Hemostatic effects of fibrinogen γ-chain dodecapeptide-conjugated polymerized albumin particles in vitro and in vivo

BACKGROUND: Prototypes of platelet (PLT) substitutes have been 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 the fibrinogen domain. STUDY DESIGN AND METHODS: H12 was conjugated to the surface of polymerized albumin particles (polyAlb) as biocompatible and biodegradable particles with a mean diameter of 260 ± 60 nm, and the hemostatic ability of H12-conjugated polyAlb (H12-polyAlb) under flow conditions and thrombocytopenic rats have been studied. RESULTS: H12-polyAlb enhanced the in vitro thrombus formation of activated PLTs on a collagen-immobilized plate when exposed to the flowing thrombocytopenic imitation blood. Furthermore, the analysis of the tail bleeding time of rats that were made thrombocytopenic by busulfan injection showed that H12-polyAlb had a hemostatic effect. Based on the bleeding time and the amount injected, the hemostatic capacity of 20 H12-polyAlb was estimated to correspond to that of one PLT. CONCLUSION: These results were important first steps toward the development of PLT substitutes and indicated that H12-polyAlb may be a suitable candidate for an alternative to human PLT concentrates transfused into thrombocytopenic patients in the future.