7/5/23, 10:17 AM Perioperative management of patients receiving anticoagulants - UpToDate Official reprint from UpToDate www.uptodate.com 2023 UpToDate, Inc. and/or its affiliates. All Rights Reserved. Perioperative management of patients receiving anticoagulants : James D Douketis, MD, FRCPC, FACP, FCCP, Gregory YH Lip, MD, FRCPE, FESC, FACC : Lawrence LK Leung, MD : Jennifer S Tirnauer, MD All topics are updated as new evidence becomes available and our peer review process is complete. Literature review current through: Jun 2023. This topic last updated: Nov 18, 2022. INTRODUCTION The management of anticoagulation in patients undergoing surgical procedures is challenging, since 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. Other clinical issues are anticoagulant specific. For those taking a vitamin K antagonist, it takes several days until the anticoagulant effect is reduced and then re-established perioperatively; the risks and benefits of "bridging" with a shorter acting agent, such as heparin, during this time are unclear. The direct oral anticoagulants (DOACs; dabigatran, factor Xa inhibitors [rivaroxaban, apixaban, edoxaban]) have shorter half-lives, making them easier to discontinue and resume rapidly. 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".) https://www.uptodate.com/contents/perioperative-management-of-patients-receiving-anticoagulants/print 1/65 7/5/23, 10:17 AM Perioperative management of patients receiving anticoagulants - UpToDate 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 "Anticoagulation 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" and "Prevention of venous thromboembolism in adults undergoing hip fracture repair or hip or knee replacement" and "Prevention of venous thromboembolism (VTE) in adults undergoing non-major extremity orthopedic surgery".) 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 can increase mortality rates [1-6]. Our approach to perioperative management of anticoagulation takes into account and balances these risks, along with specific features of the anticoagulant the patient is taking [7]. Much of our approach is based on nonrandomized and observational studies and expert opinion, as there are few large, well-designed, randomized, placebo-controlled trials in this clinical domain. In addition, 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. Thus, our approach discussed herein 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 at Thrombosis Canada; a similar approach is provided on the IPRO-MAPPP website in the United States: Estimate thromboembolic risk The higher the thromboembolic risk, the greater the importance of minimizing the interval without anticoagulation ( table 1). We estimate https://www.uptodate.com/contents/perioperative-management-of-patients-receiving-anticoagulants/print 2/65 7/5/23, 10:17 AM Perioperative management of patients receiving anticoagulants - UpToDate thromboembolic risk for patients with atrial fibrillation based on age and comorbidities. For those with a recent deep vein thrombosis (DVT) or pulmonary embolism (PE), we estimate the risk based on the interval since diagnosis. For patients with a recent (within the previous one to three months) stroke, PE or DVT, in whom the risk of recurrent thromboembolism is markedly increased, we prefer to delay surgery when possible until the risk lessens and is close to baseline. (See 'Estimating thromboembolic risk' below.) 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. Warfarin requires earlier discontinuation than the DOACs (dabigatran, rivaroxaban, apixaban, edoxaban). Additional considerations may be required in individuals with reduced kidney and/or liver 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. (See 'Bridging anticoagulation' below.) Example cases The following examples illustrate our decision-making process using this approach in general terms; management of every case must be individualized based on the judgment of the treating clinicians: A 76-year-old female with nonvalvular atrial fibrillation, hypertension, and prior stroke three months ago, receiving warfarin, requires elective hip replacement with neuraxial anesthesia; kidney function is normal, and weight is 75 kg. This patient has a very high thromboembolic risk ( table 1) and a high bleeding risk ( table 2). Omit warfarin for five days before the procedure (last dose on preoperative day minus 6). https://www.uptodate.com/contents/perioperative-management-of-patients-receiving-anticoagulants/print 3/65 7/5/23, 10:17 AM Perioperative management of patients receiving anticoagulants - UpToDate Preoperative bridging with therapeutic-dose low molecular weight (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 venous thromboembolism (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 international normalized ratio (INR) is therapeutic. A 70-year-old male with nonvalvular atrial fibrillation, diabetes, and hypertension (CHA DS -VASc score = 3) receiving dabigatran who requires a colon resection for cancer; 2 2 kidney function is normal. This patient has a moderate thrombotic risk ( table 1) and a high bleeding risk ( table 2). Omit dabigatran for two days before the procedure (last dose of dabigatran on day minus 3). No bridging. Resume dabigatran on postoperative day 2 or 3, 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 DVT four months ago, receiving apixaban 5 mg twice daily, who requires a colonoscopy because of a personal history of premalignant colorectal polyps; kidney function is normal. This patient has a high thrombotic risk ( table 1) and a low bleeding risk ( table 2). 