent). A composite endpoint that included major
bleeding, myocardial infarction, stroke, systemic embolism, hospitalization, or death within
30 days was also higher in those who received bridging (13 versus 6.3 percent). In the
Dresden NOAC registry, over 800 patients who were receiving dabigatran, rivaroxaban, or
apixaban for any indication and underwent an invasive procedure had similar rates of major
cardiovascular events if they received bridging, no bridging, or no anticoagulant
discontinuation [61]. Bridging was not an independent risk factor for major bleeding;
however, individuals undergoing major procedures were more likely to receive bridging and
to have major bleeding.
A potential role for bridging in reducing the risk of "rebound hypercoagulability" has also
been proposed; however, this premise is not supported by data from the BRIDGE trial
discussed above [56].
Of note, management of perioperative anticoagulation in patients with mechanical heart

valves is discussed in detail separately. (See "Antithrombotic therapy for prosthetic heart
valves: Management of bleeding and invasive procedures", section on 'Management of
antithrombotic therapy for invasive procedures'.)
Bridging is generally not used for the shorter-acting direct oral thrombin inhibitors or factor
Xa inhibitors. However, bridging may be appropriate for individuals on these agents who
have a very high thromboembolic risk and a more prolonged interruption of their
anticoagulant (eg, due to postoperative intestinal ileus that prevents oral intake). (See
'Dabigatran' above and 'Rivaroxaban' above and 'Apixaban' above and 'Edoxaban' above.)
When to bridge: Preoperative, postoperative, or both — Once a decision to use

bridging has been made, the next decision is whether to use bridging before the procedure,
after the procedure, or both ( table 9). Sample bridging protocols are provided on the
Thrombosis Canada website.
● Atrial fibrillation – As noted above, we suggest not using bridging for most patients
with atrial fibrillation. (See 'Whether to use bridging' above.)
However, for those for individuals for whom bridging is used due to a very high risk of
thromboembolism, we use bridging both preoperatively and postoperatively [14].
Warfarin is usually resumed 12 to 24 hours after surgery, typically the evening of the day
of surgery or the evening of the day after surgery, as long as adequate hemostasis has
been achieved. (See 'Warfarin' above.)
● Venous thromboembolism
• First three months – For individuals within the first three months after an acute
episode of VTE, we use bridging both preoperatively and postoperatively, typically
with therapeutic-dose LMW heparin (eg, enoxaparin 1 mg/kg twice daily) [14]. This
practice is based on the high incidence of recurrence without anticoagulation. While
postoperative intravenous heparin doubles the rate of bleeding, there is a net
reduction in serious morbidity in such patients because the risk of postoperative
recurrent VTE is high (see 'Preoperative timing of bridging' below and 'Postoperative
timing of bridging' below) In selected patients in whom surgery cannot be delayed
beyond the first month after the diagnosis of an acute VTE, it may be appropriate to
use a temporary inferior vena cava (IVC) filter, especially if bridging anticoagulation
cannot be used postoperatively due to high bleeding risk. (See "Overview of the
treatment of lower extremity deep vein thrombosis (DVT)", section on 'Patients with
contraindications to anticoagulation' and "Treatment, prognosis, and follow-up of
acute pulmonary embolism in adults", section on 'Inferior vena cava filters'.)
• Greater than three months – For individuals greater than three months after an
acute episode of VTE, we generally use postoperative bridging, typically with a low
dose LMW heparin regimen (eg, enoxaparin 40 mg daily), but not preoperative
bridging [62]. For patients who are undergoing a minor procedure or day surgery,
bridging is probably not justified. This practice is based on the significantly reduced
risk of VTE recurrence after the first month [63,64]. (See 'Postoperative timing of
bridging' below.)
Heparin product and dose — Two types of heparin products are available: LMW heparins
and unfractionated heparin. LMW heparins have similar efficacy compared with
unfractionated heparin, are more convenient to use, and generally do not require
monitoring. Intravenous unfractionated heparin is less costly and can be reversed more
rapidly than subcutaneous LMW heparin; it may be a reasonable alternative in some
individuals.
● We prefer LMW heparin for bridging anticoagulation in individuals with a very high risk
of arterial thromboembolism (eg, rheumatic heart disease, atrial fibrillation with recent
embolic stroke, high-risk mechanical heart valve) and those with a moderate risk of
thromboembolism (eg, active cancer) [27,28,65].
Perioperative anticoagulation management in individuals with prosthetic heart valves is

discussed in detail separately. (See "Antithrombotic therapy for prosthetic heart valves:
Management of bleeding and invasive procedures", section on 'Management of
antithrombotic therapy for invasive procedures'.)
● For individuals with renal insufficiency and/or those requiring hemodialysis, intravenous
or subcutaneous unfractionated heparin can be used more easily because dosing is
unaffected by renal clearance [66]. (See "Heparin and LMW heparin: Dosing and adverse
effects", section on 'Dosing'.)
We do not use any of the direct oral anticoagulants (eg, dabigatran, rivaroxaban, apixaban,
edoxaban) for bridging, as there are no data on the safety or efficacy of these agents for
perioperative bridging.
Heparins can be dosed at prophylactic doses, therapeutic doses, or doses intermediate

between the two. Of note, the term "therapeutic dose" refers to doses typically used for
treatment of thromboembolic disease, despite the fact that in this case it is being used
prophylactically (ie, to prevent thromboembolism). There are no clinical trial data or practice
standards to guide dosing, and clinical judgment is required to determine the appropriate
dose for each patient [58,67,68].
● Therapeutic dosing – Therapeutic dosing (also called "full dose") is appropriate for
bridging anticoagulation for individuals with a potential arterial thromboembolic source
(eg, atrial fibrillation, mechanical heart valve) or VTE within the preceding month. Typical
regimens include enoxaparin, 1 mg/kg subcutaneously twice daily or dalteparin, 100
units /kg subcutaneously twice daily.
● Intermediate dosing – Intermediate dose anticoagulation may be appropriate for

individuals with atrial fibrillation or VTE within the preceding month when bridging is
needed but concerns about bleeding are greater. Typical regimens include enoxaparin,
40 mg twice daily, or dalteparin, 5000 units subcutaneously twice daily.
● Prophylactic dosing – Prophylactic dose anticoagulation (also called "low dose")

generally is not used for bridging in patients with atrial fibrillation, because there is no
evidence that prophylactic dose heparin prevents stroke in this setting. This dose level
may be reasonable in patients who have had a VTE event between within the preceding
3 to 12 months. Typical prophylactic regimens include enoxaparin, 40 mg once daily, or
dalteparin 5000 units subcutaneously once daily.
The use of prophylactic dose heparin for postoperative VTE prevention in patients not
receiving ongoing anticoagulation is discussed separately. (See "Prevention of venous
thromboembolic disease in adult nonorthopedic surgical patients".)
Additional details regarding heparin products, including dose adjustments for obesity and
renal impairment are provided separately. (See "Heparin and LMW heparin: Dosing and
adverse effects".)
Timing of bridging
Preoperative timing of bridging — We generally initiate heparin bridging three days

