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- Title
Increased adhesive properties of platelets in sickle cell disease: roles for α<sub>IIb</sub>β<sub>3</sub>-mediated ligand binding, diminished cAMP signalling and increased phosphodiesterase 3A activity.
- Authors
Proença-Ferreira, Renata; Franco-Penteado, Carla F.; Traina, Fabiola; Saad, Sara T. O.; Costa, Fernando F.; Conran, Nicola
- Abstract
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 ( icAMP) were observed by flow cytometry and enzyme-linked immunosorbent assay. SCD-PLTs demonstrated significantly greater adhesion than CON-PLTs to FB. Participation of the αIIbβ3-integrin in SCD-PLT adhesion was implicated by increased αIIbβ3 activation and data showing that an αIIbβ3-function-inhibiting antibody significantly diminished SCD-PLT adhesion to FB. Platelet activation was potentated by reductions in icAMP; 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 αIIbβ3-integrin activation and icAMP correlated significantly with fetal haemoglobin in SCD. Accordingly, hydroxycarbamide therapy was associated with lower PLT adhesion and higher icAMP. 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.
- Subjects
BLOOD platelets; SICKLE cell anemia; LIGAND binding (Biochemistry); PHOSPHODIESTERASES; FIBRINOGEN; ENZYME-linked immunosorbent assay
- Publication
British Journal of Haematology, 2010, Vol 149, Issue 2, p280
- ISSN
0007-1048
- Publication type
Article
- DOI
10.1111/j.1365-2141.2010.08087.x