TGFβ1 plasma levels and clot lysis assay to better characterize patients after a first unprovoked episode of pulmonary embolism

Abstract

AbstractIntroductionThe 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.MethodsAnalyses 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, assessed for the absence or presence of residual pulmonary vascular obstruction (RPVO < or ≥5%, respectively) and followed during two years. Quantitative assessment of fibrinolytic (D-dimer, tPA, uPA, TFPI) and tissue remodeling (TGFß1) markers, and a tissue-factor-based turbidimetric clot lysis assay (CLA) were performed one month after warfarin discontinuation.ResultsAmong the 371 patients included in PADIS-PE, 23 were eligible. Six (26%) patients presented RPVO ≥ 5%, symptomatic recurrent VTE occurred in nine (39%) patients. Clot formation and lysis parameters were not associated with RPVO. TGFß1 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 TGFß1 was observed. In multivariable analysis, time to peak was associated with VTE recurrence.ConclusionIn adult patients with a first unprovoked PE and a PVO index ≥30%, TGFß1 plasma level was associated with RPVO, whereas clot formation parameters measured with CLA were associated with VTE recurrence.