181 – What is the most optimal VTE prophylaxis for patients undergoing ACL reconstruction?
Mohammad S Abdelaal, Usama H Saleh, Hamed Vahedi.
Response/Recommendation: There is a small risk of venous thromboembolism (VTE) following anterior cruciate ligament (ACL) reconstruction in healthy adult patients. There is moderate- to low-evidence supporting the use of low-molecular-weight heparin (LMWH), aspirin (ASA), or rivaroxaban in the prevention of pulmonary embolism (PE) and symptomatic deep venous thrombosis (DVT). Similarly, there is a very low level of evidence supporting the use of LMWH in preventing asymptomatic DVT when compared to no treatment. No difference in the rate of adverse events (including major and minor bleeding) between LMWH, ASA, and rivaroxaban has been shown, although data on this safety endpoint is limited due to low numbers of events in existing studies. To this end, appropriate risk stratification, considering factors such as medical comorbidities, weight-bearing status, and the use of immobilization, is therefore necessary.
Strength of Recommendation: Moderate.
Rationale: There is lack of high-quality studies on the optimal VTE prophylaxis for ACL reconstruction patients postoperatively. In general, the incidence of VTE after ACL reconstruction is low, although complications can be devastating. Gaskill et al.1, analyzed the United States Military Healthcare System (MHS) database across a seven-year period, which included 16,558 patients with a mean age of 29 years. The authors found that the risk of VTE was 0.53% (0.33% DVT and 0.21% PE). Jameson et al.2, used the English National Health Service (NHS) database and found an incidence of VTE of 0.4% in 13,941 patients, with a mean age of 29 years in patients who underwent ACL reconstruction. Maletis et al.3, analyzed the Kaiser Permanente ACL reconstruction registry and reported an incidence of VTE of 0.3% in 16,192 patients with a mean age of 30 years. An increased odds of VTE was identified in patients aged ≥ 35 years with a history of nicotine use, anticoagulant use, concomitant high tibial osteotomy, concomitant posterior cruciate ligament reconstruction, tourniquet time of more than 120 minutes and an operating time of more than 90 minutes1,4.
Thromboprophylaxis recommendations after knee arthroscopic surgery vary from one country to another. According to the guidelines of the American College of Chest Physicians (ACCP)5, the risk associated with arthroscopic surgery has been considered to be low, and while some societies have advocated for routine thromboprophylaxis after ACL reconstruction, the ACCP guidelines recommend against its routine use after arthroscopic procedures except in patients with previous VTE2,4,6. Although the ACCP guidelines do recommend routine thromboprophylaxis for “major” orthopaedic procedures5, as arthroscopic procedures become more common and complex, the line between basic arthroscopic and “major” orthopaedic procedures is becoming more ambiguous. The National Institute for Clinical Health and Excellence (NICE) guidelines do not recommend thromboprophylaxis after knee arthroscopy if the surgery is below 90 minutes and the patient is at low risk7. In contrast, pharmacological prophylaxis after knee arthroscopic surgery is recommended by the French Society of Anaesthesia and Intensive Care8. Also, according to a recent survey in Germany, most surgeons use anticoagulants as routine thromboprophylaxis after outpatient arthroscopic procedures of the knee9.
LMWH is a very common anticoagulant used after knee arthroscopy. In a meta-analysis of 8 randomized clinical trials (RCT) including 4,113 patients performed by Zhu et al.10, the authors found that LMWH had efficacy in preventing VTE (relative risk [RR], 0.22 95% confidence interval [CI], 0.06 – 0.73]; p = .01) for patients mainly undergoing ACL reconstruction and did not increase the risk of bleeding (RR, 1.12 95% CI, 0.72 – 1.74). Interestingly, they found that LMWH was conversely not effective in preventing VTE in patients undergoing simple knee arthroscopy and increased the risk of bleeding (RR, 1.64 95% CI, 1.18 – 2.28). In an RCT study by Marlovits et al.15, on 175 ACL reconstruction patients receiving enoxaparin 40 mg once daily 12 to 18 hours pre-surgery and 3 to 8 days post-surgery, patients were randomized to 40 mg enoxaparin (n=87) or placebo (n=88) once daily for 20 days. DVT was confirmed by magnetic resonance venography (MRV) at the end of the study period (23 to 28 days after surgery). Two DVT (2.8%) were detected in the enoxaparin group vs. 28 (41.2%) in placebo group, including 1 (1.4%) proximal DVT in the enoxaparin group vs. 6 (8.8%) in the placebo group. None of the patients developed PE postoperatively. No major bleeding occurred, and minor bleeding rate was similar in both groups.
As an alternative antithrombotic agent, ASA has been widely used in orthopaedic surgery. Kayne et al.12, conducted an RCT on a series of 170 arthroscopy patients (23 ACL reconstruction) and compared a group of 63 patients who were given ASA 325 mg for 14 days with 104 patients who were given no medical prophylaxis. No VTE event was detected based on bilateral, whole leg, compression venous duplex ultrasonography 10 to 14 days postoperatively. Similarly, Munoa et al.18, compared medical prophylaxis (rivaroxaban or Bemiparin) vs. mechanical prophylaxis (compression stocking) and did not find any VTE events in their small series of 60 ACL reconstruction patients.
