Platelet aggregation (PA) has been shown to be decreased in pulmonary arterial hypertension (PAH) associated with the Eisenmenger syndrome (PAH-ES). Platelets probably become “exhausted” following chronic endogenous activation, with decreased response when aggregation is analyzed in vitro.
We analyzed platelet aggregation before and during administration of phosphodiesterase-5 inhibitors (PDE-5is, sildenafil and tadalafil) in PAH-ES adults.
Twenty-three naïve patients were aged 25 (18-40) years (median and interquartile range). Sildenafil (20mg t.i.d., n=11) or tadalafil (single daily dose of 40mg, n=12) were administered orally, and laboratory data were obtained at baseline, 3 and 6 months of treatment. Whole blood ADP-induced PA was analyzed by the impedance method.
At baseline, patients had decreased oxygen saturation (O2 sat. 87% ([80-92]%), increased hematocrit (Htc 54% [49-61%]) and platelet count of 210 (180-261) x 109 pl/L. Compared to normals, PA was 47% decreased and directly influenced by platelet count (R2= 0.54, p<0.001). Treatment with PDE-5is was followed by decrease in Htc (p<0.001), although resting O2 sat., did not change. There was a mild decrease in platelet count (p=0.093), particularly in the sildenafil group. Compared to baseline, PA improved (p=0.048) with further increase when it was normalized by platelet count (p=0.014). There were no differences between treatment groups.
In PAH-ES patients, in vitro PA was improved by treatment with PDE-5is. We speculate that this might be due to improvement of chronic endogenous platelet activation.