Thrombolytic therapy in preterm infants: Fifteen‐year experience

Abstract

Objective To report a single‐center experience with thrombolytic therapy using recombinant tissue plasminogen activator (rt‐PA) in preterm neonates with severe thrombotic events, in terms of thrombus resolution and bleeding complications. Study design This retrospective study included 21 preterm neonates with severe venous thrombotic events admitted to the neonatal intensive care unit, identified in our pharmacy database from January 2001 to December 2016, and treated with rt‐PA until complete or partial clot lysis, no‐response or bleeding complications. Our primary outcome was thrombus resolution. Results Twenty‐one preterm neonates were treated with rt‐PA for an average of 2.9 cycles. Seventeen patients (80.9%) had superior vena cava thrombosis and superior vena cava syndrome. All patients had a central venous catheter, parenteral nutrition, mechanical ventilation, and sepsis. Fifteen patients (71.4%) were extremely preterm, 11 (52.4%) were extremely low birth weight, and seven (33.3%) were very low birth weight. The patency rate was 85.7%, complete lysis occurred in 11 (52.4%) patients, and partial lysis in seven (33.3%). Minor bleeding occurred in five (23.8%) patients, three patients (14.2%) had clinically relevant nonmajor bleeding events, and major bleeding occurred in six (28%) patients. Conclusion In this study, the rate of thrombus resolution in preterm neonates treated with rt‐PA were similar to the percentages reported in children and adolescents, with a high rate of bleeding. Therefore, rt‐PA thrombolytic therapy should only be considered as a treatment option for severe life‐threatening thrombosis in premature neonates for whom the benefits of the thrombolytic treatment outweigh the risks of bleeding.

Is recombinant tissue plasminogen activator treatment a safe choice in very and extremely preterm infants with intracardiac thrombosis?

“…Bolus dose of rt-TPA was administrated in nine cases with a dosage range of 0.05–1 mg/kg intravenously 14 15 18–21 24. We found that the following continuous infusion of rt-TPA was highly heterogeneous both in terms of dosage (range 0.01–1.2 mg/kg/hour)13 23 and duration (range 1–13 days) 13–15 18 19 21 23. Low-dose rt-TPA was given to 16 of 28 neonates,13–18 20 22 24 while the remaining subjects received high-dose rt-TPA 13 14 18 19 21 23.…”

“…Reviewing the literature, 12 studies which reported 28 very or extremely preterm neonates who had pharmacological thrombolysis with rt-TPA for intracardiac thrombi were found13–24 (table 1). Their GA ranged from 23 to 31 weeks14 25 with a birth weight from 544 to 1300 g 13 21. The age at diagnosis of thrombosis was from 1 to 54 days of life 18 20.…”

“…We found that the following continuous infusion of rt-TPA was highly heterogeneous both in terms of dosage (range 0.01–1.2 mg/kg/hour)13 23 and duration (range 1–13 days) 13–15 18 19 21 23. Low-dose rt-TPA was given to 16 of 28 neonates,13–18 20 22 24 while the remaining subjects received high-dose rt-TPA 13 14 18 19 21 23. Major complications occurred in four neonates (14%): three developed intraventricular haemorrhage (IVH), whose severity was not detailed, and one pulmonary haemorrhage 13 14 23.…”

“…Low-dose rt-TPA was given to 16 of 28 neonates,13–18 20 22 24 while the remaining subjects received high-dose rt-TPA 13 14 18 19 21 23. Major complications occurred in four neonates (14%): three developed intraventricular haemorrhage (IVH), whose severity was not detailed, and one pulmonary haemorrhage 13 14 23. Three of these adverse events occurred in patients treated with high-dose rt-TPA 14 23.…”

“…Major complications occurred in four neonates (14%): three developed intraventricular haemorrhage (IVH), whose severity was not detailed, and one pulmonary haemorrhage 13 14 23. Three of these adverse events occurred in patients treated with high-dose rt-TPA 14 23. Complete resolution of clot was reported in 20 cases (71.4%),13–18 20–22 25 26 partial resolution in 4 (14%)13 14 16 23 and no resolution in 2 (7.1%) 13.…”