Hemostatic effects of fibrinogen gamma-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 gamma-chain carboxy-terminal sequence (gamma 400-411) and exists only in the fibrinogen domain.


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.


CONCLUSIONS
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.
Graduate School of Science and Engineering and the Advanced Research Institute for Science and Engineering, Waseda University, Tokyo.
Yosuke
Y
Okamura
Shinji
S
Takeoka
Yuji
Y
Teramura
Hitomi
H
Maruyama
Eishun
E
Tsuchida
Makoto
M
Handa
Yasuo
Y
Ikeda
D000418:Albumins / Q000378:metabolism*; D000818:Animals; D001760:Bleeding Time; D001792:Blood Platelets / Q000378:metabolism; D001802:Blood Substitutes / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism*; D002066:Busulfan / Q000494:pharmacology; D002232:Carbocyanines; D002448:Cell Adhesion; D020099:Coated Materials, Biocompatible / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism; D024042:Collagen Type I / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005340:Fibrinogen / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism*; D005456:Fluorescent Dyes; D006490:Hemostatics / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008660:Metabolism; D008863:Microspheres; D009842:Oligopeptides / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism; D015539:Platelet Activation; D010974:Platelet Aggregation; D010975:Platelet Aggregation Inhibitors / Q000138:chemical synthesis / Q000737:chemistry; D010976:Platelet Count; D051381:Rats; D017208:Rats, Wistar; D012996:Solutions; D013921:Thrombocytopenia / Q000378:metabolism
D000418:Albumins; D001802:Blood Substitutes; D002232:Carbocyanines; D020099:Coated Materials, Biocompatible; D024042:Collagen Type I; D005456:Fluorescent Dyes; D006490:Hemostatics; D009842:Oligopeptides; D010975:Platelet Aggregation Inhibitors; D012996:Solutions; C027539:fibrinopeptides gamma; C007392:3,3'-dihexyl-2,2'-oxacarbocyanine; D005340:Fibrinogen; D002066:Busulfan