Eric S. Schwenk, Thomas Volk, Alessandro Squizzato.
Response/Recommendation: Acenocoumarol should be stopped 3 days, warfarin and fluindione should be stopped 5 days, and phenprocoumon should be stopped 7 days prior to elective orthopedic surgery. Direct-acting oral anticoagulants (DOAC) (apixaban, edoxaban, dabigatran, and rivaroxaban) should be omitted at least two days prior to elective orthopedic surgery with an additional day added for dabigatran in patients with a creatinine clearance (CrCl) < 80 mL/min and two to three additional days for patients with a CrCl >30 mL/min but < 80 mL/min.
Strength of Recommendation: Limited recommendation; low level of evidence.
Rationale: Orthopedic surgery, and specifically total joint arthroplasty, is considered to be associated with a high risk of bleeding1,2. The quality of evidence supporting a specific timeframe to stop chronic anticoagulation prior to undergoing elective orthopaedic surgery is limited. For this specific question, we: 1) searched the literature for relevant articles in respect to lower extremity surgery and 2) retrieved relevant society guidelines. We did not address upper extremity surgery, spine surgery, or trauma surgery as these topics are addressed elsewhere. Further, we did not include anti-platelet agents in our searches because these are addressed elsewhere in this document. However, a number of studies conducted in the setting of other surgery types, while limited by their design, provided some relevant data and were considered. Croci et al., retrospectively studied consecutive spine surgery patients and found that among those taking DOAC, there was no difference between the mean discontinuation time among those who had a bleeding event3. In contrast, Young et al., compared patients undergoing spinal fusion who were chronically taking warfarin to those who were not and found that despite stopping warfarin 7 days prior to surgery and achieving normal international normalized ratio (INR) levels, warfarin patients had greater blood loss and had greater odds of receiving a postoperative blood transfusion4.
A retrospective study among total knee arthroplasty (TKA) patients found no difference in 30-day complication rates between patients who did and did not stop antithrombotic agents prior to surgery5. Their institutional protocol included cessation of warfarin 5 days prior to surgery. However, DOAC were not included in the study. An additional study by Radovanovic et al., found that TKA patients who routinely stopped warfarin 3-5 days prior to surgery and achieved an INR of less than 1.4 had a greater blood transfusion rate (40% vs. 13%, p=0.03) and longer operative times than controls6. Conversely, a retrospective study of 48 patients compared a cohort who continued warfarin uninterrupted perioperatively in the setting of TKA to a cohort who was not taking warfarin. The authors found that there were no differences in blood transfusion rates (24% vs. 38%, p=0.178). Another retrospective analysis of TKA patients compared 38 patients taking warfarin who continued perioperatively to 39 patients who had warfarin stopped 1 week prior to surgery and found no difference in the adjusted risk ratio of receiving a blood transfusion or experiencing a wound complication7.
The Perioperative Anticoagulation Use for Surgery Evaluation (PAUSE) trial was a multicenter observational cohort study of over 3,000 patients with atrial fibrillation who were taking a DOAC (apixaban, dabigatran, or rivaroxaban) and separated patients into low- and high-bleeding-risk surgeries, the latter of which included hip and knee arthroplasty. Patients who underwent high-bleeding-risk surgery stopped DOAC 2 days before their procedure unless they were taking dabigatran and had a CrCl < 50 mL/min, in which case this time was extended. They found that within the high-bleeding-risk group, major bleeding events occurred in less than 3% of patients with this regimen2. It was not known how many orthopedic patients experienced a bleeding complication.
A sub-analysis of patients in the PAUSE trial found that separating patients into residual levels of > 50 ng/mL or ≤ 50 ng/mL did not result in significant association with major and nonmajor bleeding events, suggesting that checking residual drug levels prior to surgery does not help to predict bleeding events when drugs are stopped at the times used in the study8.
