Recombinant human tissue plasminogen activator for the treatment of established severe venocclusive disease of the liver after bone marrow transplantation.
Seven patients were treated with recombinant human tissue plasminogen activator (tPA) for severe hepatic venocclusive disease (VOD) that developed after bone marrow transplantation for hematologic malignancy. Recombinant human tPA (10 mg/d x 2 days) and heparin (1,000 U bolus followed by continuous intravenous infusion of 150 U/kg/d x 10 days) were begun a median of 9 days (range, 4 to 18 days) posttransplant. The median total serum bilirubin and percent weight gain from baseline were 19.4 mg/dL (range, 14.6 to 34.9 mg/dL) and 9.1% (range, 1% to 18.5%), respectively, at the start of tPA administration. Five patients responded to therapy with prompt reduction in total serum bilirubin within 96 hours of starting tPA. Three patients are alive 178 to 379 days posttransplant without evidence of VOD. No patient had significant hemorrhagic complications with tPA. We conclude that recombinant human tPA can be administered to patients with severe VOD at the dosage described. Whereas preliminary data suggests that recombinant human tPA can alter the natural history of severe VOD, further study is necessary to determine its efficacy.
Bearman
S I
SI
Division of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle.
Shuhart
M C
MC
Hinds
M S
MS
McDonald
G B
GB
D000328:Adult; D001663:Bilirubin / Q000097:blood; D016026:Bone Marrow Transplantation / Q000009:adverse effects*; D006493:Heparin / Q000627:therapeutic use; D006504:Hepatic Veno-Occlusive Disease / Q000188:drug therapy* / Q000209:etiology; D006801:Humans; D008875:Middle Aged; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000627:therapeutic use; D015912:Thrombolytic Therapy; D010959:Tissue Plasminogen Activator / Q000008:administration & dosage / Q000627:therapeutic use*
D011994:Recombinant Proteins; D006493:Heparin; D010959:Tissue Plasminogen Activator; D001663:Bilirubin