Treprostinil treatment decreases circulating platelet microvesicles and their procoagulant activity in pediatric pulmonary hypertension

Pediatr Pulmonol. 2019 Jan;54(1):66-72. doi: 10.1002/ppul.24190. Epub 2018 Nov 28.


Background: Pulmonary arterial hypertension (PAH) results from pulmonary vascular disease and may eventually lead to right heart failure and death. Vasodilator therapy has greatly improved PAH prognosis. Circulating microvesicles are considered as surrogate markers of endothelial and hematopoietic cell activation.

Aim: Thus, our purpose was to determine if MVs are upregulated in pediatric PAH such as reported in adult patients, and to analyze the impact of vasodilator therapies on MV count and function.

Patients: Population study consisted of 26 patients of median age 6.09 years, with Congenital Heart Disease (CHD) and elevated pulmonary vascular resistance (CHD-PAH) or idiopathic PAH (iPAH).

Results: Compared to healthy controls, all circulating MV subpopulations were found higher in untreated PAH patients. No significant differences of annexin-V+ total MV, endothelial, or leukocyte derived-MV counts were found between untreated patients and those receiving oral vasodilator therapies. Conversely, platelet MVs were significantly lower in the group treated with SC-treprostinil compared with both untreated PAH and oral therapy groups (P = 0.01), and exhibited a significant decrease of phospholipid procoagulant activity. Control samples treated in vitro with treprostinil at therapeutic concentrations showed as expected a significant decrease of platelet aggregation but also a reduced spontaneous MV generation.

Conclusion: Our results suggest that treprostinil, besides vasodilation, might exert its beneficial effect through an inhibition of platelet activation, resulting in a decreased number and procoagulant activity of circulating MVs.

Keywords: microvesicles; platelets; prostacyclin analogues; pulmonary hypertension.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Antihypertensive Agents / administration & dosage*
  • Cell-Derived Microparticles / drug effects
  • Child
  • Child, Preschool
  • Coagulants / chemistry
  • Epoprostenol / administration & dosage
  • Epoprostenol / analogs & derivatives*
  • Familial Primary Pulmonary Hypertension / drug therapy*
  • Female
  • Heart Defects, Congenital / complications
  • Heart Defects, Congenital / drug therapy
  • Humans
  • Hypertension, Pulmonary / drug therapy*
  • Infant
  • Lung / physiopathology
  • Male
  • Pulmonary Arterial Hypertension / complications
  • Pulmonary Arterial Hypertension / drug therapy
  • Pulmonary Circulation / drug effects
  • Vasodilator Agents / administration & dosage
  • Young Adult


  • Antihypertensive Agents
  • Coagulants
  • Vasodilator Agents
  • Epoprostenol
  • treprostinil