OrthoBuzz occasionally receives posts from guest bloggers. In response to a three recent studies, the following commentary comes from Jeffrey B. Stambough, MD.
Throughout the last decade, we’ve experienced a boom in anticoagulation options to help prevent venous thromboembolism (VTE) associated with orthopaedic procedures. The use of aggressive anticoagulation, such as warfarin and various heparin formulations, is being questioned, largely due to concerns about bleeding risks and wound complications. Along with the newer direct oral anticoagulants such as rivaroxaban, over-the-counter aspirin (ASA) is gaining prominence as an anticoagulant due to its high efficacy, low cost, convenience for patients, favorable side-effect profile, and cardioprotective attributes. Current guidelines include the use of all these thromboprophylactic agents, but three recent studies lend credence to using aspirin as the primary VTE prophylactic agent when performing total joint arthroplasty (TJA).
In a March 20, 2019 JBJS study analyzing >31,000 TJAs performed at a single institution over 17 years, Rondon et al. found a 3-fold lower 30-day and 2-fold lower 1-year mortality rate in patients receiving ASA (81mg or 325 mg twice daily), compared to those who received non-aspirin thromboprophylaxis (mainly warfarin). No mortality differences were noted between the two ASA dosing regimens. While investigating specific causes of death, the authors discovered that the primary cause of death in the non-ASA cohort was cardiac related at all time points.
A second study, from the April 3, 2019 JBJS, looked into the effects of 3 antithrombotic agents on symptomatic VTE rates and periprosthetic infections in high-risk patients undergoing primary or revision TJA. When compared to the two more potent agents (warfarin and low-molecular-weight heparin), ASA proved more effective at reducing pulmonary embolism (PE) and VTE rates in high-risk patients, and it was also associated with lower rates of periprosthetic joint infection when compared with warfarin. Thus, it seems that even in patients deemed to be higher risk for developing VTE, ASA may be a safe, effective option.
Lastly, Runner et al. gleaned VTE prophylaxis data from >22,000 TJA cases submitted by surgeons sitting for Part 2 of ABOS between 2014 and 2016. The findings, reported in the April 2019 issue of the Journal of Arthroplasty, showed similar trends to those seen in the two previously mentioned studies: Mild (distal or superficial deep vein thrombosis [DVT]), moderate (nonfatal PE, proximal DVT) and severe (fatal PE) VTE events, as well as death, were significantly less frequent in those who received ASA compared to more aggressive agents (heparin or one of its analogs, direct oral agents, or warfarin). Also, patients who received ASA with or without mechanical prophylaxis had significantly lower complication rates (95.5% vs. 93.0%, p<0.001).
One firmly held dogma in medicine is that patients who are at higher risk for VTE should be treated with stronger anticoagulation medications. However, these 3 studies support the idea that less aggressive anticoagulation medication (specifically, low-dose aspirin) may be the more effective and safer option for most patients. In our ongoing quest to improve patient outcomes and mitigate risk around the TJA episode, we should consider using aspirin for thromboprophylaxis unless there is an explicit contraindication in a specific patient.
However, we should also keep in mind that these three studies have the common limitations of all retrospective analyses. Recent randomized trials have shown aspirin to be “noninferior” to other anticoagulants for VTE prevention, and in less than 2 years, we should have even more definitive answers to this question from the randomized, multicenter PEPPER trial, with its estimated 25,000 participants.
Jeffrey B. Stambough, MD is an orthopaedic hip and knee surgeon, an assistant professor of orthopaedic surgery at University of Arkansas for Medical Sciences, and a member of the JBJS Social Media Advisory Board.
Perioperative anticoagulation for patients undergoing orthopaedic surgery remains a challenge. Currently, there is insufficient evidence to provide definitive recommendations for care. Recent estimates suggest that, in the U.S. alone, there are over two million patients with atrial fibrillation who receive warfarin each year. Moreover, >100,000 heart valve replacements are performed annually.
In the September 2015 issue of JBJS Reviews, Dundon et al. review current recommendations for perioperative management of patients on existing anticoagulation therapy. They note that cessation of warfarin is based on risk stratification for thromboembolic events and bleeding risk, with cessation and bridging therapy being recommended if patients are at high risk for thromboembolic events or bleeding. On the basis of their assessment of published reports, they recommend that warfarin should be withdrawn and that bridging therapy should be instituted five days prior to surgery. Cessation and regular dosing should be resumed twelve to twenty-four hours after the operation.
