parks-fang-2023-periprocedural-anticoagulation.pdf

Annals of Internal MedicineT In the ClinicT Periprocedural Anticoagulation M anagement of patients taking anticoagulants around the time of a procedure is a common and complex clinical scenario. Providing evidence-based care requires estimation of risk for thrombosis and bleeding, knowledge of commo...

Annals of Internal MedicineT In the ClinicT Periprocedural Anticoagulation M anagement of patients taking anticoagulants around the time of a procedure is a common and complex clinical scenario. Providing evidence-based care requires estimation of risk for thrombosis and bleeding, knowledge of commonly used medications, multidisciplinary communication and collaboration, and patient engagement and education. This review provides a standardized, evidence-based approach to periprocedural management of anticoagulation, based on current evidence and expert clinical guidelines. CME/MOC activity available at Annals.org. Physician Writers Anna L. Parks, MD Margaret C. Fang, MD, MPH University of Utah School of Medicine, Salt Lake City, Utah (A.L.P.) University of California, San Francisco, San Francisco, California (M.C.F.) doi:10.7326/AITC202304180 This article was published at Annals.org on 11 April 2023. CME Objective: To review current evidence for pharmacology, clinical evaluation, periprocedural management, consultation, follow-up, and practice improvement of periprocedural anticoagulation. Funding Source: American College of Physicians. Disclosures: All relevant financial relationships have been mitigated. Disclosures can also be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms. do?msNum=M22-2614. With the assistance of additional physician writers, the editors of Annals of Internal Medicine develop In the Clinic using MKSAP and other resources of the American College of Physicians. In the Clinic does not necessarily represent official ACP clinical policy. For ACP clinical guidelines, please go to https://www.acponline.org/clinical_information/ guidelines/. © 2023 American College of Physicians Downloaded from https://annals.org by Universidad Nacional Autonoma on 02/12/2024. Pharmacology Clinical Evaluation Periprocedural Management Consultation and Follow-up Practice Improvement 1. Douketis JD, Spyropoulos AC, Kaatz S, et al; BRIDGE Investigators. Perioperative bridging anticoagulation in patients with atrial fibrillation. N Engl J Med. 2015;373:823-33. [PMID: 26095867] 2. Wheelock KM, Ross JS, Murugiah K, et al. Clinician trends in prescribing direct oral anticoagulants for US Medicare beneficiaries. JAMA Netw Open. 2021;4: e2137288. [PMID: 34870678] 3. Douketis JD, Spyropoulos AC, Murad MH, et al. Executive summary: perioperative management of antithrombotic therapy: an American College of Chest Physicians clinical practice guideline. Chest. 2022;162:1127-39. [PMID: 35964703] 4. Douketis JD, Spyropoulos AC, Spencer FA, et al. Perioperative management of antithrombotic therapy: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012;141:e326Se350S. [PMID: 22315266] 5. Alalwan AA, Voils SA, Hartzema AG. Trends in utilization of warfarin and direct oral anticoagulants in older adult patients with atrial fibrillation. Am J Health Syst Pharm. 2017;74:1237-44. [PMID: 28652320] 6. Cuker A, Burnett A, Triller D, et al. Reversal of direct oral anticoagulants: guidance from the Anticoagulation Forum. Am J Hematol. 2019;94:697709. [PMID: 30916798] 7. Spyropoulos AC, Brohi K, Caprini J, et al; SSC Subcommittee on Perioperative and Critical Care Thrombosis and Haemostasis of the International Society on Thrombosis and Haemostasis. Scientific and Standardization Committee Communication: guidance document on the periprocedural management of patients on chronic oral anticoagulant therapy: recommendations for standardized reporting of procedural/surgical bleed risk and patient-specific thromboembolic risk. J Thromb Haemost. 