before a planned procedure (ie, two days after stopping warfarin), when the PT/INR has
started to drop below the therapeutic range.
● LMW heparin – We discontinue LMW heparin 24 hours before the planned surgery or
procedure, based on a biologic half-life of most subcutaneous LMW heparins of
approximately three to five hours [8,65,69]. If a twice-daily LMW heparin regimen is
given, the evening dose the night before surgery is omitted, whereas if a once-daily
regimen is given (eg, dalteparin 200 international units/kg), one-half of the total daily
dose is given on the morning of the day before surgery. This ensures that no significant
residual anticoagulant will be present at the time of surgery, based on studies that have
shown a residual anticoagulant effect at 24 hours after stopping therapeutic-dose LMW
heparin, and it is consistent with the 2012 ACCP Guidelines [8,12,70,71].
● Unfractionated heparin – For therapeutic dose unfractionated heparin, we continue the

intravenous infusion until four to five hours before the procedure, based on the biologic
half-life of intravenous unfractionated heparin of approximately 45 minutes [8,69,70]. If
subcutaneous unfractionated heparin is used, typically with a dose of approximately 250
international units/kg twice daily, the last dose can be given the evening before the
procedure.
Postoperative timing of bridging — Postoperative resumption of unfractionated

heparin and LMW heparin is similar, based on the onset of anticoagulation at approximately
one hour after administration for both forms of heparin, and peak anticoagulant activity at
approximately three to five hours.
● The resumption of bridging, especially when given as a therapeutic-dose regimen,

should be delayed until there is adequate hemostasis based on a clinical assessment of
the wound site, drainage fluid amount, and expected postoperative bleeding; coupled,
where appropriate, with hemoglobin levels [72]. This assessment will vary depending on
the surgery type and individual patient considerations, and it may be difficult for surgery
where ongoing bleeding is not readily apparent (eg, cardiac, intracranial).
● For those undergoing major surgery or those with a high bleeding risk procedure,
therapeutic-dose unfractionated heparin or LMW heparin should be delayed for 48 to 72
hours after hemostasis has been secured [8].
● For most minor procedures associated with a low bleeding risk in which bridging is used
(eg, laparoscopic hernia repair), therapeutic-dose unfractionated heparin or LMW
heparin can usually be resumed 24 hours after the procedure.
Resumption of bridging anticoagulation too early, especially the use of therapeutic dose
heparin within 24 hours after surgery, is associated with a two- to fourfold increased risk for
major bleeding compared with no bridging or prophylactic dose heparin. The increased
bleeding risk was demonstrated in the Prospective peri-operative enoxaparin cohort trial
(PROSPECT), which evaluated bleeding risk in a cohort of 260 patients undergoing major
surgery whose treating physicians used bridging anticoagulation [73]. In this trial, nine
patients had major postoperative bleeding (3.5 percent), most on postoperative day 0, and
19 (7.3 percent) had minor bleeding.
Postoperatively, warfarin is generally resumed on the same postoperative day as the

heparin. Heparin can be discontinued when the INR reaches the therapeutic range for
individuals at moderate thromboembolism risk.
Individuals with heparin-induced thrombocytopenia — Heparin-induced

thrombocytopenia (HIT) is a potentially life-threatening condition in which heparin-induced
antibodies to platelets can cause thrombocytopenia and/or venous or arterial thrombosis.
(See "Clinical presentation and diagnosis of heparin-induced thrombocytopenia".)
Patients with HIT should not receive any heparin (eg, they should not receive heparin
flushes, unfractionated heparin, or LMW heparin). Non-heparin anticoagulants that can be
used in patients with HIT are discussed separately. (See "Management of heparin-induced
thrombocytopenia", section on 'Anticoagulation'.)
URGENT/EMERGENCY INVASIVE PROCEDURE
Reversal of the patient's usual anticoagulant may be required for more urgent or emergency
surgery or procedures, or to treat perioperative bleeding. Agents with a potential
prothrombotic effect (eg, prothrombin complex concentrates [PCCs], plasma products,
immediate reversal agents) should be reserved for the treatment of severe, life-threatening
bleeding or anticipated severe bleeding (eg, intracranial hemorrhage, emergency major
surgery with elevated prothrombin time/international normalized ratio [PT/INR]). Agent-
specific strategies include the following:
● Warfarin – For individuals who require reversal of warfarin or other vitamin K

antagonists, the appropriate reversal strategy is determined by the degree of
anticoagulation (eg, PT/INR, clinical bleeding), urgency of the procedure, and degree of
bleeding risk ( table 10).
• If semi-urgent reversal of warfarin is required (eg, within one to two days), warfarin
should be withheld and vitamin K administered (eg, 2.5 to 5 mg of oral or
intravenous vitamin K). (See "Management of warfarin-associated bleeding or
supratherapeutic INR", section on 'Urgent surgery/procedure'.)
• If immediate reversal is required (eg, for emergency surgery or active bleeding), this
can be achieved via the use of prothrombin complex concentrates (PCCs) or plasma
products (eg, Fresh Frozen Plasma [FFP]; Plasma Frozen Within 24 Hours After
Phlebotomy [PF24]) along with vitamin K ( table 11) [74,75]. The 4-factor PCCs
contain adequate amounts of all vitamin K-dependent clotting factors, whereas 3-
factor PCCs may require supplementation with FFP for adequate factor VII (
table 12). Of note, there is a thrombotic risk associated with these products, and
they should be used only if there is life-threatening bleeding and prolongation of
the INR by a vitamin K antagonist [75]. (See "Management of warfarin-associated
bleeding or supratherapeutic INR", section on 'Serious/life-threatening bleeding'.)
● Dabigatran – Dabigatran is an oral direct thrombin inhibitor; it can be reversed by

idarucizumab ( table 13). In an open-label study involving 503 patients who had
bleeding or required emergency surgery, idarucizumab effectively reversed the
anticoagulant effect of dabigatran [76]. The use of this agent as well as other potential
strategies for individuals receiving dabigatran who are at great risk of serious bleeding
with an emergency procedure are presented separately. (See "Management of bleeding
in patients receiving direct oral anticoagulants".)
● Rivaroxaban, apixaban, and edoxaban – Rivaroxaban, apixaban, and edoxaban are oral
direct factor Xa inhibitors; these anticoagulants can be reversed by andexanet alfa,
approved in May of 2018. PCCs have been used in cases of potentially life-threatening
bleeding, but this is not based on high-quality evidence ( table 13). These and other
potential strategies for individuals receiving these agents who are at great risk of
serious bleeding with an urgent/emergency procedure are presented separately. (See
"Management of bleeding in patients receiving direct oral anticoagulants".)
Algorithms for anticoagulant reversal depending on the severity of bleeding are provided by
various societies and groups such as Thrombosis Canada.
Additional discussions of postoperative bleeding are presented separately. (See

