Hemostatic effects of fibrinogen γ‐chain dodecapeptide‐conjugated polymerized albumin particles in vitro and in vivo

Abstract

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.

Characterization of In Vitro Hemostatic Peptide Effects by Thromboelastography

“…This explains the observed biphasic effects of the peptide on blood coagulation and is consistent with decreased R and MA by its analog of fibrinogen g365-380 in TEG when added to a mixture of fibrinogen and thrombin. When attached to a polymer substrate, 44 the peptide is expected to promote platelet aggregation, leading to improved hemostatic ability as demonstrated by albumin particles carrying fibrinogen g-chain sequence 400-411.…”

Decoration of fibrinogen γ-chain peptide on adenosine diphosphate-encapsulated liposomes enhances binding of the liposomes to activated platelets

“…We previously reported that H12-(ADP)Lipo enhances the platelet aggregation in PRP and significantly reduces the bleeding times in thrombocytopenic rat and rabbit models and that H12-(ADP)Lipo is more efficient than H12-Lipo or (ADP)Lipo (Okamura et al, 2005a(Okamura et al, ,b, 2007. It is thought that the hemostatic effect of H12-(ADP)Lipo is based on the following sequential events: binding to activated platelets, releasing ADP that further activates platelets to form a thrombus, and bridging platelets to make large aggregates for hemostasis.…”

“…doi:10.1016/j.ijpharm.2011.01.014 has high specificity toward GPIIb/IIIa on platelets (Ruoslahti et al, 1996). In fact, H12-coated polymerized albumin and H12-coated polyethylene glycol-modified liposomes show specific interaction with activated platelets, augment platelet-mediated thrombus formation on collagen-immobilized surfaces under flow condition in vitro, and prolong hemostatic ability in vivo to correct bleeding time in a dose-dependent manner in thrombocytopenic rat and rabbit models (Okamura et al, 2005a(Okamura et al, ,b, 2007.…”

Intravenous hemostats: challenges in translation to patients

“…The use of ADP there may enhance platelet aggregation by activation of additional platelets. 22,23 These particles are entirely synthetic, but still offer a significant improvement in bleeding time in both thrombocytopenic rat and thrombocytopenic rabbit models when compared with saline as a treatment. 22 …”

“…There are well-established protocols for inducing thrombocytopenia either chemically (busulfan) 66 , radiation-therapy, or repeat blood draws/transfusion, and have been tested in conjunction with other synthetic platelet treatments. 11,21,22,61 …”