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• W2028236795 abstract "Summary Whilst high pro‐coagulant activity is reported in sickle cell disease (SCD), the precise role of platelets (PLTs) in SCD inflammatory and vaso‐occlusive processes is unclear. Adhesion of PLTs from healthy controls (CON), SCD individuals (SCD) and SCD patients on hydroxycarbamide (SCDHC) to fibrinogen (FB) was compared using static adhesion assays. PLT adhesion molecules and intraplatelet cyclic adenosine monophosphate ( i cAMP) were observed by flow cytometry and enzyme‐linked immunosorbent assay. SCD‐PLTs demonstrated significantly greater adhesion than CON‐PLTs to FB. Participation of the α IIb β 3 ‐integrin in SCD‐PLT adhesion was implicated by increased α IIb β 3 activation and data showing that an α IIb β 3 ‐function‐inhibiting antibody significantly diminished SCD‐PLT adhesion to FB. Platelet activation was potentated by reductions in i cAMP; cAMP levels were decreased in SCD‐PLTs, being comparable to those of thrombin‐stimulated CON‐PLTs. Furthermore, SCD‐PLT adhesion to FB was significantly reduced by cilostazol, an inhibitor of cAMP‐hydrolyzing phosphodiesterase 3A (PDE3A). Both α IIb β 3 ‐integrin activation and i cAMP correlated significantly with fetal haemoglobin in SCD. Accordingly, hydroxycarbamide therapy was associated with lower PLT adhesion and higher i cAMP. SCD‐PLTs may be capable of adhering to proteins encountered on the inflamed vascular wall and, potentially, participate in vaso‐occlusive processes. Hydroxycarbamide and, speculatively, nitric oxide donor or cyclic‐nucleotide‐targeted therapies may aid in the reversal of PLT adhesive properties in SCD." @default.
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• W2028236795 date "2010-03-22" @default.
• W2028236795 modified "2023-10-17" @default.
• W2028236795 title "Increased adhesive properties of platelets in sickle cell disease: roles for α_IIbβ₃-mediated ligand binding, diminished cAMP signalling and increased phosphodiesterase 3A activity" @default.
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• W2028236795 doi "https://doi.org/10.1111/j.1365-2141.2010.08087.x" @default.
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