Elevated factor XI is associated with left atrial appendage thrombi of unknown origin: links to unfavorable fibrin clot properties

Background Left atrial appendage thrombi (LAAT) of unknown origin have been reported to be linked to formation denser and poorly lysable fibrin networks. Elevated factor (F)XI is associated with thromboembolism, including left ventricular thrombus. Purpose We investigated whether FXI is elevated in such patients and might predispose to LAAT recurrence and its complications. Methods We studied 36 consecutive patients with LAAT of unknown origin following resolution of thrombus during anticoagulant treatment, versus 36 matched controls. Plasma FXI levels were assessed, along with von Willebrand factor (vWF), clot permeability (Ks), and clot lysis time (CLT). Ischemic cerebrovascular events and LAAT recurrence were evaluated during 18-140 months, long-term follow-up. Results FXI levels were 17% higher in the LAAT group compared to controls (p<0.001). FXI >120% was also more common in LAAT than in controls (55.6% vs. 19.4%, p=0.0015). Among LAAT patients, FXI levels >120% were associated with smoking, higher fibrinogen levels, and lower vWF (all p<0.05). FXI correlated positively with fibrinogen and CLT, and inversely with Ks (all p<0.05). FXI>120% characterized subjects who experienced ischemic cerebrovascular events and recurrent LAAT during follow-up (55% vs. 12.5%, p=0.0061). Multivariate analysis showed that increasing FXI was associated with cerebrovascular events while off anticoagulation (OR for 10%: 1.79, 95% CI: 1.06-3.04, p=0.031). Conclusion Elevated FXI may predispose to LAAT of unknown origin and its recurrence following withdrawal of anticoagulation. FXI might help identify patients with LAAT who may require prolonged anticoagulation.