Comparative studies of purified poloxamer 188 using clot‐based and viscoelastic measurements of coagulation (833.5)

Abstract

Poloxamer 188 (P188; Mast Therapeutics, Inc.)is a surface‐active, non‐ionic block copolymer which binds to hydrophobic surfaces on damaged cells improving membrane hydration and lowering adhesion and viscosity. We compared the effect of this agent using various clot based, chromogenic and viscoelastic measurements of blood coagulation. Whole blood activated clotting time ACT) studies were carried out in healthy individuals (n=10) at a concentration range of 1.872‐15.0mg/mL. TEG analysis was carried out on TEG 5000 (Haemoscope Corp, Niles, IL) at concentrations of 0‐0.45 mg/mL. The effect of P188 on normal plasma clotting parameters, such as PT and aPTT, was measured at a concentration range of 0‐10 mg/mL. The effect of P188 on thrombin‐induced clot formation was investigated using a fibrinokinetic method. The effect of P188 on thrombin generation was measured using the fluormetric method (Technoclone, Vienna, Austria). The anti‐protease effects of P188 were studied using chromogenic substrate methods using isolated biochemical systems. At concentrations up to 10 mg/mL, P188 did not produce any modification of ACT or the standard clotting assays. In the TEG analysis, P188 produced a concentration dependent hypocoagulant effect in as evidenced by increased angle and shortening of maximum amplitude (MA). In fibrinokinetic studies, P188 produced an increase in the fibrin clot density and rate of fibrin polymerization. The marked discordance between TEG and other coagulation tests suggest that P188’s effect on viscosity and adhesive interactions result in an artifact in TEG analysis and an incorrect indication of a hypocoagulant effect.