BLOOD CONSERVATION AND TRANSFUSION ALTERNATIVES Prolonged hemostatic ability of polyethylene glycol–modified polymerized albumin particles carrying fibrinogen g-chain dodecapeptide Yosuke Okamura, Toshinori Fujie, Hitomi Maruyama, Makoto Handa, Yasuo Ikeda, and Shinji Takeoka BACKGROUND: Second-generation platelet (PLT) sub- stitutes for treatment of bleeding were studied and the focus was on a dodecapeptide, HHLGGAKQAGDV (H12), which is a fibrinogen g-chain carboxy-terminal sequence (g 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 t1/2 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 t1/2 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 t1/2 and maintained specific binding ability to activated PLTs. The particles dose depen- dently shortened the tail bleeding time of thrombocy- topenic rats 6 hours after injection. CONCLUSION: H12-PEG-polyAlb may be a suitable candidate for treatment of bleeding into thrombocy- topenic patients as an alternative to PLT concentrate transfusion. P latelet (PLT) transfusion plays an important role in the supportive therapy of thrombocytopenia caused by cancer or hematologic malignancies or in the perioperative period. The shortage of PLT concentrates, however, has always been a serious issue because of the short storage life (72 hr in Japan), insufficient donation, and the greater rate of demand than ABBREVIATIONS: GP = glycoprotein; H12-PEG-polyAlb = poly- merized albumin particles carrying H12 at the end of the polyethylene glycol chains; MALPEG-NHS =a-(3-[3-maleimido- 1-oxopropyl]amino) propyl-w-succinimidyl carboxypentyloxy polyethylene glycol; mPEG-NHS =a-methoxy-w-succinimidyl carboxypentyloxy monofunctional PEG; PGE1 = prostaglandin E1; polyAlb = polymerized albumin particles; rHSA = recombi- nant human serum albumin. From the Department of Applied Chemistry, Graduate School of Science and Engineering,Waseda University, Tokyo; and the Department of Internal Medicine and the Department of Transfusion Medicine & Cell Therapy, School of Medicine, Keio University, Tokyo, Japan. Address reprint requests to: Shinji Takeoka, Department of Applied Chemistry, Graduate School of Science and Engineering, Waseda University, Tokyo 169-8555, Japan; e-mail: takeoka@waseda.jp. This work was supported in part by Health and Labor Sciences Research Grants (Research on Pharmaceutical and Medical Safety, ST, MH, andYI); Ministry of Health, Labor and Welfare, Japan, and grants-in-aid from the JSPS, Japan (No. 15300171, ST); Ministry of Education, Culture, Sports, Science and Technology (Leading Project for Biosimulation, MH); and 21COE “Practical Nano-Chemistry” and “Consolidated Research Institute for Advanced Science and Medical Care” from MEXT (ST), Japan. YO was the recipient of a Research Fellowship from the JSPS for Young Scientists. Received for publication October 6, 2006; revision received December 25, 2006, and accepted January 2, 2007. doi: 10.1111/j.1537-2995.2007.01265.x TRANSFUSION 2007;47:1254-1262. 1254 TRANSFUSION Volume 47, July 2007