2019;17:1966-72. [PMID: 31436045] An estimated 6 million people in the United States take anticoagulants, and clinicians are likely to encounter situations where they need to weigh the risks and benefits to patients of temporarily stopping use of anticoagulants for invasive procedures. The periprocedural period is complex for clinicians and patients alike. The landscape of anticoagulant management continues to evolve, most notably with the widespread adoption of direct oral anticoagulants (DOACs). In addition, bridging anticoagulation—the use of shorter-acting parenteral anticoagulants when oral anticoagulants are held—has been falling out of favor due to newer evidence suggesting limited benefit (1, 2). Navigating the safest periprocedural anticoagulation plan thus requires understanding an individual patient's risks for bleeding and thrombosis, pharmacokinetics of individual anticoagulants, and details of the procedure as well as appropriate counseling of patients. A standardized and evidence-based approach to management is essential to prevent adverse events. In this article, we review periprocedural management of anticoagulants; we will not review management of other antithrombotic agents, such as antiplatelets, which have separate indications and recommendations. Our recommendations incorporate the 2022 American College of Chest Physicians (CHEST) updated guidelines for perioperative management of antithrombotic therapy along with other international society guidelines (3). What is the prevalence of antithrombotic use in patients undergoing procedures? More than 6 million Americans take anticoagulants to treat or prevent thrombosis associated with conditions such as atrial fibrillation (AF), venous thromboembolism (VTE), or mechanical heart valves (4). DOACs, which include a direct thrombin inhibitor (dabigatran) and factor Xa inhibitors (rivaroxaban, apixaban, edoxaban), are becoming the most frequently prescribed new anticoagulants, but vitamin K antagonists (VKAs), most commonly warfarin, remain the most prevalent anticoagulant in the United States (2, 5). Each year, at least 250 000 people taking anticoagulants need to temporarily interrupt use of their medication for an invasive procedure (4). Pharmacology What anticoagulants are commonly encountered in the periprocedural setting, and what is their duration of action? Understanding the mechanism and duration of action of anticoagulants will help clinicians know when to interrupt or resume therapy. Three major categories of anticoagulants are summarized in Appendix Table 1 (available at Annals.org): VKAs, DOACs, and heparins (low-molecular-weight heparin [LMWH], unfractionated heparin [UFH], and fondaparinux). Appendix Table 1 summarizes how individual medications differ by mechanism and onset of action, half-life, route of elimination, and reversal strategies and the implications of these differences for periprocedural management. © 2023 American College of Physicians ITC50 In the Clinic How should clinicians approach periprocedural management of anticoagulation? The key steps in the periprocedural evaluation of anticoagulation are as follows (Figure). First, clinicians should evaluate bleeding risk for the procedure and the patient. Next, the patient's risk for thrombosis should be assessed. If interruption of anticoagulation is warranted, a periprocedural plan to ensure normalization of hemostasis should be created, based on whether the patient is taking a VKA or a DOAC. Bridging should be used sparingly and only in select circumstances. Finally, a postoperative plan for resumption of therapeutic anticoagulation should be developed. Annals of Internal Medicine Downloaded from https://annals.org by Universidad Nacional Autonoma on 02/12/2024. April 2023 Figure. Key steps in the evaluation of periprocedural anticoagulation. Estimate bleeding risk (procedure and patient) Before procedure Estimate thrombotic risk Interrupt anticoagulation? No Yes Determine hold time to ensure hemostasis normalization based on anticoagulant Bridging anticoagulation in rare cases of high thrombotic risk? Yes After procedure Resume anticoagulation based on bleeding risk and anticoagulant What is the risk for bleeding with periprocedural anticoagulation? The first step in periprocedural management is evaluation of the procedure's bleeding risk. This will inform whether antithrombotic therapy needs to be stopped and, if so, for how long. However, estimates of periprocedural bleeding risk are derived from observational