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Disclosures: Gregory YH Lip, MD, FRCPE, FESC, FACC Speaker’s Bureau: Bayer; BMS/Pfizer; Boehringer Ingelheim; Daiichi-Sankyo; Medtronic; Sanofi Aventis [Atrial fibrillation and thrombosis (Rivaroxaban; Dabigatran; Edoxaban; Apixaban)]. Consultant/Advisory Boards: Bayer; Astellas; Merck; Sanofi; BMS/Pfizer; Daiichi-Sankyo; Biotronik; Medtronic; Portola; Boehringer Ingelheim [Atrial fibrillation and thrombosis (Rivaroxaban; Dabigatran; Edoxaban; Apixaban)]. James D Douketis, MD, FRCPC, FACP, FCCP Consultant/Advisory Boards: Boehringer [venous thromboembolic disease (dabigatran)]; Bayer [venous thromboembolic disease (rivaroxaban)]; BMS [venous thromboembolic disease (apixaban)]; Pfizer [venous thromboembolic disease (dalteparin)]; Sanofi [venous thromboembolic disease (enoxaparini)]; Leo [venous thromboembolic disease [venous thromboembolic disease (tinzaparin)]; Medicines Co [venous thromboembolic disease (cangrelor)]. Lawrence LK Leung, MD Nothing to disclose. Jennifer S Tirnauer, MD Employee of UpToDate, Inc.

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Literature review current through: Jul 2014. | This topic last updated: Jul 21, 2014.

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 target-specific 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 they lack a specific antidote or reversal strategy, which raises concerns about treatment of bleeding and management of patients who require an urgent 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.

(See "Therapeutic use of warfarin and other vitamin K antagonists".)

(See "Therapeutic use of heparin and low molecular weight heparin".)

(See "Anticoagulation with direct thrombin inhibitors and factor Xa inhibitors".)

(See "Perioperative medication management", section on 'Medications affecting hemostasis'.)

Perioperative venous thromboembolism prevention in patients not receiving ongoing anticoagulation is also discussed separately. (See "Prevention of venous thromboembolic disease in surgical patients".)

OVERVIEW OF OUR 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.

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 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 target-specific anticoagulants. Thus, this approach should be used as a guideline and should not substitute for clinician judgment in decisions about perioperative anticoagulant management.

Our approach to decision making is outlined as follows:

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 target-specific oral anticoagulants (eg, dabigatran, rivaroxaban, apixaban) (table 2 and algorithm 1). (See 'Timing of anticoagulant interruption' below.)

Determine whether to use bridging anticoagulation – For patients receiving warfarin, the interval without an anticoagulant may be as long as five to six days due to the long half-life of warfarin and time to reach the therapeutic INR range. The use of heparin or low molecular weight (LMW) heparin to reduce the interval without anticoagulation (ie, bridging anticoagulation) may be appropriate for some patients, especially those who have a high thromboembolic risk. (See 'Bridging anticoagulation' below.)

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. The magnitude of this issue was illustrated in the Randomized Evaluation of Long-Term Anticoagulant Therapy (RE-LY) trial, which randomized 18,113 patients with non-valvular atrial fibrillation to warfarin or dabigatran for stroke prevention [7]. One-fourth of the patients required an invasive procedure or surgery during a two-year period.

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. There were no differences according to the anticoagulant used (ie, warfarin or dabigatran) or the dabigatran dose. However, urgent surgery was associated with a higher risk of ischemic stroke or systemic embolism than elective surgery (1.8 versus 0.4, 1.4 versus 0.4, and 2.8 versus 0.3 percent for warfarin, dabigatran 150 mg twice daily, and dabigatran 110 mg twice daily, respectively).

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]. Risk scores that incorporate these variables, including CHADS2, CHA2DS2-VASc, are discussed in detail separately (table 3 and table 4) (calculator 1); of note, use of these scores has not been prospectively validated in the perioperative setting. (See "Risk of embolization in nonvalvular atrial fibrillation".)

Prosthetic heart valve — The risks of thromboembolism and perioperative management of patients with prosthetic heart valves are discussed separately. (See "Complications of prosthetic heart valves", section on 'Embolism' and "Complications of prosthetic heart valves", section on 'Valve thrombosis' and "Antithrombotic therapy in patients with prosthetic heart valves", section on 'Interruption of warfarin for surgical procedures'.)

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 emergent 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 "Evaluation of the patient with established venous thrombosis", section on 'Screening for inherited thrombophilia' and "Approach to the diagnosis and therapy of lower extremity deep vein thrombosis", section on 'Screening for a hypercoagulable state'.)

