Recombinant tissue plasminogen activator (rtPA) for the treatment of hepatic veno-occlusive disease (VOD).
Seventeen patients who developed hepatic veno-occlusive disease (VOD) following hematopoietic stem cell transplantation were treated with recombinant tissue plasminogen activator (rtPA) with or without heparin. rtPA was started a median of 13 days post transplant (range 4-35). All patients received rtPA at a dose of 10 mg/day as a starting dose, and 12 patients also received heparin (1500 U bolus; then 100 U/kg/day as a continuous i.v. infusion). The median number of days of rtPA therapy was 2.5 (1-12). The median total serum bilirubin level was 116 mmol/l (range 63-194) at the beginning of treatment. Six patients showed a response to rtPA treatment (29%). It was observed that by day 2 of rtPA therapy, bilirubin levels in responders showed a downwards trend as compared to those in nonresponders. In all except one patient this response was observed after two doses of rtPA. Seven out of the 11 non-responders had a past history of liver dysfunction, compared with none of the responders. There were no differences between the two groups in terms of day of onset of liver dysfunction, manifestations of disease, maximum bilirubin and creatinine levels, and day of commencing treatment. No patient experienced severe hemorrhagic complications during therapy. Four responders survived for more than 100 days compared to none of the non-responders. Probability of survival was 33% at day 100. It is difficult to unequivocally establish the role of rtPA in the treatment of VOD. The importance of bilirubin levels on days 2 or 3 of therapy in predicting outcome should be established, as should the optimum dose of rtPA and optimum duration of therapy.
Kulkarni
S
S
Department of Medical Oncology, Royal Marsden NHS Trust, Sutton, Surrey, UK.
Rodriguez
M
M
Lafuente
A
A
Mateos
P
P
Mehta
J
J
Singhal
S
S
Saso
R
R
Tait
D
D
Treleaven
J G
JG
Powles
R L
RL
D000328:Adult; D001663:Bilirubin / Q000097:blood; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects; D006504:Hepatic Veno-Occlusive Disease / Q000209:etiology / Q000401:mortality / Q000628:therapy*; D006801:Humans; D008875:Middle Aged; D011994:Recombinant Proteins / Q000627:therapeutic use; D010959:Tissue Plasminogen Activator / Q000627:therapeutic use*
D011994:Recombinant Proteins; D010959:Tissue Plasminogen Activator; D001663:Bilirubin