Guidelines from relevant societies, such as the American Society of Regional Anesthesia and Pain Medicine (ASRA), American Academy of Orthopedic Surgeons (AAOS), and American College of Cardiologists (ACC), should be taken into consideration when advising patients on when to stop an anticoagulant. In particular, if neuraxial (spinal or epidural) anesthesia is preferred for the procedure, the risk of epidural hematoma should be factored into patient recommendations. The 2018 Evidence-Based Guidelines for Regional Anesthesia in the Patient Receiving Antithrombotic or Thrombolytic Therapy from the American Society of Regional Anesthesia and Pain Medicine recommend a preoperative cessation time of 72 hours for apixaban and rivaroxaban and a range of times from 72-120 hours for dabigatran depending on the CrCl9. These guidelines are followed by many anesthesiologists but are more stringent than those published by others. In contrast, the AAOS currently recommends a cessation time of 2 days for all DOAC (assuming a CrCl > 50 mL/min), even if neuraxial anesthesia is planned10. Finally, the guidelines from the ACC recommend cessation at least 48 hours prior to high-bleeding-risk procedures if the CrCl > 50 mL/min for apixaban, edoxaban, and rivaroxaban and a graded approach of 48-120 hours prior to a high-bleeding-risk procedure for dabigatran, depending on the CrCl11.
The more restrictive recommendation for cessation time made by ASRA likely reflects the potentially devastating nature of an epidural hematoma. We do not recommend routine assessment of DOAC plasma levels because of the difficulty in interpretation, lack of widespread availability, and unknown level beyond which clinically significant bleeding events, including epidural hematomas, occur. We agree with ASRA and AAOS that the INR should be checked within 24 hours of surgery for patients taking warfarin or another vitamin K antagonist to ensure appropriate response10,12.
1. Douketis JD, Spyropoulos AC, Kaatz S, et al. Perioperative Bridging Anticoagulation in Patients with Atrial Fibrillation. N Engl J Med. 2015;373(9):823-833. doi:10.1056/NEJMoa1501035
2. 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(11):1469-1478. doi:10.1001/jamainternmed.2019.2431
3. Croci DM, Dalolio M, Guzman R, et al. Direct Oral Anticoagulants in Patients Undergoing Spine Surgery. World Neurosurg. 2019;125:e1034-e1041. doi:10.1016/j.wneu.2019.01.236
4. Young EY, Ahmadinia K, Bajwa N, Ahn NU. Does chronic warfarin cause increased blood loss and transfusion during lumbar spinal surgery? Spine J. 2013;13(10):1253-1258. doi:10.1016/j.spinee.2013.05.052
5. Hwang J-Y, Oh S, Kim C-S, Chang J-E, Min S-W. Perioperative complications following preoperative cessation of antithrombotic agents for total knee arthroplasty: A retrospective study. Medicine (Baltimore). 2016;95(48):e5487. doi:10.1097/MD.0000000000005487
6. Radovanovic I, Queally J, Bahari S, Sproule J, McElwain J. Anticoagulant use and its effect on bleeding and complications in total knee arthroplasty. Acta Orthop Belg. 2012;78(2):187-191.
7. Rhodes DA, Severson EP, Hodrick JT, Dunn HK, Hofmann AA. Discontinuation of warfarin is unnecessary in total knee arthroplasty. Clin Orthop Relat Res. 2010;468(1):120-126. doi:10.1007/s11999-009-1128-8
8. Tafur AJ, Clark NP, Spyropoulos AC, et al. Predictors of Bleeding in the Perioperative Anticoagulant Use for Surgery Evaluation Study. J Am Heart Assoc. 2020;9(19):e017316. doi:10.1161/JAHA.120.017316
9. Horlocker TT, Vandermeuelen E, Kopp SL, Gogarten W, Leffert LR, Benzon HT. Regional Anesthesia in the Patient Receiving Antithrombotic or Thrombolytic Therapy: American Society of Regional Anesthesia and Pain Medicine Evidence-Based Guidelines (Fourth Edition). Reg Anesth Pain Med. 2018;43(3):263-309. doi:10.1097/AAP.0000000000000763
10. Barlow BT, Hannon MT, Waldron JE. Preoperative Management of Antithrombotics in Arthroplasty. J Am Acad Orthop Surg. 2019;27(23):878-886. doi:10.5435/JAAOS-D-17-00827
11. 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(7):871-898. doi:10.1016/j.jacc.2016.11.024
12. Hebl JR, Dilger JA, Byer DE, et al. A pre-emptive multimodal pathway featuring peripheral nerve block improves perioperative outcomes after major orthopedic surgery. Reg Anesth Pain Med. 2008;33(6):510-517.