3.4 Symptomatic crises in CAS patients are associated with
formation of PMPs.
PMPs (also known as microvesicles) are particles of less than 1µm
diameter which are split from platelet cell membranes under conditions
of platelet activation or apoptosis, and interact with vascular
endothelium to modulate both inflammatory changes and eventual
(Pope et al. , 2016;
Rosinska et al. , 2017). In our
experiments (Fig. 4 ), plasma PMP content varied according to
group of subjects/patients (ANOVA: p = 0.03), and increased
significantly (p = 0.02, Bonferroni post hoc test) among patients
evaluated during the acute phase of CAS (Fig. 4 ).
3.5 GTN/NAC infusion reverses both platelet resistance to
NO and SD-1 release during acute phases of
CAS.
Anti-aggregatory effects of SNP were studied in whole blood samples
obtained from CAS patients in acute crises, before and during (2-12 hrs)
GTN/NAC intravenous infusion (Fig. 5 ). Following the initiation
of infusion of GTN/NAC, platelet aggregation in response to ADP
decreased marginally from 10.6 ± 0.5 to 9.1 ± 0.5 ohms (p = 0.05).
Furthermore, GTN/ NAC therapy significantly augmented anti-aggregatory
responses to SNP (n = 11; p = 0.003, Fig. 5A ).
There was a substantial fall in plasma SD-1 concentrations post onset of
GTN/NAC treatment (n = 6; p = 0.002; Fig. 5B ).