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 and when hemostasis is secured. If the patient requires polyp removal, delay resumption of apixaban for one to two more days. https://www.uptodate.com/contents/perioperative-management-of-patients-receiving-anticoagulants/print 4/65 7/5/23, 10:17 AM Perioperative management of patients receiving anticoagulants - UpToDate A 68-year-old female with nonvalvular atrial fibrillation, hypertension, and congestive heart failure (CHA DS -VASc score = 4), receiving rivaroxaban 15 mg daily in the morning, 2 2 requires a dental cleaning and two dental extractions; creatinine clearance (CrCl) is 35 mL/min. This patient has a moderate thrombotic risk ( table 1) and a low bleeding risk ( table 2). 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. 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 CHA DS -VASc score ( table 3) (calculator 1), which incorporates these 2 2 variables, is discussed in detail separately, but use of risk scores has not been prospectively validated in the perioperative setting. 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]. In these trials, a total of 15,000 to 20,000 patients were randomly assigned to warfarin versus one of the direct oral anticoagulants (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 in RE-LY, the perioperative thromboembolic risk was 1.2 percent, based on a https://www.uptodate.com/contents/perioperative-management-of-patients-receiving-anticoagulants/print 5/65 7/5/23, 10:17 AM Perioperative management of patients receiving anticoagulants - UpToDate composite endpoint of stroke, cardiovascular death, and pulmonary embolus (PE) [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 "Anticoagulation for prosthetic heart valves: Management of bleeding and invasive procedures", section on 'Planning 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 (eg, within the previous three months) are likely to benefit from delaying surgery, if possible. There are no high-quality data to determine when risk declines to baseline. 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 [DVT], PE) 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".) https://www.uptodate.com/contents/perioperative-management-of-patients-receiving-anticoagulants/print 6/65 7/5/23, 10:17 AM Perioperative management of patients receiving anticoagulants - UpToDate Individuals with cancer have a moderate risk, and those with a thromboembolic 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]. Thus, patients with a recent arterial embolism are likely to benefit from delaying elective surgery, if such a delay is possible. The vast majority of cases are due to atrial fibrillation; other less common cardiac sources include paradoxical embolism, nonbacterial thrombotic endocarditis in a patient with malignancy, dilated or poorly contractile left ventricle, or left ventricular aneurysm [18-20]. ESTIMATING PROCEDURAL BLEEDING RISK The risk of bleeding is dominated by the type of surgery or procedure. Comorbidities (eg, older age, reduced kidney 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 2) [2]. These categories do not substitute for clinical judgment 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]. https://www.uptodate.com/contents/perioperative-management-of-patients-receiving-anticoagulants/print 7/65 7/5/23, 10:17 AM Perioperative management of patients receiving anticoagulants - UpToDate 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 "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 (cardiac catheterization, pacemaker implantation, cardiac surgery) [24]. The HAS-BLED score assigns one point each for hypertension, abnormal kidney or liver function (two points for both), stroke, bleeding tendency, labile INRs, elderly age, and antiplatelet drugs or alcohol ( table 4). Nearly all of the patients in the BORDER study 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 (hazard ration [HR] 11.8, 95% CI 5.6-24.9) [24]. 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 https://www.uptodate.com/contents/perioperative-management-of-patients-receiving-anticoagulants/print 8/65 7/5/23, 10:17 AM Perioperative management of patients receiving anticoagulants - UpToDate 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. Our approach is illustrated in the algorithm ( algorithm 1) and summarized as follows: 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.) In contrast, individuals undergoing selected low bleeding risk surgery often can continue their anticoagulant; in certain cases, continuation of the anticoagulant may be 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 (nonsteroidal antiinflammatory drugs [NSAIDs], aspirin) should be avoided for routine analgesia unless the benefit outweighs the increased risk of bleeding; 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]. Perioperative aspirin use is 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 (VTE) 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 three months), attempts should be made to delay elective surgery, if possible, https://www.uptodate.com/contents/perioperative-management-of-patients-receiving-anticoagulants/print 9/65 7/5/23, 10:17 AM Perioperative management of patients receiving anticoagulants - UpToDate 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]. 