Local low-dose urokinase treatment of acquired intracardiac thrombi in preterm infants

Aspesberro, F.; Beghetti, Maurice; Oberhänsli, I; Özşahin, Hülya; Humbert, James R.; Rimensberger, Peter C.

doi:10.1007/s004310051182

Cited by 20 publications

(16 citation statements)

References 15 publications

(22 reference statements)

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“…Catheter-directed thrombolysis Catheter-directed thrombolysis (CDT) has been reported in 13 patients in the neonatal period (Anderson et al 1991;Aspesberro et al 1999;Dillon et al 1993;Gerling et al 2002;Khan et al 2008;Klinge et al 1998;Pritchard et al 1985;Rehan et al 1994;Ries et al 2002;Rogers et al 1989;Ryan and Andrew 1992;Wang et al 2003). In these reports, rtPA (dosage 0.01-0.1-0.5 mg/kg/h [min-median-max]) was used in 8 patients, while 4 patients received streptokinase and one was treated with urokinase.…”

Section: Interventionalmentioning

confidence: 99%

Thrombosis in the critically ill neonate: incidence, diagnosis, and management

Nold¹

2008

VHRM

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Among children, newborn infants are most vulnerable to development of thrombosis and serious thromboembolic complications. Amongst newborns, those neonates who are critically ill, both term and preterm, are at greatest risk for developing symptomatic thromboembolic disease. The most important risk factors are infl ammation, DIC, impaired liver function, fl uctuations in cardiac output, and congenital heart disease, as well as exogenous risk factors such as central venous or arterial catheters. In most clinically symptomatic infants, diagnosis is made by ultrasound, venography, or CT or MRI angiograms. However, clinically asymptomatic vessel thrombosis is sometimes picked up by screening investigations or during routine imaging for other indications. Acute management of thrombosis and thromboembolism comprises a variety of approaches, including simple observation, treatment with unfractionated or low molecular weight heparin, as well as more aggressive interventions such as thrombolytic therapy or catheter-directed revascularization. Long-term follow-up is dependent on the underlying diagnosis. In the majority of infants, stabilization of the patients' general condition and hemodynamics, which allows removal of indwelling catheters, renders long-term anticoagulation superfl uous. Nevertheless, in certain types of congenital heart disease or inherited thrombophilia, long-term prophylaxis may be warranted. This review article focuses on pathophysiology, diagnosis, and acute and long-term management of thrombosis in critically ill term and preterm neonates.

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Section: Interventionalmentioning

confidence: 99%

Thrombosis in the critically ill neonate: incidence, diagnosis, and management

Nold¹

2008

VHRM

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“…(34) Local lowdose urokinase treatment (in doses ranging from 1,000 to 2,500 U/kg per hour) was effective in treating intracardiac thrombi in three extremely low-birthweight preterm infants who had significant contraindications to systemic fibrinolytic therapy. (35) Another study of 26 neonates who had catheter-related central venous thrombosis showed a success rate of only 50% with local administration of urokinase at a dose of 4,400 U/kg per hour. (36) rTPA.…”

Section: Thrombolytic Agentsmentioning

confidence: 98%

Management of Vascular Thrombosis and Spasm in the Newborn

Ramasethu

2005

NeoReviews

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“…During treatment, coagulation factors remained stable but fibrinogen levels dropped slightly in these infants. An identical concept has been successfully used with urokinase (1000 to 3000 U/kg/h) in preterm infants with intracardiac thrombosis [23] and tPA (0.01 to 0.05 mg/kg/h) in infants with vena cava thrombosis. [60,61] No complications such as cerebral haemorrhages were observed in any of these patients, with the exception of one being treated with tPA in whom the infusion caused a decrease in fibrinogen concentration and an increase in fibrin degradation products, indicating a systemic proteolytic state.…”

Section: Systemic Versus Local and High Dose Versus Low Dose Thrombomentioning

confidence: 98%

“…Although no clinical trials of thrombolytic treatment in neonates have been reported, there are many case reports suggesting that thrombolytic treatment may be efficient in treating intracardiac thrombosis in neonates born at term and in preterm infants [20,[22][23][24][25]27,28,33,[37][38][39]41] (table I).…”

Section: Medical Treatmentmentioning

confidence: 99%

“…Whether these thrombogenic circumstances dictate higher doses of antithrombotic agents such as urokinase or tissue plasminogen activator in neonatal than in adult thromboses is, however, open to question; thus, this concept has been questioned by others who showed effective fibrinolysis, although only in a small number of newborn infants, at much lower infrasystemic doses of urokinase, streptokinase or rt-PA, respectively. [23,[59][60][61] Actually, several different approaches in terms of the choice of the thrombolytic agent and the doses used are defended by different authors, usually based on their limited personal experience with a few patients. This is well reflected in table I, giving an overview of the published case reports and series of preterm infants presenting with intracardiac thrombosis treated with thrombolytic agents.…”

Section: Medical Treatmentmentioning

confidence: 99%

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Management of Preterm Infants with Intracardiac Thrombi

2001

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Improvement in neonatal care has led to improvements in survival and patient outcome in preterm infants; however, this improved survival has been associated with the development of secondary complications, such as catheter-associated intravascular and intracardiac thrombus formation with a non-negligible morbidity and mortality. The sick preterm infant is at high risk of catheter-related thrombus formation because of the combination of a high prothrombotic activity, low levels of natural anticoagulants, and various imbalances in the fibrinolytic systems. Based on clinical experience in adults and children, and several neonatal case reports demonstrating the efficacy and tolerability of specific thrombolytic treatment, this approach should be recommended as a first choice treatment in the premature infant with intracardiac or intravascular thrombosis. The thrombolytic agents of choice are urokinase or tissue plasminogen activator (tPA); however, none of them have proven to be superior to the other in terms of efficacy or tolerability, either in adult patients or premature infants. In the past, it has been suggested that newborn infants may require higher doses of thrombolytic agents than adults for effective systemic thrombolysis; however, based on more recent in vitro studies, it seems unlikely that this is true. Nevertheless, systemic (high dose) fibrinolysis is of concern as premature neonates present an increased risk of cerebral haemorrhage during the first weeks of life; therefore, low dose treatment has been proposed with, if possible, direct infusion of the fibrinolytic agent into, or close to, the thrombus. This approach has proven to be efficient and well tolerated in several small case series of newborn and preterm infants. Recommended doses are 1000 to 3000 U/kg/h for urokinase or 0.01 to 0.05 mg/kg/h for tPA. A systemic proteolytic state will not be induced by this low dose; however, specific monitoring of fibrinogen plasma levels has to be recommended. Fibrinogen levels should remain above 100 mg/dL during low dose treatment. Lower levels of fibrinogen will indicate the presence of an unwanted systemic fibrinolytic state. After successful thrombolysis, a follow-up treatment, preferentially with low-molecular-weight heparin for neonates at adjusted doses, should be instituted for at least 6 weeks in the absence of any persisting thrombophilic factor. A longer course (3 to 6 months) of anticoagulation therapy is recommended when thrombophilic factors (i.e. hereditary thrombophilia or central venous catheter still in place) are present. Furthermore, it is recommended that any neonate with thrombosis should be evaluated for hereditary thrombophilia later in life.

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Local low-dose urokinase treatment of acquired intracardiac thrombi in preterm infants

Cited by 20 publications

References 15 publications

Thrombosis in the critically ill neonate: incidence, diagnosis, and management

Thrombosis in the critically ill neonate: incidence, diagnosis, and management

Management of Vascular Thrombosis and Spasm in the Newborn

Management of Preterm Infants with Intracardiac Thrombi

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