Platelet transfusion is a critical component of modern medical care. To make platelets readily available to patients, a reliable method for storage of platelet concentrates (PC) is required. Recent advances have been based on the development of """"""""second generation"""""""" containers which allow increased oxygen transport into the PC. Federal regulations permit storage in these containers for five days and there is data to support extension to seven days. However, after seven days of storage, there is a 25-50% reduction in in vivo vialbility after storage. The goal of this project will be to fill gaps in our knowledge concerning seven-day storage. PC will be stored at 20-24 degrees C for seven days in """"""""second generation"""""""" containers such as Fenwal's PL-732 and Cutter's CLX. For all PC, objective measurements which reflect platelet metabolism and morphologic and functional integrity will be made. Four specific areas will be examined: 1) Adenine nucleotide metabolism: Using high pressure liquid chromatography, high voltage electrophoresis, a firefly luminescence, we will follow the decline of platelet nucleotides and the increase in plasma hypoxanthine, and, using C 14-adenine and C14-hypoxanthine, we will assess the flux between intra platelete compartments and plasma, 2) Substrates in energy metabolism: Using thin layer chromatography, gas chromatography and C14-fatty acids, we will examine the role of lipid as substrate for oxidative energy metabolism. The role of aerobic glycolysis during PC storage will be examined by adding inhibitors of function and by storing in the absence of glucose, 3) Platelet morphology: Platelet density distributions will be examined to determine if morphologically abnormal forms after storage are concentrated in light fractions as they were in """"""""first generation"""""""" containers. In addition, the effects of storage at 30 degrees C, slow forms of agitation, and addition of diethylhexylphthalate (DEHP) on platelet morphology will be examined. 4) Platelet function: In vitro function (aggregation and ATP release using a lumiaggregometer) of platelets will be compared after storage in three """"""""second generation"""""""" containers"""""""" PL-732, CLX, and Terumo's DEHP container. With this knowledge, we hope to improve the quality of the product we provide to patients with the long-range goal of making seven-day stored PC as close as possible to fresh PC.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Research Project (R01)
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Hematology Subcommittee 2 (HEM)
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Thomas Jefferson University
Schools of Medicine
United States
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Murphy, S (1995) The oxidation of exogenously added organic anions by platelets facilitates maintenance of pH during their storage for transfusion at 22 degrees C. Blood 85:1929-35
Murphy, S; Shimizu, T; Miripol, J (1995) Platelet storage for transfusion in synthetic media: further optimization of ingredients and definition of their roles. Blood 86:3951-60
Shimizu, T; Murphy, S (1993) Roles of acetate and phosphate in the successful storage of platelet concentrates prepared with an acetate-containing additive solution. Transfusion 33:304-10
Bertolini, F; Murphy, S; Rebulla, P et al. (1992) Role of acetate during platelet storage in a synthetic medium. Transfusion 32:152-6
Murphy, S; Munoz, S; Parry-Billings, M et al. (1992) Amino acid metabolism during platelet storage for transfusion. Br J Haematol 81:585-90
Murphy, S; Kagen, L; Holme, S et al. (1991) Platelet storage in synthetic media lacking glucose and bicarbonate. Transfusion 31:16-20
Edenbrandt, C M; Murphy, S (1990) Adenine and guanine nucleotide metabolism during platelet storage at 22 degrees C. Blood 76:1884-92
Cesar, J; DiMinno, G; Alam, I et al. (1987) Plasma free fatty acid metabolism during storage of platelet concentrates for transfusion. Transfusion 27:434-7
Murphy, S (1986) Use of an arithmetic model for evaluation of in vivo platelet survival. Transfusion 26:26-7
Di Minno, G; Cerbone, A; Usberti, M et al. (1986) Platelet dysfunction in uremia. II. Correction by arachidonic acid of the impaired exposure of fibrinogen receptors by adenosine diphosphate or collagen. J Lab Clin Med 108:246-52

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