Background Primary pulmonary hypertension (PPH) is characterized by vascular injury of pulmonary arterioles, in which endothelial dysfunction may play a major role. Although continuous infusion of prostacyclin (prostaglandin I₂, a potent vasodilator released by vascular endothelial cells) improves the clinical status and survival in PPH, its mechanism or mechanisms of action remain unclear.

Methods and Results We measured endothelium-derived clotting factors and assayed platelet aggregation in 64 patients (26 adults and 38 children) with PPH before long-term PGI₂ therapy. Repeat studies were performed in 42 patients (18 adults, 24 children) after one year of PGI₂ therapy. At baseline, 87% of adults and 79% of children had abnormal platelet aggregation. In addition, factor VIII, von Willebrand (vW) antigen, and ristocetin cofactor levels were abnormally high in 92%, 72%, and 52%, respectively, of the adults versus 29%, 16%, and 16%, respectively, of the children (P<.005 adults versus children). With long-term PGI₂, platelet aggregation normalized in 83% of the adults and 80% of the children who had platelet aggregation abnormalities at baseline (P<.01). Factor VIII, vW antigen, and ristocetin cofactor also decreased with long-term PGI₂ in both groups (P<.02). The ratio of ristocetin cofactor to vW antigen, which may reflect biological activity of vW factor, increased with long-term PGI₂ in adults from an abnormally low level (0.6±0.2) to normal level (1.1±0.4), and in children the ratio increased from 0.8±0.3 to 1.3±0.4 (normal, 0.8 to 1.4).

Conclusions Alterations in the coagulation system may contribute to the pathogenesis of PPH; the normalization of these endothelial markers concomitant with improvement in hemodynamic parameters with long-term PGI₂ suggests that long-term PGI₂ remodels the pulmonary vascular bed with subsequent decreases in endothelial cell injury and hypercoagulability.