Improvement of von Willebrand factor proteolysis after prostacyclin infusion in severe pulmonary arterial hypertension

Background-The presence of dysfunctional von Willebrand factor (vWF) in pul monary arterial hypertension (PAH) was suggested to be related to increased proteolysis. Methods and Results-In 10 patients with severe PAH, we studied the proteoly sis of plasma vWF (VWF levels, multimeric distribution, proteolytic pattern , and cleaving protease activity) and hemodynamic variables (mean pulmonary artery pressure, cardiac index, and total pulmonary vascular resistance) a t baseline and 30 days after initiation of continuous prostacyclin infusion . At baseline, VWF levels were significantly increased, VWF proteolysis was excessive, and vWF-cleaving protease activity remained normal. These biolo gical abnormalities were reversible and paralleled the improvement of hemod ynamics under vasodilator treatment with prostacyclin. Conclusions-The excessive proteolysis of vWF in PAH is likely to be related to an increased susceptibility of VWF to proteases induced by high shear r ates rather than to an enhanced release of enzymes.