title: Comparison of dosage schedules of rt-PA in the treatment of proximal deep vein thrombosis.
abstract: This study assessed the efficacy and safety of increasing durations of constant-dose intravenous recombinant tissue-type plasminogen activator (rt-PA) in the treatment of deep vein thrombosis. Patients with venogram-documented proximal lower limb (popliteal, iliofemoral) or upper limb (axillary, subclavian) thrombi were given an initial 2-hour rt-PA infusion at 4 micrograms/kg/min, followed by a maintenance infusion of 1 microgram/kg/min for an additional 4, 22, or 33 hours (mean total rt-PA dosages of 54, 127, and 185 mg). A new quantitative venogram scoring system was applied to the study, based on measurements of thrombus volume before and after completion of treatment. Whereas none of the seven patients given treatment for 6 hours and only one of four given treatment for 24 hours showed significant lysis, four of seven who received a prolonged infusion for 35 hours showed lysis of more than 40% of the original thrombus. Overall, the prolonged 35-hour infusion induced 51% lysis of original thrombus, representing a thrombus volume of 16.7 ml dissolved. Hemorrhagic complications were common in all three groups, with four of 18 patients having significant bleeding, including one massive gastrointestinal hemorrhage, two patients with a decrease in hematocrit of more than 10%, and one patient with an intracranial hemorrhage who recovered completely. Pharmacokinetics of the rt-PA showed a steady state antigen concentration of 240 ng/ml and activity of 200 IU/ml during the initial 2-hour infusion and a postinfusion half-life of 5 minutes. Plasma fibrinogen concentrations decreased to approximately 40% to 50% of initial values with all three treatment regimens, but the nadir fibrinogen concentrations did not correlate with either therapeutic efficacy or bleeding complications. One patient with systemic lupus erythematosus had an unusual allergic reaction that manifested primarily as angioedema. This study suggests that rt-PA infusion of 35 hours induces greater thrombolysis of deep vein thrombosis than does a shorter course of 6 or 24 hours, without an increase in hemorrhagic complications.
authors.affiliation: Department of Medicine, University of Rochester School of Medicine & Dentistry, NY.
authors.forename: V J
authors.initials: VJ
authors.lastname: Marder
authors.forename: B
authors.initials: B
authors.lastname: Brenner
authors.forename: S
authors.initials: S
authors.lastname: Totterman
authors.forename: C W
authors.initials: CW
authors.lastname: Francis
authors.forename: R
authors.initials: R
authors.lastname: Rubin
authors.forename: A K
authors.initials: AK
authors.lastname: Rao
authors.forename: C M
authors.initials: CM
authors.lastname: Kessler
authors.forename: H C
authors.initials: HC
authors.lastname: Kwaan
authors.forename: G V
authors.initials: GV
authors.lastname: Sharma
authors.forename: K L
authors.initials: KL
authors.lastname: Fong
mesh_terms: D000328:Adult; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins / Q000008:administration & dosage; D013924:Thrombophlebitis / Q000188:drug therapy*; D010959:Tissue Plasminogen Activator / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics
chemical_list: D011994:Recombinant Proteins; D010959:Tissue Plasminogen Activator