title: Treatment of hepatic veno-occlusive disease with low-dose tissue plasminogen activator: impact on coagulation profile.
abstract: 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 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.
authors.affiliation: Bone Marrow Transplant Program, Temple University Health Science Center, Philadelphia, PA, USA.
authors.forename: S L
authors.initials: SL
authors.lastname: Goldberg
authors.forename: J
authors.initials: J
authors.lastname: Shubert
authors.forename: A K
authors.initials: AK
authors.lastname: Rao
authors.forename: I
authors.initials: I
authors.lastname: Redei
authors.forename: T R
authors.initials: TR
authors.lastname: Klumpp
authors.forename: K F
authors.initials: KF
authors.lastname: Mangan
mesh_terms: D000293:Adolescent; D001777:Blood Coagulation / Q000187:drug effects*; D016026:Bone Marrow Transplantation / Q000009:adverse effects*; D006504:Hepatic Veno-Occlusive Disease / Q000188:drug therapy*; D006801:Humans; D008297:Male; D011994:Recombinant Proteins / Q000627:therapeutic use; D010959:Tissue Plasminogen Activator / Q000627:therapeutic use*
chemical_list: D011994:Recombinant Proteins; D010959:Tissue Plasminogen Activator