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Mechanisms of platelet clearance and translation to improve platelet storage.

Authors
  • Quach, M Edward1, 2
  • Chen, Wenchun1, 2
  • Li, Renhao1, 2
  • 1 Aflac Cancer and Blood Disorders Center, Children's Healthcare of Atlanta, Atlanta, GA; and.
  • 2 Department of Pediatrics, School of Medicine, Emory University, Atlanta, GA.
Type
Published Article
Journal
Blood
Publisher
American Society of Hematology
Publication Date
Apr 05, 2018
Volume
131
Issue
14
Pages
1512–1521
Identifiers
DOI: 10.1182/blood-2017-08-743229
PMID: 29475962
Source
Medline
Language
English
License
Unknown

Abstract

Hundreds of billions of platelets are cleared daily from circulation via efficient and highly regulated mechanisms. These mechanisms may be stimulated by exogenous reagents or environmental changes to accelerate platelet clearance, leading to thrombocytopenia. The interplay between antiapoptotic Bcl-xL and proapoptotic molecules Bax and Bak sets an internal clock for the platelet lifespan, and BH3-only proteins, mitochondrial permeabilization, and phosphatidylserine (PS) exposure may also contribute to apoptosis-induced platelet clearance. Binding of plasma von Willebrand factor or antibodies to the ligand-binding domain of glycoprotein Ibα (GPIbα) on platelets can activate GPIb-IX in a shear-dependent manner by inducing unfolding of the mechanosensory domain therein, and trigger downstream signaling in the platelet including desialylation and PS exposure. Deglycosylated platelets are recognized by the Ashwell-Morell receptor and potentially other scavenger receptors, and are rapidly cleared by hepatocytes and/or macrophages. Inhibitors of platelet clearance pathways, including inhibitors of GPIbα shedding, neuraminidases, and platelet signaling, are efficacious at preserving the viability of platelets during storage and improving their recovery and survival in vivo. Overall, common mechanisms of platelet clearance have begun to emerge, suggesting potential strategies to extend the shelf-life of platelets stored at room temperature or to enable refrigerated storage. © 2018 by The American Society of Hematology.

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