Majd Tarabichi, Diana Fernández-Rodríguez.
Response/Recommendation: Yes, aspirin (ASA) appears to confer a lower risk of postoperative wound problems compared to other chemoprophylactic agents, although the quality of evidence remains limited.
Strength of Recommendation: Limited.
Rationale: The prevention of venous thromboembolism (VTE) following orthopaedic procedures is of paramount importance1,2. While there is a broad range of chemoprophylactic agents in the surgeon’s armamentarium, emerging evidence has drawn attention to the consequences of aggressive anticoagulation regimens3. Current guidelines from the American College of Chest Physicians (ACCP) and the American Academy of Orthopaedic Surgeons (AAOS) have not been able to recommend the single most optimal chemoprophylactic agent4,5. Postoperative wound complications including wound drainage and hematoma have been documented as a harbinger for periprosthetic joint infection (PJI)6–9. Furthermore, the use of more potent anticoagulation may not lead to a significant risk reduction compared to less potent regimens10. Thus, it is critical to balance the risk of thrombosis against the risk of bleeding complications associated with these potent regimens. In this article, we summarize the literature evaluating the relationship between different chemoprophylaxis options and wound complications following orthopaedic procedures.
Warfarin: The association between warfarin and postoperative wound problems is well documented. Several retrospective studies have demonstrated a lower rate of wound complications in patients taking ASA when compared to warfarin11–14. A retrospective cohort study of 5,516 patients comparing persistent wound drainage in patients taking ASA and warfarin found that the warfarin group had a greater than two-fold increase in the rate of persistent wound drainage compared to ASA, although there was no difference in VTE rates15. Huang et al., in a review of 30,270 patients, showed a lower incidence of PJI in their ASA cohort compared to the warfarin cohort. Warfarin was also associated with increased VTE events in this study12. Other studies have also demonstrated similar results13,14,16.
Warfarin has also been compared to no chemoprophylaxis, and this comparison has revealed an increased infection rate. Sachs et al., demonstrated the aforementioned findings while observing no difference in VTE rates in patients with no chemoprophylaxis compared to warfarin11. Warfarin use prior to total joint arthroplasty (TJA) has also been shown to be an independent risk factor for postoperative wound drainage, superficial and deep infection16.
The results of studies comparing warfarin to agents other than ASA have yielded varying results. Retrospective studies assessing the infection rates with low-molecular-weight heparin (LMWH) and warfarin have demonstrated higher rates of surgical site infection and reoperation at 3 months, as well as an increased time to a dry wound9,17. Colwell et al., and Francis et al., both performed randomized controlled trials (RCT) comparing ximelagatran, a direct thrombin inhibitor, and warfarin and found a comparable rate of wound complications postoperatively following TJA18,19. In regards to bridging, Kleiner et al., found that bridging with LMWH was associated with a longer duration to a dry wound and increased cost of care following total hip arthroplasty (THA)20.
Other disadvantages inherent to warfarin include the need for continuous lab monitoring and delayed onset of action. Parvizi et al., demonstrated that the incidence of VTE following TJA was highest in the first week after surgery, and suggested that the delayed onset of action could be an explanation for these findings21.
Low-molecular-weight Heparin (LMWH): The use of LMWH has been extensively studied in the literature, often as a comparison group for other novel anticoagulants. In retrospective cohort study comparing rivaroxaban and enoxaparin in patients undergoing TJA, rivaroxaban demonstrated a near three-fold increase in wound complications (5.0% vs. 1.8%), although this did not reach significance likely due to the lack of statistical power22. Kulshrestha et al., performed an RCT in total knee arthroplasty (TKA) patients comparing protocols in which enoxaparin was given routinely vs. the selective use of enoxaparin in high-risk patients and ASA in low-risk patients. Routine use of enoxaparin yielded an eight-fold increase in the incidence of wound complications postoperatively23. Burnett et al compared a 10-day course of enoxaparin following TJA to their previous warfarin regimen and demonstrated a three-fold increase in reoperation rate due to wound complications24. Two meta-analyses found no difference in wound complication rate between ASA and enoxaparin following TJA, although this could be due to the limited level-1 data evaluating ASA prospectively25,26. Jones et al., compared no chemoprophylaxis, ASA, and enoxaparin in patients undergoing TJA and found significantly higher rates of wound drainage with ASA (odds ratio [OR] = 3.64) and enoxaparin (OR = 4.92) when compared to no anticoagulation. The ASA group had a lower incidence of wound drainage (29.9%) compared to the enoxaparin group (36.5%), and this was statistically significant27. Agaba et al., reported that enoxaparin had a higher rate of incision and drainage (I&D) compared to rivaroxaban in a study of 72,670 patients undergoing THA, and noted that this rate was lower than that of the ASA and warfarin groups28. More recently, another database study by Watts et al., of 85,938 TJA patients who received rivaroxaban, ASA or enoxaparin was conducted. The majority received ASA (n = 61,426), demonstrating a significant shift in practice. ASA had a lower rate of wound complications compared to enoxaparin and rivaroxaban, although the latter comparison did not reach statistical significance29.
Factor Xa Inhibitors: Factor Xa inhibitors are a predominant class of novel oral anticoagulants (NOAC). These drugs were introduced to avoid laboratory monitoring and the need for bridging as seen with warfarin. Current data regarding their risk of wound complications and infection remains mixed. In studies previously mentioned, Sindali et al., found a three-fold increase in wound complications with rivaroxaban, while Agaba et al., reported a higher rate of I&D with enoxaparin22,28. Brimmo et al., compared 159 patients given rivaroxaban following TJA to 480 patients given alternative chemoprophylaxis (322 enoxaparin, 161 ASA)30. The Rivaroxaban group had a PJI incidence of 2.5% compared to 0.2% in the alternative group, which was statistically significant. In a meta-analysis of 24,385 patients, Russell et al., found a decreased risk of deep venous thrombosis (DVT) in patients on apixaban and rivaroxaban, but no difference in reoperation for postoperative wound infection when compared to enoxaparin31.
Direct Thrombin Inhibitors: Direct thrombin inhibitors have also had inconsistent results in the literature. In a meta-analysis comparing dabigatran with LMWH and Factor Xa inhibitors, the authors found no difference with regard to wound complication rates32. Gill et al., performed a prospective study comparing dabigatran and dalteparin, noting that the reoperation rate for wound complications in the dabigatran group was 7% compared to 1% in the dalteparin group33. The increased rate of wound drainage with dabigatran has also been shown in studies comparing this agent with ASA, enoxaparin, and Factor Xa inhibitors34–36. In comparison to warfarin, ximelagatran showed no difference in the rate of wound complications, as discussed previously18,19.
Aspirin (ASA): ASA may reduce the incidence of wound complications and PJI when compared to warfarin, Factor Xa inhibitors, LMWH, and direct thrombin inhibitors, as mentioned in the above sections12,23,29,30,34. ASA has also demonstrated efficacy in patients at high-risk of VTE10. Notwithstanding, there is still limited prospective data evaluating the safety and efficacy of ASA, and high-level trials are currently ongoing37.
Conclusion: Currently, lower-level evidence suggests that ASA may be of similar efficacy to other pharmacologic agents while reducing the risk of wound complications. This data is limited by the lack of level-1 studies investigating the safety and efficacy of ASA. Future prospective studies will need to include ASA as an investigational arm while evaluating wound complications as a primary endpoint, as most RCT have only focused on the efficacy of these agents in preventing VTE events.
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