Daniel Guss, Christopher W. DiGiovanni, Donald J. McBride.
Response/Recommendation: There is contradictory data on the role of chemoprophylaxis for the prevention of venous thromboembolism (VTE) events after total ankle arthroplasty (TAA). VTE rates after TAA appear to be substantially lower than those after total hip or knee arthroplasty in the absence of chemoprophylaxis, but they are certainly not negligible. Subpopulations of patients such as those with a prior history of VTE or known thrombophilia may be at sufficiently heightened risk to justify chemoprophylaxis. The implications of prolonged below-knee immobilization or non-weight-bearing, as well as the risk-benefit ratio of chemoprophylaxis in the perioperative setting, needs to be further elucidated.
Strength of Recommendation: Limited.
Rationale: While routine use of chemoprophylaxis is widely recommended following hip and knee arthroplasty, studies examining the rate of VTE events such as deep vein thrombosis (DVT) and pulmonary embolism (PE) after TAA are scarce and remain confounded by methodological limitations1,2. It is also critical not to make overgeneralized recommendations that equate arthroplasty procedures across all joints. Hip and knee arthroplasties are more proximal procedures that technically entail complete dislocation of the involved joints, potentially kinking major vessels during surgery. Moreover, immediate postoperative mobilization and weight-bearing are generally permitted following these procedures. In contrast, TAA is a more distal procedure whereby the ankle joint is not fully dislocated, and the surrounding vasculature is not acutely distracted or angulated, and patients generally undergo a period of immobilization and non-weight-bearing. It is therefore plausible that the TAA procedure may not increase the incidence of DVT or PE per se, but rather, the superimposed host-specific risk factors in patients undergoing TAA may account for this reported incidence3,4.
A retrospective study by Jameson et al., examining the rates of VTE after foot and ankle (F&A) surgery within the National Health Service (NHS) found that among 1,633 patients who underwent TAA, there was only a single non-fatal PE (0.06%) and no DVT4. The authors concluded that “venous thromboembolism following foot and ankle surgery is extremely rare” and that “prophylaxis is not required in most of these patients.” However, the study relied on a hospital admissions database and identified patients who were readmitted to an NHS hospital for DVT or PE following a F&A procedure. Since a substantial number of VTE events never require inpatient readmission, the reported data may underestimate the actual rate of VTE after F&A surgery.
A large-scale meta-analysis by Calder et al., pooled 43,381 patients across 28 studies to assess the rate of VTE after both operative and nonoperative management of F&A conditions5. This was a heterogeneous mix of retrospective cohort, prospective cohort, and randomized controlled studies, some of which focused solely on nonoperative management. The authors found that overall rates of clinically symptomatic VTE were 0.6 % (95 % confidence interval [CI] 0.4–0.8 %) and 1 % (95 % CI 0.2–1.7 %) with and without the use of chemoprophylaxis, respectively. Rates were higher among patients who underwent radiologic assessment with ultrasound or venography irrespective of symptoms, wherein the incidence of VTE with and without chemoprophylaxis was 12.5 % (95 % CI 6.8–18.2 %) and 10.5 % (95 % CI 5.0–15.9 %), respectively. They also found that patients undergoing management of achilles tendon ruptures had a higher rate of VTE compared to the general population (7% clinical and 35.3% radiological), prompting the authors to recommend chemoprophylaxis for this specific surgical population, although they did not comment on patients undergoing TAA.
A review article by Barg et al., examined the incidence of VTE after TAA among 31 studies published between 1999 and 2013 and found a wide variation in VTE rates ranging from 0 to 9.8%, and concluded that “the incidence of thromboembolic complications was comparable with that of symptomatic deep vein thrombosis in patients with total knee or hip replacement”6. One major confounder in analyzing these data collectively, however, was that a formal meta-analysis was not performed and the use of chemoprophylaxis was common but nonetheless variable amongst both individual patients as well as between studies. Manual tabulation of the included studies revealed that 3,613 patients underwent 3,826 TAA, yielding an overall DVT rate of 1.3% and PE rate of 0.03%7. Given substantial variability in the use of chemoprophylaxis as well as the non-inclusion of patient risk factors for VTE, a definite conclusion could not be drawn from this study.
A separate study by Barg et al., evaluated the rate of symptomatic VTE among 665 patients who underwent 701 TAA, all of whom received low-molecular-weight heparin (LMWH) for six weeks postoperatively8. The authors found a DVT rate of 3.9% and concluded that “the incidence of symptomatic DVT after total ankle replacement and use of low-molecular-weight heparin is comparable with that in patients undergoing total knee or hip replacement.” The study did not explicitly recommend the routine use of chemoprophylaxis after TAA, but given that chemoprophylaxis is routinely administered after hip and knee arthroplasty, some may argue that this would imply that a similar recommendation should be followed for TAA1,2.
