Abstract
Biomarker assessment from blood samples is frequently based on measurements in serum or plasma. By doing so, the biomarker content of blood cells is neglected. The potential importance of platelets in such studies is exemplified by knowledge obtained from recent studies on cancer. Circulating platelets contain vast amounts of bioactive proteins in their granules, such as growth factors, chemokines, cytokines, and proteases, which they can secrete on activation. 1 Sabrkhany S Griffioen AW oude Egbrink MG The role of blood platelets in tumor angiogenesis. Biochim Biophys Acta. 2011; 1815: 189-196 Crossref PubMed Scopus (126) Google Scholar These proteins are either synthesised or taken up by the megakaryocytes that produce the platelets, or selectively absorbed from the blood by the circulating platelets themselves. 2 Klement GL Yip TT Cassiola F et al. Platelets actively sequester angiogenesis regulators. Blood. 2009; 113: 2835-2842 Crossref PubMed Scopus (255) Google Scholar , 3 Zaslavsky A Baek KH Lynch RC et al. Platelet-derived thrombospondin-1 is a critical negative regulator and potential biomarker of angiogenesis. Blood. 2010; 115: 4605-4613 Crossref PubMed Scopus (144) Google Scholar As a result, the concentration of these potential biomarkers is much higher inside platelets than in plasma. 2 Klement GL Yip TT Cassiola F et al. Platelets actively sequester angiogenesis regulators. Blood. 2009; 113: 2835-2842 Crossref PubMed Scopus (255) Google Scholar , 4 Peterson JE Zurakowski D Italiano JE et al. Normal ranges of angiogenesis regulatory proteins in human platelets. Am J Hematol. 2010; 85: 487-493 Crossref PubMed Scopus (124) Google Scholar In addition, platelets from—for example—patients with cancer might have a higher growth factor content than do platelets from healthy controls. 5 Peterson JE Zurakowski D Italiano JE et al. VEGF, PF4 and PDGF are elevated in platelets of colorectal cancer patients. Angiogenesis. 2012; 15: 265-273 Crossref PubMed Scopus (169) Google Scholar Animal studies have shown that platelets are able to sequester angiogenesis regulatory proteins secreted from clinically undetectable tumours (measuring <1 mm3), resulting in higher concentrations of these proteins in platelets without significant changes in plasma concentrations. 2 Klement GL Yip TT Cassiola F et al. Platelets actively sequester angiogenesis regulators. Blood. 2009; 113: 2835-2842 Crossref PubMed Scopus (255) Google Scholar In diseases other than cancer, platelet characteristics and content are also potentially interesting biomarkers. 6 Kamath S Blann AD Caine GJ et al. Platelet P-selectin levels in relation to plasma soluble P-selectin and beta-thromboglobulin levels in atrial fibrillation. Stroke. 2002; 33: 1237-1242 Crossref PubMed Scopus (64) Google Scholar Therefore, use of measurements exclusively from plasma or serum may not be sufficient for the understanding of underlying biological processes and could obscure the presence of biomarkers.
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