However, the issue of perioperative bridging is currently under debate. The authors of this article could find no double-blind, randomized, controlled trials in which patients undergoing vitamin-K antagonist therapy who had received bridging with low-molecular-weight heparin or unfractionated heparin were compared with patients undergoing vitamin-K antagonist therapy who had received no bridging therapy. Bridging therapy with therapeutic-dose intravenous unfractionated heparin should be stopped four to six hours before surgery, but patients receiving therapeutic-dose subcutaneous low-molecular-weight heparin should take the last dose approximately twenty-four hours prior to surgery.
The authors recommended that patients in high cerebrovascular and cardiovascular risk groups should maintain aspirin with bridging therapy and may also maintain clopidogrel in emergencies as long as they are not undergoing a high-risk procedure. For patients who take rivaroxaban or dabigatran, emergency surgery is permissible as long as levels of the drug are ≤30 ng/mL at the time of admission.
These recommendations are based on careful and critical analyses of available data; however, as noted above, there are no critical evidence-based studies in the area of perioperative management of anticoagulation in patients who are undergoing orthopaedic surgery. The concepts and ideas presented in this article should be considered as recommendations at best.
Thomas Einhorn, Editor
The overall rate of symptomatic lower-extremity deep vein thrombosis (DVT) following arthroscopic ACL procedures is reported to be <0.3%, and guidelines from the American College of Chest Physicians recommend against DVT prophylaxis prior to arthroscopic knee surgery, unless a patient has risk factors for blood clots. But some patients are unknowingly at high risk for clots, as a case report by Ackerman et al. in the June 10, 2105 JBJS Case Connector shows.
A 45-year-old woman presented for arthroscopic ACL reconstruction in her left knee. Unbeknownst to her or her surgeons, the patient had asymptomatic May-Thurner syndrome—an anatomic variant of the iliac blood vessels in which the right common iliac artery crosses over the left common iliac vein, compressing the vein against the lumbar spine.
Nine days after ACL surgery, the patient showed up in the ED with pain and swelling in the operative leg. Ultrasound revealed an extensive DVT extending distally from the common femoral vein. Imaging of the chest and cardiac workups were negative for heart or lung thromboembolism.
A heparin drip was started, and a vascular surgeon ordered a left-leg venograph, which revealed a large clot extending from the origin of the left common iliac vein to the insertion site of the catheter in the popliteal vein. Severe stenosis of the left common iliac vein confirmed May-Thurner syndrome (see image below).
Treatment consisted of an infusion of tissue plasminogen activator (Alteplase) directly to the clot, continued intravenous heparin, and an angioplasty with stents to open the stenosed left common iliac vein. Mechanical thrombolysis and aspiration of a residual femoral vein thrombus was accomplished with a Trellis device.
Postoperatively the patient was transitioned to therapeutic warfarin for six months and instructed to wear compression stockings. She completed her ACL physical therapy protocol uneventfully, and one year after the ACL reconstruction, the knee graft was stable and there was no evidence of post-thrombotic syndrome.
The authors remind orthopaedists that May-Thurner syndrome, which is more common in women than men, should be suspected in the presence of an extensive iliofemoral DVT. They emphasize that multimodal and aggressive treatment, in consultation with a vascular specialist, should be initiated to bust the clot and reduce the risk of post-thrombotic syndrome. Post-clot, such patients should be maintained on warfarin for a minimum of six months, and patients with stents often require lifelong aspirin therapy.
A recent meta-analysis of eight randomized trials (1,408 total patients) compared aspirin to anticoagulants such as warfarin and dabigatran for preventing venous thromboembolism (VTE) after hip and knee arthroplasty and hip-fracture repair. The analysis found that the overall prophylactic power of these two medical approaches was essentially equal following major lower-extremity surgery. However, the comparison, appearing in the Journal of Hospital Medicine, found a slightly higher (but statistically nonsignificant) risk of deep vein thrombosis (DVT) with aspirin following hip-fracture repair. Conversely, the risk of bleeding after hip-fracture surgery was lower with aspirin than with anticoagulants.
For additional insight into VTE prophylaxis, view the FREE recorded JBJS webinar “Preventing Arthroplasty-Associated Venous Thromboembolism.” Register here.