THE EFFECT OF POLOXAMER-188 ON THE RATE OF INVITRO THROMBOLYSIS MEDIATED BY T-PA AND STREPTOKINASE

Poloxamer 188 is a nonionic block copolymer surfactant which is undergoing clinical trials as a haemorheologic agent. A simulated thrombus preparation was designed to evaluate its effects on fibrinolysis and thrombolysis under flow conditions similar to those which might be encountered within an occlusive coronary thrombus. 125I labelled human fibrinogen (20 μCi/ml) was mixed with platelet-poor citrated plasma, recalcified, and allowed to clot for 1 h at 37°C in a tuberculin syringe filled with small glass beads. This produced a fibrin clot permeated with microscopic channels simulating those of a recently formed thrombus. After washing the plasma bead clots for 30 min with normal saline, heparinised blood containing tissue plasminogen activator (t-PA) or streptokinase, with and without 0.1% poloxamer 188, was added to the columns and rates of flow and elution of 12 125-fibrin degradation products were measured. Poloxamer 188 alone had no ability to lyse fibrin. However, it increased the rate at which t-PA or streptokinase caused lysis of simulated thrombi by as much as 4-fold. This accelerated lysis was associated with up to a 20-fold increase in flow through the thrombus and with elution of larger fragments of fibrin, but not with increased plasmin activity as assessed with a colourimetric substrate. Consequently, poloxamer 188 appeared to accelerate thrombolysis without directly affecting any of the components of the fibrinolytic system. We propose that the ability of poloxamer 188 to modulate thrombolysis is due to its haemorheologic properties. © 1990.