Fibrinogen levels and clot properties identify patients that benefit from catheter-directed thrombolysis after DVT

Ultrasound-accelerated catheter-directed thrombolysis (UA-CDT) to improve patency after deep vein thrombosis (DVT) has not conclusively been shown to prevent post-thrombotic syndrome (PTS) but might benefit patients who are unlikely to obtain patency with standard treatment. We hypothesized that these patients could be selected based on their fibrin clot properties. To study this, patients with acute iliofemoral DVT from the CAVA trial had blood samples taken at inclusion. Fibrin clot properties in plasma were determined by turbidimetric clotting (lag time and maximal turbidity) and lysis assays (time to 50% lysis and lysis rate), permeation assay (Ks), and confocal microscopy (fiber density), as well as levels of fibrin clot modifiers fibrinogen and C-reactive protein (CRP). Patency was defined as > 90% iliofemoral vein compressibility at 12-month ultrasound. PTS was defined as ≥ 5 Villalta score at 6 or 12 months. In total 91 of 152 patients were included, namely 43 with additional UA-CDT and 48 with standard treatment. Patients with additional UA-CDT more often obtained patency (55.8 vs. 27.1%; p = 0.005) Patients who obtained patency had longer lag times and lower maximal turbidity, fibrinogen, and CRP; only maximal turbidity and fibrinogen remained associated when adjusting for treatment, thrombus load, and body-mass index. Fibrinogen levels had an optimal cut-off at 4.85 g/L. Low fibrinogen levels best predicted patency (OR 5.59 [2.00-15.62]). Additional UA-CDT decreased the risk of PTS only in patients with high fibrinogen (OR 4.67 [1.14-19.07]). Therefore, additional UA-CDT might prevent PTS in selected patients based on routinely measured fibrinogen levels. The study was registered at ClinicalTrials.gov (nr. NCT00970619).