Assessing the outcome of systemic tissue plasminogen activator for the management of venous and arterial thrombosis in pediatrics

This study sought to ascertain the outcomes of systemic thrombolytic therapy used in a cohort of infants and children. Complete thrombus resolution was achieved in 81% of patients with arterial thromboses (n=16) compared to 0% of children with venous thromboses (n=10). A major bleeding rate of 11.5% occurred across the entire cohort (n=3, all arterial). In our cohort, no patient with venous thromboembolism achieved complete resolution of their thrombosis after thrombolytic therapy. More cohort studies reporting the outcome of uniform protocols of thrombolytic therapy in children are required.     

Thrombolysis with low dose tissue plasminogen activator.

Two cases of vena caval thrombosis in infants were successfully treated with low dose (0.01-0.05 mg/kg/hour) local infusions of tissue plasminogen activator after conventional anticoagulant treatment had been unsuccessful. This approach is useful for clots associated with indwelling intravascular catheters, and a low dose infusion of tissue plasminogen activator as a regional application is recommended to achieve clot lysis with minimal systemic effects.     

Successful thrombolysis by prolonged low-dose alteplase in catheter-directed infusion

Catheter-directed thrombolysis is a sophisticated method in the treatment of thromboembolism with maximum effect on the thrombus and minimal systemic effect. The consequences are enhanced local thrombolysis and a reduction in general bleeding tendency, compared with systemic thrombolysis. At our institution, two children had successful thrombolysis by prolonged continuous catheter-directed low-dose alteplase. The first patient, a boy with Fontan physiology, was successfully treated for a massive pulmonary thromboembolism by catheter-directed very low-dose alteplase for five days. The second patient, who suffered from relapsing nephrotic syndrome, achieved satisfactory thrombolysis of an arterial leg thrombosis after four days of continuous catheter-directed low-dose alteplase.

Conclusion: Although catheter-directed thrombolysis seems to be a valuable method in thrombolytic therapy, there is a lack of evidence-based recommendations concerning dosage, effect of bolus, simultaneous anticoagulation and duration of treatment for children.     

Low-dose tissue plasminogen activator thrombolysis in children

PURPOSE: To compare results of low-dose tissue plasminogen activator (TPA) in children with arterial and venous thrombi relative to standard published dosing. METHODS: Subjects consisted of all consecutive children with objectively confirmed thrombi for whom TPA thrombolysis was clinically ordered by the authors. Initial dosing used published standard dose (0.1-0.5 mg/kg per hour). With experience, a low-dose regimen (0.01-0.06 mg/kg per hour) was given in an attempt to derive a minimal effective dose. RESULTS: Thirty-five children were treated with TPA. Either standard or low-dose infusions of TPA resulted in complete thrombolysis of 28 of 29 (97%) acute thrombi, while all 6 chronic thrombi had a partial response. In contrast to the recommended adult-derived dosages of 0.1 to 0.5 mg/kg per hour, the authors found that initial doses of less than 0.01 mg/kg per hour were effective in 12 of 17 patients with acute thrombosis. Neonates required 0.06 mg/kg per hour. Route of administration (local or systemic) did not affect efficacy. Major bleeding occurred in only one extremely preterm infant. Minor bleeding, primarily oozing at intravenous sites, occurred in 27% of children during TPA infusions. Prophylactic unfractionated or low-molecular-weight heparin was infused concomitant with TPA in 42% of the children and did not increase the risk of bleeding. CONCLUSIONS: TPA in very low doses appears to be safe and effective for thrombolysis of acute thromboses in most children, given appropriate patient selection.     

Recombinant tissue plasminogen activator in the treatment of central venous catheter occlusion in children

Tissue plasminogen activator was used to treat 228 children with 320 central venous catheter (CVC) occlusion events. Patency was restored in 91% of CVCs after 1 to 3 treatments, with no adverse events. Tissue plasminogen activator is effective in restoring patency to occluded CVCs and is a viable alternative to CVC removal or urokinase treatment.     

Continuous infusion of low-dose urokinase in the treatment of central venous catheter thrombosis in infants and children

Thrombotic occlusion is a frequent complication associated with the use of central venous catheters. The purpose of this study was to evaluate the efficacy of a continuous infusion of low-dose urokinase (200 U/kg/h) in clearing catheters that had not cleared after two bolus doses of urokinase in a pediatric oncology population. Fifty-eight incidents of catheter-related occlusions (49 Hickman-type catheters/nine implantable ports) as documented by radiographic dye study occurred in 227 pediatric oncology patients with 254 central venous catheters during a 1-year period. Fourteen of 58 catheters failed to clear after two bolus instillations of urokinase (5,000 U and 10,000 U). Thirteen catheters were treated for 24 hours with urokinase, 200 U/kg/h, and one catheter with urokinase, 100 U/kg/h for 24 hours. Twelve catheters were used for study. Coagulation studies were monitored preinfusion, 12 hours into the infusion, and postinfusion. Patency was reestablished in 11/12 catheters (92%) with a mean infusion time of 28.7 hours. No coagulation abnormalities or clinical bleeding associated with the urokinase infusion occurred. Only one patient exhibited a prolonged partial thromboplastin time (greater than 150 seconds); this was associated with a heparin effect. These data indicate that low-dose urokinase may be a safe and effective means to clear occluded central venous catheters in children.     

