Recombinant human tissue plasminogen activator for the treatment of severe hepatic veno-occlusive disease in pediatric bone marrow transplant patients.

Nine pediatric patients were treated with recombinant human tissue plasminogen activator (tPA) for severe hepatic veno-occlusive disease (VOD) which developed after bone marrow transplantation. Recombinant human tPA (5-10 mg/day x 2-4 days) and heparin were begun a median of 15 days (range, 11-32 days) post-transplant. A second course was given if the patient did not respond. The median total serum bilirubin and percent weight gain above baseline were 5.5 mg/dl (range, 1.3-26.1 mg/dl) and 22% (range, 7-44%) respectively at the start of tPA administration. Three patients had their heparin infusion interrupted or discontinued for bleeding symptoms, none of which were life-threatening. Five of the nine patients had complete resolution of their VOD. Another patient was salvaged with a partial maternal liver transplant. We conclude that the incidence and severity of bleeding complications with these doses of tPA and heparin do not preclude their use in pediatric patients. Further study in a larger group setting will be necessary to determine the optimal dosing regimen as well as treatment efficacy.