des Déserts Marc Danguy, de Moreuil Claire, Elhasnaoui Jamal, Gourhant Lenaïck, Gourdou-Latyszenok Virginie, Espinasse Benjamin, Menguy Juliette, Tromeur Cécile, Corre Rozenn Le, Mao Raphael Le, Kraemmer Daniel, Sanchez Olivier, Couturaud Francis, Lemarié Catherine A
Univ Brest, Inserm, UMR 1304-GETBO, Brest, France.
Department of Anaesthesia and Intensive Care, Clermont-Tonnerre Military Hospital, FCRIN INNOVTE, Brest, France.
J Thromb Thrombolysis. 2025 Jun 22. doi: 10.1007/s11239-025-03113-2.
The pathophysiology of residual pulmonary vascular obstruction (RPVO) and recurrent venous thromboembolism (VTE) after unprovoked pulmonary embolism (PE) remains poorly understood. The purpose was to evaluate fibrinolytic and tissue remodeling markers as indicators of RPVO and recurrence after a first unprovoked PE. Analyses were conducted in the 18 to 70-year-old patients included in the PADIS-PE trial, with a pulmonary vascular obstruction (PVO) index ≥ 30% at PE diagnosis. After an initial six-month vitamin K antagonist treatment, patients were randomised to receive placebo or warfarin for 18 months and assessed for the absence or presence of residual pulmonary vascular obstruction (RPVO < or ≥ 5%, respectively). Quantitative assessment of fibrinolytic (D-dimer, tPA, uPA, TFPI) and tissue remodeling (TGFβ1) markers, and a tissue-factor-based turbidimetric clot lysis assay (CLA) were performed one month after warfarin discontinuation. Symptomatic recurrent VTE was monitored for 42 months after randomisation. Among the 371 patients included in PADIS-PE, 23 fulfilled clinico-radiological criteria and had an available blood sample. Six (26%) patients presented RPVO ≥ 5% and symptomatic recurrent VTE occurred in nine (39%) patients. Clot formation and lysis parameters were not associated with RPVO. TGFβ1 plasma levels were higher in patients with RPVO. Clot formation potential measured with CLA was higher in patients with recurrent VTE. No association between recurrent VTE and TGFβ1 was observed. In adult patients with a first unprovoked PE and a PVO index ≥ 30%, TGFβ1 plasma levels were associated with RPVO, whereas clot formation parameters measured with CLA were associated with VTE recurrence.
不明原因肺栓塞（PE）后残留肺血管阻塞（RPVO）和复发性静脉血栓栓塞（VTE）的病理生理学仍知之甚少。目的是评估纤维蛋白溶解和组织重塑标志物，作为首次不明原因PE后RPVO和复发的指标。对纳入PADIS-PE试验的18至70岁患者进行分析，这些患者在PE诊断时肺血管阻塞（PVO）指数≥30%。在最初6个月的维生素K拮抗剂治疗后，患者被随机分配接受安慰剂或华法林治疗18个月，并评估是否存在残留肺血管阻塞（RPVO分别<或≥5%）。在停用华法林1个月后，对纤维蛋白溶解标志物（D-二聚体、组织型纤溶酶原激活剂、尿激酶型纤溶酶原激活剂、组织因子途径抑制物）和组织重塑标志物（转化生长因子β1）进行定量评估，并进行基于组织因子的比浊法凝块溶解试验（CLA）。随机分组后对有症状的复发性VTE进行42个月的监测。在PADIS-PE纳入的371例患者中，23例符合临床放射学标准且有可用血样。6例（26%）患者出现RPVO≥5%，9例（39%）患者出现有症状的复发性VTE。凝块形成和溶解参数与RPVO无关。RPVO患者的转化生长因子β1血浆水平较高。复发性VTE患者用CLA测得的凝块形成潜力较高。未观察到复发性VTE与转化生长因子β1之间存在关联。在首次不明原因PE且PVO指数≥30%的成年患者中，转化生长因子β1血浆水平与RPVO相关，而用CLA测得的凝块形成参数与VTE复发相关。
