Conversely, ET-1 activity is increased in PAH and mediates diverseeffects including vasoconstriction, remodelling and proliferation viaETA and ETB receptors.81 While the direct role of ET-1 in coagulation is unclear, sixmonths of dual ET receptor antagonism with macitentan in patients withPAH due to congenital heart disease was associated with improvementsin coagulation abnormalities.82 Thromboxane levels are also elevated in PAH, which is relevantto this review as thromboxane is a potent vasoconstrictor, plateletagonist and mitogen. This evidence concerns the gene EDN1 and congenital heart disease.