Thrombolysis in neonates: navigating the balance between efficacy and risk—a systematic review

Neonatal thrombosis is an uncommon condition, but its incidence has increased over recent decades. This has led to a clinical challenge: the growing need for thrombolysis, in a highly vulnerable population. Thrombolysis in neonates is distinct in several important aspects, with an immature hemostatic system, resulting in lower plasminogen and tissue plasminogen activator levels. Bleeding is the most serious complication of thrombolytic therapy in this population, as neonates are particularly vulnerable due to immature and fragile vasculature. A systematic review of all published studies until September 2025 that pertained to the dosing, safety, or efficacy of thrombolytic agents in preterm and term neonates was performed. Studies were identified through the Medline database. Data on dosages of different thrombolytic agents, bleeding events, and thrombus resolution were descriptively analyzed. A total of 44 studies, representing 265 patients, were included. The use of thrombolytic agents among neonates was highly heterogeneous. Based on descriptive aggregation of published cases, the efficacy of thrombolysis was comparable between full-term and preterm neonates, with restoration of flow in 87.2% and 85.2%, respectively. In full-term neonates, major bleeding occurred in 10.5% and minor bleeding in 29.1%. In preterm neonates, major bleeding was observed in 14.8% and minor bleeding in 16.4%. The overall thrombolysis-related mortality was 2.3%. Thrombolysis in neonates remains a rare intervention but appears to be effective in both full-term and preterm neonates. However, evidence is limited and heterogeneous. Nevertheless, its use requires careful risk–benefit consideration due to substantial bleeding complications, particularly in preterm neonates.