Effects of Poloxamer 188 on fibrin network structure, whole blood clot premeability and fibrinolysis.
The effects of Poloxamer 188 (0-5 mg/ml) on the permeability, turbidity, compaction, and fibrinolysis of fibrin network developed in human plasma, and on the permeability and fibrinolysis of network developed in whole blood were examined. Poloxamer 188 was found to increase network permeability and compaction in plasma. In networks in plasma, effects on the fibre mass-length ratio from turbidity and fibrinolysis with recombinant tissue plasminogen activator were small. Poloxamer did not alter the fibrinolysis with streptokinase. The increase in fibrin network permeability at low poloxamer concentrations was not attributable to an increase in fibre thickness, but results from alterations in the arrangement of fibrin fibres. Poloxamer also significantly increased the permeability of networks developed in whole blood. Studies with the platelet inhibitor cytochalasin B demonstrated that this effect in whole blood networks was partly from facilitation of platelet induced clot retraction. Poloxamer was not found to affect streptokinase induced fibrinolysis of whole blood networks. The effects of poloxamer support the hypothesis that depletion flocculation of fibrin intermediaries by soluble macromolecules is a significant determinant of network permeability. The therapeutic use of poloxamer will result in altered fibrin function in particular its permeability and mechanical stability. These alterations may contribute to its described antithrombotic and rheological effects.
van Gelder
J M
JM
Vascular and Thrombosis Research Unit, Woden Valley Hospital, A.C.T., Australia.
Nair
C H
CH
Dhall
D P
DP
D001777:Blood Coagulation / Q000187:drug effects*; D003018:Clot Retraction; D005337:Fibrin / Q000737:chemistry / Q000187:drug effects*; D005342:Fibrinolysis / Q000187:drug effects*; D005343:Fibrinolytic Agents / Q000494:pharmacology*; D006801:Humans; D009391:Nephelometry and Turbidimetry; D010539:Permeability / Q000187:drug effects; D011060:Poloxalene / Q000494:pharmacology*; D011994:Recombinant Proteins / Q000494:pharmacology; D013300:Streptokinase / Q000494:pharmacology; D013501:Surface-Active Agents / Q000494:pharmacology*; D010959:Tissue Plasminogen Activator / Q000494:pharmacology
D005343:Fibrinolytic Agents; D011994:Recombinant Proteins; D013501:Surface-Active Agents; D005337:Fibrin; D011060:Poloxalene; D013300:Streptokinase; D010959:Tissue Plasminogen Activator