Prostacyclin analogues decrease platelet aggregation but have no effect on thrombin generation, fibrin clot structure, and fibrinolysis in pulmonary arterial hypertension: PAPAYA coagulation

Abstract

Prostacyclin (PGI₂) analogues (epoprostenol, treprostonil, iloprost) are the cornerstone of pulmonary arterial hypertension (PAH) treatment. PGI₂ analogues inhibit platelet reactivity, but their impact on coagulation and fibrinolysis parameters has not been elucidated. We compared platelet reactivity, thrombin generation, clot permeation, and lysis properties in patients with PAH treated with PGI₂ analogues (n = 20) and those not receiving PGI₂ analogues (n = 20). Platelet reactivity was lower in patients treated with PGI₂ analogues, compared to the control group, as evaluated with arachidonic acid (ASPI), adenosine diphosphate (ADP), and thrombin receptor-activating peptide-6 (TRAP) tests (p = .009, p = .02, p = .007, respectively). In the subgroup analysis, both treprostinil and epoprostenol decreased platelet reactivity to the similar extent. There were no differences regarding thrombin generation, clot permeation, and lysis parameters in patients receiving and not receiving PGI₂ analogues (p ≥ .60 for all). In the subgroup analysis, there were no differences regarding coagulation and fibrinolysis parameters between treprostinil, epoprostenol, and no PGI₂ analogues. To conclude, patients with PAH treated with PGI₂ analogues have reduced platelet reactivity, but similar clot formation and lysis parameters, compared to patients not receiving PGI₂ analogues. Further randomized clinical trials are required to confirm these findings.

Keywords: Fibrin clot; fibrinolysis; platelet reactivity; prostacyclin analogues; pulmonary arterial hypertension; thrombin generation.