Antioxidant prevents clearance of hemostatically competent platelets after long‐term cold storage. Issue 2 (27th November 2020)

• Record Type: Journal Article
• Authors: Hegde, Shailaja; Wellendorf, Ashley M.; Zheng, Yi; Cancelas, Jose A.
• Is Part Of: Transfusion. Volume 61:Issue 2(2021)
• Page Start: 557
• Page End: 567
• Publication Date: 2020-11-27
• Subjects: mitochondrial uncoupling -- platelet cold storage -- reactive oxygen species -- survival and bleeding time correction; Hematology -- Periodicals; Blood -- Transfusion -- Periodicals; Blood Group Antigens -- Periodicals; Blood Preservation -- Periodicals; Blood Transfusion -- Periodicals; 615
• DOI: 10.1111/trf.16200
• Languages: English
• ISSNs: 0041-1132

Abstract

Abstract: Background: Cold storage of platelets (PLTs) has the potential advantage of prolonging storage time while reducing posttransfusion infection given the decreased likelihood of bacterial outgrowth during storage and possibly beneficial effects in treating bleeding patients. However, cold storage reduces PLT survival through the induction of complex storage lesions, which are more accentuated when storage is prolonged. Study Design and Methods: Whole blood–derived PLT‐rich plasma concentrates from seven PLT pools (n = 5 donors per pool). PLT additive solution was added (67%/33% plasma) and the product was split into 50‐mL bags. Split units were stored in the presence or absence of 1 mM of N‐acetylcysteine (NAC) under agitation for up to 14 days at room temperature or in the cold and were analyzed for PLT activation, fibrinogen‐dependent spreading, microparticle formation, mitochondrial respiratory activity, reactive oxygen species (ROS) generation, as well as in vivo survival and bleeding time correction in immunodeficient mice. Results: Cold storage of PLTs for 7 days or longer induces significant PLT activation, cytoskeletal damage, impaired fibrinogen spreading, enhances mitochondrial metabolic decoupling and ROS generation, and increases macrophage‐dependent phagocytosis and macrophage‐independent clearance. Addition of NAC prevents PLT clearance and allows a correction of the prolonged bleeding time in thrombocytopenic, aspirin‐treated, immunodeficient mice. Conclusions: Long‐term cold storage induces mitochondrial uncoupling and increased proton leak and ROS generation. The resulting ROS is a crucial contributor to the increased macrophage‐dependent and ‐independent clearance of functional PLTs and can be prevented by the antioxidant NAC in a magnesium‐containing additive solution.