"Postoperative complications among patients undergoing cardiac surgery", section on
'Hematologic dysfunction'.)
NEURAXIAL ANESTHESIA
Neuraxial (ie, spinal or epidural) anesthesia should not be used in anticoagulated

individuals, due to the risk of potentially catastrophic bleeding into the epidural space. The
increased risk of bleeding applies both at the time of catheter placement and the time of
removal.
If neuraxial anesthesia is considered for surgical anesthesia or postoperative pain control,

the timing of anesthesia and anticoagulant administration should be coordinated to
optimize the safe use of both. Early consultation with the anesthesiologist is advised. This
subject is discussed in detail separately. (See "Neuraxial anesthesia/analgesia techniques in
the patient receiving anticoagulant or antiplatelet medication".)
The timing of anticoagulant use in patients receiving neuraxial anesthesia is illustrated by

evidence-based guidelines from the American Society of Regional Anesthesia (ASRA), which
suggest the following [77,78]:
● Prophylactic dose LMW heparin (eg, enoxaparin 40 mg once daily):
• Before surgery, wait at least 10 to 12 hours after the last dose of LMW heparin is
administered before a spinal/epidural catheter is placed.
• After surgery, when there is adequate surgical site hemostasis, wait at least six to
eight hours after catheter removal before resuming treatment with LMW heparins.
● Therapeutic dose LMW heparin (eg, enoxaparin, 1 mg/kg twice daily):
• Before surgery, wait at least 24 hours after the last dose of LMW heparin is
administered before a spinal/epidural catheter is placed.
• After surgery, when there is adequate surgical site hemostasis, for twice daily
dosing, wait at least 24 hours after catheter removal before resuming therapeutic-
dose LMW heparin. For once daily dosing, wait at least six to eight hours after
catheter removal before the first dose; the second postoperative dose should occur
no sooner than 24 hours after the first dose.
SOCIETY GUIDELINE LINKS
Links to society and government-sponsored guidelines from selected countries and regions
around the world are provided separately. (See "Society guideline links: Anticoagulation".)
INFORMATION FOR PATIENTS
UpToDate offers two types of patient education materials, "The Basics" and "Beyond the
Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th
grade reading level, and they answer the four or five key questions a patient might have
about a given condition. These articles are best for patients who want a general overview
and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are
longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th
grade reading level and are best for patients who want in-depth information and are
comfortable with some medical jargon.
Here are the patient education articles that are relevant to this topic. We encourage you to
print or e-mail these topics to your patients. (You can also locate patient education articles
on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)
● Basics topics (see "Patient education: Staying safe while taking an oral medicine to
prevent or treat blood clots (The Basics)" and "Patient education: Choosing an oral
medicine to prevent or treat blood clots (The Basics)")
● Beyond the Basics topics (see "Patient education: Warfarin (Beyond the Basics)")
SUMMARY AND RECOMMENDATIONS
● Interruption of anticoagulation temporarily increases thromboembolic risk, and

continuing anticoagulation increases the risk of bleeding associated with invasive
procedures; both of these outcomes adversely affect mortality. We take into account
these risks, along with specific features of the anticoagulant the patient is taking.
Internet-based resources and case examples are provided above. (See 'Overview of our
approach' above.)
● Thromboembolic risk – Those at very high or high thromboembolic risk should limit the
period without anticoagulation to the shortest possible interval. The major factors that
increase thromboembolic risk are atrial fibrillation, prosthetic heart valves, and recent
venous or arterial thromboembolism (eg, within the preceding three months) ( table 1
). If thromboembolic risk is transiently increased (eg, recent stroke, recent pulmonary
embolism), we prefer to delay surgery until the risk returns to baseline, if possible. (See
'Estimating thromboembolic risk' above.)
• Atrial fibrillation – In the RE-LY trial, the perioperative thromboembolic risk was 1.2
percent based on a composite endpoint of stroke, cardiovascular death, and
pulmonary embolus. We estimate thromboembolic risk for patients with atrial
fibrillation based on clinical variables including age and comorbidities. (See 'Atrial
fibrillation' above and "Atrial fibrillation: Anticoagulant therapy to prevent
thromboembolism".)
• Prosthetic heart valve – The risks of thromboembolism and perioperative

management of patients with bioprosthetic and mechanical heart valves are
discussed separately. (See "Antithrombotic therapy for prosthetic heart valves:

Management of bleeding and invasive procedures", section on 'Management of
antithrombotic therapy for invasive procedures' and "Diagnosis of mechanical
prosthetic valve thrombosis or obstruction".)
• Recent thromboembolism – The perioperative risk of venous thromboembolism

(VTE) is greatest in individuals with an event within the prior three months, and
those with a history of VTE associated with a high-risk inherited thrombophilia.
Patients who require surgery within the first three months following an episode of
VTE are likely to benefit from delaying elective surgery, even if the delay is only for a
few weeks. The risk of recurrent arterial embolism from any cardiac source is
approximately 0.5 percent per day in the first month after an acute event. (See
'Recent thromboembolism' above.)
● Bleeding risk – A higher bleeding risk confers a greater need for perioperative
hemostasis, and hence a longer period of anticoagulant interruption. Bleeding risk is
dominated by the type and urgency of surgery ( table 3); some patient comorbidities
(eg, older age, decreased renal function) and medications that affect hemostasis also
contribute. (See 'Estimating procedural bleeding risk' above and 'Deciding whether to
interrupt anticoagulation' above.)
• High risk – High bleeding risk procedures include coronary artery bypass surgery,
kidney biopsy, and any procedure lasting >45 minutes. In general, the anticoagulant
must be discontinued if the surgical bleeding risk is high. (See 'Settings requiring
anticoagulant interruption' above.)
• Low risk – Low bleeding risk procedures include dental extractions, minor skin
surgery, cholecystectomy, carpal tunnel repair, and abdominal hysterectomy.
Individuals undergoing selected low bleeding risk surgery often can continue their
anticoagulant. (See 'Settings in which continuing the anticoagulant may be
preferable' above.)
• Cardiac implantable device or catheter ablation for atrial fibrillation –

Continuing warfarin was associated with a lower risk of bleeding in patients on the
BRUISE CONTROL trial who were undergoing implantation of a cardiac implantable
electronic device (eg, pacemaker, implantable cardioverter-defibrillator) and
patients on the COMPARE trial who were undergoing catheter ablation for atrial
fibrillation. (See 'Overview of whether to interrupt' above and "Cardiac implantable
electronic devices: Periprocedural complications".)
● Timing of interruption – If a decision has been made to interrupt the anticoagulant,

the timing of discontinuation and reinitiation depends on the specific agent used (
table 2). (See 'Timing of anticoagulant interruption' above and 'Warfarin' above and
'Dabigatran' above and 'Rivaroxaban' above and 'Apixaban' above and 'Edoxaban'
above.)
● Bridging – Bridging anticoagulation involves the administration of a short-acting

