Personalised viscoelastometry-guided systemic thrombolysis for high- and intermediate-high-risk acute pulmonary embolism in the ICU: a single-centre randomised controlled interventional feasibility trial.

Abstract

Background: Systemic thrombolysis is recommended for high-risk pulmonary embolism, but is associated with a substantial bleeding risk due to thrombolysis-induced coagulopathy. However, recent advances in precision and personalised care offer the potential to reduce mortality as well as the incidence of chronic thromboembolic pulmonary hypertension and post-pulmonary embolism impairment, thereby improving long-term outcomes. Our primary objective was to evaluate the feasibility of a viscoelastic testing-guided, low-dose, prolonged systemic thrombolysis protocol in acute pulmonary embolism. Exploratory secondary objectives included assessment of the safety and efficacy of the protocol using an individualised approach tailored to each patient's coagulation profile.

Methods: This single-centre, prospective, randomised interventional feasibility trial was conducted at Semmelweis University (Budapest, Hungary). Adult pulmonary embolism patients were randomly assigned to a control group (CG) receiving the ESC-recommended 100 mg/2 h dose of rtPA or a viscoelastometry-guided group (VGG), in which the rtPA dose and duration were adjusted based on viscoelastic tests. Transthoracic echocardiography (TTE) was performed every two hours to monitor right ventricular (RV) function and determine cessation of systemic thrombolysis in VGG. The primary outcome was feasibility; the secondary outcome was safety and efficacy.

Results: Among 33 enrolled patients, 19 were included in the analysis (CG: 7; VGG: 12). Patients in the VGG received significantly lower doses of rtPA (median 32.00 mg [IQR 20.95-42.75 mg]) despite longer infusion duration (median 8.5 h [IQR 6.6-10.0]) and showed no coagulopathy. RV dysfunction persisted in two CG patients, whereas in the VGG it resolved in all patients. Major bleeding occurred in two patients in the CG and in one patient in the VGG.

Conclusions: Viscoelastometry-guided, individualised, low-dose systemic thrombolysis is feasible and supports a personalised approach to thrombolysis in the management of pulmonary embolism.