Low-Dose Tissue Plasminogen Activator Thrombolysis in Children
Purpose: To compare results of low-dose tissue plasminogen ac- tivator (TPA) in children with arterial and venous thrombi relative to standard published dosing. Methods: Subjects consisted of all consecutive children with ob- jectively 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 stan- dard or low-dose infusions of TPA resulted in complete throm- bolysis 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 infu- sions. Prophylactic unfractionated or low-molecular-weight hepa- rin 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 ef- fective for thrombolysis of acute thromboses in most children, given appropriate patient selection.
Published in 2003.