studies or expert opinion and are imprecise (7). In general, periprocedural bleeding risk is driven by procedural factors, such as site or length of the procedure, although patient characteristics, choice of anesthetic (for example, neuraxial anesthesia), and other aspects may play a role. To guide clinicians, a 3-tier classification system dividing procedures into minimal, low to moderate, and high bleeding risk at 30 days has been proposed (Table 1) (7). About 20% of patients assessed for perioperative management of anticoagulation in the United States and Canada are scheduled to undergo procedures that are considered to carry minimal risk, where data suggest that bleeding rates are very low, even when the procedure April 2023 No Annals of Internal Medicine is done while the patient is receiving anticoagulation (4, 9, 10). Minimal-risk procedures, including most dental, dermatologic, cardiac device, and endoscopic procedures as well as arthrocentesis and electroconvulsive therapy, can safely be performed without stopping anticoagulation. The decision to proceed while the patient is receiving anticoagulation should be made with the proceduralist, and additional options can be considered if there is concern about bleeding. These include allowing the international normalized ratio (INR) to become subtherapeutic without complete reversal of a VKA or skipping 1 or 2 doses of a DOAC before the procedure. Procedures with greater than minimal risk but less than a 2% risk for postprocedural major bleeding, such as intraabdominal surgery or coronary angiography, are low- to moderate-risk procedures. High-risk procedures (such as vascular surgery or neurosurgery) are associated with bleeding rates greater than 2% (11, 12). Anticoagulation should be interrupted for procedures that have more than minimal bleeding risk. In the Clinic ITC51 8. Doherty JU, Gluckman TJ, Hucker WJ, et al. 2017 ACC expert consensus decision pathway for periprocedural management of anticoagulation in patients with nonvalvular atrial fibrillation: a report of the American College of Cardiology Clinical Expert Consensus Document Task Force. J Am Coll Cardiol. 2017;69:871-98. [PMID: 28081965] 9. Douketis JD, Johnson JA, Turpie AG. Low-molecularweight heparin as bridging anticoagulation during interruption of warfarin: assessment of a standardized periprocedural anticoagulation regimen. Arch Intern Med. 2004;164: 1319-26. [PMID: 15226166] 10. Spyropoulos AC, Turpie AG, Dunn AS, et al; REGIMEN Investigators. Clinical outcomes with unfractionated heparin or low-molecular-weight heparin as bridging therapy in patients on longterm oral anticoagulants: the REGIMEN registry. J Thromb Haemost. 2006;4:1246-52. [PMID: 16706967] 11. Clark NP, Douketis JD, Hasselblad V, et al; BRIDGE Investigators. Predictors of perioperative major bleeding in patients who interrupt warfarin for an elective surgery or procedure: analysis of the BRIDGE trial. Am Heart J. 2018;195:108-14. [PMID: 29224638] 12. Douketis JD, Spyropoulos AC, Duncan J, et al. Perioperative management of patients with atrial fibrillation receiving a direct oral anticoagulant. JAMA Intern Med. 2019;179:1469-78. [PMID: 31380891] 13. Otto CM, Nishimura RA, Bonow RO, et al. 2020 ACC/AHA guideline for the management of patients with valvular heart disease: a report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. Circulation. 2021;143: e72-e227. [PMID: 33332150] 14. Witt DM, Nieuwlaat R, Clark NP, et al. American Society of Hematology 2018 guidelines for management of venous thromboembolism: optimal management of anticoagulation therapy. Blood Adv. 2018;2:325791. [PMID: 30482765] © 2023 American College of Physicians Downloaded from https://annals.org by Universidad Nacional Autonoma on 02/12/2024. Table 1. Stratification of Bleeding Risk Associated With Procedures* Risk Category 30-Day Risk for Major Bleeding Type of Surgery or Procedure Recommendation High >2% Stop anticoagulation Low/moderate 0%–2% Minimal 0% Cardiac surgery (heart valve replacement, CABG) Vascular surgery (AAA repair, peripheral artery bypass) Neurosurgery (intracranial or spinal) Urologic surgery (renal, prostate, or bladder) Major cancer surgery Reconstructive plastic surgery