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Bioengineering (Focus Group – BE)

(126) Novel Intravenous Anticoagulant: Development and Testing for Safe, Effective Thrombosis Prevention

Introduction: Fibrin polymerization, the final step of blood clotting, is initiated by thrombin cleavage of fibrinopeptides A (FpAs) from fibrinogen. The release of FpA exposes an N-terminal α-chain motif Gly-Pro-Arg (GPR), called knob‘A’, which is complementary to pockets or holes ‘a’ of another fibrin molecule, and this non-covalent ‘A:a’ knob-hole interaction drives fibrin polymerization (1). The peptide GPRP mimics the knob‘A’ structure and competitively inhibits the knob-hole interactions, impairing fibrin polymerization. Disruption of fibrin formation represents a novel strategy for anticoagulation.

Learning Objectives:

  • Examine the dose-dependent anticoagulant effects of GPRP-dextran.
  • Evaluate GPRP-dextran' window by assessing fibrinogen reduction and normal bleeding time maintenance
  • Assess the duration and stability of GPRP-dextran's anticoagulant effects in vivo.