title: The influence of bevacizumab on platelet function.
abstract: Systemic treatment with bevacizumab is associated with increased rates of arterial and venous thromboembolism and haemorrhage. In order to investigate the pathophysiological mechanism involved, platelet adhesive and aggregatory functions were tested with a platelet function analyser (PFA-100®) in an in vitro study and in a longitudinal clinical observation study. For the in vitro study, blood from ten healthy volunteers was incubated with different concentrations of bevacizumab (0-1000 μg/ml plasma) and vascular endothelial growth factor (0-500 μg/ml). In the clinical observation study, PFA-100® closure times (CTs) and soluble P-selectin (sP-selectin) serum levels as a serological marker of platelet activation were assessed in 20 patients with metastatic cancer who were treated with bevacizumab in addition to cytotoxic chemotherapy. No significant changes of PFA-100® CTs were observed in the in vitro study. In the clinical observation study, mean PFA-100® CTs after treatment with bevacizumab were unchanged. sP-selectin was decreased after bevacizumab infusion by 18% (p = 0.045), which could suggest an inhibitory action on platelets. Our data do not support the view that increased platelet activation or increased platelet adhesiveness and aggregation by bevacizumab are relevant mechanisms for thrombus formation in clinical practice.
authors.affiliation: Division of Oncology, Department of Medicine, Kantonsspital Graubünden, Loéstrasse, Chur, CH. fehrmartin@yahoo.de
authors.forename: M
authors.initials: M
authors.lastname: Fehr
authors.forename: S
authors.initials: S
authors.lastname: Catschegn
authors.forename: W H
authors.initials: WH
authors.lastname: Reinhart
authors.forename: J
authors.initials: J
authors.lastname: Madon
authors.forename: L
authors.initials: L
authors.lastname: Asmis
authors.forename: R
authors.initials: R
authors.lastname: Cathomas
authors.forename: R
authors.initials: R
authors.lastname: von Moos
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D061067:Antibodies, Monoclonal, Humanized / Q000494:pharmacology*; D000941:Antigens / Q000097:blood / Q000276:immunology; D000068258:Bevacizumab; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D019007:P-Selectin / Q000097:blood; D010973:Platelet Adhesiveness / Q000187:drug effects*; D010974:Platelet Aggregation / Q000187:drug effects*; D010979:Platelet Function Tests; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology; D014841:von Willebrand Factor / Q000276:immunology
chemical_list: D020533:Angiogenesis Inhibitors; D061067:Antibodies, Monoclonal, Humanized; D000941:Antigens; D019007:P-Selectin; D042461:Vascular Endothelial Growth Factor A; D014841:von Willebrand Factor; D000068258:Bevacizumab