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Arterioscler Thromb Vasc Biol. 2017 Dec;37(12):2271-2279. doi: 10.1161/ATVBAHA.117.310062. Epub 2017 Nov 2.

Refrigeration-Induced Binding of von Willebrand Factor Facilitates Fast Clearance of Refrigerated Platelets.

Author information

1
From the Aflac Cancer and Blood Disorders Center, Children's Healthcare of Atlanta, GA (W.C., S.A.D., Y.W., C.D.J., R.L.); Department of Pediatrics (W.C., S.A.D., Y.W., C.D.J., R.L.) and Department of Pathology (C.D.J.), Emory University School of Medicine, Atlanta, GA; Blood Research Institute, BloodCenter of Wisconsin, Milwaukee (K.M.H.); and Department of Physiology and Biophysics, University of Arkansas for Medical Sciences, Little Rock (J.W.).
2
From the Aflac Cancer and Blood Disorders Center, Children's Healthcare of Atlanta, GA (W.C., S.A.D., Y.W., C.D.J., R.L.); Department of Pediatrics (W.C., S.A.D., Y.W., C.D.J., R.L.) and Department of Pathology (C.D.J.), Emory University School of Medicine, Atlanta, GA; Blood Research Institute, BloodCenter of Wisconsin, Milwaukee (K.M.H.); and Department of Physiology and Biophysics, University of Arkansas for Medical Sciences, Little Rock (J.W.). renhao.li@emory.edu.

Abstract

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.

KEYWORDS:

phosphatidylserine; platelet transfusion; refrigeration; temperature; von Willebrand factor

PMID:
29097365
PMCID:
PMC5699930
DOI:
10.1161/ATVBAHA.117.310062
[Indexed for MEDLINE]
Free PMC Article

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