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Early Intracardiac Thrombosis in Preterm Infants and Thrombolysis with Recombinant Tissue Type Plasminogen Activator

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Early Intracardiac Thrombosis in Preterm Infants and Thrombolysis with Recombinant Tissue Type Plasminogen Activator F66 Arch Dis Child Fetal Neonatal Ed 2001;85:F66–F72 Arch Dis Child Fetal Neonatal Ed: first published as 10.1136/fn.85.1.F66 on 1 July 2001. Downloaded from CASE REPORT Early intracardiac thrombosis in preterm infants and thrombolysis with recombinant tissue type plasminogen activator F Ferrari, F Vagnarelli, G Gargano, M F Roversi, O Biagioni, A Ranzi, G B Cavazzuti Abstract and superior or inferior vena cava syndrome45; Objectives—To determine the incidence of occlusion of the right pulmonary artery has catheter related thrombosis and to test the also been reported.6 eYcacy of recombinant tissue type plas- Cardiotomy with surgical removal of the minogen activator (rt-PA) in preterm thrombus can be performed even in preterm infants. infants,7 but it has a high rate of mortality and, Study design—From January 1995 to De- being a hazardous procedure, is considered too cember 1998, echocardiography was per- risky.6 formed in the first few days of life in 76 Thrombolytic agents such as heparin and very low birthweight (< 1500 g) infants out streptokinase are no longer considered to be of a total of 147 having an umbilical cath- the ideal treatment in the neonatal period, as eter placed. When intracardiac thrombo- they lead to a systemic coagulopathic state.8 sis was diagnosed, rt-PA infusion was per- Newer plasminogen activators, including formed. recombinant tissue type plasminogen activator Results—Four infants (5%) developed an (rt-PA), are more clot selective and may repre- intracardiac thrombosis during the first sent a good alternative for thrombolytic few days of life. In three of them, rt-PA at treatment in neonatal practice.9–12 a dose of 0.4–0.5 mg/kg in a 20–30 minute The incidence of atrial thrombosis in pre- bolus led to dissolution of the clot. One term infants is as yet unknown. Since the early patient received a three hour infusion 1990s, echocardiography has been routinely after the bolus, at a dose of 0.1 mg/kg/h, performed in low birthweight infants in our with resolution of the thrombus. No neonatal intensive care unit, and cardiac systemic eVects were observed after rt-PA thrombi in all preterm infants with an umbili- cal catheter have been systematically screened infusion. http://fn.bmj.com/ Conclusions—Early thrombosis may since 1994. This report investigates the inci- occur as a complication of umbilical cath- dence of right atrial catheter related thrombosis eterisation in preterm infants; early in preterm infants and describes the eYcacy echocardiographic detection of this disor- and safeness of rt-PA treatment. der allows complete, safe, and rapid lysis with rt-PA. Methods (Arch Dis Child Fetal Neonatal Ed 2001;85:F66–F72) Over a four year period (from January 1995 to on October 2, 2021 by guest. Protected copyright. Department of December 1998), a total of 147 newborn Paediatrics, Division Keywords: recombinant tissue type plasminogen activa- of Neonatology, tor; thrombosis; very low birthweight infants; echo- infants weighing 1500 g or less were admitted Modena University, cardiography to our neonatal intensive care unit; 96 (65.3%) Italy of these had a central venous umbilical catheter F Ferrari F Vagnarelli placed (poly(vinyl chloride) umbilical vessel G Gargano Central venous catheters are commonly used catheter; Sherwood Medical, Argyle infusion, M F Roversi for drug administration and parenteral nutri- Tullamore, Ireland) during the first day of life. O Biagioni G B Cavazzuti tion. Their use in low birthweight and critically The position of the catheter tip was confirmed ill infants has led to an increased incidence of by chest radiograph. In 76 of the 96 preterm Department of thrombotic events.1 It has been calculated2 that infants, the tip of the catheter, according to Embryology, Histology up to 48% of central venous catheters can current practice,13 was located at the outlet of and Genetics A Ranzi become obstructed by a thrombus in extremely the inferior vena cava or in the right atrium. In low birthweight infants (< 1000 g). another 20 infants, the catheter impinged on Correspondence to: The development of intracardiac thrombosis the portal system and was withdrawn 1–2 cm. Prof Ferrari, Department of Paediatrics, Division of is a rare but severe complication of indwelling These 20 infants were excluded from the study. Neonatology, University central lines.34 It is usually observed several No heparin was added to the fluids. The Hospital, Via del Pozzo, 41100 Modena, Italy days after the line placement and, in small pre- catheter was used for the infusion of 8–12% [email protected] term infants, can lead to