prothrombotic clot properties can predict venous ulcers in patients following deep vein thrombosis: a cohort study

Venous ulcers are the most severe manifestation of post-thrombotic syndrome (pts). we have previously demonstrated that formation of compact fibrin clots resistant to lysis is observed in patients following deep-vein thrombosis (dvt) who developed pts. the current study investigated whether unfavourable fibrin clot properties can predict post-thrombotic venous ulcers. in a cohort study on 186 consecutive patients following dvt, we determined plasma fibrin clot characteristics, including clot permeability and lysability, inflammatory markers, thrombin generation, fibrinolysis proteins at 3 months since the index event. occurrence of pts and venous ulcers was recorded during follow-up (median, 53; range 24 to 76 months). fifty-seven dvt patients (30.6%) developed pts, including 12 subjects (6.45%) with a venous ulcer (4 individuals with recurrent ulcers). patients who developed ulcers compared with the remainder had at enrolment 13.0% lower clot permeability (ks), 17.4% longer clot lysis time (clt), 13.1% longer lag phase of clot formation, and 5.0% higher maximum absorbance, with no difference in fibrinogen, c-reactive protein, and thrombin generation. the baseline prothrombotic fibrin clot phenotype (ks ≤ 6.5 × 10−9 cm2 and clt > 100 min) was associated with a higher risk of ulcers [hazard ratio (hr), 5.37; 95% confidence interval (ci), 1.3–21.5]. a multivariate model adjusted for age, sex, and fibrinogen showed that independent predictors of the ulcer occurrence were body mass index (hr 1.53; 95% ci 1.30–1.86), clt (hr 1.43; 95% ci 1.04–2.05), and α2-antiplasmin (hr 0.95; 95% ci 0.90–0.99). this study suggests that formation of denser fibrin clots with impaired fibrinolysis predisposes to post-thrombotic venous ulcers.