The role of
thrombus-binding in the fibrinolytic response to the acylated
streptokinase.plasminogen activator complex,
BRL 26921, has been examined using human plasma clots, radiolabelled with 125I-fibrin, in vitro. When clots were briefly exposed to
BRL 26921, washed and returned to homologous plasma, lysis continued for up to 3 hours and attained approximately 25% of that lysis achieved by incubating with
BRL 26921 for 5 hours. This continuing lysis was potentiated by return of exposed clots to alpha 2-antiplasmin-depleted plasma, or
buffer and is attributed to an initial uptake of
BRL 26921 rather than the binding of exogenous
plasmin that was observed for
streptokinase and high concentrations of
urokinase. The sustained lysis is not explained by transfer of loosely-associated surface material or by dissociation of agent from the clot with reuptake from a dilute systemic pool. The response can be attributed, at least in part, to specific
fibrin binding, mediated by kringles 1-4, for a low-molecular weight
plasminogen (Val442) variant was less active.