life threatening events dextrose solution and drugs; the umbilical line Accepted 11 September such as valvular obstruction with heart failure, was not used for infusion of packed red blood 2000 pulmonary and/or systemic thromboembolism, cells. www.archdischild.com Thrombolysis in preterm infants F67 Arch Dis Child Fetal Neonatal Ed: first published as 10.1136/fn.85.1.F66 on 1 July 2001. Downloaded from Table 1 Clinical characteristics of the patients and recombinant tissue type plasminogen activator (rt-PA) therapy GA Birth weight (g) Cardiac Dose and duration of rt-PA therapy for complete Case Sex (weeks) percentile Prenatal and postnatal clinical data symptoms dissolution of the clot 1 M 28 640 PROM; Apgar at 1 min: 2; at 5 min: No 0.5 mg/kg in 20 min 5; IPPV for 2 days; streptococcal <5th group B sepsis; death on the 2nd day 2 M 30 1220 PROM; Apgar at 1 min: 3; at 5 min: Yes 0.5 mg/kg in 30 min 25th 7; IPPV for 6 days; PDA 3 F 33 1440 Caesarean section for maternal No 0.4 mg/kg in 30 min hypertension; Apgar at 1 min: 6; at 5 5th–10th min: 9; IPPV for 3 days 4 M 26 1155 >95th Abruptio placentae; Apgar at 1 min: 6; Yes 0.4 mg/kg in 30 min followed by 0.1/mg/kg/h for 3 at 5 min: 8; right pneumothorax; left hours atelectasia; HFOV for 4 days; CPAP for 6 days GA, Gestational age; PROM, premature rupture of membranes; IPPV, intermittent positive pressure ventilation; HFOV, high frequency oscillatory ventilation; CPAP, continuous positive airway pressure; PDA, patent ductus arteriosus. Echo-Doppler cardiography (Acuson the 5th centile), had the umbilical line 128XP/10 with 7.5 Hz transducer; examina- positioned at 3 hours of life. The echocardio- tion recorded on videotapes and printouts) was graphy performed at 14 hours of life showed routinely performed as part of an initial evalu- the tip of the catheter protruding beyond the ation of respiratory distress in all preterm foramen ovalis, with a tip related elongated infants with an umbilical venous catheter, and fibrin aggregation (2 mm × 8 mm) in the left it was repeated within one to four days. atrium. No cardiac symptomatology was As described by Dillon et al,14 after the diag- present at the time of diagnosis. Removal of the nosis of thrombosis, a bolus of 0.4–0.5 mg/kg thrombotic formation was achieved with a 20 rt-PA (Actilyse; Boehringer, Ingelheim, Ger- minute bolus of rt-PA. many) was administered through the catheter This small patient died on the 3rd day of life over 20–30 minutes; local infusion was main- after progressive deterioration of cardiac, tained at a dose of 0.1 mg/kg/h, if necessary. respiratory, and renal functions. Streptococcal The treatment was considered successful when group B sepsis was diagnosed on the basis of Doppler echocardiography showed that the positive blood and pharyngeal swab cultures. A thrombus had been completely dissolved. In post mortem study of the lungs showed the four infants aVected by thrombosis, blood bilateral pneumonia; no signs of pulmonary samples were taken for measurement of emboli or cerebral haemorrhage were ob- prothrombin time, partial thromboplastin served. time, fibrinogen levels, and platelet count In patient 2, echocardiography performed on before and soon after rt-PA administration. the 4th day of life showed a tip related throm- Serial cerebral ultrasound scans showed no bus(3mm×8 mm) floating in the right atrium. cerebral haemorrhages in the treated infants. An inconstant tachycardia was present. Disso- At the time the thrombus was detected, none lution of the clot was achieved with a 30 minute of the patients was polycythaemic—that is, the bolus of rt-PA. venous packed cell volume was more than In patient 3, echocardiography on the 2nd 60%. No congenital malformation, including day of life showed an intra-atrial line tip http://fn.bmj.com/ congenital heart defect, was present in the roundish clot (5 mm × 2.5 mm) (fig 1). No series of patients. cardiac signs were present, and a 30 minute bolus of rt-PA led to the disappearance of the Case reports echogenic formation. Echocardiography performed after line inser- Patient 4 had the echocardiograph scan on tion showed catheter related thrombus forma- the 2nd day of life, when a cardiac systolic tion in four of the 76 preterm infants (5.3%; murmur and transient sinus bradycardia were on October 2, 2021 by guest. Protected copyright. 95% confidence interval 0.3% to 10.3%) with present at clinical examination. A dishomoge- an umbilical venous catheter near or in the neous thrombotic (8 mm × 2 mm) formation right atrium. was hanging in the right atrium, intermittently Tables 1 and 2 list the clinical characteristics reaching the tricuspid valve; a fibrin thread was and coagulation assessment respectively of the stretched through the foramen ovalis, across four patients. the left section of the heart and aortic isthmus Patient 1, an infant of extremely low (fig 2a,b).
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