anticoagulant, typically a low molecular weight (LMW) heparin, during the interruption
of a longer-acting agent, typically warfarin. The intent is to minimize the risk of
perioperative thromboembolism.
For selected patients on warfarin (eg, mechanical mitral valve; stroke, systemic
embolism, or transient ischemic attack within the previous 12 weeks; mechanical aortic
valve and additional stroke risk factors; atrial fibrillation and very high risk of stroke [eg,
CHADS2 score of 5 or 6]; venous thromboembolism within the previous 12 weeks; recent
coronary stenting; previous thromboembolism during interruption of chronic
anticoagulation), we suggest the use of bridging (Grade 2C).
For most other patients on warfarin with atrial fibrillation or VTE, we suggest not using
bridging (Grade 2B). We feel more strongly about avoiding bridging the lower the
baseline thromboembolic risk and the higher the bleeding risk.
In contrast to individuals on warfarin, bridging usually is not required for individuals

receiving a direct thrombin inhibitor or factor Xa inhibitor, because these agents have
shorter half-lives ( table 2). (See 'Appropriate settings for bridging' above.)
• Agent – When bridging is used, we prefer LMW heparin for most patients. An
exception is an individual with renal insufficiency and/or hemodialysis requirement,
for whom intravenous or subcutaneous unfractionated heparin can be used more
easily. We do not use dabigatran, rivaroxaban, apixaban, or edoxaban for bridging.
Non-heparin anticoagulants that can be used in patients with heparin-induced
thrombocytopenia are discussed separately. (See 'Heparin product and dose'
above.)
• Timing – Bridging can be used preoperatively, postoperatively, or both, depending

on the underlying condition for which the patient is being anticoagulated ( table 9
). The timing depends on the heparin product used and the procedural bleeding
risk. Importantly, resumption of bridging anticoagulation too early is associated
with an increased risk for major bleeding. (See 'When to bridge: Preoperative,
postoperative, or both' above and 'Timing of bridging' above.)
• Heart valve – Perioperative anticoagulation in individuals with prosthetic heart

valves is presented separately. (See "Antithrombotic therapy for prosthetic heart
valves: Management of bleeding and invasive procedures", section on 'Management
of antithrombotic therapy for invasive procedures'.)
● Urgent/Emergency procedure – Reversal of the patient's usual anticoagulant may be

required for more urgent or emergency procedures, or to treat perioperative bleeding.
Agents with a potential prothrombotic effect (eg, immediate reversal agents,
prothrombin complex concentrates, plasma products) should be reserved for the
treatment of life-threatening, severe bleeding or anticipated severe bleeding (eg,
intracranial hemorrhage, emergency major surgery with elevated prothrombin
time/international normalized ratio [PT/INR]). (See 'Urgent/emergency invasive
procedure' above and "Management of bleeding in patients receiving direct oral
anticoagulants".)
Use of UpToDate is subject to the Subscription and License Agreement.
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Topic 1312 Version 71.0
GRAPHICS
Perioperative thrombotic risk
Indication for anticoagulant therapy

Risk stratum
Mechanical heart valve Atrial fibrillation VTE
Very high thrombotic risk* Any mitral valve prosthesis CHA 2 DS 2 -VASc score of ≥6 Recent (within three months)
Any caged-ball or tilting disc (or CHADS 2 score of 5-6) VTE
aortic valve prosthesis Recent (within three months) Severe thrombophilia (eg,
Recent (within six months) stroke or transient ischemic deficiency of protein C,
stroke or transient ischemic attack protein S, or antithrombin;
attack antiphospholipid antibodies;
Rheumatic valvular heart
multiple abnormalities)
disease
High thrombotic risk Bileaflet aortic valve CHA 2 DS 2 -VASc score of 4-5 VTE within the past 3 to 12
prosthesis and one or more or CHADS 2 score of 3-4 months
of the of following risk Nonsevere thrombophilia
factors: atrial fibrillation, (eg, heterozygous factor V
prior stroke or transient Leiden or prothrombin gene
ischemic attack, mutation)
hypertension, diabetes,
Recurrent VTE
congestive heart failure, age
>75 years Active cancer (treated within
six months or palliative)
Moderate thrombotic risk Bileaflet aortic valve CHA 2 DS 2 -VASc score of 2-3 VTE >12 months previous
prosthesis without atrial or CHADS 2 score of 0-2 and no other risk factors
fibrillation and no other risk (assuming no prior stroke or
factors for stroke transient ischemic attack)
Refer to UpToDate topics on perioperative anticoagulation management for details.
VTE: venous thromboembolism; CHADS 2 : congestive heart failure, hypertension, age ≥75 years, diabetes mellitus, and stroke or
transient ischemic attack; CHA 2 DS 2 -VASc: congestive heart failure, hypertension, age ≥75 years (2 points), diabetes mellitus, prior
stroke or transient ischemic attack or thromboembolism (2 points), vascular disease (peripheral artery disease, myocardial
infarction, or aortic plaque), age 65-74 years, sex category female.
* Very high-risk patients may also include those with a prior stroke or transient ischemic attack occurring >3 months before the
planned surgery and a CHA 2 DS 2 -VASc score <6 (or CHADS 2 score <5), those with prior thromboembolism during temporary
interruption of anticoagulation, or those undergoing certain types of surgery associated with an increased risk for stroke or other
thromboembolism (eg, cardiac valve replacement, carotid endarterectomy, major vascular surgery).
Modified from Douketis JD, Spyropoulos AC, Spencer FA, et al. Perioperative management of antithrombotic therapy: Antithrombotic Therapy
and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 2012; 141(2
Suppl):e326S. Copyright © 2012. Reproduced with permission from the American College of Chest Physicians.
Graphic 86930 Version 5.0
Perioperative management of oral direct thrombin inhibitors and factor Xa inhibitors
Interval between last dose

and procedure
Renal NOTE: No anticoagulant is Resumption after procedure
Anticoagulant function and administered the day of the
dose procedure
High bleeding Low bleeding High bleeding Low bleeding

risk risk risk risk
Dabigatran CrCl >50 Give last dose Give last dose two
mL/minute three days before days before
Dose 150 mg procedure (ie, procedure (ie,
twice daily skip four doses on skip two doses on
the two days the day before
before the the procedure)
procedure)
CrCl 30 to 50 Give last dose five Give last dose

mL/minute days before three days before
Dose 150 mg procedure (ie, procedure (ie,
twice daily skip eight doses skip four doses on
on the four days the two days
before the before the
procedure) procedure)
Rivaroxaban CrCl >50 Give last dose Give last dose two
Dose 20 mg once procedure (ie, procedure (ie,
daily skip two doses on skip one dose on
the two days the day before Resume 48 to 72
CrCl 30 to 50 Resume 24 hours
before the the procedure) hours after
mL/minute after surgery (ie,
procedure) surgery (ie,
postoperative day
Dose 15 mg once postoperative day
1)
daily 2 to 3)
Apixaban CrCl >50 Give last dose Give last dose two
Dose 5 mg twice procedure (ie, procedure (ie,
daily skip four doses on skip two doses on
CrCl ≤50 before the the procedure)
mL/minute procedure)
Dose 2.5 mg twice
daily
Edoxaban CrCl 51 to 95 Give the last dose Give the last dose
mL/minute three days before two days before
Dose 60 mg once the procedure (ie, the procedure (ie,
daily skip two doses on skip one dose on
CrCl ≤50 before the the procedure)
mL/minute* procedure)
Dose 30 mg once
daily
Bleeding risk is determined primarily by the type of surgery; patient comorbidities may also play a role. In patients
undergoing neuraxial anesthesia or a very high bleeding risk procedure, a longer period of interruption may be warranted.
In many low bleeding risk procedures, the anticoagulant does not need to be interrupted. Bridging anticoagulation may be
appropriate preoperatively in patients with a very high thromboembolic risk who require more prolonged interruption of
the anticoagulant (eg, for renal insufficiency) and/or postoperatively in patients who are unable to resume the
anticoagulant (eg, unable to take oral medication due to intestinal ileus). Refer to the UpToDate topics on perioperative
management of patients receiving anticoagulants for further details.
CrCl: creatinine clearance.

