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FcγRIIa amplifies platelet activation and greater platelet expression of FcγRIIa identifies patients at greater risk of subsequent cardiovascular events. Thus, platelet expression of FcγRIIa may be useful to guide therapy. Because platelet function tests are impacted by preparative procedures and substantial intra-individual variability, we examined the impact of these factors on platelet expression of FcγRIIa in blood from healthy subjects and in patients after myocardial infarction (MI). Platelet expression of FcγRIIa was quantified with the use of flow cytometry. Blood was taken from healthy subjects and 114 patients after a MI in whom platelet expression of FcγRIIa was quantified before discharge and at 6 ± 1 months. Neither anticoagulants nor the antiplatelet agent cangrelor changed platelet expression of FcγRIIa. Intra-individual variation in platelet FcγRIIa expression was 8.5% ± 5% over the course of 1 month in healthy subjects. Platelet FcγRIIa expression was within 20% of the baseline value after 6 months in 71% of patients after MI. In summary, because FcγRIIa is a protein on the surface of platelets, assay conditions and antiplatelet agents do not change expression. Intra-individual variability in platelet expression of FcγRIIa is modest. Accordingly, platelet expression of FcγRIIa is a marker of increased platelet reactivity that can be reliably and repeatedly measured.Clinical Trial Registration: NCT02505217.

Whole genome sequencing of an individual completely devoid of plasma- and platelet-derived factor V (FV) identified 167 variants in his F5 gene including previously identified and damaging missense mutations at rs6027 and Leu90Ser. Because the administration of fresh frozen plasma (FFP) prevents gastrointestinal bleeding in this individual, its effects on his plasma- and platelet-derived FV concentrations were assessed. The patient's plasma FV levels peaked by 2 hours following FFP administration and were undetectable 96 hours later. In contrast, increased platelet-derived FV/Va concentrations were observed within 6 hours, peaked at 24 hours, decreased slowly over 7 days, and originated from megakaryocyte endocytosis and intracellular processing of plasma FV. Ten days after transfusion, no thrombin was generated in a tissue factor-initiated whole blood clotting assay unless exogenous FV was added, consistent with the complete absence of plasma FV. In marked contrast, release of the patient's platelet-derived FV/Va (7% of normal) following platelet activation resulted in robust thrombin generation, similar to that in an individual with normal plasma- and platelet-derived FV concentrations. Thus, total FV deficiency can be corrected by plasma administration, which partially repletes and sustains the platelet cofactor pool, thereby highlighting the critical role of platelet-derived FV/Va in ensuring hemostatic competence., (© 2015 by The American Society of Hematology.)

While platelets are well known to play a central role in hemostasis and thrombosis, there is emerging experimental evidence to suggest that they also mediate tumor cell growth, dissemination, and angiogenesis. An increase in platelet number (thrombocytosis) and activity is seen in patients with a wide spectrum of malignancies, and the former is correlated with a decrease in overall survival and poorer prognosis. Preclinical data suggest that circulating tumor cell partnerships with platelets in the blood facilitate tumor metastases through direct interactions and secreted bioactive proteins. Platelets form aggregates with tumor cells, thereby protecting them from host immune surveillance through physical shielding and induction of "platelet mimicry." There is also laboratory evidence to suggest that activated platelets interact with cancer cells within the tumor microenvironment through paracrine signaling and direct contact, thereby promoting tumor cell growth and survival. For example, platelets release mediators of both tumor angiogenesis and osteoclast resorption. The interplay between platelets and tumor cells is complex and bidirectional with involvement of multiple other components within the tumor microenvironment, including immune cells, endothelial cells, and the extracellular matrix. We review the role of platelets in tumor progression, emphasizing the opportunity these interactions afford to target platelets and platelet function to improve patient outcomes in the cancer prevention and treatment setting., (© 2013 Wiley Periodicals, Inc.)