Individuals with cancer have a moderate risk, and those with a provoked 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 (ie, approximately 1 percent per day), and diminishes over the following two months [9-11]. 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 [11-13].

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 [14]. 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) [15-17].

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 may also contribute [3,18,19].

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 6) [2]. Neuraxial, intracranial, and cardiac procedures are especially concerning because the location of potential bleeding increases the risk of serious complications. (See "Neuraxial (spinal, epidural) anesthesia in the patient receiving antithrombotic medication (anticoagulant)".)

Major bleeding is generally defined as bleeding that is fatal, intracranial, 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 [20].

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 (spinal, epidural) anesthesia in the patient receiving antithrombotic medication (anticoagulant)".)

Gastrointestinal procedures – (See "Management of anticoagulants in patients undergoing endoscopic procedures", section on 'Elective procedures in anticoagulated patients'.)

Percutaneous coronary intervention (eg, angioplasty, atherectomy, stenting) – (See "Antithrombotic therapy for percutaneous coronary intervention: General use", section on 'Patients who require warfarin' and "Triple antithrombotic therapy in patients with cardiovascular disease", section on 'Management of anticoagulation'.)  

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 'Antithrombotic agents'.)

Dental and cutaneous procedures are generally associated with a low risk of bleeding.

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 [21-27]. Bleeding can be further reduced with the use of topical hemostatic agents (eg, tranexamic acid or aminocaproic acid mouthwash, used four times daily for at least two days) [8,26,28-31]. (See 'Surgical bleeding risk low' below.)

An exception is multiple tooth extractions, which we consider high bleeding risk. (See 'Surgical bleeding risk high' below.)

Cutaneous procedures – Cutaneous procedures (eg, skin biopsy, tumor excision) are also generally considered to confer a low bleeding risk of bleeding; the potential for local control measures further reduces concerns about bleeding risk. (See 'Surgical bleeding risk low' 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) [32]. 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 7).

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 high or moderate thromboembolic risk should limit the period without anticoagulation to the shortest possible interval; this typically involves the use of a bridging agent (eg, a low molecular weight [LMW] heparin) if the patient's usual anticoagulant is a vitamin K antagonist. Often, bridging is not required for those with high or moderate thromboembolic risk who are receiving a direct thrombin inhibitor or factor Xa inhibitor, because of the shorter half-lives of these agents. (See 'Surgical bleeding risk high' below and 'Timing of anticoagulant interruption' below and 'Surgical bleeding risk low' below.)

In contrast, individuals undergoing selected low bleeding risk surgery often can continue their anticoagulant. (See 'Surgical bleeding risk low' below.)

Of note, continuing warfarin may be associated with a lower risk of bleeding than interrupting warfarin and using bridging in some settings. This was demonstrated in the BRUISE CONTROL trial, which randomized patients on warfarin who were undergoing implantation of a cardiac implantable electronic device (eg, pacemaker, implantable cardioverter-defibrillator) to continuation of warfarin or bridging with heparin [33]. In this trial, bridging was associated with more postoperative bleeding than was continuation of warfarin. Potential explanations include initiation of post-procedure 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. A benefit of warfarin continuation rather than discontinuation with bridging was also reported in the COMPARE trial, which randomized patients with atrial fibrillation undergoing catheter ablation to continued warfarin or discontinuation of warfarin with bridging [34]. In this trial, patients randomized to continue warfarin had a lower risk of stroke and less bleeding. (See "Implantable cardioverter-defibrillators: Complications", section on 'Bleeding' and "Catheter ablation to prevent recurrent atrial fibrillation: Anticoagulation", section on 'Uninterrupted warfarin compared to heparin bridge'.)

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, non-steroidal antiinflammatory 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. In 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 [35]. Issues associated with perioperative aspirin use are discussed in detail separately. (See "Perioperative medication management", section on 'Medications affecting hemostasis'.)

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 surgical patients".)

Surgical bleeding risk high — 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 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 [36]. (See "Risk of embolization in nonvalvular atrial fibrillation", section on 'Imaging predictors'.)

Individuals with a temporarily high or moderate thromboembolic risk in whom surgery cannot be delayed (eg, potentially curative cancer surgery) 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. (See 'Timing of anticoagulant interruption' below and 'Bridging anticoagulation' below.)

In the setting of acute venous thromboembolism within the past two to four weeks and surgery that cannot be delayed, we also place a temporary vena caval filter that can be removed after surgery, especially for patients anticipated to have a longer interval of anticoagulant interruption (eg, extensive surgery with long recovery period).