* Product information varies in different countries regarding a lower limit of CrCl below which the drug should not be used. As an
example, product information in the United States specifies avoiding use with CrCl <15 mL/minute.
Procedural bleeding risk
High bleeding risk procedure (two-day risk of major bleed 2 to 4%)

Any major operation of duration >45 minutes
Abdominal aortic aneurysm repair
Coronary artery bypass
Endoscopically guided fine-needle aspiration
Foot/hand/shoulder surgery
Heart valve replacement
Hip replacement
Kidney biopsy
Knee replacement
Laminectomy
Neurosurgical/urologic/head and neck/abdominal/breast cancer surgery
Polypectomy, variceal treatment, biliary sphincterectomy, pneumatic dilatation
Transurethral prostate resection
Vascular and general surgery
Low bleeding risk procedure (two-day risk of major bleed 0 to 2%)

Abdominal hernia repair
Abdominal hysterectomy
Arthroscopic surgery lasting <45 minutes
Axillary node dissection
Bronchoscopy with or without biopsy
Carpal tunnel repair
Cataract and noncataract eye surgery
Central venous catheter removal
Cholecystectomy
Cutaneous and bladder/prostate/thyroid/breast/lymph node biopsies
Dilatation and curettage
Gastrointestinal endoscopy ± biopsy, enteroscopy, biliary/pancreatic stent without sphincterotomy, endosonography without
fine-needle aspiration
Hemorrhoidal surgery
Hydrocele repair
Noncoronary angiography
Pacemaker and cardiac defibrillator insertion and electrophysiologic testing
Thoracentesis
Tooth extractions
This table is based on definitions derived from surgical/subspecialty societies in anticoagulant bridging or anticoagulant
bridging management studies. Refer to UpToDate content on management of anticoagulants in patients
undergoing gastrointestinal procedures for information on bleeding risks of additional gastrointestinal procedures.
Adapted from research originally published in Blood. Spyropoulos AC, Douketis JD. How I treat anticoagulated patients undergoing an
elective procedure or surgery. Blood 2012; 120:2954. Copyright © 2012 the American Society of Hematology.
Clinical risk factors for stroke, transient ischemic attack, and systemic embolism in the
CHA 2 DS 2 -VASc score
(A) The risk factor-based approach expressed as a point based scoring system, with the acronym
CHA 2 DS 2 -VASc
(NOTE: maximum score is 9 since age may contribute 0, 1, or 2 points)
CHA 2 DS 2 -VASc risk factor Points
Congestive heart failure +1

Signs/symptoms of heart failure or objective evidence of reduced left
ventricular ejection fraction
Hypertension +1
Resting blood pressure >140/90 mmHg on at least two occasions or
current antihypertensive treatment
Age 75 years or older +2
Diabetes mellitus +1
Fasting glucose >125 mg/dL (7 mmol/L) or treatment with oral
hypoglycemic agent and/or insulin
Previous stroke, transient ischamic attack, or thromboembolism +2
Vascular disease +1
Previous myocardial infarction, peripheral artery disease, or aortic plaque
Age 65-74 years +1
Sex category (female) +1

(B) Adjusted stroke rate according to CHA 2 DS 2 -VASc score

CHA 2 DS 2 -VASc score Patients Stroke and thromboembolism event
(n = 73,538) rate at one-year follow-up (%)
0 6369 0.78
1 8203 2.01
2 12,771 3.71
3 17,371 5.92
4 13,887 9.27
5 8942 15.26
6 4244 19.74
7 1420 21.50
8 285 22.38
9 46 23.64
CHA 2 DS 2 -VASc: Congestive heart failure, Hypertension, Age (≥75) (doubled), Diabetes, Stroke (doubled), Vascular disease, Age (65-
74), Sex.
Part A from: Kirchhof P, Benussi S, Kotecha D, et al. 2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration
with EACTS. Europace 2016; 18(11):1609-1678. By permission of Oxford University Press on behalf of the European Society of Cardiology.
Copyright © 2016 Oxford University Press. Available at: www.escardio.org/.
Causes of lower extremity arterial occlusion
Native arterial Arterial thrombosis

Arterial embolus Arterial injury
thrombosis following intervention
Atherosclerotic plaque Vein bypass graft Cardiac source Iatrogenic

Aneurysm thrombosis Prosthetic bypass graft Atrial fibrillation Thromboembolism
Arterial dissection Angioplasty site Closure devices
Myocardial infarction
Arterial Stent/stent-graft site Device embolization
Endocarditis
entrapment/compression Traumatic
(eg, popliteal entrapment) Valvular disease
Thrombophilia Atrial myxoma
Low flow state Prosthetic valves

Arterial source
Aneurysm
Atherosclerotic
plaque
Paradoxical embolus
Clinical characteristics comprising the HAS-BLED bleeding risk score
Letter Clinical characteristic* Points

H Hypertension (ie, uncontrolled blood pressure) 1
A Abnormal renal and liver function (1 point each) 1 or 2
S Stroke 1
B Bleeding tendency or predisposition 1
L Labile INRs (for patients taking warfarin) 1
E Elderly (age greater than 65 years) 1
D Drugs (concomitant aspirin or NSAIDs) or excess alcohol use (1 point 1 or 2

each)
Maximum 9 points

HAS-BLED score Bleeds per 100 patient-years ¶

(total points)
0 1.13
1 1.02
2 1.88
3 3.74
4 8.70
5 to 9 Insufficient data
The HAS-BLED bleeding risk score has only been validated in patients with atrial fibrillation receiving warfarin. Refer to
UpToDate topics on anticoagulation in patients with atrial fibrillation and on specific anticoagulants for further information
and other bleeding risk scores and their performance relative to clinical judgment.
INR: international normalized ratio; NSAIDs: nonsteroidal antiinflammatory drugs.

