LAUSR

This month, readers are re-introduced to a classic review of platelets for transfusion from the TRANSFUSION archives. Since the introduction of platelets as a rescue therapy and prophylaxis for bleeding due to thrombocytopenia secondary to chemotherapy, there have been countless investigations into the preparation and storage methods for platelets to provide the optimal product for patients, including extending the storage time to alleviate inventory challenges. Since his early days as a fellow at the NIH to his leadership role at the Versiti Blood Center in Milwaukee and the Medical College of Wisconsin, Richard Aster has been a leader in the field with 185 PUBMED manuscripts related to platelets encompassing: methods of preparation and storage, anticoagulation, in vivo kinetics of transfused platelets, alloimmunization, heparin-induced thrombocytopenia, neonatal alloimmune thrombocytopenia, platelet compatibility, and other areas. As one of the longest continuously NIH-funded investigators, Dr Aster has made many contributions to this important area, and only recently retired. Along with his colleagues, Drs. Becker and Filip, Dr. Aster presents a brief review of the development of platelets for transfusion, highlighting many aspects of platelet preparation that are critical for providing the most effective product for treatment of patients. Quite interestingly, nearly all of these key points are still at the forefront of current efforts and needs for continued learning and development. ANTICOAGULATION and pH: Platelets were first prepared for transfusion using the strong divalent ion chelator EDTA (calcium dissociation constant KD,CaCitrate 1 = 0.02 nM). 2 While this approach avoided platelet aggregation, and the platelets remained effective against bleeding, the post-transfusion increments of these cells were poor. Zucker and Borrelli observed that the classic platelet discoid shape was maintained in citrateanticoagulated platelets but not in platelets prepared with EDTA. Of note, the discoid shape is the basis for the swirling phenomenon often used for a quality measure of platelets. Aster and Jandl examined citrateanticoagulated versus EDTA-anticoagulated platelets, and in radiolabeling studies, demonstrated that platelets were cleared by the liver and spleen. Anticoagulants containing citrate (KD,CaCitrate 1 = 0.6 mM) resulted in platelets with superior post-transfusion recoveries. Further, Aster demonstrated that when the pH was <6.8, aggregation was avoided. In early work, platelets prepared in ACD-A were additionally acidified with either citric acid or additional ACD-A before pelleting, thus permitting resuspension of the platelet concentrate. Later, it was observed that holding the pelleted platelet for 1 h also permitted resuspension, a standard step in the production of platelets from platelet rich plasma (PRP-platelets). This is likely due to local hypoxia in the platelet biomass that upregulates glycolysis, lactic acid production, and local decline in pH. This phenomenon also impacts platelets that are transported in our current platelet distribution network. Aster and colleagues also observed that warming of platelets to 37°C helped disperse aggregates; a trick sometimes employed by those of us doing laboratory investigations of platelets. COLD PLATELETS: Early platelets for transfusion were stored in the refrigerator, just as red cells and whole blood were stored. Following Murphy's and Gardener's seminal work demonstrating that storage of platelets at room temperature improved the circulation time of transfused platelets, the field began to move away from refrigerated platelet storage, although with some moving more slowly desiring to answer some important questions. Received: 7 March 2022 Accepted: 7 March 2022