Fibrinolytic Therapy of Deep Vein Thrombosis with Continuous Intravenous Infusion of a Recombinant Tissue Plasminogen Activator

Abstract

Recombinant human rt-PA was administered to 22 patients with deep vein thrombosis at a dosage of 30 to 120 mg/day (0.5 to 1.76 mg/kg body weight/24 hr) over 2 to 10 days. rt-PA induced phlebographically documented substantial recanalization in 18 of 21 patients. The lowest dose of 0.5 mg/kg/24 hr tested here was thrombolytically effective, whereas a dose of 0.95 mg/kg/24 hours and more led to hemorrhagic complications and premature discontinuation of therapy in four of six patients. Blood clotting analysis did not reveal any substantial decrease in fibrinogen concentrations, whereas the euglobulin clot lysis time and thromboelastography demonstrated a systemic fibrinolytic effect. Therapy with rt-PA can thus be considered as an alternative and effective method of therapy in treatment of deep vein thrombosis. The results of this study show that even a dosage of lower than 0.5 mg/kg/24 hr might prove to be effective. Further studies would be required to show whether the fibrin specificity of rt-PA leads to a superiority of this fibrinolytic substance over the conventional thrombolytic agents, streptokinase and urokinase.

Double-Blind, Randomized Comparison of Systemic Continuous Infusion of 0.25 Versus 0.50 mg/kg/24 h of Alteplase over 3 to 7 Days for Treatment of Deep Venous Thrombosis in Heparinized Patients: Results of the European Thrombolysis with rt-PA in Venous Thrombosis (ETTT) Trial

“…The fibrin selectivity of this agent, compared to urokinase and streptokinase, suggests that its use might improve the risk-benefit ratio of thrombolytic therapy for DVL However, preliminary studies with the single-chain form of rt-PA, alteplase, (7)(8)(9) showed that short-duration (4-8 h) high dose (50-100 -g) infusions of this agent over 14. days yielded only limited success in terms of phlebographic rec analization and were associated with a risk of major bleeding of 30% (7).In a limited series of 7 patients, Zimmermann et al reported promising results with continuous infusions of 0.71 to 1.76 mdkglz4h for 2-4 days (10) and also observed a marked thrombolytic effect following 0.5 mglkglza h for 2-8 days (11).…”

“…The individual values of the Marder's venographic scores in the two groups are displayed in Fig. 1-. Thrombolysis was associated with improvements of the scores which decreased on average (median, range) from L8 units (6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25) to 13 units in Group I (median decrease 3.0 units, n -1-5, p _ 0.32) and from 17.5 units (3-33) to 15.5 units (0-27) in Group II (median decrease 4.0 units, n _ 16, p _ 0.23). All paired venograms except three (one in Group I and two in Group II) were considered as being suitable for comparative qualitative assessment.…”

Intermittent Regional Therapy with rt-PA is not Superior to Systemic Thrombolysis in Deep Vein Thrombosis (DVT) - a German Multicenter Trial

“…When considering this therapy for a patient, the benefits and risks of this procedure must be weighed diligently (1)(2)(3)(4)(5)(6)(7)(8)(9). Numerous at tempts have been suggested including new drugs such as rt-PA (10)(11)(12)(13)(14)(15)(16)(17), new techniques (lysis block-technique, hyperthermic fi brinolysis) and new application schedules (18)(19)(20)(21) to improve treatment results. As far as our own results are concerned, sys temic intermittent application of ultra-high-dose streptokinase (UHSK), introduced by Martin et al in 1985 (22)(23)(24)(25)(26) seems to be the most effective treatment protocol (27).…”