For individuals with a chronically high thromboembolic risk (eg, rheumatic heart disease; CHA2DS2-VASc score ≥4; CHADS2 score 5 or 6) and many with a moderate thromboembolic risk (eg, atrial fibrillation with a CHA2DS2-VASc score 2 to 3 or a CHADS2 score of 3 to 4), we use bridging anticoagulation to minimize the period when anticoagulation is not being used. (See 'Appropriate settings for bridging' below.)

Individuals with a low 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 [37,38].

Surgical bleeding risk low — Individuals undergoing selected surgery that confers a low risk of bleeding (eg, cataract extraction) are often best served by continuing their anticoagulant. For those receiving warfarin or another vitamin K antagonist, it is important to confirm that the INR does not exceed the therapeutic range.

If a decision is made to discontinue the anticoagulant (eg, patient with renal insufficiency), bridging is used for those with a moderate-high thromboembolic risk, and not used for those with a low thromboembolic risk. (See 'Bridging anticoagulation' 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. If a moderate or high bleeding risk surgery is required urgently or emergently, reversal of the anticoagulant may also be required. (See 'Urgent anticoagulant reversal' below.)

Data to guide the timing of anticoagulant interruption are evolving, and much of our practice is based on expert opinion as we await results from ongoing trials. 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 (spinal, epidural) anesthesia in the patient receiving antithrombotic medication (anticoagulant)" and "Antithrombotic therapy in patients with prosthetic heart valves".)

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 [7]. 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, which is standardized across institutions using an international normalized ratio (PT/INR).

Discontinuation – We discontinue warfarin five days before elective surgery (ie, last dose of warfarin is given on day minus 6) and, when possible, check the PT/INR on the day before surgery (algorithm 1) [8,11,39,40]. 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) [39]. Normalization of the INR may take longer in patients receiving higher-intensity anticoagulation (INR 2.5 to 3.5), and in elderly individuals [41]. Half-lives of other vitamin K antagonists also differ (eg, 8 to 11 hours for acenocoumarol; three to five days for phenprocoumon; approximately three days for fluindione). (See "Therapeutic use of warfarin and other vitamin K antagonists", section on 'Biological properties'.)

For a procedure that requires more rapid normalization of the INR, additional interventions may be needed to actively reverse the anticoagulant. (See 'Urgent anticoagulant reversal' 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) [11]. Thus, for patients at high or moderate thromboembolic risk, bridging may be appropriate.

Use of bridging – We generally treat individuals at high or moderate risk of thromboembolism who require interruption of warfarin with a bridging agent (eg, therapeutic dose subcutaneous low molecular weight [LMW] heparin) starting three days before surgery (algorithm 1). (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 – 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, it takes approximately five days for the INR to rise above 2.0, but the full anticoagulant effect of warfarin will take four to six days. Thus, we generally treat individuals at high risk and some individuals with a moderate 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).

DiscontinuationDabigatran can be discontinued two to three days before a surgical procedure in patients with normal or mildly impaired renal function (ie, creatinine clearance >50 mL/minute), with the longer interval used for higher bleeding risk procedures and the shorter interval for surgeries with less bleeding risk. Thus, for high bleeding risk procedures, the patient will skip four doses of dabigatran, 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 12 to 14 hours in patients with normal renal function (table 2) [2,42-44].

For those with renal insufficiency (eg, creatinine clearance between 30 and 50 mL/minute), dabigatran should be discontinued two to four days before the procedure.

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.)

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 8). Importantly, the reliability of aPTT testing may depend on the specific assay used; if available, a diluted plasma thrombin time may be preferable [43,45,46]. (See "Anticoagulation with direct thrombin inhibitors and factor Xa inhibitors", 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 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).

Rivaroxaban — Rivaroxaban is a direct factor Xa inhibitor; it reversibly blocks the enzymatic function of factor Xa in converting prothrombin to thrombin.

DiscontinuationRivaroxaban can be discontinued 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 the 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 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.)

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 (table 9).

Unlike the PT/INR for warfarin, routine coagulation tests have not been validated for 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 8) [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 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).

Apixaban — Apixaban is a direct factor Xa inhibitor; it reversibly blocks the enzymatic function of factor Xa in converting prothrombin to thrombin.

DiscontinuationApixaban can be discontinued 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 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 the apixaban elimination half-life of 7 to 11 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 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 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.)

Unlike the PT/INR for warfarin, routine coagulation tests have not been validated for 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 8). 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 high thromboembolic risk and are unable to take oral medications postoperatively due to intestinal ileus from gastrointestinal surgery. (See 'Bridging anticoagulation' below.)

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).

