Prolonged hemostatic ability of polyethylene glycol-modified polymerized albumin particles carrying fibrinogen γ-chain dodecapeptide

BACKGROUND: Second-generation platelet (PLT) substitutes for treatment of bleeding were studied and the focus was on a dodecapeptide, HHLGGAKQAGDV (H12), which is a fibrinogen γ-chain carboxy-terminal sequence (γ 400-411) and exists only in a fibrinogen domain. STUDY DESIGN AND METHODS: H12 was conjugated to the surface of polymerized albumin particles (polyAlb) modified with polyethylene glycol (PEG) chains to produce biocompatible particles (H12-PEG-polyAlb) that had prolonged blood circulation t_1/2 and were more stable in vitro and in vivo compared with H12-polyAlb (not modified with PEG). H12-PEG-polyAlb was administered intravenously into thrombocytopenic rats and the t_1/2 of the particles and the tail bleeding time were measured to evaluate the prolongation in the hemostatic effect. RESULTS: H12-PEG-polyAlb particles modified with PEG prolonged the t_1/2 and maintained specific binding ability to activated PLTs. The particles dose dependently shortened the tail bleeding time of thrombocytopenic rats 6 hours after injection. CONCLUSION: H12-PEG-polyAlb may be a suitable candidate for treatment of bleeding into thrombocytopenic patients as an alternative to PLT concentrate transfusion.