Safety and outcomes of thrombolysis with tissue plasminogen activator for treatment of intravascular thrombosis in children.

OBJECTIVES: In this study, we tried to determine the safety and outcomes of thrombolysis with tissue plasminogen activator of intravascular thrombus. STUDY DESIGN: Eighty consecutive children were treated between 1985 and 1999 in a tertiary care setting in a retrospective case series. There were 65 arterial thrombi (56 after cardiac catheterization) and 15 venous thrombi treated with tPA at an average dose of tPA of 0.5 mg/kg/hour for a median duration of 6 hours. RESULTS: Clot resolution was complete in 65% of children, partial in 20%, and there was no effect in 15%. There were major complications in 40%, minor complications in 30%, and no complications in 30%. Two patients had cerebral ischemia secondary to hypotension because of profound bleeding, with intracranial hemorrhage in 2 additional patients. Clot resolution was not related to patient age or weight, dose, and duration of tPA therapy and fibrinogen levels. However, complications were more likely in patients who weighed less, had a longer duration of therapy, a greater decrease in fibrinogen levels, and who failed to have resolution of their clot. CONCLUSIONS: tPA therapy can be effective in the thrombolysis of intravascular thrombus in children, but is associated with a low margin of safety and an unknown risk-benefit ratio.     

Use of tissue plasminogen activator (rt-PA) in young children with cancer and dysfunctional central venous catheters

PURPOSE: To determine the efficacy and safety of low, nonescalating dose tissue plasminogen activator (rt-PA) in restoring the patency of occluded central venous access devices (CVCs) in children with cancer who weigh less than 30 kg. PATIENTS AND METHODS: A single-center review of the use of rt-PA (0.5 mg indwelling for 30 minutes in the CVC) was conducted in 42 cancer patients with large bore central venous access devices implanted over a 2-year period. All patients weighed less than 30 kg. None had been previously treated with a thrombolytic agent. The efficacy for restoring function to CVCs was measured and correlated with patient age, weight and CVC lumen size. Propensity to rethrombose following an initial occlusion and treatment was also determined. RESULTS: Of 235 doses of rt-PA administered in a 2-year period, 55 doses administered to 42 patients met the eligibility criteria as outlined. Twenty-nine patients (69%) had function restored with a single dose; 8 patients (19%) required 2 doses, and 5 patients (12%) failed 2 doses; for an overall success rate of 88%. No significant adverse events occurred. Of the 37 cleared CVCs, 14 (38%) reoccluded within 1 month. A higher proportion of patients initially treated with one rt-PA (71%) experienced another CVC dysfunction within 1 month, compared with 29% CVC dysfunction in those requiring >1 dose. CONCLUSIONS: This article describes the use of rt-PA (0.5 mg, without dose escalation) to lyse CVC-associated thrombi specifically in small children with cancer, a patient population in which it is particularly desirable to minimize the degree of fibrinolysis. One dose of 0.5 mg rt-PA, with an additional dose if necessary, is as safe and effective as previously reported escalating dose regimens for CVC clot lysis. There is no statistically significant correlation of treatment failure with patient age, weight, or catheter lumen size, and no significant propensity for rapid rethrombosis following a single dysfunction and treatment. Patients initially treated with a single dose of rt-PA appear to have more subsequent dysfunctions in the month after treatment, an observation that warrants further study.     

Successful treatment of aortic thrombosis after umbilical catheterization with tissue plasminogen activator

An infant presented 10 days after removal of a high umbilical arterial catheter with total occlusion of the distal abdominal aorta. Complete dissolution was achieved with a combination of iv tissue plasminogen activator and heparin. Ultrasound examination confirmed the diagnosis and subsequent resolution of the thrombus.     

