Gregg Klein, William V. Arnold, Ajay Srivastava.
Response/Recommendation: There is limited evidence to recommend against delaying emergent orthopaedic surgery in the setting of antiplatelet use. Literature pertaining to this topic is of low quality with no randomized controlled trials (RCT) to date and most studies focus on hip fracture surgery. These studies primarily concentrate on aspirin (ASA), and/or clopidogrel with few investigations about other antiplatelet medications like ticagrelor, prasugrel, etc. Higher quality research is needed before a more definitive recommendation can be made.
Strength of Recommendation: Low.
Rationale: Antiplatelet medications are used in patients for the management and prevention of cardiovascular or cerebrovascular events. Due to the irreversible inhibitory action on platelets, there is a question as to surgical timing and continuation of antiplatelet medication in order to minimize blood loss and postoperative complications, such as hematoma or wound complications. The American Academy of Orthopaedic Surgery (AAOS) makes a limited recommendation against delaying hip fracture surgery in their 2014 clinical practice guideline citing six low-strength studies which suggested no difference in outcome or improved outcome in not delaying surgery for patients on ASA and/or clopidogrel1.
There are few moderate-quality studies that address this question. Yang et al.’s 2020 systematic review and meta-analysis investigated a delay in surgery (> 5 days) compared to early surgery in hip fracture patients on ASA and/or clopidogrel therapy2. They noted a significant decrease in mortality (odds ratio [OR] = 0.43; 95% confidence interval [CI], 0.23-0.79; p = 0.006) between patients treated early compared to late surgery. They did find that early surgery was associated with a statistically significant difference in blood loss (weighted mean difference [WMD] = 0.75; 95% CI, 0.50-1.00; p < 0.001) yet this yielded no significant difference in transfusion rate. There was a significant decrease in length of hospital stay in the early surgery group (WMD = − 6.05; 95% CI, −7.06-5.04; p < 0.001) with no identified differences in acute coronary syndrome, cerebrovascular events, or venous thromboembolism amongst these groups. Of note, their analysis did demonstrate an increase in the mean number of units transfused for patients on ASA and clopidogrel dual antiplatelet therapy (WMD = 0.69; 95% CI, 0.10-1.28; p = 0.02) compared to no therapy or ASA alone groups.
Doleman and Moppett’s 2015 meta-analysis and review investigated patients taking clopidogrel vs. no therapy with a subgroup analysis of early and late surgery for hip fractures3. They found that while there was a significant increase in patients on clopidogrel receiving a transfusion, there was no significant difference in transfusion between early and late surgery groups (OR 0.44; 95% CI: 0.15–1.30). They did identify a significantly reduced length of stay between the early and delayed surgery groups favoring a shorter stay for the early surgery cohorts (WMD= 7.09 days; 95% CI -10.14 to 4.04).
Ohmori et al.’s 2020 retrospective cohort of 206 patients evaluated perioperative hidden blood loss and transfusion requirements between propensity score-matched hip fracture patients on ASA vs. no antiplatelet medication4. They found no significant difference in perioperative blood loss of 598 mL for patients on ASA versus the control group blood loss of 556 mL (p=0.14). In addition, they found no significant difference in blood transfusion requirements between the two groups (48% vs. 38%, p=0.21) with a higher transfusion requirement in the ASA group.
Continuing antiplatelet medication throughout the perioperative period was investigated in several studies. Abdulhamidet, in 2020 published a retrospective study of 325 patients with hip fractures comparing patients on long-term ASA or clopidogrel therapy that was continued throughout the hospitalization with a control group5. They found no significant increase in intraoperative blood loss or duration of surgery. A prospective cohort study of 44 patients with hip fractures in 2011 by Chechik et al., evaluated clopidogrel and/or ASA use compared with a control group6. Postoperative hemoglobin drops were significantly greater among patients treated with clopidogrel (1,091± 654 ml, range 178–3,487, p = 0.005) and higher still in patients treated with ASA and clopidogrel (1,312±686 ml, range 392–2,877, p = 0.0003) compared to those without antiplatelet therapy. Despite this, there was no increase in early (30-day) mortality although the study was underpowered. Jang et al., in 2019 published a cohort study of 162 patients undergoing cephalon-medullary nail placement for proximal femur fractures with continued antiplatelet medication and no operative delay7. Patients on ASA and/or clopidogrel were continued on their antiplatelet therapy throughout the surgical period. There was no significant difference in estimated blood loss or postoperative hemoglobin. Despite this, there was a significant increase in total transfusion (695.3 ± 487.5 vs 956.6 ± 519.5 p=0.003).
