Department of Biochemistry, Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, The Netherlands.
Thrombosis Expertise Center, Heart + Vascular Center, Maastricht University Medical Center, Maastricht, The Netherlands.
Blood Adv. 2024 Jun 11;8(11):2924-2932. doi: 10.1182/bloodadvances.2023012493.
Ultrasound-accelerated catheter-directed thrombolysis (UA-CDT) to improve patency after deep vein thrombosis (DVT) has not conclusively been shown to prevent postthrombotic 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 (Ultrasound-Accelerated Catheter-Directed Thrombolysis Versus Anticoagulation for the Prevention of Post-thrombotic Syndrome) 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, 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, including 43 with additional UA-CDT and 48 with standard treatment. Patients with additional UA-CDT more often obtained patency (55.8 vs 27.1%) 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 cutoff at 4.85 g/L. Low fibrinogen levels best predicted patency. Additional UA-CDT decreased the risk of PTS only in patients with high fibrinogen. Therefore, additional UA-CDT might prevent PTS in selected patients based on routinely measured fibrinogen levels. This study was registered at www.ClinicalTrials.gov as #NCT00970619.
超声加速导管溶栓(UA-CDT)改善深静脉血栓(DVT)后再通率,不能明确预防血栓后综合征(PTS),但可能对那些不太可能通过标准治疗获得再通的患者有益。我们假设可以根据纤维蛋白凝块特性选择这些患者。为此,CAVA 试验(超声加速导管溶栓与抗凝预防血栓后综合征比较)中急性髂股 DVT 患者入选时采血。通过比浊法测定血浆中的纤维蛋白凝块特性(延迟时间和最大浊度)和溶解试验(达到 50%溶解的时间和溶解率)、渗透试验和共聚焦显微镜(纤维密度)以及纤维蛋白凝块修饰物纤维蛋白原和 C 反应蛋白(CRP)的水平。再通定义为 12 个月超声检查时髂股静脉可压缩性>90%。PTS 定义为 6 或 12 个月时 Villalta 评分≥5。共纳入 152 例患者中的 91 例,其中 43 例接受额外的 UA-CDT,48 例接受标准治疗。接受额外 UA-CDT 的患者再通率更高(55.8% vs 27.1%)。获得再通的患者延迟时间更长,最大浊度、纤维蛋白原和 CRP 水平更低;仅当调整治疗、血栓负荷和体重指数时,最大浊度和纤维蛋白原仍与再通相关。纤维蛋白原水平的最佳截断值为 4.85 g/L。低纤维蛋白原水平最能预测再通。仅在纤维蛋白原水平高的患者中,额外的 UA-CDT 降低了 PTS 的风险。因此,根据常规测量的纤维蛋白原水平,额外的 UA-CDT 可能在选定的患者中预防 PTS。该研究在 www.ClinicalTrials.gov 注册,编号为 #NCT00970619。