Reteplase in the treatment of peripheral arterial and venous occlusions: a pilot study.

PURPOSE: Reteplase, a truncated mutant of tissue plasminogen activator, has been used successfully in the treatment of acute coronary occlusion, but, heretofore, it has not been investigated in the setting of peripheral vascular occlusion. Reteplase is a potential recombinant thrombolytic agent that may offer an appropriate alternative to currently employed plasminogen activators.
MATERIALS AND METHODS: Over a 6-month period reteplase was used to treat peripheral vascular occlusions at five centers in the United States. The agent was used in peripheral arterial occlusion (n = 26, 70.3%) or venous occlusion (n = 11, 29.7%), in doses ranging from 0.5 to 2.0 U/h, infused directly into the thrombus. A lacing dose (4.3 +/- 0.9 U) was employed in 17 patients (45.9%), and 25 patients (67.6%) received concurrent heparin therapy in a subtherapeutic dose (n = 14, 37.8%) or as full therapeutic anticoagulation (n = 11, 29.7%).
RESULTS: The 26 patients with arterial occlusions received a total dose of reteplase that averaged 20.5 U +/- 5.3 (mean +/- SEM), ranging from 3.5 to 82 U. The duration of infusion was 19.3 hours +/- 2.4 with a range of 0.2-36 hours. Complete dissolution of the occluding thrombus was achieved in 23 patients (88.5%). Hemorrhagic complications developed in eight patients (30.8%) and were major in five patients (19.2%). No patient experienced intracranial bleeding. Although there was no association between the dose regimen and thrombolytic efficacy, bleeding complications appeared to be more frequent as the dose was increased from 0.5 to 2.0 U/h. The 11 patients treated for deep venous thrombi received an average of 32.6 U +/- 7.4 of reteplase, ranging from 6 to 75 U over a mean length of time of 31.1 hours +/- 7.3 (range, 4-84 hours). Complete dissolution of thrombus occurred in eight patients (72.7%). Hemorrhagic complications developed in three patients (27.3%) and one of the episodes was major (9.1%). No patient experienced intracranial hemorrhage.
CONCLUSIONS: Reteplase appears to be an acceptable alternative thrombolytic agent with a satisfactory safety and efficacy profile in the setting of peripheral arterial and venous occlusion. As such, it may provide an attractive alternative for the treatment of peripheral arterial and venous thrombotic occlusions. However, definitive conclusions must await the results of controlled comparisons of reteplase to other thrombolytic agents.