title: The clearance mechanism of chilled blood platelets.
abstract: Platelet transfusion is a very common lifesaving medical procedure. Not widely known is the fact that platelets, unlike other blood cells, rapidly leave the circulation if refrigerated prior to transfusion. This peculiarity requires blood services to store platelets at room temperature, limiting platelet supplies for clinical needs. Here, we describe the mechanism of this clearance system, a longstanding mystery. Chilling platelets clusters their von Willebrand (vWf) receptors, eliciting recognition of mouse and human platelets by hepatic macrophage complement type 3 (CR3) receptors. CR3-expressing but not CR3-deficient mice exposed to cold rapidly decrease platelet counts. Cooling primes platelets for activation. We propose that platelets are thermosensors, primed at peripheral sites where most injuries occurred throughout evolution. Clearance prevents pathologic thrombosis by primed platelets. Chilled platelets bind vWf and function normally in vitro and ex vivo after transfusion into CR3-deficient mice. Therefore, GPIb modification might permit cold platelet storage.
authors.affiliation: Division of Hematology, Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA. khofmeister@rics.bwh.harvard.edu
authors.forename: Karin M
authors.initials: KM
authors.lastname: Hoffmeister
authors.forename: Thomas W
authors.initials: TW
authors.lastname: Felbinger
authors.forename: Hervé
authors.initials: H
authors.lastname: Falet
authors.forename: Cécile V
authors.initials: CV
authors.lastname: Denis
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Bergmeier
authors.forename: Tanya N
authors.initials: TN
authors.lastname: Mayadas
authors.forename: Ulrich H
authors.initials: UH
authors.lastname: von Andrian
authors.forename: Denisa D
authors.initials: DD
authors.lastname: Wagner
authors.forename: Thomas P
authors.initials: TP
authors.lastname: Stossel
authors.forename: John H
authors.initials: JH
authors.lastname: Hartwig
mesh_terms: D000818:Animals; D001792:Blood Platelets / Q000378:metabolism / Q000502:physiology*; D002470:Cell Survival; D003080:Cold Temperature; D006801:Humans; D066298:In Vitro Techniques; D007728:Kupffer Cells / Q000378:metabolism; D008099:Liver / Q000166:cytology / Q000502:physiology; D016177:Macrophage-1 Antigen / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D010587:Phagocytosis; D015539:Platelet Activation; D014841:von Willebrand Factor / Q000378:metabolism
chemical_list: D016177:Macrophage-1 Antigen; D014841:von Willebrand Factor