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 gamma-chain carboxy-terminal sequence (gamma 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.