Colonoscopy with polypectomy† Major orthopedic surgery (e.g., total hip or knee replacement) Major intra-abdominal surgery (e.g., colectomy, hysterectomy) Major intrathoracic surgery (e.g., lobectomy, esophagectomy) Transfemoral or transradial coronary angiography Most common cutaneous procedures Laparoscopic cholecystectomy or ventral/ inguinal hernia repair Endoscopy or colonoscopy without polypectomy Pacemaker and AICD placement Minor dental procedures Minor dermatologic procedures (excision of basal and squamous cell carcinomas, actinic keratosis, malignant or premalignant nevi) Cataract removal Electroconvulsive therapy Arthrocentesis Stop anticoagulation May not require interruption of anticoagulation AAA = abdominal aortic aneurysm; AICD = automatic implantable cardioverter-defibrillator; CABG = coronary artery bypass grafting. * Data are from references 7 and 8. † Anticoagulation can be continued if no polypectomy is anticipated. 15. Baudet EM, Puel V, McBride JT, et al. Longterm results of valve replacement with the St. Jude Medical prosthesis. J Thorac Cardiovasc Surg. 1995;109:858-70. [PMID: 7739245] 16. Hering D, Piper C, Bergemann R, et al. Thromboembolic and bleeding complications following St. Jude medical valve replacement: results of the German Experience with LowIntensity Anticoagulation Study. Chest. 2005;127:53-9. [PMID: 15653962] 17. Cannegieter SC, Rosendaal FR, Wintzen AR, et al. Optimal oral anticoagulant therapy in patients with mechanical heart valves. N Engl J Med. 1995;333:11-17. [PMID: 7776988] 18. Lip GY, Nieuwlaat R, Pisters R, et al. Refining clinical risk stratification for predicting stroke and thromboembolism in atrial fibrillation using a novel risk factor-based approach: the Euro Heart Survey on Atrial Fibrillation. Chest. 2010;137:263-72. [PMID: 19762550] Because anticoagulation must be held for most invasive procedures, assessment of bleeding risk should be followed by estimation of the risk for thrombosis without anticoagulation. This guides whether bridging therapy should be considered and informs the necessary discussion with patients. Consensus guidelines for thromboembolic risk stratification are available for patients with a mechanical heart valve, chronic AF, or VTE (4, 8, 13, 14). What is the risk for thrombosis in patients with mechanical heart valves? For mechanical heart valves, the risk for arterial thromboembolism (ATE) in the form of ischemic stroke hinges on 3 factors: valve type, valve position, and time since valve placement (Table 2). Older caged-ball and tilting-disk valve models have higher thrombosis rates than newer bileaflet models (2.5%, © 2023 American College of Physicians ITC52 In the Clinic 0.7%, and 0.5% per year, respectively). Mechanical valves in the mitral position are associated with higher risk for thrombosis (22% per year without anticoagulation) than those in the aortic position (12% per year without anticoagulation). Valves placed within the previous 3 months carry the highest risk for thrombosis; valves placed within 1 year also carry higher risk for ATE (17). Other factors that increase ATE risk include the presence of additional cardiac comorbidities (AF, left ventricular dysfunction), prior ATE, hypercoagulable disorder, pregnancy, and older age; a valve placed within 1 year or the presence of any of these additional prothrombotic conditions should prompt consultation with a cardiologist. The 2022 CHEST guidance update similarly recommends against bridging except in patients at high risk for thromboembolism (those with older-generation valves, Annals of Internal Medicine Downloaded from https://annals.org by Universidad Nacional Autonoma on 02/12/2024. April 2023 Table 2. Stratification of ATE Risk Associated With Mechanical Heart Valves* Risk Factor Risk for ATE Without Anticoagulation Type of valve Caged-ball Tilting-disk Bileaflet 2.5% per year 0.7% per year 0.5% per year Position of valve Mitral Aortic 22% per year 12% per year Time since placement 12 mo previously  No other risk factors VTE = venous thromboembolism. * Reproduced from Blood Advances, vol. 2, Witt DM, Nieuwlaat R, Clark NP, et al, American Society of Hematology 2018 guidelines for management of venous thromboembolism: