Reduced plasma fibrin clot permeability and susceptibility to lysis are associated with increased risk of postthrombotic syndrome

Abstract

Background: The postthrombotic syndrome (PTS) is a severe complication of deep vein thrombosis (DVT). Reduced plasma clot permeability and lysability have been linked to DVT and residual vein obstruction. Objectives: We investigated whether altered fibrin clot properties are associated with the occurrence of PTS. Patients and Methods: Plasma fibrin clot permeability (Ks) and lysability were investigated in a cohort of 197 consecutive patients aged 18 to 65 years recruited 3 months following the first-ever DVT. Patients with severe thrombophilia or comorbidities known to adversely affect clot phenotype were ineligible. Results: During a 1-year follow-up PTS developed in 48 (24%) patients, who were characterized by lower Ks, prolonged fibrin clot lysis time (CLT) and slower release of D-dimer from clots (D-Drate), together with higher plasma D-dimer, C-reactive protein and thrombin-activatable fibrinolysis inhibitor (TAFI). No PTS-associated differences in fibrinogen, thrombin generation, factor VIII, other fibrinolysis proteins and the quality of anticoagulation were observed. Ks (r = -0.71), CLT (r = 0.45), D-Drate (r = -0.30) and TAFI activity (r = 0.38) were associated with the Villalta scale (all P < 0.05). Recurrent VTE occurred also more commonly in PTS patients during follow-up and the 26 (13.2%) patients had lower Ks, longer CLT and lower D-Drate (all P < 0.05). A multivariate model adjusted for age, body mass index, fibrinogen and glucose showed that independent predictors of PTS were idiopathic DVT, plasma D-dimer, Ks, D-Drate, tissue plasminogen activator and TAFI activity. Conclusions: This study demonstrates that formation of more compact fibrin clots displaying impaired susceptibility to lysis predisposes to PTS.