Plasminogen activators have immense clinical significance as thromboly
tic agents for management of stroke and myocardial infarction. Tissue-
type plasminogen activator (tPA) is generally preferred as being effec
tive and safer than either urokinase or streptokinase type activators.
Large-scale production of tPA became possible through groundbreaking
developments in cell lines and bioprocess technology. Nevertheless, at
thousands of dollars per treatment, tPA remains expensive. Enhancing
cellular productivity and downstream product recovery through new appr
oaches continue to be major challenges as discussed in this review. Re
cent clinical experience suggests the need for yet better fibrinolytic
agents and attempts are underway to modify the tPA molecule to second
generation products. Emerging trends in this field are outlined.