In contrast, Perrotta et al.11, updated their previous systematic review of pharmacological or non-pharmacological interventions to reduce thromboembolic risk after knee arthroscopy. They concluded that for the outcome of PE and symptomatic DVT in low-risk patients undergoing knee arthroscopic procedures, there was moderate to very low-certainty evidence of no clear benefit regarding the use of LMWH, ASA or rivaroxaban compared to placebo or no intervention for VTE prevention. Interestingly, the incidence of symptomatic DVT was higher in the compression stocking group compared to LMWH, ASA, and rivaroxaban. Compression stocking had a 2% incidence of symptomatic DVT, while the literature reports an incidence below 0.5%11. Schmitz et al., used data from the Swedish Knee Ligament Register (SKLR) between 2006 and 2013, and analyzed 26,014 primary and revision ACL reconstruction. They found no difference in the incidence of VTE between those with and those without thromboprophylaxis4 and recommended against the routine use of thromboprophylaxis, except older patients. Further, in an RCT involving 1,451 patients undergoing arthroscopy of the knee, thromboprophylaxis with LMWH for 8 days after knee arthroscopy conferred no benefit12. Interestingly, using the MHS data1, 147 patients (0.89%) who received thromboprophylaxis were found to have an increased risk of VTE. This unanticipated finding suggests that the patients receiving thromboprophylaxis had probably been those deemed to have an increased risk of VTE. The authors nonetheless concluded that they could not recommend routine thromboprophylaxis for patients undergoing arthroscopic surgery of the knee.
The routine use of thromboprophylaxis is not without risks, which must be taken into account when deciding to prescribe anticoagulants to knee arthroscopy patients. Bleeding adverse events following below-knee surgery is significantly higher (odds ratio 2.79) in patients receiving thromboprophylaxis compared to those receiving no prophylaxis13. To this end, appropriate risk stratification, considering factors such as medical comorbidities, weight-bearing status, and the use of immobilization, is therefore necessary when deciding whether to prescribe VTE prophylaxis to knee arthroscopy patients after surgery.
References:
1. Gaskill T, Pullen M, Bryant B, Sicignano N, Evans AM, DeMaio M. The Prevalence of Symptomatic Deep Venous Thrombosis and Pulmonary Embolism After Anterior Cruciate Ligament Reconstruction. Am J Sports Med. 2015;43(11):2714-2719. doi:10.1177/0363546515601970
2. Jameson SS, Dowen D, James P, Serrano-Pedraza I, Reed MR, Deehan D. Complications following anterior cruciate ligament reconstruction in the English NHS. Knee. 2012;19(1):14-19. doi:10.1016/j.knee.2010.11.011
3. Maletis GB, Inacio MCS, Reynolds S, Funahashi TT. Incidence of symptomatic venous thromboembolism after elective knee arthroscopy. J Bone Joint Surg Am. 2012;94(8):714-720. doi:10.2106/JBJS.J.01759
4. Kraus Schmitz J, Lindgren V, Janarv PM, Forssblad M, Stålman A. Deep venous thrombosis and pulmonary embolism after anterior cruciate ligament reconstruction: incidence, outcome, and risk factors. Bone Joint J. 2019;101-B(1):34-40. doi:10.1302/0301-620X.101B1.BJJ-2018-0646.R1
5. Falck-Ytter Y, Francis CW, Johanson NA, et al. Prevention of VTE in orthopedic surgery patients: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012;141(2 Suppl):e278S-e325S. doi:10.1378/chest.11-2404
6. Ye S, Dongyang C, Zhihong X, et al. The incidence of deep venous thrombosis after arthroscopically assisted anterior cruciate ligament reconstruction. Arthroscopy. 2013;29(4):742-747. doi:10.1016/j.arthro.2013.01.017
7. Recommendations | Venous thromboembolism in over 16s: reducing the risk of hospital-acquired deep vein thrombosis or pulmonary embolism | Guidance | NICE. Accessed June 23, 2021. https://www.nice.org.uk/guidance/ng89/chapter/recommendations#interventions-for-people-having-orthopaedic-surgery
8. Samama CM, Gafsou B, Jeandel T, et al. [French Society of Anaesthesia and Intensive Care. Guidelines on perioperative venous thromboembolism prophylaxis. Update 2011. Short text]. Ann Fr Anesth Reanim. 2011;30(12):947-951. doi:10.1016/j.annfar.2011.10.008
9. Müller-Rath R, Ingenhoven E, Mumme T, Schumacher M, Miltner O. [Perioperative management in outpatient arthroscopy of the knee joint]. Z Orthop Unfall. 2010;148(3):282-287. doi:10.1055/s-0029-1240784
10. Zhu J, Jiang H, Marshall B, Li J, Tang X. Low-Molecular-Weight Heparin for the Prevention of Venous Thromboembolism in Patients Undergoing Knee Arthroscopic Surgery and Anterior Cruciate Ligament Reconstruction: A Meta-analysis of Randomized Controlled Trials. Am J Sports Med. 2019;47(8):1994-2002. doi:10.1177/0363546518782705
11. Perrotta C, Chahla J, Badariotti G, Ramos J. Interventions for preventing venous thromboembolism in adults undergoing knee arthroscopy. Cochrane Database Syst Rev. 2020;5:CD005259. doi:10.1002/14651858.CD005259.pub4
12. van Adrichem RA, Nemeth B, Algra A, et al. Thromboprophylaxis after Knee Arthroscopy and Lower-Leg Casting. New England Journal of Medicine. 2017;376(6):515-525. doi:10.1056/NEJMoa1613303
13. Heijboer RRO, Lubberts B, Guss D, Johnson AH, Moon DK, DiGiovanni CW. Venous Thromboembolism and Bleeding Adverse Events in Lower Leg, Ankle, and Foot Orthopaedic Surgery with and without Anticoagulants. J Bone Joint Surg Am. 2019;101(6):539-546. doi:10.2106/JBJS.18.00346