Treatment of hepatic veno-occlusive disease with low-dose tissue plasminogen activator: impact on coagulation profile
Goldberg, S.L.; Shubert, J.; Rao, A.K.; Redei, I.; Klumpp, T.R.; Mangan, K.F.
Bone Marrow Transplantation 18(3): 633-636
1996
ISSN/ISBN: 0268-3369 PMID: 8879629 Document Number: 464306
An 18-year-old white male developed severe hepatic veno-occlusive disease (VOD) during an autologous bone marrow transplant for primary refractory nodular sclerosing Hodgkin's disease. As a result of VOD-induced hepatic dysfunction, coagulation studies revealed depression of vitamin K dependent procoagulant factor VII. Intravenous recombinant tissue plasminogen activator 20 mg over 4 h on 4 consecutive days and continuous heparin infusion (1000 unit bolus followed by 150 units/kg/day) resulted in rapid reversal of the VOD syndrome. During treatment, procoagulant factors II, VII, IX and X levels increased indicating the return of hepatic synthesizing capacity. Factor V levels, which were elevated pre-therapy, also rose dramatically. Plasma antigen levels of protein C, a natural anticoagulant, remained severely depressed. No clinical evidence of bleeding and only minimal systemic fibrinolysis was noted. Despite concerns regarding the use of lytic therapy in a thrombocytopenic post-BMT patient, serial measurements of coagulation parameters during severe VOD suggested that low dose rt-PA improved portions of the systemic hemostatic profile.