Effects of poloxamer 188 on the assembly, structure and dissolution of fibrin clots.
Poloxamer 188, N.F. (RheothRx), a nonionic block copolymer composed of 2 hydrophilic polyoxyethylene chains connected by a hydrophobic polyoxypropylene chain, normalizes the viscosity of whole blood high in soluble fibrin(ogen) complexes. Normalization may be via a poloxamer 188-induced decrease in fibrin(ogen)-red cell interaction. Our study examined the influences of poloxamer 188 on fibrin assembly and structure. Studies were performed in both purified and plasma systems with a poloxamer 188 concentration range of 0.1-20 mg/ml and specific clotting conditions (fibrinogen 1 mg/ml, thrombin 1 NIH u/ml, pH 7.4 [Tris 0.05 M], ionic strength 0.15 and calcium 5 mM). Fibrin assembly was accelerated in the presence of poloxamer 188. As poloxamer 188 concentration was increased from 0 to 8 mg/ml in plasma: a) the lag phase prior to initial turbidity rise decreased from 25 to less than 5 s; b) the final gel optical density (OD) increased from 0.65 to 1.28 and c) fiber size (mass/length ratio [mu]) increased from 4.3 to 12.6 x 10(13) daltons/cm. Similar results were seen in the purified system with a poloxamer 188 concentration range of 0-8 mg/ml. OD increased from 0.26 to 0.51, and mu increased from 2.3 to 5.3 x 10(13) daltons/cm. Above 8 mg/ml, precipitation of fibrinogen was noted in this system. Since large fibrin fibers tend to be degraded more rapidly, possible poloxamer mediated enhancement of r-tPA-mediated clot lysis was investigated. With r-tPA (70 lu/ml) present at the time of clotting, clot lysis in the presence of ploxamer 188 (8 mg/ml) was 50% complete at 1,600 s compared to 2,540 s for the control. Thus, poloxamer 188-induced alterations in fibrin structure and fibrin-cell interactions may explain some of this agent's interesting hemorrheologic and antithrombotic properties.
Carr
M E
ME
Department of Medicine, Medical College of Virginia, Richmond.
Powers
P L
PL
Jones
M R
MR
D001777:Blood Coagulation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005337:Fibrin / Q000187:drug effects / Q000502:physiology*; D005340:Fibrinogen / Q000302:isolation & purification / Q000502:physiology; D005342:Fibrinolysis / Q000187:drug effects; D005782:Gels; D006801:Humans; D007700:Kinetics; D011060:Poloxalene / Q000494:pharmacology*; D011994:Recombinant Proteins / Q000494:pharmacology; D012016:Reference Values; D010959:Tissue Plasminogen Activator / Q000494:pharmacology
D005782:Gels; D011994:Recombinant Proteins; D005337:Fibrin; D005340:Fibrinogen; D011060:Poloxalene; D010959:Tissue Plasminogen Activator