Horne et al., performed a retrospective chart review of symptomatic VTE rates among 637 patients undergoing 664 TAA9. The participating surgeons used LMWH for two weeks only if “risk factors” were identified, including a prior history of VTE or coagulopathy, as well as continued antiplatelet or anticoagulation therapy among patients who were taking these medications preoperatively. Overall, they reported that two patients (0.31%) developed a DVT alone, and two patients (0.31%) developed a DVT and PE. Among the 434 patients who were not on chemoprophylaxis preoperatively or postoperatively, only two (0.46%) developed a DVT. The authors concluded that “patients without identifiable risk factors do not appear to require chemoprophylaxis.” In this study, however, 203 patients (31.9%) either had a history of VTE or known thrombophilia and were therefore given chemoprophylaxis for two weeks, or were on preoperative aspirin, warfarin, LMWH, rivaroxaban (Xarelto), clopidogrel (Plavix), or dabigatran etexilate (Pradaxa) that was restarted immediately postoperatively. Presumably, it was the latter group of patients who had a heightened comorbidity burden and would be of interest to F&A surgeons. However, the authors noted that there were no bleeding events requiring reoperation, nor wound complications associated with chemoprophylaxis, although the rates of operative complications were not clearly reported.
Other studies examining complications after TAA have reported DVT rates between 0% and 5.4%, but were retrospective in nature, as well as inconsistent in the indications for chemoprophylaxis, duration of use, and length of immobilization and non-weight-bearing postoperatively10–17.
The study by Horne et al., did raise the specter of catastrophic complications from VTE9. One patient with a prior history of DVT developed bilateral DVT and a saddle PE four weeks postoperatively despite being prescribed LMWH for the first two weeks, which was as per standard protocol. A second patient who was not prescribed chemoprophylaxis developed bilateral PE with dyspnea and increased oxygen requirement on the second postoperative day. Another patient without a history of VTE developed a femoral DVT diagnosed at 3 months, while a fourth developed DVT while on aspirin. Thus, 3 of the 4 VTE events occurred in the absence of chemoprophylaxis, either because patients were never prescribed prophylaxis or because the length of prescription had expired. Given that the authors explicitly reported no complications associated with the use of chemoprophylaxis but did note the occurrence of several VTE events, one might conversely conclude that the use of such agents should be liberalized. It is thus evident that VTE risk-benefit analysis following F&A surgery is arguably more nuanced than that reported by this or any other study in current literature.
While VTE remains a genuine but poorly defined risk following TAA and other F&A procedures, it should be noted that numerous other studies have also highlighted the risk of complications related to the use of chemoprophylaxis. A study by Heijboer et al., compared the rate of VTE and adverse bleeding events among two matched cohorts of 5,286 patients undergoing F&A surgery with and without chemoprophylaxis using propensity score matching18. They found a three-fold reduction in VTE events, although there was a two-fold increase in bleeding events. Less frequently discussed is the risk of an immunogenic form of heparin-induced thrombocytopenia (HIT), which may occur in 0.2% of patients19. HIT carries an amputation rate of 22% and a mortality rate of 11%, with a published case report describing a mortality after a single dose of LMWH after F&A surgery20. Separately, the study by Barg et al., noted that while there were no bleeding complications, three patients (0.5%) developed thrombocytopenia by day seven with platelet counts that fell below 100,000/mm3 and resolved after stopping LMWH8. Notwithstanding, the risks of chemoprophylactic agents following F&A and other types of orthopaedic surgery are rarely discussed in current literature.
It is worth noting that below-knee cast immobilization and non-weight bearing status have also been implicated as a risk factor for VTE21–25. Not all of these studies demonstrated a protective effect with chemoprophylaxis, and some instead showed a higher risk of VTE with the use of chemoprophylaxis, largely because of the selection bias with the use of such agents in higher-risk patients. The study by Barg et al., did show a higher rate of VTE associated with a non-weight bearing status (odds ratio 3.57, 95% CI 2.18 to 5.85, p < 0.001)8.
In F&A surgery compared to hip and knee arthroplasty, inherent patient risk factors play a disproportionate role in precipitating a VTE. Risk factors identified in the literature have included age >50 years, splint or cast immobilization, achilles tendon ruptures, increased comorbidity burden as reflected by a Charlson comorbidity index >2, varicose veins, history of VTE either in a given individual or first-degree relative, known hypercoagulability disorder, and inflammatory arthritis3,4,21,26–28. These factors should be kept in mind when considering chemoprophylaxis after TAA, especially since patient risk factors arguably supersede procedural risk factors when it comes to F&A surgery.
In summary, there is enormous variability in the reported rate of VTE events after TAA. While the rate is certainly lower compared to the rate following total hip or knee arthroplasty without the use of chemoprophylaxis, it is certainly not negligible, and subpopulations of patients with superimposed comorbidities clearly remain at heightened risk. This includes patients with a prior history of VTE or hypercoagulability. Unfortunately, current data are generally retrospective and limited in their ability to discern patient-specific risk factors, and few studies have evaluated the downsides of using chemoprophylaxis. Large-scale, prospective randomized controlled trials are necessary to identify patients at risk of VTE after TAA in order to facilitate risk-benefit discussions between patients and providers.
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