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

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.