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Progressive Heart Failure in the Neonate: Treatment with Tissue Type Plasminogen Activator

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Progressive Heart Failure in the Neonate: Treatment with Tissue Type Plasminogen Activator Archives ofDisease in Childhood 1992; 67: 443-445 443 Intracardiac thrombus formation with rapidly Arch Dis Child: first published as 10.1136/adc.67.4_Spec_No.443 on 1 April 1992. Downloaded from progressive heart failure in the neonate: treatment with tissue type plasminogen activator B Van Overmeire, P J Van Reempts, K J Van Acker Abstract oedema, and hepatosplenomegaly. Auscultation A newborn is described in whom the use of a revealed a gallop rhythm, an additional click central venous line was complicated by that could be differentiated from the third heart septicaemia and by intracardiac thrombus sound, and a holosystolic grade III murmur that formation with tricuspid valve insufficiency had been absent previously and was situated and heart failure. Besides antibiotics, treat- parasternally in the left fourth intercostal space. ment consisted of tissue type plasminogen Acute heart failure was diagnosed. Echocardio- activator (tPA) for three days. This treatment graphy showed no congenital heart disease but a resulted in the disappearance of the thrombus vegetation on the atrial side of the septal leaflet and the tricuspid insufficiency. No adverse of the tricuspid valve, measuring 2 x 3 mm effects were noted. Treatment with tPA (fig 1). The right atrium was dilated. Echo should be considered in intracardiac thrombus Doppler revealed moderate tricupsid valve in- formation with rapidlyprogressive heartfailure sufficiency with the jet lining the free margin of in the neonate. the vegetation. Laboratory investigations showed microscopic haematuria, thrombocytopenia with a platelet As central catheters are used extensively in count of 28x l09/l, white cell count of 5 x 109/l neonates for parenteral nutrition or adminis- with 39% polymorphonuclear neutrophils, tration ofmedication, formation ofboth infected haemoglobin concentration of 104 g/l, and a and non-infected thrombi on the endocardium packed cell volume of 0-35. C reactive protein is increasingly observed. Especially in neonates was increased to 92 mg/l (normal value is <5 with very low birth weight such thrombus mg/l). There was a slight metabolic acidosis but formation may lead to life threatening situations. no other electrolyte disturbances. Treatment of these cases is difficult. 1-3 Because of the acutely deteriorating clinical We report on our experience with tissue type condition it was decided to attempt lysis of the plasminogen activator (tPA), a new thrombolytic vegetation. Tissue type plasminogen activator agent, in a newborn with rapidly progressive (tPA, Actilyse, Boehringer Ingelheim) was heart failure due to thrombus formation on the administered through the central venous line in tricuspid valve. a dose of 0 5 mg/kg during 10 minutes followed http://adc.bmj.com/ by a continuous infusion of 0-2 mg/kg/hour. The antibiotic treatment was continued. The Case report patient's general condition rapidly improved The patient was a girl with intrauterine growth and tachycardia and generalised oedema dis- retardation who was born by caesarean section appeared. One day after the start of the treat- because of fetal distress. Gestational age was 32 ment with tPA, the holosystolic murmur weeks, birth weight 900 g, and height 35 cm. disappeared, two dimensional echocardiography on October 1, 2021 by guest. Protected copyright. Apgar scores were 8 and 8 at 1 and 5 minutes showed a diminution of the vegetation on the respectively. On the second day a central tricuspid valve, and echo Doppler showed a venous line was introduced via the right brachial decrease of the tricuspid valve insufficiency. vein for parenteral nutrition. On chest radio- However, an echodense mass seen on the graphy, the tip of the catheter was located at the septum in the right ventricle, probably a entrance of the right atrium. No umbilical catheters were used. There were no problems until the 10th day when lethargy, mottling of the skin, increasingly frequent episodes of apnoea and bradycardia, and increasing oxygen Department of Paediatrics, demand developed. Division of Neonatology, The suspected diagnosis of septicaemia was University Hospital, confirmed later by growth of coagulase negative Antwerp, Belgium B Van Overmeire staphylococcus in three bottles from two separate P J Van Reempts peripheral blood cultures. These staphylococci K J Van Acker all had the same susceptibility profile to anti- Correspondence to: biotics. Treatment with cefotaxime, amikacin, Dr B Van Overmeire, Division of Neonatology, and vancomycin and supportive medication was University Hospital started. of Antwerp, Wilrijkstraat, situation 10 B-2650 Antwerpen, On the 12th day of life the clinical Figure I Ultrasoundfour chamber view ofthe heart Belgium. again deteriorated with impaired peripheral showing the vegetation (arrow) on the tricuspid valve. Accepted 21 October 1991 circulation, tachycardia, tachypnoea, generalised LV=left ventricle, RV=right ventricle, LA =left atrium. 