* Hypertension is defined as systolic blood pressure >160 mmHg. Abnormal renal function is defined as the presence of chronic
dialysis, renal transplantation, or serum creatinine ≥200 micromol/L. Abnormal liver function is defined as chronic hepatic disease
(eg, cirrhosis) or biochemical evidence of significant hepatic derangement (eg, bilirubin more than two times the upper limit of
normal, plus one or more of aspartate transaminase, alanine transaminase, and/or alkaline phosphatase more than three times the
upper limit of normal). Bleeding predisposition includes chronic bleeding disorder or previous bleeding requiring hospitalization or
transfusion. Labile INRs for a patient on warfarin include unstable INRs, excessively high INRs, or <60% time in therapeutic range.
¶ Based on initial validation cohort from Pisters R. A novel-user-friendly score (HAS-BLED) to assess 1-year risk of major bleeding in
patients with atrial fibrillation: the Euro Heart Survey. Chest 2010; 138:1093. Actual rates of bleeding in contemporary cohorts may
vary from these estimates.
Original figure modified for this publication. Lip GY. Implications of the CHA2DS2-VASc and HAS-BLED Scores for thromboprophylaxis in
atrial fibrillation. Am J Med 2011; 124:111. Table used with the permission of Elsevier Inc. All rights reserved.
Expected effects of anticoagulant drugs on commonly used coagulation tests
Brand Anti-factor Xa
Drug class Drug PT aPTT
name(s) activity
Vitamin K Warfarin Coumadin, ↑ ↑/–* –

antagonists Jantoven
Acenocoumarol Sintrom ↑ ↑/–* –
Heparins Unfractionated –¶ ↑ ↑
heparin
LMW heparins – ↑/– ↑

Enoxaparin Lovenox
Dalteparin Fragmin
Nadroparin Fraxiparine
Fondaparinux Arixtra – ↑/– ↑
Direct thrombin Argatroban Acova ↑ ↑ –

inhibitors
Dabigatran Pradaxa ↑/– ↑ –
Direct factor Xa Rivaroxaban Xarelto ↑/– ↑/– ↑Δ

inhibitors
Apixaban Eliquis ↑/– ↑/– ↑Δ
Edoxaban Lixiana, Savaysa ↑ Δ
Betrixaban Bevyxxa ↑ Δ
PT and aPTT are measured in seconds; anti-factor Xa activity is measured in units/mL. Upward arrow (↑) signifies an
increase above normal due to the anticoagulant (prolongation of PT or aPTT; increase in anti-factor Xa activity). The effect
magnitude will vary depending on the reagent formulation and instrument used. Dash (–) signifies no appreciable effect.
Normal ranges for the PT, aPTT, and anti-factor Xa activity vary among laboratories and should be reported from the testing
laboratory along with the patient result. Refer to the UpToDate topic on coagulation testing for details.
PT: prothrombin time; aPTT: activated partial thromboplastin time; LMW heparin: low molecular weight heparin.
* Warfarin has a weak effect on most aPTT reagents. However, warfarin use will increase the sensitivity of the aPTT to heparin
effect.
¶ While heparin, LMW heparin, and fondaparinux should, in theory, prolong the PT as indirect thrombin inhibitors, in practice most
PT reagents contain heparin-binding chemicals that block any heparin effect below a concentration of 1 unit/mL. Above
concentrations of 1 unit/mL, heparin effect on the PT may be observed.
Δ Anti-factor Xa activity testing must be calibrated for the specific anticoagulant; this information should be verified with the clinical
laboratory. Data are not available for betrixaban but would be expected to be similar to other direct factor Xa inhibitors.
Some of the data are from: Samuelson BT, Cuker A, Crowther M, Garcia DA. Laboratory assessment of the anticoagulant activity of direct
oral anticoagulants: A systematic review. Chest 2017; 151:127.
Comparison of the CHADS2 and CHA2DS2-VASc risk stratification scores for subjects with
nonvalvular AF
Definition and scores for CHADS 2 and Stroke risk stratification with the CHADS 2 and
CHA 2 DS 2 -VASc CHA 2 DS 2 -VASc scores
CHADS 2 acronym Score CHADS 2 acronym Unadjusted ischemic stroke rate
(% per year)*
Congestive HF 1
0 0.6%
Hypertension 1
1 3.0%
Age ≥75 years 1
2 4.2%
Diabetes mellitus 1
3 7.1%
Stroke/TIA/TE 2
4 11.1%
Maximum score 6
5 12.5%
CHA 2 DS 2 -VASc acronym Score
6 13.0%
Congestive HF 1
CHA 2 DS 2 -VASc Unadjusted ischemic stroke rate
Hypertension 1
acronym (% per year)*
Age ≥75 years 2
0 0.2%
Diabetes mellitus 1
1 0.6%
Stroke/TIA/TE 2
2 2.2%
Vascular disease (prior MI, PAD, or aortic 1
3 3.2%
plaque)
4 4.8%
Age 65 to 74 years 1
5 7.2%
Sex category (ie, female sex) 1
6 9.7%
Maximum score 9
7 11.2%
8 10.8%
9 12.2%
AF: atrial fibrillation; CHADS 2 : Congestive heart failure, Hypertension, Age ≥75 years, Diabetes mellitus, Prior Stroke or TIA or
Thromboembolism (doubled); CHA 2 DS 2 -VASc: Congestive heart failure, Hypertension, Age ≥75 years (doubled), Diabetes mellitus,
Prior Stroke or TIA or thromboembolism (doubled), Vascular disease, Age 65-74 years, Sex category; HF: heart failure; LV: left
ventricular; MI: myocardial infarction; PAD: peripheral artery disease; TE: thromboembolic; TIA: transient ischemic attack.
* These unadjusted (not adjusted for possible use of aspirin) stroke rates were published in 2012 [1]. Actual rates of stroke in
contemporary cohorts might vary from these estimates.
Reference:
1. Friberg L, Rosenqvist M, Lip GY. Evaluation of risk stratification schemes for ischaemic stroke and bleeding in 182 678 patients with
atrial fibrillation: the Swedish Atrial Fibrillation cohort study. Eur Heart J 2012; 33:1500.
Original figure modified for this publication. January CT, Wann LS, Alpert JS, et al. 2014 AHA/ACC/HRS Guideline for the Management of
Patients With Atrial Fibrillation: A Report of the American College of Cardiology/American Heart Association Task Force on Practice
Guidelines and the Heart Rhythm Society. J Am Coll Cardiol 2014. DOI: 10.1016/j.jacc.2014.03.022. Table used with the permission of Elsevier
Inc. All rights reserved.
Recommendations for preoperative and postoperative anticoagulation in patients on a

