Elevated Factor XI is Associated with First and Recurrent Left Atrial Appendage Thrombus of Unknown Origin

Formation of denser and poorly lysable fibrin networks characterizes patients with left atrial appendage thrombus (LAAT) of unknown origin. Elevated factor (F)XI is associated with thromboembolism, including left ventricular thrombus. We investigated whether FXI is increased in LAAT and might predispose to its recurrence and complications.In a case-control study, we studied 36 consecutive patients with LAAT of unknown origin following thrombus resolution, versus 36 age-, sex-, and diabetes-matched controls, all without current anticoagulant treatment. Plasma FXI levels were assessed, along with von Willebrand factor (vWF), clot permeability (Ks), clot lysis time (CLT), fibrinolysis proteins, thrombin generation, and platelet markers. Ischemic cerebrovascular events and LAAT recurrence were evaluated during a median follow-up of 10 years.FXI levels were 14% higher in the LAAT group compared with controls (p < 0.001). FXI >120% was more common in the former group (p = 0.0015). Current smoking and fibrinogen were associated with FXI >120%. In LAAT patients, FXI correlated positively with fibrinogen and CLT, while inversely with vWF and Ks. Most recurrent LAAT (n = 10 out of 11 in total) or cerebrovascular events (n = 18 out of 23 in total) occurred in patients with baseline FXI >120% (both p < 0.001). FXI was associated with LAAT recurrence (OR for 10% = 2.73, 95% CI: 1.32-5.66) and cerebrovascular events (OR for 10%: 1.79, 95% CI: 1.06-3.04).Higher FXI is associated with LAAT of unknown origin, its recurrence and occurrence of cerebrovascular events following anticoagulation withdrawal. Further studies are needed to evaluate whether FXI may help identify patients with LAAT who require prolonged anticoagulation.