Elevated plasma factor XI is associated with postthrombotic syndrome

• Published in: Thrombosis research Vol. 241; p. 109086
• Main Authors: Stępień, Konrad, Siudut, Jakub, Zalewski, Jarosław, Nowakowski, Tomasz, Undas, Anetta
• Format: Journal Article
• Language: English
• Published: United States Elsevier Ltd 01.09.2024
• Subjects: Adult; Factor XI; Factor XI - metabolism; Female; Fibrin clot; Humans; Male; Middle Aged; Postthrombotic syndrome; Postthrombotic Syndrome - blood; Thrombin generation; Venous thromboembolism; Venous Thrombosis - blood; CRP; Postthrombotic syndrome; DVT; LDL-C; F; VTE; Ks; Thrombin generation; CLT; HR; PTS; Factor XI; K-W; TAFI; PAI-1; Venous thromboembolism; BMI; OR; IL; Fibrin clot; tPA; CI; IQR; VKA; D-Dmax; PE; CAT; α2AP; D-Drate
• ISSN: 0049-3848; 1879-2472; 1879-2472
• DOI: 10.1016/j.thromres.2024.109086

Postthrombotic syndrome (PTS), a common complication of deep vein thrombosis (DVT), is largely inflammatory by nature with contribution of prothrombotic mechanisms. The role of factor (F)XI in PTS has not been explored yet. We investigated whether elevated FXI is associated with PTS occurrence. We enrolled 180 consecutive patients (aged 43 ± 13 years) with first-ever DVT. After 3 months FXI levels were measured, along with inflammatory markers, thrombin generation, plasma clot permeability (Ks), clot lysis time (CLT), and fibrinolysis proteins. We assessed PTS using the Villalta score and recorded symptomatic venous thromboembolism (VTE) at a 1-year and venous ulcers at a median 53 months follow-up. Baseline median FXI was 102 % [IQR 92–113 %] and showed positive association with Villalta score (R = 0.474, P < 0.001). Patients with PTS (n = 48, 26.7 %) had 16.1 % higher FXI (P < 0.001) and FXI ≥120 % occurred more often in PTS patients (odds ratio [OR] 5.55, 95 % confidence interval [CI] 2.28–13.47). There were associations of baseline FXI with Ks and CLT along with thrombin activatable fibrinolysis inhibitor (TAFI) activity, C-reactive protein, and interleukin-6, but not with fibrinogen, or thrombin generation. After age adjustment higher FXI was independently associated with PTS occurrence (OR per 1 % 1.06, 95 % CI 1.02–1.09) and VTE recurrence (OR 1.03, 95 % CI 1.01–1.06). At long-term follow-up, patients with venous ulcers had 13.6 % higher baseline FXI (P = 0.002). Elevated FXI in association with inflammation and prothrombotic fibrin clot properties may contribute to the development of PTS following DVT. •Elevated FXI 3 months after deep vein thrombosis predisposes to PTS occurrence.•Higher FXI is associated with VTE recurrence and venous ulcers development.•Higher FXI is correlated with denser fibrin clot structure and impaired fibrinolysis.