Refrigeration-Induced Binding of von Willebrand Factor Facilitates Fast Clearance of Refrigerated Platelets. Arterioscler Thromb Vasc Biol 2017 Dec;37(12):2271-2279
Date
11/04/2017Pubmed ID
29097365Pubmed Central ID
PMC5699930DOI
10.1161/ATVBAHA.117.310062Scopus ID
2-s2.0-85038262852 (requires institutional sign-in at Scopus site) 42 CitationsAbstract
OBJECTIVE: Apheresis platelets for transfusion treatment are currently stored at room temperature because after refrigeration platelets are rapidly cleared on transfusion. In this study, the role of von Willebrand factor (VWF) in the clearance of refrigerated platelets is addressed.
APPROACH AND RESULTS: Human and murine platelets were refrigerated in gas-permeable bags at 4°C for 24 hours. VWF binding, platelet signaling events, and platelet post-transfusion recovery and survival were measured. After refrigeration, the binding of plasma VWF to platelets was drastically increased, confirming earlier studies. The binding was blocked by peptide OS1 that bound specifically to platelet glycoprotein (GP)Ibα and was absent in VWF-/- plasma. Although surface expression of GPIbα was reduced after refrigeration, refrigeration-induced VWF binding under physiological shear induced unfolding of the GPIbα mechanosensory domain on the platelet, as evidenced by increased exposure of a linear epitope therein. Refrigeration and shear treatment also induced small elevation of intracellular Ca2+, phosphatidylserine exposure, and desialylation of platelets, which were absent in VWF-/- platelets or inhibited by OS1, which is a monomeric 11-residue peptide (CTERMALHNLC). Furthermore, refrigerated VWF-/- platelets displayed increased post-transfusion recovery and survival than wild-type ones. Similarly, adding OS1 to transgenic murine platelets expressing only human GPIbα during refrigeration improved their post-transfusion recovery and survival.
CONCLUSIONS: Refrigeration-induced binding of VWF to platelets facilitates their rapid clearance by inducing GPIbα-mediated signaling. Our results suggest that inhibition of the VWF-GPIbα interaction may be a potential strategy to enable refrigeration of platelets for transfusion treatment.
Author List
Chen W, Druzak SA, Wang Y, Josephson CD, Hoffmeister KM, Ware J, Li RAuthor
Karin Hoffmeister MD Professor in the Biochemistry department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsBinding, Competitive
Blood Platelets
Blood Preservation
Cold Temperature
Genotype
Humans
Mice, Inbred C57BL
Mice, Knockout
Mice, Transgenic
Peptides
Phenotype
Platelet Activation
Platelet Glycoprotein GPIb-IX Complex
Platelet Transfusion
Protein Binding
Protein Conformation
Protein Unfolding
Refrigeration
Signal Transduction
Structure-Activity Relationship
Time Factors
von Willebrand Factor