Article prostacyclin analogues inhibit platelet reactivity, extracellular vesicle release and thrombus formation in patients with pulmonary arterial hypertension

Aleksandra Gąsecka, Marta Banaszkiewicz, Rienk Nieuwland, Edwin van der Pol, Najat Hajji, Hubert Mutwil, Sylwester Rogula, Wiktoria Rutkowska, Kinga Pluta, Ceren Eyileten, Marek Postuła, Szymon Darocha, Zenon Huczek, Grzegorz Opolski, Krzysztof J. Filipiak, Adam Torbicki, Marcin Kurzyna

Research output: Contribution to journalArticleAcademicpeer-review

14 Citations (Scopus)


(1) Background: Prostacyclin analogues (epoprostenol, treprostinil, and iloprost) induce va-sodilation in pulmonary arterial hypertension (PAH) but also inhibit platelet function. (2) Objectives: We assessed platelet function in PAH patients treated with prostacyclin analogues and not receiving prostacyclin analogues. (3) Methods: Venous blood was collected from 42 patients treated with prosta-cyclin analogues (49.5 ± 15.9 years, 81% female) and 38 patients not receiving prostacyclin analogues (55.5 ± 15.6 years, 74% female). Platelet reactivity was analyzed by impedance aggregometry using arachidonic acid (AA; 0.5 mM), adenosine diphosphate (ADP; 6.5 µM), and thrombin receptor-activating peptide (TRAP; 32 µM) as agonists. In a subset of patients, concentrations of extracellular vesicles (EVs) from all platelets (CD61+), activated platelets (CD61+/CD62P+), leukocytes (CD45+), and endothelial cells (CD146+) were analyzed by flow cytometry. Platelet-rich thrombus formation was measured using a whole blood perfusion system. (4) Results: Compared to controls, PAH patients treated with prostacyclin analogues had lower platelet reactivity in response to AA and ADP (p = 0.01 for both), lower concentrations of platelet and leukocyte EVs (p ≤ 0.04), delayed thrombus formation (p ≤ 0.003), and decreased thrombus size (p = 0.008). Epoprostenol did not affect platelet reactivity but decreased the concentrations of platelet and leukocyte EVs (p ≤ 0.04). Treprostinil decreased platelet reactivity in response to AA and ADP (p ≤ 0.02) but had no effect on the concentrations of EVs. All prostacyclin analogues delayed thrombus formation and decreased thrombus size (p ≤ 0.04). (5) Conclusions: PAH patients treated with prostacyclin analogues had impaired platelet reactivity, EV release, and thrombus formation, compared to patients not receiving prostacyclin analogues.
Original languageEnglish
Article number1024
Pages (from-to)1-15
Number of pages15
JournalJournal of Clinical Medicine
Issue number5
Publication statusPublished - 1 Mar 2021


  • Extracellular vesicles
  • Platelet reactivity
  • Prostacyclin analogues
  • Pulmonary arterial hypertension
  • Thrombus formation

Cite this