Gregg R. Klein, William V. Arnold, Minal Cordeiro, Mathew Mead, Ajay Srivastava.
Response/Recommendation: There is insufficient evidence to recommend continuing or discontinuing antiplatelet medications prior to an elective orthopaedic procedure. Literature pertaining to this subject is of low quality and most studies pertain only to aspirin (ASA) and do not investigate other antiplatelet medications such as clopidogrel, ticagrelor, prasugrel, etc. Higher-quality studies are needed before more definitive recommendations can be made.
Strength of Recommendation: Low.
Rationale: Antiplatelet drug therapy has become increasingly more common in the treatment of cardiovascular disease. Continuation of these medications may reduce cardiovascular events in the perioperative period, but due to their inhibitory effect on platelets, there is concern that they may also lead to an increase in blood loss, transfusion requirements, or post-operative hematoma formation if they are not discontinued prior to surgery. The American Academy of Orthopaedic Surgeons (AAOS) recommends in its 2011 guidelines that antiplatelet medications be discontinued before total hip arthroplasty (THA) or total knee arthroplasty (TKA) based on three cardiac studies which did not contain any arthroplasty cases1. Similarly, the American College of Chest Physicians (ACCP) also recommends stopping ASA in low-risk patients for 7-10 days prior to surgery2.
Several studies have concluded that continuation of antiplatelet medications through the perioperative period may be associated with higher risk of bleeding and need for post-operative blood transfusion; however, all are either case-control studies or case series and are of low or moderate quality3–5. Chen et al., reported on their series of 1,655 patients who underwent unilateral or simultaneous bilateral TKA and found higher calculated blood loss (969.1 ± 324.9 vs. 904.0 ± 315.5 ml), transfusion amounts (1.3 ± 1.5 vs. 1.0 ± 1.3 IU), and percentage of transfused patients (53.0% vs. 40.2%) in unilateral TKA patients on continued ASA monotherapy versus those in whom ASA was withheld perioperatively. They found no difference in overall complication rate, however3.
Cossetto et al., prospectively studied 63 patients who were continued on ASA in the perioperative period and underwent TKA or THA and compared them to 76 controls who were not taking ASA6. They found no difference in mean postoperative blood drainage, drop in hemoglobin level, intra-operative blood loss, or operative time. Similarly, a retrospective review comparing 175 patients undergoing TKA or THA which either discontinued or continued their ASA through the perioperative period showed no difference in blood loss, post-operative change in hemoglobin, or transfusion rate7. Discontinuation of ASA prior to surgery trended towards an increase in cardiac complications, but this was not significant (p=0.107). Schwab et al., reported similar findings in their retrospective review of 198 unicondylar knee arthroplasty (UKA) and TKA patients who continued ASA through the perioperative period compared to 403 UKA and TKA patients not on ASA8. They found no difference in estimated blood loss, postoperative hemoglobin change, or transfusion rates. Findings of no difference in complications or blood loss while taking antiplatelets through the perioperative period have also been duplicated in several other lower-quality studies9–15.
The vast majority of studies on this topic pertain to ASA only and do not investigate clopidogrel, ticagrelor, prasugrel, or other novel antiplatelet medications. These drugs differ in terms of mechanism of action, peak onset, duration of effect, and method of excretion and therefore warrant specific evaluation in elective orthopaedic procedures before recommendations regarding their continuation or discontinuation in the perioperative period can be made. Clopidogrel has received the most study. Jacob et al., published their retrospective review of 142 patients taking clopidogrel prior to TKA/THA and found that 24 (16.9%) patients had continued clopidogrel during the perioperative period5. Patients who remained on clopidogrel through the perioperative period had a higher rate of blood transfusion within 24 hours of surgery, as well as during the length of their hospitalization (31.8% vs. 7.7%; p=0.004 and 37.5% vs. 15.3%; p=0.02, respectively). There was no difference in cardiac events postoperatively between the two groups. Nandi et al., reported their experiences with 114 patients who were continued on clopidogrel during elective THA/TKA vs. withholding clopidogrel for 1-4 days or 5+ days prior to surgery16. They found higher rates of reoperation for infection, cellulitis, and wound drainage in patients who had clopidogrel continued through the perioperative period, however, there was substantial risk of Type I error, as there were only 8 patients in this group. Another underpowered yet persuasive article by Tescione et al., reviewed platelet function with thrombolelastogram (TEG) in patients who were on clopidogrel and reported that 4/9 patients still had normal platelet function17. They proposed an algorithm whereby a TEG could be done prior to surgery to assist in the decision of whether to delay surgery in these patients who did have abnormal platelet function.