vitamin K antagonist
Indication Before surgery After surgery
Venous thromboembolism
Within first month IV heparin or SQ LMWH IV heparin or SQ LMWH
Second/third month No change* IV heparin or SQ LMWH
≥3 months No change* SQ heparin or LWMH
Arterial thromboembolism
Recent, within one month IV heparin or SQ LMWH IV heparin or SQ LMWH
Prophylaxis (eg, non-valvular AF, mechanical heart valve) No change* Resume oral anticoagulation ¶
NOTE: Warfarin should be withheld to allow the INR to fall spontaneously to 1.5 to 2 before surgery is performed.
IV: intravenous; SQ: subcutaneous; LMWH: low molecular weight heparin; AF: atrial fibrillation; INR: international normalized ratio.
* If the patient is hospitalized, SQ heparin or LMWH should be administered, but hospitalization is not recommended solely for this
purpose.
¶ Can use SQ heparin or SQ LMWH if the surgery carries a high risk of postoperative thromboembolism.
Reversing anticoagulation in warfarin-associated bleeding
Management
Time to anticoagulation reversal Comments and cautions
option
Discontinuing warfarin 5 to 14 days Five days is typical for patients with an INR in
therapy the therapeutic range
Vitamin K* 6 to 24 hours to correct the INR, longer to fully Recovery of factors X and II (prothrombin) takes
reverse anticoagulation longer than 24 hours
Risk of anaphylaxis with intravenous injection
Impaired response to warfarin lasting up to one
week may occur after large doses (ie, >5 mg)
Fresh frozen plasma Depends on the time it takes to complete the Effect is transient and concomitant vitamin K
infusion; typically 12 to 32 hours for complete must be administered
reversal Potential for volume overload (2 to 4 L to
normalize INR)
Potential for TRALI
Potential for viral transmission
Prothrombin complex 15 minutes after 10-minute to 1-hour infusion Effect is transient, and concomitant vitamin K
concentrate must be administered; limited availability
Cost
Variable factor VII content depending on the
product: a 4-factor PCC is preferred
Potentially prothrombotic
Recombinant factor 15 minutes after bolus infusion Effect is transient, and concomitant vitamin K
VIIa must be administered
Cost
Potentially prothrombotic
Please refer to the UpToDate topic on warfarin reversal in intracerebral hemorrhage for further details of management.
INR: international normalized ratio; TRALI: transfusion-related acute lung injury; PCC: prothrombin complex concentrate.
* A total of 10 mg intravenously by slow infusion given over 10 minutes.
Adapted with permission from: Aguilar MI, Hart RG, Kase CS, et al. Treatment of warfarin-associated intercerebral hemorrhage: Literature
review and expert opinion. Mayo Clin Proc 2007; 82:82. Copyright © 2007 Dowden Health Media.
Emergency reversal of anticoagulation from warfarin for life-threatening hemorrhage in

adults: Suggested approaches based upon available resources
A. If 4-factor prothrombin complex concentrate (4F PCC) is available (preferred approach):
1. Give 4F PCC* 1500 to 2000 units ¶ IV over 10 minutes. Check INR 15 minutes after completion of the infusion. If INR is
not ≤1.5, give additional 4F PCC (refer to topic or drug reference for details).
2. Give vitamin K 10 mg IV over 10 to 20 minutes.
B. If 3-factor prothrombin complex concentrate (3F PCC) is available but 4F PCC is not available:
1. Give 3F PCC* 1500 to 2000 units ¶ IV over 10 minutes. Check INR 15 minutes after completion of the infusion. If INR is
not ≤1.5, give additional 3F PCC (refer to topic or drug reference for details).
2. Give Factor VIIa 20 mcg/kg IV OR give FFP 2 units IV by rapid infusion. Factor VIIa may be preferred if volume overload is
a concern.
C. If neither 3F PCC nor 4F PCC is available:
1. Give FFP 2 units IV by rapid infusion. Check INR 15 minutes after completion of infusion. If INR ≥1.5, administer 2
additional units of FFP IV rapid infusion. Repeat process until INR ≤1.5. May wish to administer loop diuretic between FFP
infusions if volume overload is a concern.
These products and doses are for use in life-threatening bleeding only. Evidence of life-threatening bleeding and over-
anticoagulation with a vitamin K antagonist (eg, warfarin) are required. Anaphylaxis and transfusion reactions can occur.
It may be reasonable to thaw 4 units of FFP while awaiting the PT/INR. The transfusion service may substitute other plasma
products for FFP (eg, Plasma Frozen Within 24 Hours After Phlebotomy [PF24]); these products are considered clinically
interchangeable. PCC will reverse anticoagulation within minutes of administration; FFP administration can take hours due
to the volume required; vitamin K effect takes 12 to 24 hours, but administration of vitamin K is needed to counteract the
long half-life of warfarin. Subsequent monitoring of the PT/INR is needed to guide further therapy. Refer to topics on
warfarin reversal in individual situations for further management.
PCC: unactivated prothrombin complex concentrate; 4F PCC: PCC containing coagulation factors II, VII, IX, X, protein S and protein C;
3F PCC: PCC containing factors II, IX, and X and only trace factor VII; FFP: fresh frozen plasma; PT: prothrombin time; INR:
international normalized ratio; FEIBA: factor eight inhibitor bypassing agent.
* Before use, check product label to confirm factor types (3 versus 4 factor) and concentration. Activated complexes and single-
factor IX products (ie, FEIBA, AlphaNine, Mononine, Immunine, BeneFix) are NOT used for warfarin reversal.
¶ PCC doses shown are those suggested for initial treatment of emergency conditions. Subsequent treatment is based on INR and
patient weight if available. Refer to topic and Lexicomp drug reference included with UpToDate for INR-based dosing.
PCC products available in the United States*
Unactivated prothrombin complex concentrates (PCCs)

4 factor: Contains inactive forms of 4 factors: Factors II, VII, IX, and X
Kcentra Also contains heparin
3 factor: Contains inactive forms of 3 factors: Factors II, IX, and X

Profilnine Contains little or no factor VII
Does not contain heparin
Activated prothrombin complex concentrate (aPCC)

