EFFECTS OF POLOXAMER-407 ON THE ASSEMBLY, STRUCTURE AND DISSOLUTION OF FIBRIN CLOTS

Poloxamer 407 has shown clinical promise in suppressing surgically rel ated adhesion formation. The mechanisms by which this occurs are not w ell understood Since poloxamer 188 has rather dramatic fibrin altering properties, the present study was performed to evaluate the effects o f poloxamer 407 on fibrin assembly, structure and dissolution. Studies were performed in platelet-rich plasma (PRP), platelet-poor plasma (P PP) and a purified protein system. Poloxamer 407 enhanced the rate of fibrin assembly, and increased final gel turbidity. As poloxamer 407 c oncentration rose from 0 to 20 mg/ml in the purified protein system, t he final gel optical density (OD) increased from 0.30 to 0.95, and fib er size (mass/length ratio [mu]) increased from 2.4 to 13.4 x 10(13) d altons/cm. Precipitation was noted in the purified system at poloxamer 407 concentrations greater than or equal to 20 mg/ml. Over a poloxame r 407 range of 0-20 mg/ml, mu increased from 2.64 to 13.2 x 10(13) dal tons/cm in PRP. In PPP, mu increased from 2.95 to 9.25 x 10(13) dalton s/cm. In contrast to results with poloxamer 188, clot lysis with tPA ( 43 IU/ml) was prolonged in the presence of poloxamer 407. At 20 mg of poloxamer 407 per mi, clot lysis was less than 18% complete after 3000 s. For the control, lysis was 50% complete after 1350 s. Poloxamer 40 7 inhibition of fibrinolysis was due to inhibition of plasminogen acti vation or plasmin activity. The fibrin altering properties of poloxame r 407 may partially explain some of this agent's interesting clinical properties.