Antithrombotic Therapy in Children: Adverse Effects of Thrombolytic Therapy

Dose Response: Thrombolytic agents are used in low doses, usually to restore catheter patency, and in higher doses to lyse large vessel thrombi or PE. Table 9 presents the most commonly used dose regimens for thrombolytic therapy in pediatric patients with arterial or VTE complications. These protocols come from two level IV studies and several level V studies. The optimal doses for each of UK, SK, and tPA are not known for pediatric patients. Based upon the Thrombolysis in Myocardial Infarction II trial, doses of 150 mg rt-PA caused more bleeds into the central nervous system than 100 mg (1.5% vs 0.5% respectively). It seems likely that there will be an upper dose limit based on safety.
Route of admin istration : There are no published studies that compare local to systemic thrombolytic therapy in children. From 1966 to 1997, there were 70 cases reported in the English language literature of local thrombolytic therapy in children, excluding femoral artery thrombosis following cardiac catheter and low dose thrombolysis to unblock central venous lines (CVLs). Complete or partial lysis was achieved in 70% of cases, with major bleeding occurring in 11% of children. A recent level IV study reported successful lysis in only one of seven patients and five major complications in three patients. At this time, there is no evidence to suggest that there is an advantage of local over systemic thrombolytic therapy. In addition, the small vessel size in children may increase the risk of local vessel injury with new thrombus formation. Local therapy may be appropriate for catheter related thrombosis when the catheter is already in situ.
Adverse Effects of Thrombolytic Therapy: Based upon a composite review of the literature (255 patients), and two level IV studies, the incidence of bleeding requiring treatment with packed RBCs occurs in approximately 20% of pediatric patients read more asthma inhalers.103 The most frequent problem was bleeding at sites of invasive procedures that required treatment with blood products. A recent review of the literature specifically examined the incidence of intracerebral hemorrhage (ICH) during thrombolytic therapy in children. There was no information about concurrent heparin administration in this study. In total, ICH was found in 14 of 929 patients analyzed (1.5%). When subdivided according to age, ICH was identified in 2 of 468 children (0.4%) after the neonatal period, 1 of 83 term infants (1.2%), and 11 of 86 preterm infants (13.8%). In the largest study of premature infants included in this review, however, the incidence of ICH was the same in the control arm that did not receive thrombolytic therapy. The incidence of ICH in adults treated with thrombolytic therapy also varies with age and is between 0.3 and 5.0%.

Table 9—Thrombolytic Therapy for Pediatric Patients

Low Dose for Blocked Catheters
Regimen Monitoring
Instillation UK (5,000 U/mL) 1.5-3 mU lumen 2-4 h None
Infusion UK (150 U/kg/h) per lumen 12-48 h Fibrinogen, TCT* PT, APTT
Systemic Thrombolytic Therapyf
Load,
U/kg Maintenance Monitoring
UK 4,400 4,400 U/kg/h 6-12 h Fibrinogen, TCT* PT, APTT
SK 2,000 2,000 U/kg/h 6-12 h Same
tPA None 0.1-0.6 mg/kg/h for 6 h Same