RECOMBINANT HUMAN TISSUE-PLASMINOGEN ACTIVATOR FOR THE TREATMENT OF SEVERE HEPATIC VENOOCCLUSIVE DISEASE IN PEDIATRIC BONE-MARROW TRANSPLANT PATIENTS

Nine pediatric patients were treated with recombinant human tissue pla sminogen activator (tPA) for severe hepatic veno-occlusive disease (VO D) which developed after bone marrow transplantation. Recombinant huma n tPA (5-10 mg/day x 2-4 days) and heparin were begun a median of 15 d ays (range, 11-32 days) posttransplant. A second course was given if t he patient did not respond. The median total serum bilirubin and perce nt weight gain above baseline were 5.5 mg/dl (range, 1.3-26.1 mg/dl) a nd 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 t he nine patients had complete resolution of their VOD. Another patient was salvaged with a partial maternal liver transplant. We conclude th at the incidence and severity of bleeding complications with these dos es of tPA and heparin do not preclude their use in pediatric patients. Further study in a larger group setting will be necessary to determin e the optimal dosing regimen as well as treatment efficacy.