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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 (<jats:italic>i<\/jats:italic>cAMP) were observed by flow cytometry and enzyme\u2010linked immunosorbent assay. SCD\u2010PLTs demonstrated significantly greater adhesion than CON\u2010PLTs to FB. Participation of the \u03b1<jats:sub>IIb<\/jats:sub>\u03b2<jats:sub>3<\/jats:sub>\u2010integrin in SCD\u2010PLT adhesion was implicated by increased \u03b1<jats:sub>IIb<\/jats:sub>\u03b2<jats:sub>3<\/jats:sub>activation and data showing that an \u03b1<jats:sub>IIb<\/jats:sub>\u03b2<jats:sub>3<\/jats:sub>\u2010function\u2010inhibiting antibody significantly diminished SCD\u2010PLT adhesion to FB. Platelet activation was potentated by reductions in<jats:italic>i<\/jats:italic>cAMP; cAMP levels were decreased in SCD\u2010PLTs, being comparable to those of thrombin\u2010stimulated CON\u2010PLTs. Furthermore, SCD\u2010PLT adhesion to FB was significantly reduced by cilostazol, an inhibitor of cAMP\u2010hydrolyzing phosphodiesterase 3A (PDE3A). Both \u03b1<jats:sub>IIb<\/jats:sub>\u03b2<jats:sub>3<\/jats:sub>\u2010integrin activation and<jats:italic>i<\/jats:italic>cAMP correlated significantly with fetal haemoglobin in SCD. Accordingly, hydroxycarbamide therapy was associated with lower PLT adhesion and higher<jats:italic>i<\/jats:italic>cAMP. SCD\u2010PLTs may be capable of adhering to proteins encountered on the inflamed vascular wall and, potentially, participate in vaso\u2010occlusive processes. Hydroxycarbamide and, speculatively, nitric oxide donor or cyclic\u2010nucleotide\u2010targeted therapies may aid in the reversal of PLT adhesive properties in SCD.<\/jats:p>","DOI":"10.1111\/j.1365-2141.2010.08087.x","type":"journal-article","created":{"date-parts":[[2010,2,5]],"date-time":"2010-02-05T09:28:09Z","timestamp":1265362089000},"page":"280-288","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Increased adhesive properties of platelets in sickle cell disease: roles for \u03b1<sub>IIb<\/sub>\u03b2<sub>3<\/sub>\u2010mediated ligand binding, diminished cAMP signalling and increased phosphodiesterase 3A activity"],"prefix":"10.1111","volume":"149","author":[{"given":"Renata","family":"Proen\u00e7a\u2010Ferreira","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carla F.","family":"Franco\u2010Penteado","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabiola","family":"Traina","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara T. 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