14 – Should venous thromboembolism (VTE) screening be performed in asymptomatic patients undergoing orthopaedic surgery?

Daniel Caldeira, Aymard de Ladoucette, Taylor D’Amore.

Response/Recommendation: Venous thromboembolism (VTE) screening with ultrasound is not recommended for asymptomatic patients before or after major orthopaedic surgery.

Strength of Recommendation: Moderate for post-operative screening and limited for pre-operative screening.

Rationale: Venographic studies show that venous thromboembolism (VTE) incidence after orthopaedic surgery was higher than 40% in the absence of thromboprophylaxis1–5.  The use of antithrombotic strategies (both mechanical and pharmacological) has significantly reduced the VTE rates.

In this context, the clinical balance of treating asymptomatic VTE is still controversial, and the diagnostic yield of systematic screening is still debated.

Following the review of the literature, two randomized controlled trials (RCT) provided information about the clinical value of systematic screening post-operatively.

The RCT by Robinson et al., randomized 1,024 patients submitted to knee and/or hip arthroplasty to post-discharge systematic venous ultrasound screening (518 patients) or sham ultrasound screening (506 patients).  The systematic screening arm found 13 asymptomatic (2.5%) deep venous thrombosis (DVT) events and 4 DVT events with negative screening exams.  Additionally, 1 patient treated with warfarin for an asymptomatic DVT had a major bleeding event.  In the sham arm, there were 3 DVT and 2 pulmonary embolisms (PE) events totaling 5 symptomatic patients6.  The risk of symptomatic VTE was not decreased with systematic screening (relative risk [RR] 0.78, 95% confidence interval [CI] 0.21-2.89, p=0.71) nor was the risk of symptomatic events (RR 0.98, 95% CI 0.28-3.35, p=0.97).

The RCT by Schmidt et al., enrolled 346 patients that underwent hip or knee replacement and received prophylactic nadroparin for 10 days7.  Patients were randomized to ultrasound systematic screening of DVT (with low-molecular-weight heparin [LMWH] treatment in those with asymptomatic DVT) or extended prophylaxis with nadroparin for 35 days7.  The incidence of symptomatic VTE after screening of asymptomatic DVT (6 of 110 patients without DVT in the screening) was similar to extended thromboprophylaxis (7 of 172 patients) (RR 1.34, 95% CI 0.46-3.88).  The major bleeding risk was not statistically different among strategies (RR 4.94, 95% CI 0.23-102, p=0.30*) nor overall bleeding risk (RR 0.99, 95% CI 0.25-3.88, p=0.99).

Regarding bias risk, both studies samples’ sizes smaller than those required to evaluate symptomatic VTE at the rates found in the studies which led us to consider the studies to have a moderate quality**8,9.

Thus, the best available evidence did not show improvements of clinical outcomes with systematic DVT screening after major orthopedic surgery.  Additionally, Tsuda et al., followed patients after elective total hip arthroplasty and found that asymptomatic distal DVT which developed post-operatively could be treated without anticoagulation.  All DVT remained benign and 93% of them ultimately resolved10.  Similarly, Wang et al., found that following total knee arthroplasty (TKA), DVT in the calf disappeared spontaneously with time11.  In patients undergoing elective shoulder surgery, asymptomatic VTE occurred in 5.7% of patients but all were asymptomatic12.

Regarding pre-operative screening of VTE, there were not any RCT.  However, Watanabe et al., evaluated prospectively 71 patients who underwent preoperative computerized tomography (CT) scans of pulmonary and lower limb vessels before having a TKA13.  About 9% had a preoperative asymptomatic VTE (1 patient had PE [1%] and 7 had DVT [8%]), without any clinical symptoms.  In the remaining 64 patients, the surgery was performed.  These patients were evaluated for post-operative VTE and 51% had CT evidence of thrombosis (8 patients DVT plus PE; 2 patients with PE; and 22 with DVT)13.  Observational studies with ultrasound screening showed lower rates of pre-operative VTE (approximately 3%)14,15, and an interrupted time-series study showed that the period of systematic VTE ultrasound screening was not significantly different from the non-systematic period regarding post-operative thromboembolic complications15.

Overall, the frequency of post-operative VTE is much higher than pre-operative VTE, and some of the “postoperative” DVT reported in systematic screening studies may represent undetected preoperative VTE.  The current data does not inform us robustly if therapeutic anticoagulation and/or surgery postponement can avoid clinically relevant VTE events, and therefore no recommendation can be made for systematic pre-operative VTE screening.

*Zero major bleeding events in the extended prophylaxis arm. RR, 95% CI, and p-value calculated using the 0.5 correction for the zero-events arm.