optimal management of anticoagulation therapy, pp. 3257-91, copyright 2018, with permission from Elsevier. VTE that occurred in the absence of any identifiable risk factor (“unprovoked VTE”), 4.2% for VTE provoked by a nonsurgical transient risk factor (for example, hospitalization or trauma), and 0.7% for VTE provoked by surgery (22). The presence of an inherited or acquired thrombophilia that could be associated with a higher risk for recurrence of VTE, such as antiphospholipid syndrome or protein C, protein S, or antithrombin deficiency, may inform periprocedural management of anticoagulation (23, 24). Active cancer and recurrent VTE also confer a higher risk for recurrence (25, 26). Overall, the American Society of Hematology and CHEST guideline panelists suggested that bridging be considered only among patients who are at high risk for recurrent VTE (Table 3) (3, 14). Pharmacology... Temporary interruption of anticoagulation for a procedure is not uncommon. The 3 major categories of antithrombotic medications are VKAs, DOACs, and heparins, which have differing pharmacokinetics and reversal strategies. Procedural bleeding risk is categorized as minimal (1% but 2%). Risk for thrombosis with mechanical heart valves depends on the type, position, and timing of placement of the valve. For AF, stroke risk can be estimated using the CHA2DS2-VASc score. Risk for recurrent VTE is mediated by time since the index event, triggers, and prothrombotic risk factors. CLINICAL BOTTOM LINE Clinical Evaluation What should the initial evaluation include, and what is the goal of it? The goal of the initial evaluation should be to assess the risks and benefits of thrombosis and bleeding in the periprocedural period, engage in shared decision making and patient education, and coordinate periprocedural management of anticoagulation. Patients and clinicians should be aware that recommendations may be based on limited data and the “best” approach may be uncertain. After estimating risk for bleeding and thrombosis as outlined earlier, clinicians © 2023 American College of Physicians ITC54 In the Clinic should decide whether interruption of anticoagulation is warranted. For patients in whom anticoagulation is interrupted, when and how to interrupt therapy and whether to use bridging therapy should be determined by whether the patient is taking a VKA or a DOAC. A plan for restarting anticoagulation after the procedure should also be created. Clear communication of the plan with proceduralists, anesthesiologists, and the patient is essential. If anticoagulation will not be interrupted, the proceduralist should confirm that they are comfortable with this plan. A calendar Annals of Internal Medicine Downloaded from https://annals.org by Universidad Nacional Autonoma on 02/12/2024. April 2023 with specific recommendations for dosing, laboratory testing, and bridging (if applicable) should be given to the patient or their caregiver and the proceduralist before the procedure; an example is available in the CHEST 2022 guidelines (3). The absence of such a standardized framework can result in a cascade of downstream consequences, including conflicting recommendations across providers, inappropriate administration of reversal agents, changes to the anesthetic plan, or postponement of the surgery. What are the essential elements of the clinical history? Before the procedure, the first step is to determine the bleeding risk of the planned procedure via review of the chart and discussion with the patient and proceduralist. Patient-related bleeding risk factors, such as thrombocytopenia, concomitant use of nonsteroidal anti-inflammatory drugs, hepatic or renal dysfunction, and past bleeding, should also be assessed and discussed with the patient and, if possible, modified before the procedure (8). Next, risk for thromboembolism should be estimated through review of the patient's clinical history and documentation. This can include ascertaining the patient's underlying diagnosis, the timing of any thromboses, the type of anticoagulant and adherence, any prior use of bridging, and any previous periprocedural bleeding or thrombotic complications. In some cases, such as very recent stroke or