血浆因子 XI 水平升高与血栓后综合征相关。

Elevated plasma factor XI is associated with postthrombotic syndrome.

机构信息

Department of Thromboembolic Disorders, Institute of Cardiology, Jagiellonian University Medical College, Krakow, Poland; Department of Coronary Artery Disease and Heart Failure, St. John Paul II Hospital, Krakow, Poland.

Krakow Centre for Medical Research and Technologies, St. John Paul II Hospital, Krakow, Poland.

出版信息

Thromb Res. 2024 Sep;241:109086. doi: 10.1016/j.thromres.2024.109086. Epub 2024 Jul 3.

DOI:10.1016/j.thromres.2024.109086

PMID:38968817

Abstract

INTRODUCTION

Postthrombotic syndrome (PTS), a common complication of deep vein thrombosis (DVT), is largely inflammatory by nature with contribution of prothrombotic mechanisms. The role of factor (F)XI in PTS has not been explored yet. We investigated whether elevated FXI is associated with PTS occurrence.

MATERIALS AND METHODS

We enrolled 180 consecutive patients (aged 43 ± 13 years) with first-ever DVT. After 3 months FXI levels were measured, along with inflammatory markers, thrombin generation, plasma clot permeability (Ks), clot lysis time (CLT), and fibrinolysis proteins. We assessed PTS using the Villalta score and recorded symptomatic venous thromboembolism (VTE) at a 1-year and venous ulcers at a median 53 months follow-up.

RESULTS

Baseline median FXI was 102 % [IQR 92-113 %] and showed positive association with Villalta score (R = 0.474, P < 0.001). Patients with PTS (n = 48, 26.7 %) had 16.1 % higher FXI (P < 0.001) and FXI ≥120 % occurred more often in PTS patients (odds ratio [OR] 5.55, 95 % confidence interval [CI] 2.28-13.47). There were associations of baseline FXI with Ks and CLT along with thrombin activatable fibrinolysis inhibitor (TAFI) activity, C-reactive protein, and interleukin-6, but not with fibrinogen, or thrombin generation. After age adjustment higher FXI was independently associated with PTS occurrence (OR per 1 % 1.06, 95 % CI 1.02-1.09) and VTE recurrence (OR 1.03, 95 % CI 1.01-1.06). At long-term follow-up, patients with venous ulcers had 13.6 % higher baseline FXI (P = 0.002).

CONCLUSIONS

Elevated FXI in association with inflammation and prothrombotic fibrin clot properties may contribute to the development of PTS following DVT.

摘要

简介

深静脉血栓形成（DVT）后血栓后综合征（PTS）是一种常见的并发症，其本质上主要是炎症性的，同时伴有促血栓形成机制。FXI 因子在 PTS 中的作用尚未得到探索。我们研究了 FXI 升高是否与 PTS 的发生有关。

材料和方法

我们纳入了 180 例首次发生 DVT 的连续患者（年龄 43±13 岁）。3 个月后测量 FXI 水平，同时测量炎症标志物、凝血酶生成、血浆纤维蛋白溶酶原（Ks）、纤维蛋白溶解时间（CLT）和纤维蛋白溶解蛋白。我们使用 Villalta 评分评估 PTS，并在 1 年时记录有症状的静脉血栓栓塞（VTE），在中位数 53 个月的随访时记录静脉溃疡。

结果

基线时 FXI 的中位数为 102%[92-113%]，与 Villalta 评分呈正相关（R=0.474，P<0.001）。患有 PTS（n=48，26.7%）的患者 FXI 升高 16.1%（P<0.001），且 FXI≥120%的患者更常发生 PTS（比值比[OR]5.55，95%置信区间[CI]2.28-13.47）。基线 FXI 与 Ks 和 CLT 以及凝血酶可激活的纤维蛋白溶解抑制剂（TAFI）活性、C 反应蛋白和白细胞介素-6 相关，但与纤维蛋白原或凝血酶生成无关。校正年龄后，较高的 FXI 与 PTS 的发生独立相关（每增加 1%的 OR 为 1.06，95%CI 为 1.02-1.09）和 VTE 复发（OR 为 1.03，95%CI 为 1.01-1.06）。在长期随访中，患有静脉溃疡的患者基线 FXI 升高 13.6%（P=0.002）。