Thrombolysis with rt-PA in children with arterial and venous thromboses--a new therapy concept

Thrombolytic therapy usually used for thrombosis in the adult has been administered as a therapeutic regiment in pediatric patients (parental consent was sought prior to the treatment with rt-PA). We report our experience with rt-PA in 17 children and adolescents suffering from arterial (n = 4) or venous thrombosis (n = 13) due to local rhabdomyosarcoma, acute lymphoblastic leukemia, chronic myeloblastosis, sickle cell anaemia, parenteral nutrition, haemolytic uremic syndrome, central arterial and venous catheters and septicemia Thrombotic diseases have been diagnosed by Doppler ultrasound, computed tomography, angiography and phlebography. Rt-PA therapy was started immediately after diagnostic procedures had been performed. Rt-PA dose varied from 0.2 mg as a single dose to 0.8 mg/kg bw/d over a three day period in children local thrombolysis was performed. In patients requiring systemic thrombolytic therapy rt-PA was administered from 0.8 mg/kg bw/d in three days to 2.0 mg/kg bw/d over a whole period of three weeks in both groups during thrombolysis low dose heparin was added. When rt-PA infusion was terminated heparin (70 IU - 400 IU/kg bw/d) was administered for 7 to 14 days in order to prevent reocclusion. Later prophylaxis with coumarin derivatives in venous thrombosis and antiplatelet agents in arterial occlusive diseases was performed. In no patient did we see a decrease of fibrinogen and plasminogen during rt-PA therapy.(ABSTRACT TRUNCATED AT 250 WORDS)     

Early intracardiac thrombosis in preterm infants and thrombolysis with recombinant tissue type plasminogen activator.

OBJECTIVES: To determine the incidence of catheter related thrombosis and to test the efficacy of recombinant tissue type plasminogen activator (rt-PA) in preterm infants. STUDY DESIGN: From January 1995 to December 1998, echocardiography was performed in the first few days of life in 76 very low birthweight (< or = 1500 g) infants out of a total of 147 having an umbilical catheter placed. When intracardiac thrombosis was diagnosed, rt-PA infusion was performed. RESULTS: Four infants (5%) developed an intracardiac thrombosis during the first few days of life. In three of them, rt-PA at a dose of 0.4-0.5 mg/kg in a 20-30 minute bolus led to dissolution of the clot. One patient received a three hour infusion after the bolus, at a dose of 0.1 mg/kg/h, with resolution of the thrombus. No systemic effects were observed after rt-PA infusion. CONCLUSIONS: Early thrombosis may occur as a complication of umbilical catheterisation in preterm infants; early echocardiographic detection of this disorder allows complete, safe, and rapid lysis with rt-PA.     

Thrombolytic therapy using a low dose of tissue plasminogen activator in children

ObjectiveTo analyse the efficacy and side effects of low doses of tissue plasminogen activator for the treatment of acute arterial and/or venous thrombosis in children.Patients and methodsProspective observational clinical study. 18 children between 1 months and 11 years treated with low doses (0.01-0.06 mg/kg/h) of continuous intravenous thrombolytic therapy with t-PA were studied.ResultsA total of 94% of patients improved with low doses t-PA (72% complete resolution of the thrombosis and 22% partial resolution). One patient suffered a severe haemorrhage secondary to t-Pa and had to stop the treatment. The incidence of severe side effects was low (5%)ConclusionsThrombolytic therapy with low doses of t-PA (0.01-0.05 mg/kg/h) is effective in a high percentage of children with acute arterial and/or venous thrombosis and produces a relatively low frequency of side effects.     

Thrombolytic therapy with tissue plasminogen activator for superior vena cava thrombosis in an infant with sepsis

Superior vena cava syndrome is rare in infants, and rarely responds to conservative treatment. We report a 22-mo-old girl with superior vena cava syndrome due to the use of a central venous line and/or sepsis. Doppler study and computed tomography angiography of the neck showed thrombosis within the superior vena cava and jugular veins. She was admitted to a monitored setting and received recombinant tissue plasminogen activator for 2 d. The clinical features of superior vena cava syndrome disappeared completely 3 d after treatment. No complications were observed and radiological investigations showed blood flow through the thrombus after treatment. Systemic recombinant tissue plasminogen activator may be useful in the treatment of superior vena cava syndrome in children.     

Endogenous tissue plasminogen activator in neonatal cerebrospinal fluid

Tissue type plasminogen activator (tPA) plays a role in differentiation of neurones and activity-dependent structural changes in neurones. We hypothesised that tPA would also be present in CSF during fibrinolysis after intraventricular haemorrhage. We measured tPA antigen in CSF from 13 normal newborn infants and 14 infants with posthaemorrhagic ventricular dilation (PHVD). tPA was undetectable or at the limit of detection (1 g/l) in normal CSF. The CSF tPA concentration ranged from 1.3 to 3.5 g/l in the infants with PHVD. Serial tapping in one infant showed persistence of tPA in the CSF from 3 to 8 weeks of age. We conclude that endogenous tPA may be part of the physiological response to intraventricular haemorrhage or may be present as a result of passive diffusion into the CSF.