Venous thromboembolism after total joint arthroplasty: results from a Japanese multicenter cohort study

Abstract

IntroductionReal-world evidence of the effectiveness of pharmacological thromboprophylaxis for venous thromboembolism (VTE) is limited. Our objective was to assess the effectiveness and safety of thromboprophylactic regimens in Japanese patients undergoing joint replacement in a real-world setting.MethodOverall, 1,294 patients (1,073 females and 221 males) who underwent total knee arthroplasty (TKA) and 868 patients (740 females and 128 males) who underwent total hip arthroplasty (THA) in 34 Japanese national hospital organization (NHO) hospitals were enrolled. The primary efficacy outcome was the incidence of deep vein thrombosis (DVT) detected by mandatory bilateral ultrasonography up to post-operative day (POD) 10 and pulmonary embolism (PE) up to POD28. The main safety outcomes were bleeding (major or minor) and death from any cause up to POD28.ResultsPatients undergoing TKA (n = 1,294) received fondaparinux (n = 360), enoxaparin (n = 223), unfractionated heparin (n = 72), anti-platelet agents (n = 45), or no medication (n = 594). Patients undergoing THA (n = 868) received fondaparinux (n = 261), enoxaparin (n = 148), unfractionated heparin (n = 32), anti-platelet agents (n = 44), or no medication (n = 383). The incidence rates of sonographically diagnosed DVTs up to POD10 were 24.3% in patients undergoing TKA and 12.6% in patients undergoing THA, and the incidence rates of major bleeding up to POD28 were 1.2% and 2.3%, respectively. Neither fatal bleeding nor fatal pulmonary embolism occurred. Significant risk factors for postoperative VTE identified by multivariate analysis included gender (female) in both TKA and THA groups and use of a foot pump in the TKA group. Only prophylaxis with fondaparinux reduced the occurrence of VTE significantly in both groups. Propensity score matching analysis (fondaparinux versus enoxaparin) showed that the incidence of DVT was lower (relative risk 0.70, 95% confidence interval (CI) 0.58 to 0.85, P = 0.002 in TKA and relative risk 0.73, 95% CI 0.53 to 0.99, P = 0.134 in THA) but that the incidence of major bleeding was higher in the fondaparinux than in the enoxaparin group (3.4% versus 0.5%, P = 0.062 in TKA and 4.9% versus 0%, P = 0.022 in THA).ConclusionsThese findings indicate that prophylaxis with fondaparinux, not enoxaparin, reduces the risk of DVT but increases bleeding tendency in patients undergoing TKA and THA.Trial registrationUniversity Hospital Medical Information Network Clinical Trials Registry: UMIN000001366. Registered 11 September 2008.

Mechanical prophylaxis is a heparin-independent risk for anti–platelet factor 4/heparin antibody formation after orthopedic surgery

“…11 The study protocol was approved by the NHO Central Institutional Review Board. Written informed consent was obtained from each patient.…”

“…Details on each thromboprophylactic strategy (eg, dosage and duration) were described previously. 11 In this predefined substudy, duration of anticoagulation therapy was defined as the interval between the day that anticoagulation was initiated and the day that anticoagulation was terminated or that a blood sample was collected to measure anti-PF4/heparin antibodies, whichever came first. It was unlikely that patients treated with only mechanical thromboprophylaxis were exposed to heparin because heparin is not routinely used during TKA and THA in Japan, including for flushing of intraoperative catheters.…”

“…11 Approximately half of the patients were treated with either UFH, LMWH, or fondaparinux. The other half received only mechanical thromboprophylaxis that was dynamic (intermittent plantar compression device [foot pump] or intermittent pneumatic compression device [IPCD]), static (graduated compression stockings [GCSs]), or both.…”

Effects of a foot pump on the incidence of deep vein thrombosis after total knee arthroplasty in patients given edoxaban

“…For sample size calculation, we used our previously published data from Japanese patients under recent thromboprophylaxis to determine a DVT rate of $24.3% following TKA. 37 Based on these assumptions, we primarily calculated that we needed 126 patients with the foot pump and 126 patients without it to confirm a reduction in DVTs (relative risk 0.43) as demonstrated in a recent system review 39 at an a error of 0.05 and a b error of 0.80. However, we could not accumulate a sufficient sample size, and there is an undeniable possibility of the study being underpowered.…”

Induction of anti-PF4/heparin antibodies after arthroplasty for rheumatic diseases

“…The Japanese study of prevention and actual situation of VTE after total arthroplasty (J -PSVT) is a nationwide multicenter cohort study to obtain clinical data concerning the effectiveness of prophylactic treatment of VTE after arthroplasty in 34 Japanese National Hospital Organization (NHO) hospitals 17) . The major objective of this study was to determine the practical patterns of VTE prophylaxis and their outcomes including VTE and seroconversion rates of anti -PF4/heparin antibodies in Japanese patients undergoing total joint replacement (TKA or THA).…”