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Oncogenic and Angiogenic Growth Factors Accumulate during Routine Storage of Apheresis Platelet Concentrates

Authors' Affiliations: ¹ Department of Pediatrics, Washington University, St. Louis, Missouri; Departments of ² Pediatrics and ³ Surgery, School of Medicine, University of Colorado at Denver; ⁴ Bonfils Blood Center, Denver, Colorado; and ⁵ Pediatrics and Developmental Therapeutics Program, University of Colorado Cancer Center, Aurora, Colorado

Requests for reprints: Christopher C. Silliman, Bonfils Blood Center, 717 Yosemite Street, Denver, CO 80230. Phone: 303-363-2246; Fax: 303-340-2616; E-mail: christopher.silliman{at}uchsc.edu.

Purpose: Platelet concentrates are important for support of patients with malignancies requiring myelotoxic chemotherapy. During storage, 10% to 15% of platelets may become activated resulting in the release of -granules, which contain growth factors. We hypothesize that, during storage, growth factors accumulate in the plasma, specifically platelet-derived growth factor, vascular endothelial growth factor (VEGF), transforming growth factor-β, and fibroblast growth factor-2, which may adversely affect cancer patients.

Experimental Design: The concentrations of growth factors were measured by ELISA from the plasma of apheresis platelets serially throughout storage (days 1, 3, 5, and 7) and compared with concentrations in fresh plasma from healthy blood donors. Washing was evaluated as a method of growth factor removal, and an in vitro model of platelet transfusion in a patient receiving Bevacizumab (Avastin) using immunoprecipitation was employed to determine if Bevacizumab would be bound by the VEGF in apheresis platelets.

Results: VEGF, platelet-derived growth factor, and transforming growth factor-β were increased on day 1 versus fresh plasma and throughout storage reaching a relative maximum at outdate (P < 0.01, day 5 or 7). Fibroblast growth factor-2 concentrations were significantly increased on day 7 alone versus day 1 or to fresh plasma (P < 0.01). Washing removed 41 ± 11% to 56 ± 2% of the growth factors. Bevacizumab effectively bound the VEGF from apheresis platelets, with significant amounts of VEGF remaining in the supernatant.

Conclusions: Significant amounts of growth factors are present in apheresis platelets due to the isolation procedures, and these concentrations increase over storage, which may be partially removed by washing. In addition, apheresis platelet transfusion could affect cancer treatment by binding monoclonal antibodies directed against growth factors of tumor origin.