Platelet activation patterns in platelet size sub-populations: differential responses to aspirin in vitro |
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Authors: | Kiran Kumar R Mangalpally Alan Siqueiros-Garcia Muthiah Vaduganathan Jing-Fei Dong Neal S Kleiman Sasidhar Guthikonda |
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Institution: | (1) The Methodist Hospital Research Institute and The Methodist DeBakey Heart and Vascular Center, Houston, TX, USA;(2) Thrombosis Section, Department of Medicine, Baylor College of Medicine, Houston, TX, USA;(3) Department of Cardiology, The Methodist DeBakey Heart and Vascular Center, 6565 Fannin St./Mail Station F-1035, Houston, TX 77030, USA; |
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Abstract: | Abstract Circulating platelets are heterogeneous in size and structure. Whether this translates into differences in platelet function
and efficacy of antiplatelet therapy is unclear. Hence, we decided to investigate the activation patterns among different
platelet populations differentiated by size, and to compare the inhibitory effects of aspirin in these populations. Circulating
platelets from 9 healthy volunteers were separated by size and stratified into the largest and smallest quintiles. Platelets
were stimulated with 75 μM arachidonic acid (AA), 10 μM ADP or 25 μM TRAP. Alpha-granule protein secretion and expression
(P-selectin, VWF, fibrinogen), surface-protein activation (activated integrin αIIbβ3) were assessed. Platelet thromboxane
B2 (TxB2) synthesis following AA stimulation was measured in vitro before and after incubation with 265 μM aspirin. Reticulated (juvenile)
platelets were assessed using thiazole orange staining. A greater number of large platelets in the largest quintile were reticulated
compared with the smallest quintile (6.1 ± 2.8% vs. 1.2 ± 1.5% respectively, p < 0.001). Larger platelets also synthesized more TxB2 than small platelets both before (1348 ± 276 pg/mL vs. 1023 ± 214 pg/mL, respectively, p = 0.01) and after aspirin (1029 ± 190 pg/mL vs. 851 ± 159 pg/mL, respectively, p = 0.03). After stimulation with each agonist, a greater proportion of large platelets bound fibrinogen, VWF, P-selectin and
activated integrin αIIbβ3 than small platelets both in the presence and in the absence of in vitro aspirin. In an in vitro
setting, large platelets appear to be more active than small platelets and continue to be more active even after in vitro
aspirin. |
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