PB1079 - Elevated plasma factor XI is associated with postthrombotic syndrome

Background: Postthrombotic syndrome (PTS), the most common long-term complication of deep vein thrombosis (DVT), is more likely in individuals with the prothrombotic fibrin clot phenotype. To our knowledge, available studies on a thrombo-inflammatory etiology of PTS did not explore the role of factor (F) XI.

Aims: We investigated whether elevated FXI is associated with PTS occurrence and venous thromboembolism (VTE) recurrence in a cohort of DVT patients.

Methods: We enrolled 180 consecutive patients (aged 43±13 years) with first-ever DVT. After 3 months since the index event FXI levels were measured, along with fibrin clot properties, including permeability (Ks), clot lysis time (CLT), thrombin generation, and fibrinolysis proteins. We recorded the PTS occurrence using the Villalta score and documented symptomatic VTE recurrence after a 1-year follow-up.

Results: At 3 months since DVT a median FXI was 102% [IQR, 92-113%] and showed associations with age (R=0.342, P< 0.001), thrombin activatable fibrinolysis inhibitor (TAFI) activity (R=0.317, P< 0.001), CLT (R=0.377, P< 0.001), and with Ks (R=-0.385, P< 0.001), but with fibrinogen, PAI-1, thrombin generation, FVIII, high-sensitivity C-reactive protein, interleukin-6 or -10 (Figure). Patients with PTS (n=48, 26.7%) were characterized by 16.1 % higher FXI at 3 months since DVT (P < 0.001) and elevated FXI >120% occurred more often in PTS patients compared with the remainder (odds ratio [OR] 5.546, 95% confidence interval [CI] 2.282-13.474, P< 0.001), without association with PTS severity. Analogous values for DVT recurrence were OR 14.048, 95% CI 6.279-31.428, P< 0.001, respectively. After age adjustment higher FXI was independently associated with PTS occurrence (OR per 1% 1.059, 95% CI 1.028-1.090) (Table), and VTE recurrence (OR 1.026, 95% CI 1.006-1.047).

Conclusion(s): Our findings suggest that elevated FXI may predispose not only to DVT recurrence but also to PTS, which might indicate that FXI inhibitors could reduce the risk of this complication.