** For example, Schmidt et al., trial showed the highest relative risk differential among arms and the higher rate of symptomatic VTE (5.5%).  Using these data, which are conservative for sample size estimation and a power of 80% the adequate sample size would be 5,946 patients7.

References:

1.         Khazi ZM, An Q, Duchman KR, Westermann RW. Incidence and Risk Factors for Venous Thromboembolism Following Hip Arthroscopy: A Population-Based Study. Arthroscopy. 2019;35(8):2380-2384.e1. doi:10.1016/j.arthro.2019.03.054

2.         Zeng Y, Si H, Wu Y, et al. The incidence of symptomatic in-hospital VTEs in Asian patients undergoing joint arthroplasty was low: a prospective, multicenter, 17,660-patient-enrolled cohort study. Knee Surg Sports Traumatol Arthrosc. 2019;27(4):1075-1082. doi:10.1007/s00167-018-5253-3

3.         Warren JA, Sundaram K, Anis HK, Kamath AF, Higuera CA, Piuzzi NS. Have Venous Thromboembolism Rates Decreased in Total Hip and Knee Arthroplasty? J Arthroplasty. 2020;35(1):259-264. doi:10.1016/j.arth.2019.08.049

4.         Warren JA, Sundaram K, Kamath AF, et al. Venous Thromboembolism Rates Did Not Decrease in Lower Extremity Revision Total Joint Arthroplasty From 2008 to 2016. J Arthroplasty. 2019;34(11):2774-2779. doi:10.1016/j.arth.2019.05.012

5.         Lee D-K, Kim H-J, Lee D-H. Incidence of Deep Vein Thrombosis and Venous Thromboembolism following TKA in Rheumatoid Arthritis versus Osteoarthritis: A Meta-Analysis. PLoS One. 2016;11(12):e0166844. doi:10.1371/journal.pone.0166844

6.         Robinson KS, Anderson DR, Gross M, et al. Ultrasonographic screening before hospital discharge for deep venous thrombosis after arthroplasty: the post-arthroplasty screening study. A randomized, controlled trial. Ann Intern Med. 1997;127(6):439-445. doi:10.7326/0003-4819-127-6-199709150-00004

7.         Schmidt B, Michler R, Klein M, Faulmann G, Weber C, Schellong S. Ultrasound screening for distal vein thrombosis is not beneficial after major orthopedic surgery. A randomized controlled trial. Thromb Haemost. 2003;90(5):949-954. doi:10.1160/TH03-03-0154

8.         Brok J, Thorlund K, Gluud C, Wetterslev J. Trial sequential analysis reveals insufficient information size and potentially false positive results in many meta-analyses. J Clin Epidemiol. 2008;61(8):763-769. doi:10.1016/j.jclinepi.2007.10.007

9.         cpg-methodology.pdf. Accessed September 1, 2021. https://www.aaos.org/globalassets/quality-and-practice-resources/methodology/cpg-methodology.pdf

10.       Tsuda K, Takao M, Kim J, Abe H, Nakamura N, Sugano N. Asymptomatic Deep Venous Thrombosis After Elective Hip Surgery Could Be Allowed to Remain in Place Without Thromboprophylaxis After a Minimum 2-Year Follow-Up. J Arthroplasty. 2020;35(2):563-568. doi:10.1016/j.arth.2019.08.062

11.       Wang CJ, Wang JW, Weng LH, Hsu CC, Lo CF. Outcome of calf deep-vein thrombosis after total knee arthroplasty. J Bone Joint Surg Br. 2003;85(6):841-844.

12.       Takahashi H, Yamamoto N, Nagamoto H, Sano H, Tanaka M, Itoi E. Venous thromboembolism after elective shoulder surgery: a prospective cohort study of 175 patients. J Shoulder Elbow Surg. 2014;23(5):605-612. doi:10.1016/j.jse.2014.01.054

13.       Watanabe H, Sekiya H, Kariya Y, Hoshino Y, Sugimoto H, Hayasaka S. The incidence of venous thromboembolism before and after total knee arthroplasty using 16-row multidetector computed tomography. J Arthroplasty. 2011;26(8):1488-1493. doi:10.1016/j.arth.2011.01.001

14.       Barnes RW, Nix ML, Barnes CL, et al. Perioperative asymptomatic venous thrombosis: role of duplex scanning versus venography. J Vasc Surg. 1989;9(2):251-260.

15.       Meftah M, White PB, Siddiqi A, Perake VS, Kirschenbaum IH. Routine Preoperative Venous Doppler Screening Is Not Effective in Preventing Thromboembolic Events After Total Joint Arthroplasty. Orthopedics. 2018;41(2):e202-e206. doi:10.3928/01477447-20180102-04