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

Abstract

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.

• Authors: Yosuke Okamura, Toshinori Fujie, Hitomi Maruyama, Makoto Handa, Yasuo Ikeda, Shinji Takeoka
• Journal: Transfusion (Transfusion) Vol. 47 Issue 7 Pg. 1254-62 (Jul 2007) ISSN: 0041-1132 [Print] United States
• PMID: 17581161 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Albumins
• Hemostatics
• Peptide Fragments
• Polyethylene Glycols
• Fibrinogen

Topics

• Albumins (therapeutic use)
• Animals
• Blood Coagulation (drug effects)
• Blood Platelets
• Fibrinogen (therapeutic use)
• Half-Life
• Hemorrhage (drug therapy)
• Hemostatics (chemistry, therapeutic use)
• Peptide Fragments (therapeutic use)
• Polyethylene Glycols (therapeutic use)
• Rats
• Thrombocytopenia (therapy)