Mechanisms of action of an investigational new freeze-dried platelet-derived hemostatic product.

Autor:	Kuhn BJ; Department of Discovery Research, Cellphire Therapeutics, Inc, Rockville, Maryland, USA. Electronic address: bkuhn@cellphire.com., Swanson A; Department of Discovery Research, Cellphire Therapeutics, Inc, Rockville, Maryland, USA., Cherupalla AS; Department of Discovery Research, Cellphire Therapeutics, Inc, Rockville, Maryland, USA., Booth L; Department of Discovery Research, Cellphire Therapeutics, Inc, Rockville, Maryland, USA., Dickerson WM; Department of Discovery Research, Cellphire Therapeutics, Inc, Rockville, Maryland, USA., Fitzpatrick GM; Product Development, Cellphire Therapeutics, Inc, Rockville, Maryland, USA., Alexander WA; Medical Science and Clinical Development, Cellphire Therapeutics, Inc, Rockville, Maryland, USA., Moskowitz KA; Department of Discovery Research, Cellphire Therapeutics, Inc, Rockville, Maryland, USA.
Jazyk:	angličtina
Zdroj:	Journal of thrombosis and haemostasis : JTH [J Thromb Haemost] 2024 Mar; Vol. 22 (3), pp. 686-699. Date of Electronic Publication: 2023 Dec 09.
DOI:	10.1016/j.jtha.2023.11.022
Abstrakt:	Background: A safe and efficacious hemostatic product with a long shelf-life is needed to reduce mortality from hemorrhage due to trauma and improve surgical outcomes for persons with platelet deficiency or dysfunction. Thrombosomes, a trehalose-stabilized, leukoreduced, pooled blood group-O freeze-dried platelet-derived hemostatic (FPH) with a 3-year shelf-life, may satisfy this need. Objectives: To characterize the mechanism of action of FPH. Methods: FPH's ability to adhere to collagen, aggregate with and without platelets, and form clots was evaluated in vitro. Nonobese diabetic-severe combined immunodeficiency mouse models were used to assess circulation persistence and hemostatic efficacy. Results: FPH displays the morphology and surface proteins of activated platelets. FPH adheres to collagen, aggregates, and promotes clots, producing an insoluble fibrin mesh. FPH is rapidly cleared from circulation, has hemostatic efficacy comparable to apheresis platelets in a murine tail-cut, and acts in a dose-dependent manner. Conclusion: FPH is a first-in-class investigational treatment and shows strong potential as a hemostatic agent that is capable of binding exposed collagen, coaggregating with endogenous platelets, and promoting the coagulation cascade. These properties may be exploited to treat active platelet-related or diffuse vascular bleeding. FPH has the potential to fulfill a large unmet patient need as an acute hemostatic treatment in severe bleeding, such as surgery and trauma. Competing Interests: Declaration of competing interests All authors are employees and option holders at Cellphire Therapeutics, Inc. W.A.A. has a patent application for the use of FPH (Thrombosomes) for the treatment of rare platelet disorders. G.M.F., B.K., and K.M. are named on several patent applications for the use of FPH (Thrombosomes) and CPP. (Copyright © 2023 Cellphire Therapeutics, Inc. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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