Effects of poloxamer 407 on the assembly, structure and dissolution of fibrin clots

Abstract

Poloxamer 407 has shown clinical promise in suppressing surgically related adhesion formation. The mechanisms by which this occurs are not well understood. Since poloxamer 188 has rather dramatic fibrin altering properties, the present study was performed to evaluate the effects of poloxamer 407 on fibrin assembly, structure and dissolution. Studies were performed in platelet-rich plasma (PRP), platelet-poor plasma (PPP) and a purified protein system. Poloxamer 407 enhanced the rate of fibrin assembly, and increased final gel turbidity. As poloxamer 407 concentration rose from 0 to 20 mg/ml in the purified protein system, the final gel optical density (OD) increased from 0.30 to 0.95, and fiber size (mass/length ratio [mu]) increased from 2.4 to 13.4 x 10(13) daltons/cm. Precipitation was noted in the purified system at poloxamer 407 concentrations > or = 20 mg/ml. Over a poloxamer 407 range of 0-20 mg/ml, mu increased from 2.64 to 13.2 x 10(13) daltons/cm in PRP. In PPP, mu increased from 2.95 to 9.25 x 10(13) daltons/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 ml, clot lysis was less than 18% complete after 3000 s. For the control, lysis was 50% complete after 1350 s. Poloxamer 407 inhibition of fibrinolysis was due to inhibition of plasminogen activation or plasmin activity. The fibrin altering properties of poloxamer 407 may partially explain some of this agent's interesting clinical properties.