VTE, delaying surgery if possible is the safest option. What is the role of laboratory testing in the context of periprocedural anticoagulation? For patients using a VKA, clinicians should consider checking the INR 7 to 10 days before the procedure to establish a baseline while the patient is receiving therapy. If a procedure has high bleeding risk, normalization of the INR should be confirmed the day before or the day of surgery. In situations where the INR remains elevated, a small dose of vitamin K (1.25 to 2.5 mg) can be given to reduce the INR further before surgery (27). Routine periprocedural testing of DOAC levels is not recommended, although this may be warranted if DOAC clearance is affected by renal or hepatic dysfunction. Standard coagulation tests, such as the INR, do not reliably measure DOAC effect. For urgent procedures or situations when antecedent DOAC exposure is suspected, DOAC-specific laboratory tests may be performed to determine whether there is a residual anticoagulant effect. A normal thrombin time excludes the presence of dabigatran, and normal results on agent-specific chromogenic anti–factor Xa assays rule out factor Xa inhibition. Clinical Evaluation... Clinical evaluation of periprocedural anticoagulation includes assessment and mitigation of patient and procedural bleeding risk, estimation of thrombosis risk (especially if anticoagulation is held), and creation of a clear plan for interruption of anticoagulation. Periprocedural bridging is necessary only in select situations, and in all cases, a plan for resumption of anticoagulation and monitoring after the procedure is necessary. CLINICAL BOTTOM LINE Periprocedural Management Which patients should receive periprocedural (“bridging”) anticoagulation, and how should this be implemented? UFH or LMWH, during periods of subtherapeutic oral anticoagulation with VKAs. Bridging may be administered before and/or after the procedure. Bridging is defined as use of shorter-acting parenteral anticoagulants, such as The BRIDGE (Bridging Anticoagulation in Patients who Require Temporary April 2023 Annals of Internal Medicine In the Clinic ITC55 37. Connolly SJ, Milling TJ Jr , Eikelboom JW, et al; ANNEXA-4 Investigators. Andexanet alfa for acute major bleeding associated with factor Xa inhibitors. N Engl J Med. 2016;375:1131-41. [PMID: 27573206] 38. Dager WE, Kiser TH. Systemic anticoagulation considerations in chronic kidney disease. Adv Chronic Kidney Dis. 2010;17:420-7. [PMID: 20727512] 39. Cuker A, Arepally GM, Chong BH, et al. American Society of Hematology 2018 guidelines for management of venous thromboembolism: heparin-induced thrombocytopenia. Blood Adv. 2018;2:3360-92. [PMID: 30482768] 40. Caplin DM, Nikolic B, Kalva SP, et al; Society of Interventional Radiology Standards of Practice Committee. Quality improvement guidelines for the performance of inferior vena cava filter placement for the prevention of pulmonary embolism. J Vasc Interv Radiol. 2011;22:1499-1506. [PMID: 21890380] 41. American Society of Hematology. Don't use inferior vena cava (IVC) filters routinely in patients with acute VTE. 4 December 2013. Accessed at www. choosingwisely.org/ clinician-lists/americansociety-hematologyinferior-vena-cava-filtersin-patients-with-acute-vte on 5 May 2022. 42. Kelkar AH, Rajasekhar A. Inferior vena cava filters: a framework for evidencebased use. Hematology Am Soc Hematol Educ Program. 2020;2020:619-28. [PMID: 33275716] 43. Fischer SP. Development and effectiveness of an anesthesia preoperative evaluation clinic in a teaching hospital. Anesthesiology. 1996;85:196-206. [PMID: 8694365] 44. Centers for Medicare & Medicaid Services. Group Performance Information on Medicare Care Compare: 2020 Doctors and Clinicians Public Reporting. Accessed at www.cms.gov/files/ document/2020-groupperformance-information. pdf on 22 February 2023. © 2023 American College of Physicians Downloaded from https://annals.org by Universidad Nacional Autonoma on 02/12/2024. Table 4. Stratification of Risk and Bridging Recommendations for Periprocedural Arterial and Venous Thrombosis* Risk Category Mechanical Valve AF VTE High (>10% risk for ATE [per year] or VTE [per month]) Mitral Caged-ball Tilting-disk Stroke/TIA