BACKGROUND: The role of factor XI in the pathogenesis of postoperative venous 
thromboembolism is uncertain. Abelacimab is a monoclonal antibody that binds to 
factor XI and locks it in the zymogen (inactive precursor) conformation.
METHODS: In this open-label, parallel-group trial, we randomly assigned 412 
patients who were undergoing total knee arthroplasty to receive one of three 
regimens of abelacimab (30 mg, 75 mg, or 150 mg) administered postoperatively in 
a single intravenous dose or to receive 40 mg of enoxaparin administered 
subcutaneously once daily. The primary efficacy outcome was venous 
thromboembolism, detected by mandatory venography of the leg involved in the 
operation or objective confirmation of symptomatic events. The principal safety 
outcome was a composite of major or clinically relevant nonmajor bleeding up to 
30 days after surgery.
RESULTS: Venous thromboembolism occurred in 13 of 102 patients (13%) in the 
30-mg abelacimab group, 5 of 99 patients (5%) in the 75-mg abelacimab group, and 
4 of 98 patients (4%) in the 150-mg abelacimab group, as compared with 22 of 101 
patients (22%) in the enoxaparin group. The 30-mg abelacimab regimen was 
noninferior to enoxaparin, and the 75-mg and 150-mg abelacimab regimens were 
superior to enoxaparin (P<0.001). Bleeding occurred in 2%, 2%, and none of the 
patients in the 30-mg, 75-mg, and 150-mg abelacimab groups, respectively, and in 
none of the patients in the enoxaparin group.
CONCLUSIONS: This trial showed that factor XI is important for the development 
of postoperative venous thromboembolism. Factor XI inhibition with a single 
intravenous dose of abelacimab after total knee arthroplasty was effective for 
the prevention of venous thromboembolism and was associated with a low risk of 
bleeding. (Funded by Anthos Therapeutics; ANT-005 TKA EudraCT number, 
2019-003756-37.).