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 target-specific oral anticoagulants (eg, direct thrombin inhibitors, direct factor Xa inhibitors) as bridging agents; further, these 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. In general, bridging anticoagulation may be appropriate in patients who have a high thromboembolic risk and some with a moderate thromboembolic risk who will have prolonged interruption of their anticoagulant (generally a vitamin K antagonist).

Examples include individuals taking warfarin for one of the following conditions [1]:

Prior stroke or systemic embolic event

Mechanical mitral valve

Mechanical aortic valve and additional stroke risk factors

Atrial fibrillation and multiple stroke risk factors

Venous thromboembolism (VTE) within the previous three months

Recent coronary stenting

Previous thromboembolism during interruption of chronic anticoagulation

Of note, management of perioperative anticoagulation in patients with mechanical heart valves is discussed in detail separately. (See "Antithrombotic therapy in patients with prosthetic heart valves", section on 'Interruption of warfarin for surgical procedures'.)

Bridging is generally not used for the shorter-acting target-specific oral thrombin inhibitors or factor Xa inhibitors. However, bridging may be appropriate for individuals on these agents who have a 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.)

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. Alternatively, a potential role for bridging in reducing the risk of "rebound hypercoagulability" has also been proposed. This theoretical risk is based on biochemical studies in which abrupt cessation of warfarin induced markers of activated coagulation factors; clinical implications of this phenomenon and/or interventions to lessen its effects are unclear [47-49].

When to bridge: Preoperative, postoperative, or both — The other decision to make is whether to use bridging before the procedure, after the procedure, or both (table 10).

Preoperative bridging – For individuals with nonvalvular atrial fibrillation receiving warfarin for thromboprophylaxis who are undergoing a procedure associated with a very high bleeding risk (eg, intracranial, spinal, cardiac), we generally use bridging preoperatively, but not postoperatively, because postoperative bridging probably increases, rather than decreases, serious morbidity. Restarting warfarin on the second postoperative day is preferable to minimize the risk of bleeding, as long as adequate hemostasis has been achieved. (See 'Warfarin' above.)

Preoperative and postoperative bridging – For individuals considered to be at highest risk for thromboembolism, including patients with atrial fibrillation and a high CHADS2 or CHA2DS2-VASc score, patients with a mechanical mitral valve replacement, or those within the first month after an acute episode of VTE, we use bridging both preoperatively and postoperatively [11]. This practice is based on the high incidence of recurrence without anticoagulation, of approximately 1 percent per day. While postoperative intravenous heparin doubles the rate of bleeding, there is a net reduction in serious morbidity in such patients since the risk of postoperative recurrent VTE is high. (See 'Preoperative timing of bridging' below and 'Postoperative timing of bridging' below.)

Postoperative bridging – For individuals greater than one month 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 [50]. This practice is based on the significantly reduced risk of VTE recurrence after the first month, to the point that preoperative bridging is probably not justified unless there are other risk factors for thromboembolism (eg, prolonged hospitalization and immobility) [11]. Therapeutic-dose heparin is used postoperatively because the postoperative state further adds to VTE risk. (See 'Postoperative timing of bridging' below.)

The efficacy of bridging was evaluated in a systematic review and meta-analysis of 34 studies in patients undergoing elective surgery or procedures [51]. 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. Findings included the following:

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).

Comparison of patients receiving full dose heparin versus prophylactic or intermediate dose heparin showed no difference in thromboembolic events, but an increase in overall bleeding with full dose heparin (OR: 2.28; 95% CI: 1.27-4.08). (See 'Heparin product and dose' below.)

The findings from this analysis should be interpreted with caution, however, because patients may have preferentially received (or not received) bridging anticoagulation depending on their underlying thrombotic risk. Results of randomized trials of bridging in patients at high risk of thromboembolism (eg, PERIOP-2) and atrial fibrillation (eg, BRIDGE) are eagerly awaited [6,52,53].

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 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) [37,38,54].

Perioperative anticoagulation management in individuals with prosthetic heart valves is discussed in detail separately. (See "Antithrombotic therapy in patients with prosthetic heart valves", section on 'Interruption of warfarin for surgical 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 [55]. (See "Therapeutic use of heparin and low molecular weight heparin", section on 'Renal failure or insufficiency'.)

We do not use any of the newer target-specific oral anticoagulants (eg, dabigatran, rivaroxaban, apixaban) for bridging, as there are no data on the safety or efficacy of these agents for perioperative bridging. The lack of an available antidote or specific reversal strategy for these agents raises further concerns about their safety in the perioperative period.

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 [51,56,57]. We often use therapeutic or intermediate doses of heparin for bridging rather than prophylactic doses.  

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.

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.

Prophylactic dosing – Prophylactic dose anticoagulation (also called "low dose") is generally 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 two to three months. Typical prophylactic regimens include enoxaparin, 40 mg 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 surgical patients".)

