Submitted March 20, 2008
Accepted June 1, 2008
Polyphosphate enhances fibrin clot structure
Stephanie A. Smith and James H. Morrissey*
Department of Medicine, College of Medicine, University of Illinois at Urbana-Champaign, Urbana, IL, United States
Department of Biochemistry, College of Medicine, University of Illinois at Urbana-Champaign, Urbana, IL, United States
* Corresponding author; email: jhmorris{at}uiuc.edu.
Polyphosphate, a linear polymer of inorganic phosphate, is present in platelet dense granules and is secreted upon 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. Since 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 threefold 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 activator 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.
