At our institution, enoxaparin was routinely used as pharmacologic prophylaxis for DVT following TKA until October 2019 until a preliminary survey unexpectedly showed the incidence of DVT to be approximately 30% in these patients. After pharmacologic prophylaxis was stopped, this retrospective observational study was performed to obtain information on the incidence and characteristics of DVT in patients who undergo TKA without pharmacologic prophylaxis. Our hypothesis was that there would be no difference in the incidence, location, or characteristics of DVT following TKA between those with and without pharmacologic prophylaxis. Our findings were as follows: (1) the incidence of VTE in patients who underwent primary TKA without pharmacologic prophylaxis was 37%, which was not significantly different from the 31% incidence of VTE in patients who received concomitant pharmacologic prophylaxis; (2) most of the DVTs occurred in the soleal vein, with no significant in distribution between the two groups; and (3) a total of 6 knees (7.6%) had complications, most of which involved interruption of pharmacologic prophylaxis due to swelling and prolonged bleeding.
In 2008, a randomized double-blind study with 396 Japanese patients undergoing primary TKA compared the incidence of VTE in those administered enoxaparin 40 mg/day with that in those administered a placebo [16]. It found that the incidence of VTE was 29.8% in the enoxaparin group and 60.8% in the placebo group. Even taking into account the possibility of differences in patient background factors, various additional factors may have contributed to the decline in the incidence of VTE, including development of surgical techniques for TKA, changes in anesthesia methods, including ultrasound guidance in regional anesthesia [22], increased use of a multimodal analgesic pathway for TKA [23], and changes in rehabilitation programs, including early ambulation and more widespread education of medical staff and patients about VTE1. In our study, which was performed in an era of modern surgical and anesthesia techniques and postoperative management, the incidence of DVT without pharmacologic prophylaxis was 37%. This figure is comparable with that in a report on patients receiving TKA without pharmacologic prophylaxis in 2016 [14].
To the best of our knowledge, there have been no published comparisons of the location or quality of thrombus in patients undergoing current TKA with or without pharmacologic prophylaxis. It was widely known that DVT develops in the soleal vein because of stasis of blood flow [1,24]. Abe et al. investigated DVT after TKA using ultrasonography and found that all cases of DVT occurred in the soleal vein [1]. However, the results of our present study indicate that postoperative DVT is prone to occurring in the posterior tibial vein and peroneal vein as well as in the soleal vein. Therefore, DVT investigations should include not only the soleal vein but also other distal veins.
The ultrasound characteristics of DVT have been reported in the past [18]. A study described acute clots as firm or slightly deformed by compression, hypoechoic or isoechoic in echogenicity, present in a vein with an enlarged diameter, and attached to the vein wall [25]. However, in many cases, the findings overlap, making assessment of fresh thrombus difficult. Although there was no obvious difference in echogenic findings between the two groups in this study, further studies on the impact of pharmacologic prophylaxis on thrombus quality are warranted.
This study had several limitations. First, it had a retrospective design, which means that there was a possibility of patient selection bias. Although there was no significant difference in background factors between the two study groups, we cannot rule out the possibility that the incidence of VTE may have been affected by underlying diseases, including cancer [26]. However, this shortcoming may be offset to some extent by the inclusion of a control group consisting of patients who underwent TKA performed by the same surgeons at the same institution. Second, the sample size small. Nevertheless, the statistical power was relatively high. Third, only enoxaparin was used for pharmacologic prophylaxis. In recent years, the trend for prophylactic anticoagulation has been toward oral anticoagulants such as apixaban, rivaroxaban, dabigatran and edoxaban5. However, enoxaparin is still widely used as a prophylactic anticoagulant, and its non-inferiority when used as a control has been confirmed in many randomized controlled trials. Fourth, DVTs that occurred after postoperative day 7 might have been missed. In the multinational Global Orthopaedic Registry study, which included 8326 patients, the mean time to VTE after TKA was 9.7 ± 14.1 days [27]. Meanwhile, Yamaguchi et al. [28] found that symptomatic DVT peaked 4 days after TKA surgery. In another study by Song et al. [29], assessments for VTE after TKA were performed on postoperative days 3–7. Therefore, examination on postoperative day 7 can be considered appropriate. Fifth, DVT was detected by duplex ultrasonography. Unlike venography, duplex ultrasonography is minimally invasive and is considered the gold standard to date [24,26]. Contrast-enhanced CT has been reported [14], but it is difficult to use when patients have impaired renal function or when evaluating the area around the knee due to halation from the artificial joint. Finally, ethnic and cultural differences may have affected the results. All patients in this study were Asian, so care should be taken when extrapolating the results to other populations and institutions.