Studies pertaining to elective spine surgery also warrant discussion. Zhang et al., in their meta-analysis on the safety of continuing ASA therapy during spinal surgery18, identified four studies which met inclusion criteria19–22. They concluded that patients undergoing spinal surgery with continuation of ASA during the perioperative period did not have an increased risk of bleeding, post-operative blood transfusion, or longer operative times. They also noted no difference in post-operative cardiac events between the two groups, but this was thought to be underpowered, and all 4 studies included in the meta-analysis were retrospective cohort studies with some methodological flaws. Prather et al., performed a retrospective review of 37 patients undergoing one to two-level cervical and lumbar fusions who took clopidogrel through the perioperative period and matched them to 99 patients who had not been on antiplatelet therapy23. They found no difference in operative time, blood loss, post-operative complications, readmission, or 90-day mortality between the two groups. They did note, a higher drain output in patients taking clopidogrel while undergoing cervical procedures (97.4 mL vs. 43.1 mL; p=0.010) which did not translate to any difference in postoperative complications, but nonetheless, an increase in drain output is concerning due the risks of nerve, esophageal, and airway compromise associated with hematoma formation and swelling in this area. As such, the authors recommended drain use and careful monitoring for these complications in patients undergoing cervical procedures while on antiplatelet therapy.
In summary, the data surrounding continuing or withholding antiplatelet therapy through the perioperative period remains conflicting and of low quality. The majority of studies are retrospective, small in sample size, and lack randomization. Most studies pertain only to ASA and do not investigate other antiplatelet medications such as clopidogrel, ticagrelor, or prasugrel. There is insufficient evidence to recommend continuing or discontinuing antiplatelet medications prior to an elective orthopaedic procedure. Higher-quality studies are needed before more definitive recommendations can be made.
1. Mont MA, Jacobs JJ. AAOS clinical practice guideline: preventing venous thromboembolic disease in patients undergoing elective hip and knee arthroplasty. J Am Acad Orthop Surg. 2011;19(12):777-778. doi:10.5435/00124635-201112000-00008
2. Douketis JD, Spyropoulos AC, Spencer FA, et al. Perioperative management of antithrombotic therapy: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012;141(2 Suppl):e326S-e350S. doi:10.1378/chest.11-2298
3. Chen C-F, Tsai S-W, Wu P-K, Chen C-M, Chen W-M. Does continued aspirin mono-therapy lead to a higher bleeding risk after total knee arthroplasty? J Chin Med Assoc. 2019;82(1):60-65. doi:10.1016/j.jcma.2018.08.002
4. Horlocker TT, Wedel DJ, Schroeder DR, et al. Preoperative antiplatelet therapy does not increase the risk of spinal hematoma associated with regional anesthesia. Anesth Analg. 1995;80(2):303-309. doi:10.1097/00000539-199502000-00017
5. Jacob AK, Hurley SP, Loughran SM, Wetsch TM, Trousdale RT. Continuing clopidogrel during elective total hip and knee arthroplasty: assessment of bleeding risk and adverse outcomes. J Arthroplasty. 2014;29(2):325-328. doi:10.1016/j.arth.2013.06.008
6. Cossetto DJ, Goudar A, Parkinson K. Safety of peri-operative low-dose aspirin as a part of multimodal venous thromboembolic prophylaxis for total knee and hip arthroplasty. J Orthop Surg (Hong Kong). 2012;20(3):341-343. doi:10.1177/230949901202000315
7. Meier R, Marthy R, Saely CH, Kuster MS, Giesinger K, Rickli H. Comparison of preoperative continuation and discontinuation of aspirin in patients undergoing total hip or knee arthroplasty. Eur J Orthop Surg Traumatol. 2016;26(8):921-928. doi:10.1007/s00590-016-1830-7
