Introduction: Vasodilator therapy has greatly improved Pulmonary arterial hypertension (PAH) prognosis. Increased numbers of circulating microparticles (MPs) are found in adult PAH patients and might correlate with disease severity. Therefore, our purpose was to determine if MPs are upregulated in pediatric PAH, and the impact of vasodilator therapies on MPs count and function.
Methods: Population study consisted of 27 patients with Congenital Heart Disease (CHD) and elevated pulmonary vascular resistance (CHD-PAH) or idiopathic PAH (iPAH) with a median age of 6.09 years. Among the 27 patients, 12 of them never received any therapy, 8 received one or two oral vasodilators (bosentan and/or sildenafil) and 6 received a triple therapy associating bosentan, sildenafil and SC-treprostinil.
Results: Compared to healthy controls, all circulating MP subpopulations were found higher in untreated PAH patients confirming results of adult PAH patients. No significant differences were found between untreated patients and those receiving oral vasodilator therapies, whatever the combination (sildenafil and/or bosentan) or the MP subpopulation tested. Add-on therapy with SC-treprostinil did not modify annexin-V+, endothelial or leukocytes derived-MPs compared to untreated PAH. Conversely, platelet MPs were significantly lower in the group treated with SC-treprostinil compared with both untreated PAH and oral therapy groups (P = 0.01). We confirmed a significant decrease of platelet MP generation in treprostinil-treated samples in vitro. Further, MPs phospholipid-related procoagulant properties were quantified using a fibrin generation test and we found a significant decrease of phospholipid procoagulant activity decrease procoagulant potential in treprostinil treated-patients in contrast to non-treated or oral vasodilator treated patients.
Conclusions: Thus, our results suggest that treprostinil could exert its beneficial effect through antiplatelet activity and a decreased procoagulant activity of circulating MPs. Our results also suggest that initiating up-front a triple therapy could also reduce thrombotic events and thus disease worsening.