Elevated plasma factor XI is associated with postthrombotic syndrome
Konrad Stępień a) b), Jakub Siudut c), Jarosław Zalewski b) d), Tomasz Nowakowski e) f), Anetta Undas a) c)
a-Department of Thromboembolic Disorders, Institute of Cardiology, Jagiellonian University Medical College, Krakow, Poland
b-Department of Coronary Artery Disease and Heart Failure, St. John Paul II Hospital, Krakow, Poland
c-Krakow Centre for Medical Research and Technologies, St. John Paul II Hospital, Krakow, Poland
d-Department of Coronary Artery Disease and Heart Failure, Institute of Cardiology, Jagiellonian University Medical College, Krakow, Poland
e-Department of Angiology, Faculty of Medicine, Jagiellonian University Medical College, Krakow, Poland
f-Clinical Department of Angiology, University Hospital in Krakow, Krakow, Poland
Abstract
Introduction
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.
Materials and methods
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.
Results
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).
Conclusions
Elevated FXI in association with inflammation and prothrombotic fibrin clot properties may contribute to the development of PTS following DVT.