4 factor: Contains 4 factors: Factors II, VII, IX, and X. Of these, only factor VII is mostly the activated form ¶
FEIBA Does not contain heparin
The table lists 4-factor and 3-factor PCC products available in the United States. Kcentra is available as Beriplex in Canada.
Bebulin (a 3-factor PCC) was discontinued in 2018 due to decreased demand for the product. Potency is determined
differently for different products; refer to product information. All PCCs are plasma derived and contain other proteins,
including anticoagulant proteins (proteins C and S). Unactivated factors are proenzymes (inactive precursor proteins).
Activated factors have higher enzymatic activity. Refer to UpToDate topics for use of these products.
US: United States; PCC: prothrombin complex concentrate; FEIBA: factor eight inhibitor bypassing activity.
* Other 4-factor PCCs available outside the US include Octaplex and Cofact Proplex.
¶ Single-factor recombinant activated factor VII (rFVIIa) products are also available.
Direct oral anticoagulant reversal agents for life-threatening bleeding (imminent risk of
death from bleeding)
Anticoagulant Reversal agent (all are given intravenously)
Dabigatran (Pradaxa; oral thrombin inhibitor) Idarucizumab (Praxbind). Dose: 5 grams*
Oral factor Xa inhibitors: Andexanet alfa (AndexXa). Dosing for the initial bolus and
subsequent infusion depend on the dose level of the
Apixaban (Eliquis)
factor Xa inhibitor and the interval since it was last taken.
Edoxaban (Lixiana, Savaysa)
-OR-
Rivaroxaban (Xarelto)
4-factor PCC (Kcentra, Beriplex P/N, Octaplex). Dosing
can be done with a fixed dose of 2000 units OR a weight-
based dose of 25 to 50 units per kg.
Reversal agents carry a risk of life-threatening thrombosis and should only be used under the direction of a specialist with
expertise in their use and/or in a patient at imminent risk of death from bleeding. In general, a single dose is given; dosing
may be repeated in rare situations in which the oral anticoagulant persists for longer in the circulation, such as severe
kidney dysfunction.
Andexanet dosing is as follows:
If the patient took rivaroxaban >10 mg, apixaban >5 mg, or dose unknown within the previous 8 hours: Andexanet 800
mg bolus at 30 mg/minute followed by 960 mg infusion at 8 mg/minute for up to 120 minutes.
-OR-
If the patient took rivaroxaban ≤10 mg or apixaban ≤5 mg, or if ≥8 hours have elapsed since the last dose of a factor Xa
inhibitor: Andexanet 400 mg bolus at 30 mg/minute followed by 480 mg infusion at 4 mg/minute for up to 120 minutes.
Refer to UpToDate topics on treatment of bleeding in patients receiving a DOAC or perioperative management of patients
receiving a DOAC for additional information on administration, risks, and alternative therapies.
DOAC: direct oral anticoagulant; PCC: prothrombin complex concentrate; FEIBA: factor eight inhibitor bypassing activity.
* If idarucizumab is unavailable, an activated PCC (FEIBA, 50 to 80 units per kg intravenously) may be a reasonable alternative.
Contributor Disclosures
James D Douketis, MD, FRCPC, FACP, FCCP Consultant/Advisory Boards: Bristol-Myers Squibb;
Servier; Janssen; Leo Pharma; Pfizer; Portola; Sanofi. Gregory YH Lip, MD, FRCPE, FESC,
FACC Speaker's Bureau: Bayer [Atrial fibrillation and thrombosis (rivaroxaban)]; BMS/Pfizer [Atrial
fibrillation and thrombosis (apixaban)]; Boehringer Ingelheim [Atrial fibrillation and thrombosis
(dabigatran)]; Daiichi-Sankyo [Atrial fibrillation and thrombosis (edoxaban)]. Consultant/Advisory
Boards: Bayer/Janssen [Atrial fibrillation and thrombosis (rivaroxaban)]; BMS/Pfizer [Atrial fibrillation
and thrombosis (apixaban)]; Boehringer Ingelheim [Atrial fibrillation and thrombosis (dabigatran)];
Daiichi-Sankyo [Atrial fibrillation and thrombosis (edoxaban)]; Verseon [thrombosis (drug in
development)]. Lawrence LK Leung, MD Nothing to disclose Jennifer S Tirnauer, MD Nothing to
disclose
Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these
are addressed by vetting through a multi-level review process, and through requirements for
references to be provided to support the content. Appropriately referenced content is required of all
authors and must conform to UpToDate standards of evidence.
Conflict of interest policy

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19/10/2020 Perioperative management of patients receiving anticoagulants - UpToDate

Official reprint from UpToDate®

Perioperative management of patients receiving

The management of anticoagulation in patients undergoing surgical procedures is

Our approach to managing ongoing anticoagulation in patients undergoing surgery or an

Perioperative venous thromboembolism prevention in patients not receiving ongoing

OVERVIEW OF OUR APPROACH

General approach — Interruption of anticoagulation temporarily increases thromboembolic

Our approach to decision making is outlined as follows; this is presented in an interactive

● Estimate thromboembolic risk – A higher thromboembolic risk increases the

If thromboembolic risk is transiently increased (eg, recent stroke, recent pulmonary

'Estimating thromboembolic risk' below.)

● Determine the timing of anticoagulant interruption – The timing of anticoagulant

● Determine whether to use bridging anticoagulation – For most patients, we do not

● A 70-year-old male with non-valvular atrial fibrillation, diabetes, and hypertension

● A 68-year-old female with non-valvular atrial fibrillation, hypertension, and congestive

• Omit rivaroxaban on the day of the procedure.

ESTIMATING THROMBOEMBOLIC RISK

● ROCKET AF (rivaroxaban versus warfarin) – Of the 4692 anticoagulant interruptions in

● ARISTOTLE (apixaban versus warfarin) – During 9260 procedures performed on patients

Prosthetic heart valve — The risks of thromboembolism and perioperative management of

Recent thromboembolism — Thromboembolic risk is greater in the immediate period

Venous — The perioperative risk of venous thromboembolism (VTE) is greatest in

Arterial — The risk of recurrent arterial embolism from any cardiac source is

paradoxical embolism, non-bacterial thrombotic endocarditis in a patient with malignancy,

ESTIMATING PROCEDURAL BLEEDING RISK

● Neuraxial anesthesia – (see "Neuraxial anesthesia/analgesia techniques in the patient

● Gastrointestinal procedures – (see "Management of anticoagulants in patients

● Percutaneous coronary intervention (eg, angioplasty, atherectomy, stenting) – (see

● Ophthalmologic procedures – (see "Diabetic retinopathy: Prevention and treatment",

DECIDING WHETHER TO INTERRUPT ANTICOAGULATION

Overview of whether to interrupt — Once the thromboembolic and bleeding risks have

Practices to reduce bleeding and thromboembolic risks should be employed regardless of

● For those not receiving an anticoagulant in the immediate postoperative period,

Settings requiring anticoagulant interruption — Individuals undergoing surgery with a

● Individuals with a moderate thromboembolic risk generally can interrupt their

In contrast, patients who require temporary interruption of anticoagulation for a minor

Settings in which continuing the anticoagulant may be preferable — For individuals

• Cardiac implantable devices – We agree with a position document from the

An exception is a patient with a low risk of thromboembolic events, in whom

• Endovascular procedures and catheter ablation – Endovascular procedures

TIMING OF ANTICOAGULANT INTERRUPTION

Warfarin — Warfarin blocks a vitamin K-dependent step in clotting factor production; it

● Discontinuation – If it has been determined that warfarin discontinuation is

● Use of bridging preoperatively – We generally reserve bridging for individuals

● Restarting warfarin and postoperative bridging – We resume warfarin 12 to 24 hours

After warfarin is restarted in the perioperative setting, it takes 5 to 10 days to attain a

Dabigatran — Dabigatran is a direct thrombin inhibitor; it reversibly blocks the enzymatic

As an example, in a patient on dabigatran with a creatinine clearance >50 mL/min

prospective cohort of 541 dabigatran-treated patients undergoing surgery and was

● Restarting dabigatran – Dabigatran should be resumed postoperatively when

Rivaroxaban — Rivaroxaban is a direct factor Xa inhibitor; it reversibly blocks the enzymatic

● Discontinuation – Rivaroxaban can be omitted for approximately two to three days

● Restarting rivaroxaban – Rivaroxaban can be resumed postoperatively when

Apixaban — Apixaban is a direct factor Xa inhibitor; it reversibly blocks the enzymatic

● Restarting apixaban – Apixaban can be resumed postoperatively when hemostasis has

Edoxaban — Edoxaban is a direct factor Xa inhibitor; it reversibly blocks the enzymatic

● Restarting edoxaban – Edoxaban can be resumed postoperatively when hemostasis has

Bridging anticoagulation involves the administration of a short-acting anticoagulant,

Appropriate settings for bridging

Results of a randomized trial comparing postoperative bridging versus no bridging in

Of note, management of perioperative anticoagulation in patients with mechanical heart

When to bridge: Preoperative, postoperative, or both — Once a decision to use