Local thrombolytic therapy of acute peripheral arterial ischaemia with tissue plasminogen activator: A dose-ranging study

Abstract

Low-dose streptokinase has been established as an alternative to surgery in selected patients with acute peripheral arterial ischaemia. Tissue plasminogen activator (t-PA) is responsible for normal plasma fibrinolytic activity and has recently become available for clinical use owing to recombinant DNA technology. It has the theoretical advantage of fibrin specificity, which may result in enhanced thrombolytic effects with greater safety. Twenty-three patients with recent lower limb arterial occlusions received t-PA over a tenfold range of concentrations and five patients received low-dose streptokinase. One month after treatment with t-PA or streptokinase 19 (68 per cent) patients had limb salvage, five (18 per cent) had required amputations and four (14 per cent) had died. Systemic fibrinolytic effects were variable but basically dose related. Haemorrhage occurred most frequently at the highest t-PA concentration and was major in four (17 per cent) cases, including a fatal stroke. Plasma fibrinogen concentration fell below 1.2 gl-1 in five (22 per cent) patients who received t-PA and was found to be a significant risk factor for haemorrhage, t-PA was an effective thrombolytic agent at all concentrations studied. The dose currently used in clinical studies at this institution is 0.5 mg h-1.

Thrombolytic Therapy in Acute Lower Limb Ischemia

“…Further studies confirmed that a much lower dose (0.05 mg/h) is adequate to achieve the same therapeutic effect. 11,31,32 In two randomized trials, the limb salvage rate was significantly higher with rt-PA than with either SK (80 vs. 60%) or UK (50 vs. 37%). 33,34 Several nonrandomized trials of IAT in subacute occlu sions found shorter lysis time with rt-PA without higher complication rates.…”

“…33,34 Several nonrandomized trials of IAT in subacute occlu sions found shorter lysis time with rt-PA without higher complication rates. [30][31][32][35][36][37][38] Another great advantage of rt-PA is the short half-life of 1.5 minutes, which allows any subsequent surgical procedure to be performed im mediately after IAT. Thus, rt-PA has become the thrombo lytic agent of choice for IAT in ALLI.…”

Thrombolysis in the Peripheral Vascular System

“…A dose-ranging study for rtPA by Earnshaw et al [38] compared rtPA with low-dose SK. rtPA was effective in all concentrations studied from 0.25 mg/hr to 2.5 mg/hr, and duration of lysis was shorter than with SK.…”

A New Intra Arterial rt-PA Dosage Regimen in Peripheral Arterial Occlusion: Bolus Followed by Continuous Infusion

“…Risius and Graor (1) have compared 0.1 mg kg-1 h-l to 0.05 mg kg-1 h-1 rt-PA continuous infusion rates and selected the lowest. Other pilot studies (2,3,4) have proposed rt-PA dosages between 0.25 mg 6-r up to 10 mg 6-t. The mean infusion time was 5 h to 29 hand a successful clot lysis occurred in 80o/" to 100% of the cases.…”

“…The mean infusion time was 5 h to 29 hand a successful clot lysis occurred in 80o/" to 100% of the cases. More major bleeding complications were found in patient groups with higher doses (2,3) Expecting that shortening the infusion time could reduce the bleeding risk even with higher doses of thrombolytic drugs and that bolus injections could be more efficient than continuous infusions, we have developed a 2-stage procedure combining bolus and continuous infusion.…”