444 Van Overneire, Van Reempts, Van Acker In our patient there were sufficient indications for septicaemia by coagulase negative staphylo- Arch Dis Child: first published as 10.1136/adc.67.4_Spec_No.443 on 1 April 1992. Downloaded from coccus and this was treated with antibiotics and supportive measures. Intracardiac thrombus formation was suspected when the general condition again deteriorated, a heart murmur appeared, and heart failure developed. The diagnosis was confirmed and its functional implications established by echography. Surgical removal of the thrombus was not considered for three main reasons: presence of a severe infec- tion, haemodynamic instability, and small body size. We instead decided to use thrombolytic treatment, being well aware of the risks such treatment could engender in this critically ill Figure 2 Ultrasoundparasternal view ofthe heart showing patient. The main problem was the possibility the mass (arrow) in the right ventricle on the septum. of dissemination of a probably infected throm- LV=left ventricle, RV= right ventricle. bus. We could, however, expect that the throm- bolytic agent would also dissolve the dis- detached and entrapped part of the original seminated thrombi. vegetation (fig 2). On the third day of treatment We opted for tPA, which is a recently with tPA, this thrombus had disappeared; the introduced specific thrombolytic agent obtained original vegetation was hardly visible. One day by DNA recombination and which is identical later no thrombi could be demonstrated and the with the endogenous human glycoprotein.8 tricuspid regurgitation had disappeared com- Compared with the first generation thrombolytic pletely. Infusion of tPA was then stopped. agents urokinase and streptokinase, tPA has During this treatment no bleeding tendency at several theoretical advantages.9 First, it exerts puncture sites was observed, there were no its action on fibrin locally without activating the respiratory disturbances, no ecchymoses or plasminogen in the circulation and therefore purpura appeared, and transfontanellar echo- without causing generalised thrombolysis. graphy showed no intraventricular haemorrhages. Furthermore, because of its identity with the Activated partial thromboplastin time, pro- human endogenous glycoprotein, it has no thrombin time, and plasma fibrinogen concen- immunising capacity and has identical bio- tration remained normal. Hepatosplenomegaly chemical and kinetic properties. Finally, it has a disappeared during the days after cessation of short half life time of approximately five treatment. The central venous catheter was minutes, allowing an easier monitoring of the removed on the 37th day of life: bacterial treatment. In our patient the treatment resulted culture of the tip remained negative. Antibiotic in the diminution of the vegetation on the treatment was continued for a total of six weeks. tricuspid valve and a decrease of the tricuspid Echocardiography after three weeks and three insufficiency with improvement of the haemo- months was normal; electrocardiography and dynamic situation after one day. After three http://adc.bmj.com/ transfontanellar echography always remained days no thrombi could be demonstrated and the normal. thrombolytic treatment could be interrupted. No complications, more specifically no bleeding tendency or further dissemination of the throm- Discussion bus, were observed. These results were con- Since central catheters have been used in firmed during a follow up of three months. neonates septicaemia, mainly by coagulase tPA has been used extensively in adults but in negative staphylococcus, and thrombus for- children and certainly in neonates the experience on October 1, 2021 by guest. Protected copyright. mation are increasingly seen as complications. 1-3 is very limited. It has been used, apparently When thrombi develop on the endocardium with success, in the treatment of aortic throm- they may lead to life threatening situations such bosis in a 4 day old premature infant'0 and of a as dissemination of emboli in the lungs or the pulmonary embolism in a 19 month old boy." systemic circulation, obstruction of the valves, Recently, successful treatment with tPA of or valvular insufficiency. The latter may result various thromboembolic conditions in children in serious functional disturbances and heart from different age groups was described and failure. Endocardial vegetations of more than dosage schemes were proposed. 2 If our experi- 1-2 mm can be diagnosed by two dimensional ence is confirmed intracardiac thrombus for- sector echocardiography,
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