This abnormal “clearance” of active species of vWF may explain partly the decreased biological activity of plasma vWF that is observed in patients with pulmonary hypertension. Consistent with this hypothesis is the observation that the larger multimers of vWF are lacking when patient plasma is analyzed in agarose gels. Preliminary data obtained from a smaller group of patients in our laboratory suggest that structural abnormalities of vWF also are associated with a worrisome prognosis in patients with pulmonary hypertension. The second possibility is that vWF does not participate directly in the progression of the disase. In this case, vWF would be coexpressed with another molecule that is relevant from the pathophysiological point of view. Endothelin-1 is a likely candidate, because it acts as a dual-function mediator promoting vasoconstriction and smooth muscle cell growth and is found in large amounts in arteries in patients with pulmonary hypertension The third possibility is that a worsening of the disease process is determined by a complex and unpredictable association of biological events. In this case, the increased release of vWF from Weibel-Palade bodies could be a result of the nonspecific elevation of cytosolic free calcium within dysfunctional endothelial cells.
In conclusion, a group of patients with precapillaiy pulmonary hypertension with significantly decreased short-term life expectancy exists, to whom specific attention should be paid. These patients would be the logical candidates for heart-lung transplantation. add comment canadian family pharmacy. Several predictors of survival have been proposed for identifying such patients, including clinical, hemodynamic, and histopathological parameters. In our opinion, as many variables as possible should be taken into consideration for estimating the probability of survival in such a complex clinical situation. An advantage of including biochemical parameters in the determination of prognosis for these patients seems to be the possibility of repeated measurements by noninvasive procedures during the course of the disease. Based on our findings, we would like to suggest that biochemical indicators of endothelial dysfunction may be used as prognostic indicators in patients with pulmonary hypertension. In particular, a plasma vWF:Ag level of > 240% seems to be very specific in the identification of patients who are unlikely to survive 1 year. In addition, serial measurements of vWF :Ag levels over time may increase the likelihood of detecting such high levels. Finally, we speculate that biochemical markers might be useful for monitoring endothelial cell function during pharmacological interventions such as intravenous prostacyclin administration.