Polyphosphate enhances fibrin clot structure.
Polyphosphate, a linear polymer of inorganic phosphate, is present in platelet dense granules and is secreted on platelet activation. We recently reported that polyphosphate is a potent hemostatic regulator, serving to activate the contact pathway of blood clotting and accelerate factor V activation. Because polyphosphate did not alter thrombin clotting times, it appeared to exert all its procoagulant actions upstream of thrombin. We now report that polyphosphate enhances fibrin clot structure in a calcium-dependent manner. Fibrin clots formed in the presence of polyphosphate had up to 3-fold higher turbidity, had higher mass-length ratios, and exhibited thicker fibers in scanning electron micrographs. The ability of polyphosphate to enhance fibrin clot turbidity was independent of factor XIIIa activity. When plasmin or a combination of plasminogen and tissue plasminogen activators were included in clotting reactions, fibrin clots formed in the presence of polyphosphate exhibited prolonged clot lysis times. Release of polyphosphate from activated platelets or infectious microorganisms may play an important role in modulating fibrin clot structure and increasing its resistance to fibrinolysis. Polyphosphate may also be useful in enhancing the structure of surgical fibrin sealants.
Departments of Internal Medicine and Biochemistry, College of Medicine, University of Illinois at Urbana-Champaign, USA.
Stephanie A
SA
Smith
James H
JH
Morrissey
D001777:Blood Coagulation / Q000187:drug effects*; D002118:Calcium / Q000494:pharmacology; D003432:Cross-Linking Reagents / Q000494:pharmacology; D005337:Fibrin / Q000737:chemistry* / Q000648:ultrastructure; D005342:Fibrinolysis / Q000187:drug effects; D006493:Heparin / Q000494:pharmacology; D006801:Humans; D008855:Microscopy, Electron, Scanning; D009391:Nephelometry and Turbidimetry; D011122:Polyphosphates / Q000494:pharmacology*; D013916:Thrombelastography; D013917:Thrombin / Q000494:pharmacology; D013997:Time Factors
D003432:Cross-Linking Reagents; D011122:Polyphosphates; D005337:Fibrin; D006493:Heparin; D013917:Thrombin; D002118:Calcium