Clinical significance of circulating blood and endothelial cell microparticles in sickle-cell disease

Abstract

Increased thrombocyte activation leads to a higher likelihood of coagulation in sickle-cell disease. On the other hand, chronic inflammation and endothelial cell activation promote vaso-occlusion. The effect of circulating microparticles derived from erythrocytes, monocytes, thrombocytes, and endothelial cells on the vaso-occlusive process is unclear. This study aims to analyze the relationship between sickle-cell disease and miscellaneous organ complications by defining the circulating microparticles during the steady-state and painful crisis periods in 45 patients with sickle-cell disease. Microparticle analysis was conducted using an eight-parameter flow cytometric method, using CD61 PERCP, CD142PE, CD106 FITC, CD14 APC-H7, CD235a FITC, and Annexin-V APC monoclonal antibodies. Microparticle levels of sickle-cell patients were found to be significantly higher during both painful crisis and steady-state situations compared with the control group (for all, p < 0.001). Among these microparticles, levels of erythrocyte microparticles (eMPs) were significantly higher during crisis than in the steady-state period (eMP steady state vs. painful crisis: 7.59 ± 12.24 vs. 7.59 ± 12.24, respectively; p < 0.01). Microparticles, including eMPs, were not affected by hydroxyurea treatment. Their level did not reflect the high frequency of crisis (>3 times/year). Thrombocyte microparticle levels were found to be higher in patients with nephropathia than in those without (48.05 ± 40.23 vs. 7.67 ± 6.75, respectively; p < 0.049). Circulating microparticles seem to be involved in the pathogenesis of sickle-cell disease. eMPs may help with the management of crisis. Thrombocyte microparticles might predict renal damage induced by vaso-occlusion.

Coagulation abnormalities of sickle cell disease: Relationship with clinical outcomes and the effect of disease modifying therapies

“…There are conflicting reports on the association of platelet activation with TRV, with one study showing a correlation between activated GPIIb/IIIa receptor with TRV (73), while another showed no association between soluble CD40 ligand and TRV (40). Furthermore, higher levels of both platelet- and erythrocyte-derived microparticles have been reported in patients with histories of ACS and elevated TRV compared to those without either of these complications (143), although no significant differences were seen in the plasma concentrations of total-, endothelial cell derived-, and TF-positive microparticles in another study (91). …”

“…“Steady state” plasma levels of markers of in vivo thrombin and fibrin generation were not associated with histories of leg ulcers, retinopathy or priapism in adult SCD patients (24), nor with histories of splenic sequestration, hemolytic or aplastic crises in children (23). The number of platelet-derived microparticles was reported to be significantly higher in adult patients with albuminuria compared to those without, but no differences were observed in total microparticles or other circulating cell-derived microparticles (91). …”

“…There are inconsistent data regarding further increases of the concentration of total microparticles during acute painful episodes (38,88)(86,87). A history of at least 3 painful episodes in the previous year was associated with a higher “steady state” plasma concentration of monocyte-derived microparticles in a group of adults with HbSS and HbSβ-thalassemia (91), while another study of adult HbSS patients reported associations of painful episodes in the previous 2 years with lower concentrations of erythrocyte-derived microparticles, but higher total and platelet-derived microparticles (92). …”

“…There are conflicting reports on the effect of hydroxyurea on total, specific blood cell-derived and TF-bearing microparticles (31,78,91,173). A reduction in plasma D-dimer level in patients treated with hydroxyurea has been reported (78,174), with these studies reporting conflicting effects of hydroxyurea on circulating TAT complexes.…”

Extracellular Vesicles in Hematological Disorders

“…In children, both platelet and erythrocyte microparticle levels were positively correlated with aortic stiffness and pulmonary artery pressure, while they were found to correlate negatively with aortic distensibility 25. Nébor et al reported hydroxyurea treatment to be associated with a decrease in microparticles derived from erythrocytes and platelets,26 whereas in another study endothelial microparticle levels were not affected by hydroxyurea treatment 22…”