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.
Okamura
Yosuke
Y
Graduate School of Science and Engineering and the Advanced Research Institute for Science and Engineering, Waseda University, Tokyo.
Takeoka
Shinji
S
Teramura
Yuji
Y
Maruyama
Hitomi
H
Tsuchida
Eishun
E
Handa
Makoto
M
Ikeda
Yasuo
Y
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