Circulating von Willebrand Factor Antigen as a Predictor of Short-term Prognosis in Pulmonary Hypertension: OutcomeAlthough vWF:Ag and the etiology of pulmonary hypertension were shown to be statistically independent variables, from a biological point of view they seemed to be somewhat related to each other. Indeed, patients with primary pulmonary hypertension had relatively higher vW-F:Ag levels. We therefore speculate that these patients had a poorer short-term prognosis in part because they had more advanced endothelial cell dysfunction than patients with secondary pulmonary hypertension with similar levels of pulmonary artery pressure. This is not to say that a high vWF:Ag level is characteristic of primary pulmonary hypertension, because vWF:Ag levels in nonsurvivors with the secondary form were similarly high. Elevated vWF plasma levels seem to be a characteristic of patients with advanced disease. The possibility is raised that some patients with primary pulmonary hypertension who had relatively lower vWF: Ag levels have a more insidious disease and a better survival rate.
In our opinion, the rationale for measuring plasma vWF:Ag in patients with pulmonary hypertension seems to be the possibility of identifying patients with vWF:Ag levels of > 240%, because these levels clearly were associated with decreased life expectancy in our patients. Despite the excellent specificity of 93%, however, a plasma vWF:Ag level of > 240% was only 54% sensitive in identifying patients who are unlikely to survive 1 year. read To deal with this problem, it seems reasonable to perform serial measurements of vWF:Ag in patients with moderate to severe pulmonary hypertension and a plasma vWF: Ag level of < 240%. Plasma levels of vWF do seem to increase over time as the disease worsens. In three of our patients, changes in vWF:Ag levels correlated better with patient outcome than did initial vWF:Ag levels. A recommendation for serial measurements may not be warranted at this time because our data are limited, but this remains a possibility for future testing.
The exact pathophysiological linkage between increased vWF plasma levels and decreased short-term survival in patients with pulmonary hypertension remains to be determined. One possibility is a direct involvement of vWF in the disease process. High circulating concentrations of vWF in these patients could be associated with an increased risk of thrombotic events. As an adhesive protein, vWF is adsorbed rapidly on the surface of activated platelets and participates in platelet sequestration.