Potential association of TGFβ1 plasma levels and fibrinolysis parameters with the risk of recurrence and vascular obstruction after a first unprovoked pulmonary embolism episode

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.