Additional details regarding heparin products are provided separately. (See "Therapeutic use of heparin and low molecular weight heparin".)

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 [8,54,58]. 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 [8,9,59,60].

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 [8,58,59]. 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 [61]. 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 [62]. 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 'Initiation of a non-heparin anticoagulant'.)

URGENT ANTICOAGULANT REVERSAL — Reversal of the patient's usual anticoagulant may be required for more urgent or emergent surgery or procedures, or to treat perioperative bleeding. Agents with a potential prothrombotic effect (eg, prothrombin complex concentrates [PCCs], plasma products) should be reserved for the treatment of severe bleeding or anticipated severe bleeding (eg, intracranial hemorrhage, emergent 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 11).

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 5.0 mg of oral or intravenous vitamin K). (See "Correcting excess anticoagulation after warfarin", section on 'Surgery/invasive procedure'.)

If immediate reversal is required (eg, for emergent 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 12) [63,64]. Four-factor PCCs contain adequate amounts of all vitamin K-dependent clotting factors, whereas three-factor PCCs may require supplementation with FFP for adequate factor VII (table 13). 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 [64]. (See "Correcting excess anticoagulation after warfarin", section on 'Significant or life-threatening bleeding'.)

Dabigatran – Dabigatran is an oral direct thrombin inhibitor; there are no specific reversal agents for this class of anticoagulants. Potential strategies for treating bleeding in individuals receiving dabigatran are presented separately. (See "Anticoagulation with direct thrombin inhibitors and factor Xa inhibitors", section on 'Treatment of bleeding' and "Anticoagulation with direct thrombin inhibitors and factor Xa inhibitors", section on 'Emergency treatment of bleeding'.)

Rivaroxaban, apixaban, and edoxaban – Rivaroxaban, apixaban, and edoxaban are oral direct factor Xa inhibitors; there are no specific reversal agents for this class of anticoagulants. Potential strategies for treating bleeding in individuals receiving these agents are presented separately. (See "Anticoagulation with direct thrombin inhibitors and factor Xa inhibitors", section on 'Emergency treatment of bleeding'.)

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 (spinal, epidural) anesthesia in the patient receiving antithrombotic medication (anticoagulant)".)

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 [65,66]:

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.

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 information: Medicines to prevent blood clots: Dabigatran, rivaroxaban, apixaban (The Basics)" and "Patient information: Medicines to prevent blood clots: Warfarin (Coumadin) (The Basics)")

Beyond the Basics topics (see "Patient information: Warfarin (Coumadin) (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. (See 'Overview of our approach' above.)

Thromboembolic risk – Those at high or moderate 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 embolization".)

Prosthetic heart valve – The risks of thromboembolism and perioperative management of patients with bioprosthetic and mechanical heart valves are discussed separately. (See "Complications of prosthetic heart valves", section on 'Embolism' and "Complications of prosthetic heart valves", section on 'Valve thrombosis' and "Antithrombotic therapy in patients with prosthetic heart valves", section on 'Interruption of warfarin for surgical procedures'.)

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 6); 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 'Surgical bleeding risk high' 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 'Surgical bleeding risk low' 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 "Implantable cardioverter-defibrillators: Complications", section on 'Bleeding' and "Catheter ablation to prevent recurrent atrial fibrillation: Anticoagulation", section on 'Uninterrupted warfarin compared to heparin bridge'.)

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 (algorithm 1 and table 2). (See 'Timing of anticoagulant interruption' above and 'Warfarin' above and 'Dabigatran' above and 'Rivaroxaban' above and 'Apixaban' 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 for perioperative thromboembolism. Often, bridging is not required for individuals receiving a direct thrombin inhibitor or factor Xa inhibitor, because of the shorter half-lives of these agents (table 2). (See 'Appropriate settings for bridging' above.)

Agent – We prefer LMW heparin for most patients; for individuals with renal insufficiency and/or those requiring hemodialysis, intravenous or subcutaneous unfractionated heparin can be used more easily. We do not use dabigatran, rivaroxaban, or apixaban 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 10). 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.)

Urgent/Emergent procedure – Reversal of the patient's usual anticoagulant may be required for more urgent or emergent procedures, or to treat perioperative bleeding. Agents with a potential prothrombotic effect (eg, prothrombin complex concentrates, plasma products) should be reserved for the treatment of severe bleeding or anticipated severe bleeding (eg, intracranial hemorrhage, emergent major surgery with elevated prothrombin time/international normalized ratio (PT/INR). (See 'Urgent anticoagulant reversal' above.)

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