Mechanisms of platelet clearance and translation to improve platelet storage

被引:197
作者
Quach, M. Edward [1 ,2 ]
Chen, Wenchun [1 ,2 ]
Li, Renhao [1 ,2 ]
机构
[1] Childrens Healthcare Atlanta, Aflac Canc & Blood Disorders Ctr, Atlanta, GA USA
[2] Emory Univ, Sch Med, Dept Pediat, Atlanta, GA 30322 USA
基金
美国国家卫生研究院;
关键词
GLYCOPROTEIN-IB-ALPHA; INTRAVENOUS IMMUNOGLOBULIN-G; IMMUNE THROMBOCYTOPENIA; HEMOSTATIC FUNCTION; IN-VITRO; LIFE-SPAN; PHOSPHATIDYLSERINE EXPOSURE; ANTIPLATELET GPIIBIIIA; RELATIVE EFFICACY; RAPID CLEARANCE;
D O I
10.1182/blood-2017-08-743229
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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-x(L) 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 Ib alpha (GPIb alpha) 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 GPIba 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.
引用
收藏
页码:1512 / 1521
页数:10
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