Citation | Study group | Study type (level of evidence) | Outcome | Key results | Comments |
Hartmann et al 15 | 1 preterm infant (GA: 30 weeks, BW: 1190 g); at the age of 12 days, ECHO showed a clot in left atrium. | Case series (level 4) | To assess the efficacy and safety of thrombolytic treatment of neonatal CRT formation with rt-TPA | Treatment: bolus of rt-TPA 0.7 mg/kg followed by continuous infusion of 0.2 mg/kg/hour for 1 day. Heparin therapy 150 U/kg/day was continued for 5 days. No complications occurred. Establishment of specific protocol of rt-TPA use can improve safeness and effectiveness for clot dissolution in neonates. | In this study, 14 neonates (one <32 GA included in this Archimedes) with catheter-related thrombi were treated over a 6-year period with the same rt-TPA protocol, leading to 94% of success rate and without severe complication. |
Bose and Clarke16 | 2 preterm infants (GA: 25+5–28 weeks, BW range 727–825 g) affected by right atrium thrombi diagnosed at 13 and 21 days of life.5 | Case series (level 4) | To describe the use of rt-TPA to treat intracardiac thrombosis in extremely low birthweight preterm infants | Treatment: continuous infusion of rt-TPA from 0.02 mg/kg/hour to 0.2 mg/kg/hour for 2–3 days. In one case, a clot dissolved; in the other case, a significant clot diminution occurred but treatment was stopped because of low fibrinogen levels. rt-TPA may safely be used to treat intracardiac thrombosis although close monitoring of therapy is necessary. Treatment should be stopped if fibrinogen levels decrease to <1 g/L or if there is clinical bleeding. | In this study, four extremely low birthweight preterm infants were treated with rt-TPA for thrombosis (two intracardiac clots included in this Archimedes, two inferior vena cava thrombosis) with good response in extremely low birth weight. |
Anderson et al 17 | 1 preterm infant (GA: 26 weeks, BW: 800 g); at the age of 27 days, ECHO showed a highly mobile intracardiac clot (maximum size 8×4 mm). | Case series (level 4) | To describe the use of rt-TPA to treat intracardiac thrombosis in extremely low birthweight preterm infants | Treatment: after 3 days of conservative management, continuous infusion of rt-TPA 0.2 mg/kg/hour over 6 hours for 5 consecutive days was performed with clot dissolution. No complications occurred. | In this study, three neonates (one <32 GA included in this Archimedes) were treated for intracardiac thrombus with rt-TPA with success even in one neonate with severe thrombocytopenia that frequently can secondarily occur because of platelet consumption within the clot. |
Ferrari et al 18 | 3 preterm infants (GA: 26–30 weeks, BW range 640–1220 g) affected by right atrium thrombi diagnosed from 1 to 4 days of life. | Retrospective study (level 3) | To test the efficacy of rt-TPA in preterm infants | Treatment: bolus of rt-TPA 0.4–0.5 mg/kg in 20–30 min in all patients. One had continuous infusion of rt-TPA 0.1 mg/kg/hour for 3 hours after bolus. No complications occurred. | In this study, four infants (three <32 GA included in this Archimedes) were treated with rt-TPA with complete, safe and rapid clot dissolution. |
Giuffrè et al 19 | 2 preterm infants (GA: 27–31+5 weeks, BW range 1000–1050 g) affected by right atrium thrombi (maximum size 8×5 mm) diagnosed at 4 days of life. | Case series (level 4) | To describe the use of rt-TPA to treat intracardiac thrombosis in preterm infants | Treatment: bolus of rt-TPA 1 mg/kg in 15 min in one patient. In both neonates, continuous infusion of rt-TPA 0.5–1 mg/kg/hour for 4–6 hours with concomitant plasma 10 mL/kg infusion was performed. No complications occurred. | Two premature infants were successfully treated with rt-TPA. |
Grizante-Lopes et al 14 | 8 preterm infants (GA: 24+4–31+5 weeks, BW range 580–1250 g) affected by right atrium thrombi. | Retrospective study (level 3) | To report a single-centre experience with rt-TPA in preterm neonates with severe thrombotic events | Treatment: one patient received a bolus dose ranging from 0.2 to 0.7 mg/kg, for 10–30 min. All patients received continuous infusion of rt-TPA from 0.2 to 0.7 mg/kg/hour, for 4–6 hours. Six patients received enoxaparin for 3 months. One case of intracranial bleeding and another case of pulmonary haemorrhage occurred. In two cases, only partial clot resolution was obtained. | This retrospective study included 21 neonates (eight <32 GA included in this Archimedes) treated with rt-TPA with a rate of thrombus resolution similar to that reported in children and adolescents with a high risk of bleeding. |