Literature on this topic in non-hip fracture studies is limited. Bogunovic et al., in 2013 published a prospective cohort trial of 186 patients comparing bleeding-related complications in surgery of the hand and wrist between patients who were continued on their antiplatelet medication and those who were not on antiplatelet medication8. They found no surgical complications in either group; however, one patient in the continued medication group required a return to the operating room for surgical site bleeding. There was no difference in hematoma formation, two-point discrimination, and postoperative pain and swelling by 4 weeks. There was a finding of increased bleeding complications with high-dose antiplatelet medication, but this did not reach statistical significance.
In conclusion, patients taking antiplatelet medication may proceed with emergent orthopaedic surgery with minimal complications. The most common associated complication appears to be a tendency to increased blood loss and blood transfusion. However, the bulk of these studies focus on hip fracture patients and are of low quality9–15. High-quality RCT would best address this question.
References:
1. Roberts KC, Brox WT. AAOS Clinical Practice Guideline: Management of Hip Fractures in the Elderly. J Am Acad Orthop Surg. 2015;23(2):138-140. doi:10.5435/JAAOS-D-14-00433
2. Yang Z, Ni J, Long Z, Kuang L, Gao Y, Tao S. Is hip fracture surgery safe for patients on antiplatelet drugs and is it necessary to delay surgery? A systematic review and meta-analysis. J Orthop Surg Res. 2020;15(1):105. doi:10.1186/s13018-020-01624-7
3. Doleman B, Moppett IK. Is early hip fracture surgery safe for patients on clopidogrel? Systematic review, meta-analysis and meta-regression. Injury. 2015;46(6):954-962. doi:10.1016/j.injury.2015.03.024
4. Ohmori T, Toda K, Kanazawa T, Tada K, Yagata Y, Ito Y. Retrospective high volume comparative study suggests that patients on aspirin could have immediate surgery for hip fractures without significant blood loss. Int Orthop. 2021;45(3):543-549. doi:10.1007/s00264-021-04941-6
5. Abdulhamid AK. Evaluation of the use of anti-platelet therapy throughout the peri-operative period in patients with femoral neck fracture surgery. A retrospective cohort study. Int Orthop. 2020;44(9):1805-1813. doi:10.1007/s00264-020-04633-7
6. Chechik O, Thein R, Fichman G, Haim A, Tov TB, Steinberg EL. The effect of clopidogrel and aspirin on blood loss in hip fracture surgery. Injury. 2011;42(11):1277-1282. doi:10.1016/j.injury.2011.01.011
7. Jang C-Y, Kwak D-K, Kim D-H, Lee H-M, Hwang J-H, Yoo J-H. Perioperative antiplatelet in elderly patients aged over 70 years treated with proximal femur fracture: continue or discontinue? BMC Musculoskelet Disord. 2019;20(1):124. doi:10.1186/s12891-019-2504-5
8. Bogunovic L, Gelberman RH, Goldfarb CA, Boyer MI, Calfee RP. The impact of antiplatelet medication on hand and wrist surgery. J Hand Surg Am. 2013;38(6):1063-1070. doi:10.1016/j.jhsa.2013.03.034
9. Akaoka Y, Yamazaki H, Kodaira H, Kato H. Risk factors for the effect of anticoagulant and antiplatelet agents on perioperative blood loss following proximal femoral fractures. Medicine (Baltimore). 2016;95(27):e4120. doi:10.1097/MD.0000000000004120
10. Anekstein Y, Tamir E, Halperin N, Mirovsky Y. Aspirin therapy and bleeding during proximal femoral fracture surgery. Clin Orthop Relat Res. 2004;(418):205-208. doi:10.1097/00003086-200401000-00034
11. Chechik O, Amar E, Khashan M, Kadar A, Rosenblatt Y, Maman E. In support of early surgery for hip fractures sustained by elderly patients taking clopidogrel: a retrospective study. Drugs Aging. 2012;29(1):63-68. doi:10.2165/11598490-000000000-00000
12. Ginsel BL, Taher A, Whitehouse SL, Bell JJ, Pulle CR, Crawford RW. Effects of anticoagulants on outcome of femoral neck fracture surgery. J Orthop Surg (Hong Kong). 2015;23(1):29-32. doi:10.1177/230949901502300107
13. Feely MA, Mabry TM, Lohse CM, Sems SA, Mauck KF. Safety of clopidogrel in hip fracture surgery. Mayo Clin Proc. 2013;88(2):149-156. doi:10.1016/j.mayocp.2012.11.007
14. Humenberger M, Stockinger M, Kettner S, Siller-Matula J, Hajdu S. Impact of Antiplatelet Therapies on Patients Outcome in Osteosynthetic Surgery of Proximal Femoral Fractures. J Clin Med. 2019;8(12):E2176. doi:10.3390/jcm8122176
15. Thaler HW, Frisee F, Korninger C. Platelet aggregation inhibitors, platelet function testing, and blood loss in hip fracture surgery. J Trauma. 2010;69(5):1217-1220; discussion 1221. doi:10.1097/TA.0b013e3181f4ab6a