8. Schwab P-E, Lavand’homme P, Yombi J, Thienpont E. Aspirin mono-therapy continuation does not result in more bleeding after knee arthroplasty. Knee Surg Sports Traumatol Arthrosc. 2017;25(8):2586-2593. doi:10.1007/s00167-015-3824-0
9. Bogunovic L, Haas AK, Brophy RH, Matava MJ, Smith MV, Wright RW. The Perioperative Continuation of Aspirin in Patients Undergoing Arthroscopic Surgery of the Knee. Am J Sports Med. 2019;47(9):2138-2142. doi:10.1177/0363546519855643
10. Cho M-R, Jun CM, Choi W-K. Preoperative Temporary Discontinuation of Aspirin Medication Does Not Increase the Allogeneic Transfusion Rate and Blood Loss in Primary Total Hip Arthroplasty. Hip Pelvis. 2019;31(2):82-86. doi:10.5371/hp.2019.31.2.82
11. Hang G, Chen JY, Yew AKS, et al. Effects of continuing use of aspirin on blood loss in patients who underwent unilateral total knee arthroplasty. J Orthop Surg (Hong Kong). 2020;28(1):2309499019894390. doi:10.1177/2309499019894390
12. Hassan MK, Karlock LG. Association of Aspirin Use With Postoperative Hematoma and Bleeding Complications in Foot and Ankle Surgery: A Retrospective Study. J Foot Ankle Surg. 2019;58(5):861-864. doi:10.1053/j.jfas.2018.12.022
13. Mantz J, Samama CM, Tubach F, et al. Impact of preoperative maintenance or interruption of aspirin on thrombotic and bleeding events after elective non-cardiac surgery: the multicentre, randomized, blinded, placebo-controlled, STRATAGEM trial. Br J Anaesth. 2011;107(6):899-910. doi:10.1093/bja/aer274
14. Smilowitz NR, Oberweis BS, Nukala S, et al. Perioperative antiplatelet therapy and cardiovascular outcomes in patients undergoing joint and spine surgery. J Clin Anesth. 2016;35:163-169. doi:10.1016/j.jclinane.2016.07.028
15. Tsukada S, Kurosaka K, Nishino M, Maeda T, Hirasawa N. A Strategy of Continued Antiplatelet Agents, Vitamin K Antagonists, and Direct Oral Anticoagulants Throughout the Perioperative Period of Total Knee Arthroplasty in Patients Receiving Chronic Antithrombotic Therapy. JB JS Open Access. 2019;4(3):e0057.1-6. doi:10.2106/JBJS.OA.18.00057
16. Nandi S, Aghazadeh M, Talmo C, Robbins C, Bono J. Perioperative clopidogrel and postoperative events after hip and knee arthroplasties. Clin Orthop Relat Res. 2012;470(5):1436-1441. doi:10.1007/s11999-012-2306-7
17. Tescione M, Vadalà E, Marano G, et al. Platelet aggregometry for hip fracture surgery in patients treated with clopidogrel: a pilot study. J Clin Monit Comput. Published online May 6, 2021. doi:10.1007/s10877-021-00714-z
18. Zhang C, Wang G, Liu X, Li Y, Sun J. Safety of continuing aspirin therapy during spinal surgery: A systematic review and meta-analysis. Medicine (Baltimore). 2017;96(46):e8603. doi:10.1097/MD.0000000000008603
19. Park H-J, Kwon K-Y, Woo J-H. Comparison of blood loss according to use of aspirin in lumbar fusion patients. Eur Spine J. 2014;23(8):1777-1782. doi:10.1007/s00586-014-3294-y
20. Park JH, Ahn Y, Choi BS, et al. Antithrombotic effects of aspirin on 1- or 2-level lumbar spinal fusion surgery: a comparison between 2 groups discontinuing aspirin use before and after 7 days prior to surgery. Spine (Phila Pa 1976). 2013;38(18):1561-1565. doi:10.1097/BRS.0b013e31829a84d2
21. Soleman J, Baumgarten P, Perrig WN, Fandino J, Fathi A-R. Non-instrumented extradural lumbar spine surgery under low-dose acetylsalicylic acid: a comparative risk analysis study. Eur Spine J. 2016;25(3):732-739. doi:10.1007/s00586-015-3864-7
22. Cuellar JM, Petrizzo A, Vaswani R, Goldstein JA, Bendo JA. Does aspirin administration increase perioperative morbidity in patients with cardiac stents undergoing spinal surgery? Spine (Phila Pa 1976). 2015;40(9):629-635. doi:10.1097/BRS.0000000000000695
23. Prather JC, Montgomery TP, Crowther D, McGwin G, Ghavam C, Theiss SM. Elective spine surgery with continuation of clopidogrel anti-platelet therapy: Experiences from the community. J Clin Orthop Trauma. 2020;11(5):928-931. doi:10.1016/j.jcot.2020.06.007