Ina et al 20 | 1 preterm infant; (GA: 24 weeks, BW: 671 g); at the age of 24 days, ECHO showed a clot in left atrium. | Case report (level 4) | To describe the use of rt-TPA to treat intracardiac thrombosis in preterm infants | Treatment: bolus of rt-TPA 0.5 mg/kg followed by continuous infusion of 0.03–0.04 mg/kg/hour for 2 days with clot dissolution. Heparin therapy was continued for 2 weeks. No complications occurred. | One premature infant was successfully treated with rt-TPA. |
Kara et al 13 | 5 preterm infants (GA: 28–31 weeks, BW range 900–1300 g) affected by intracardiac thrombi (maximum size 21×9 mm). | Case series (level 4) | To report the clinical features and treatment results of preterm infants with intracardiac thrombus in a tertiary level NICU | Treatment: continuous infusion of rt-TPA from 0.01 mg/kg/hour to 0.5 mg/kg/hour, for 2–13 days. In three cases out of five, complete clot resolution was obtained. One case of intracranial bleeding occurred. | This study recorded all premature infants with intracardiac thrombus in a tertiary level NICU during a 3-year period (five <32 of GA included in this Archimedes). rt-TPA was used in clots relatively large compared with left atrium, pedunculate, mobile or snake shaped. In the other cases, they used low molecular weight heparin. |
Kurimoto et al 21 | 1 preterm infant (GA: 24 weeks, BW: 544 g); at the age of 24 days, ECHO showed intracardiac clot (maximum size 21×3 mm). | Case report (level 4) | To describe the use of rt-TPA to treat intracardiac thrombosis in preterm infants | Treatment: bolus of rt-TPA 0.05 mg/kg followed by continuous infusion of 0.45 mg/kg/hour for 6 hours with concomitant plasma 10 mL/kg infusion. No complications occurred. | One premature infant was successfully treated with rt-TPA. |
Marks et al 22 | 2 preterm infants (GA: 24–28 weeks, BW range 566–807 g) affected by intracardiac thrombi (maximum size 7.4×5 mm) diagnosed at 15 days of life. | Case series (level 4) | To describe the use of rt-TPA to treat intracardiac thrombosis in preterm infants | Treatment: continuous infusion of rt-TPA from 0.2 to 0.3 mg/kg/hour for 6 hours, repeated for 3–4 days. In one case, concomitant plasma infusion 10 mL/kg was performed. No complications occurred. | Two premature infants were successfully treated with rt-TPA. |
Al-Abdi et al 23 | 1 preterm infant (GA: 28 weeks, BW: 590 g); at the age of 15 days, ECHO showed right atrium clot (maximum size 17×6 mm). | Case report (level 4) | To describe the use of rt-TPA to treat intracardiac thrombosis in preterm infants | Treatment: continuous infusion of rt-TPA from 0.2 for 6 hours. Significant clot reduction was obtained. A germinal matrix monolateral haemorrhage occurred. Four months later, the patient died of unresponsive PH. | In this case report, a single dose of rt-TPA was effective to dissolve the clot. PH was subsequently attributed to severe BPD, pneumonia and clinically suspected sepsis, although pulmonary embolism could not be ruled out. |
Torres-Valdivieso et al 24 | 1 preterm infant (GA: 28 weeks, BW: 1060 g); at the age of 11 days, ECHO showed intracardiac clot. | Case report (level 4) | To describe the use of rt-TPA to treat intracardiac thrombosis in preterm infants | Treatment: bolus of rt-TPA 0.5 mg/kg followed by continuous infusion of 0.2 mg/kg/hour for 2 days with concomitant plasma 10 mL/kg and heparin 10 IU/kg/hour infusion. No complications occurred. Heparin therapy 20 IU/kg/hour was continued for 1 month. | One premature infant was successfully treated with rt-TPA. |
BPD, bronchopulmonary dysplasia; BW, birth weight; CRT, catheter-related thrombosis; GA, gestational age; NICU, neonatal intensive care unit; PH, pulmonary hypertension; rt-TPA, recombinant tissue plasminogen activator.