Michael Meghpara, James J. Purtill, Richard Iorio, Thomas Jakobson.
Response/Recommendation: Venous thromboembolism (VTE) after elective total joint arthroplasty (TJA) continues to occur despite various strategies in prophylaxis and should not be considered a “never event.”
Strength of Recommendation: Moderate.
Rationale: As part of an initiative to address quality of care and control healthcare costs, in 2002, the United States Centers for Medicare and Medicaid Services (CMS) defined “never events” as hospital-acquired conditions that were considered reasonably preventable1. In 2008, CMS added deep venous thrombosis (DVT) and pulmonary embolism (PE) following total knee arthroplasty (TKA) and total hip arthroplasty (THA)2.
Historically, DVT and PE were important risks for patients undergoing TJA. In a study of 7,959 patients between 1962 and 1973, Charnley et al., reported a non-fatal PE rate of 7.89% and a 1.04% rate of fatal PE which constituted the highest single cause of death after a THA3. Coventry et al., identified a cohort of 2012 THA from 1969 to 1971 of which 58 did not receive chemoprophylaxis past post-operative day five and observed a DVT rate of 3.4%, a non-fatal PE rate of 5.2%, and a fatal PE rate of 3.4%4,5. In a series performed between 1990 and 1991, Warwick et al., identified 1,162 patients undergoing THA without routine chemoprophylaxis, with DVT confirmed by venography in 1.89% of patients and a PE rate of 1.20% with a subsequent mortality rate of 0.34%6.
Early studies demonstrated a much higher incidence of VTE for TKA7,8. However, DVT in TKA patients occur distally in the calf which are less likely to progress into a PE which was observed at a rate of 1.3%9 with fatalities of 0.19 to 0.4%9,10. Stulburg et al., examined a series of 638 patients from 1974 to 1979 among which 49 patients inadvertently did not receive prophylaxis; an impressive 83% of these patients developed a DVT11.
In a prospective study with 34,397 consecutive and unselected THA or TKA procedures, 32 (0.09%) had a VTE after median of two days despite ongoing thromboprophylaxis12. All surgery was done in a fast-track setup with accelerated mobilization and discharge. Another study has shown a 90-day incidence of 0.41% of VTE after unicompartmental knee arthroplasty13. All patients received thromboprophylaxis until discharge and were operated in a fast-track setup with a median length of stay of one day.
With VTE as a common and potentially dangerous complication after TKA and THA, safe and effective strategies for prophylaxis were developed and studied. When warfarin dosage is titrated to an international normalized ratio (INR) of 1.5 to 2.0 and administered for approximately six weeks, DVT occurred at a rate of 0.2 to 1% with a non-fatal PE rate of 0.1 to 0.3%14–16. Warfarin was found to consistently decreased rates of VTE when utilized after THA or TKA but may lead to a significant risk of bleeding complications17–19.
Low-molecular-weight heparin (LMWH) has been used for post-operative VTE prophylaxis. With LMWH, DVT rates for THA have been reported from 8 to 20.8% LMWH vs. 14 to 23.2% warfarin with a non-fatal PE rate of 0 to 0.2% observed with LMWH; DVT rates for TKA ranged from 23 to 45% LMWH vs. 23.2 to 51.7% warfarin and a non-fatal PE rate of 0 to .2% LMWH vs. 0 to 0.3% warfarin20–23.
Recently, direct-acting oral anticoagulants (DOAC) have gained popularity for VTE prophylaxis due to ease of administration and lack of monitoring9. Rivaroxaban used after THA had an incidence of DVT of 0.8 to 1.6% compared to 3.4 to 6.5% for LMWH and a non-fatal PE rate of 0.1 to 0.3% vs. 0.1 to 0.5% for LMWH24,25. When rivaroxaban VTE prophylaxis was used after TKA, the DVT rate was 6.3 to 6.9% compared to 9.0 to 18.2% for LMWH and the non-fatal PE rate was 0 to 0.3% compared to 0.5% for LMWH26,27. When apixaban was used for VTE prophylaxis after THA, the DVT incidence was 1.1 versus 3.6% for LMWH and a non-fatal PE rate was 0.1 versus 0.2% for LMWH28. For VTE prophylaxis after TKA, the incidence of DVT for apixaban was 7.8 to 14.6% compared to 8.2 to 24.4% for LMWH, the non-fatal PE rate was 0.26 to 1.0% apixaban compared to 0 to 0.4% LMWH, and a fatal PE rate of 0.1 to 0.13% apixaban compared to 0% LMWH29,30. Using dabigatran for prophylaxis after THA, the incidence for DVT was 5.1 to 8.0% vs. 6.4 to 8.6% for LMWH and a non-fatal PE rate of 0.1 to 0.4% for dabigatran vs. 0.2 to 0.3% for LMWH, and a fatal PE rate of 0.1% with dabigatran31,32. For TKA, the incidence of DVT was 29.9 to 40.1% for dabigatran vs. 24.6 to 37.3% for LMWH with a non-fatal PE rate of 0 to 1.0% for dabigatran vs. 0.8% for LMWH33,34.
Aspirin (ASA) has been shown to be an effective prophylactic agent after THA and TKA with reported rates of DVT up to 2.6%, non-fatal PE rates of 0.14 to 0.6%, and a fatal PE rate of 0.7 to 0.2%35–38. A prospective randomized control trial comparing ASA to warfarin in standard-risk patients undergoing TKA or THA reported a DVT and a PE rate of 4.6% compared to 0.7% for ASA and warfarin, respectively39. For patients at “typical” risk of VTE after THA and TKA, the AAOS guidelines endorse ASA for VTE prophylaxis40.
Non-pharmacologic interventions have also decreased the incidence of VTE after TJA. Regional anesthesia, hypotensive anesthesia, intermittent pneumatic compression devices, optimized blood loss management programs, rapid rehabilitation protocols, and risk stratification protocols have all contributed to the decrease in VTE over time41–49. However, even when combined with the most aggressive of pharmacologic interventions, the rates of PE and DVT are not zero. Genetic predispositions for thromboembolism have not been well-defined and are not yet identified easily in the laboratory50–53. Until that testing is available, VTE after TJA will not be a “never event”.
Post-operative VTE has been a constant concern for orthopaedic surgeons performing TJA. Prior to prophylaxis, DVT and PE were common occurrences and a major source of fatality. Prophylaxis with warfarin, LMWH, and DOAC have decreased the rates of VTE, however, studies show persistent presence of VTE despite these investigated regimens. VTE Prophylaxis is a balance of reducing thromboembolic disease while mitigating surgical complications associated with anticoagulants15,54–56. Current strategies regarding the best prophylactic regimen for each individual patient remain under investigation40,57. With the continued presence of VTE for the currently available prophylactic regimens, VTE after THA and TKA should not be considered a “never event”.
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