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 VTE recurrence. This generally involves stopping the usual anticoagulant as close to surgery as possible, restarting it as soon as possible, and, for those on warfarin, using a bridging agent before and/or after surgery while the usual anticoagulant is not therapeutic. A temporary inferior vena cava (IVC) filter may also be appropriate in selected individuals. (See 'Timing of anticoagulant interruption' below and 'Bridging anticoagulation' below and 'Temporary IVC filters' below.) For individuals with a chronically elevated thromboembolic risk who are receiving warfarin, we often use bridging anticoagulation to minimize the period when anticoagulation is not being used. (See 'Limited indications 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 IVC filters Placement of a temporary inferior vena cava (IVC) filter is indicated in patients with a very 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. https://www.uptodate.com/contents/perioperative-management-of-patients-receiving-anticoagulants/print 10/65 7/5/23, 10:17 AM Perioperative management of patients receiving anticoagulants - UpToDate 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 judgment 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 international normalized ratio (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) 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 (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 post-procedure bridging too early (eg, https://www.uptodate.com/contents/perioperative-management-of-patients-receiving-anticoagulants/print 11/65 7/5/23, 10:17 AM Perioperative management of patients receiving anticoagulants - UpToDate 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 (DOAC), 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 impaired kidney function), bridging is reserved for those with a high to very high thromboembolic risk and not used for those with a moderate thromboembolic risk. (See 'Limited indications 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 such as warfarin, laboratory testing is a reliable indicator that the https://www.uptodate.com/contents/perioperative-management-of-patients-receiving-anticoagulants/print 12/65 7/5/23, 10:17 AM Perioperative management of patients receiving anticoagulants - UpToDate anticoagulant effect has resolved after discontinuation; for direct oral anticoagulants (DOACs), well-validated and easily accessible testing is not always available. 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]. Validated approaches have been developed to guide the timing of DOAC interruption. (See 'DOAC interruptions (overview)' below.) 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.) 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 mechanical heart valves".) Typical durations of anticoagulant interruption are illustrated by the RE-LY trial, which randomly assigned 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. Similar findings were reported in the PAUSE study, which focused on individuals with atrial fibrillation receiving a DOAC. (See 'Atrial fibrillation' above and 'DOAC interruptions (overview)' below.) Warfarin interruption Warfarin blocks a vitamin K-dependent step in clotting factor production; it impairs coagulation by interfering with the functions 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 warfarin discontinuation is appropriate, we typically omit warfarin for five days before an elective surgery (the last dose of warfarin is given on day minus 6); this duration of warfarin interruption should lead to normalization of the INR by the time of surgery and obviates the need for routine INR testing one to two days before the surgery [8,14,46,47]. This approach also appears to be safe, without exposing patients to an increased risk for perioperative bleeding [48,49]. When INR testing is not routinely done, routine use of vitamin K is avoided. https://www.uptodate.com/contents/perioperative-management-of-patients-receiving-anticoagulants/print 13/65 7/5/23, 10:17 AM Perioperative management of patients receiving anticoagulants - UpToDate There may be circumstances when preoperative INR testing is warranted, such as in patients who have a <5 day warfarin interruption or a recent high INR (>4.5). In such cases, we check the INR one to two days before the surgery, and, if the INR is >1.5, a low dose of oral vitamin K (eg, 1 to 2 mg) can be given for selected patients and/or procedures in which a normalized INR is required; this can be followed by re-checking an INR the following day. An INR in the normal (<1.3) or near-normal (1.3 to 1.4) range is 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 biologic half-life of warfarin (36 to 42 hours) and the observed time for the PT/INR to return to normal after stopping warfarin (two to three days for the INR to fall to below 2; 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 older individuals [50]. Half-lives of other vitamin K antagonists also differ (eg, 8 to 11 hours for acenocoumarol; approximately four to six days for phenprocoumon [51]; 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 [within the prior three months] stroke, mechanical heart valve, CHA DS -VASc score of 7 or 8 ( table 3) (calculator 1), 2 2 CHADS score of 5 or 6) if they require interruption of warfarin. In these cases, the bridging 2 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) and in patients who have had https://www.uptodate.com/contents/perioperative-management-of-patients-receiving-anticoagulants/print 14/65 7/5/23, 10:17 AM Perioperative management of patients receiving anticoagulants - UpToDate a thromboembolic event during a prior episode of perioperative anticoagulant interruption. This practice is based on expert opinion and has not been formally evaluated in a clinical trial. 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.