Oncogenic and angiogenic growth factors accumulate during routine storage of apheresis platelet concentrates.
OBJECTIVE
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 alpha-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-beta, and fibroblast growth factor-2, which may adversely affect cancer patients.


METHODS
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-beta 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.
Kanter
Julie
J
Department of Pediatrics, Washington University, St. Louis, Missouri, USA.
Khan
Samina Y
SY
Kelher
Marguerite
M
Gore
Lia
L
Silliman
Christopher C
CC
D020533:Angiogenesis Inhibitors / Q000627:therapeutic use; D042501:Angiogenic Proteins / Q000032:analysis / Q000097:blood / Q000378:metabolism*; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab; D001793:Blood Preservation / Q000009:adverse effects; D002273:Carcinogens / Q000032:analysis / Q000378:metabolism*; D016222:Fibroblast Growth Factor 2 / Q000032:analysis / Q000097:blood; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000032:analysis / Q000097:blood / Q000378:metabolism*; D010982:Platelet-Derived Growth Factor / Q000032:analysis; D010983:Plateletpheresis; D016212:Transforming Growth Factor beta / Q000032:analysis / Q000097:blood; D042461:Vascular Endothelial Growth Factor A / Q000032:analysis / Q000097:blood / Q000276:immunology
D020533:Angiogenesis Inhibitors; D042501:Angiogenic Proteins; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D002273:Carcinogens; D036341:Intercellular Signaling Peptides and Proteins; D010982:Platelet-Derived Growth Factor; D016212:Transforming Growth Factor beta; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; C095477:platelet-derived growth factor AB; D016222:Fibroblast Growth Factor 2; D000068258:Bevacizumab