Résumé
We evaluated the correlation between decreased biological activity and abnormalities in the multimeric structure of plasma von Willebrand factor (vWF) in 27 pulmonary hypertensive patients (median age, 21 years). The biological activity of vWF was measured by the ristocetin cofactor assay and its multimeric structure was assessed by Western immunoblotting after SDS-agarose gel electrophoresis. In spite of high antigenic activity of vWF in plasma (139 ñ 65 vs 91 ñ 27 per cent in controls, P=0.003), the biological activity expressed as a percent of the control value was decreased in pulmonary hypertensive patients (60-88 per cent activity, 95 per cent CI for the mean). High molecular weight multimers (biologically active forms) were absent in patients and there was a significant increase in the concentration of low molecular weight polymers in comparison with normals (56 ñ 12 and 35 ñ 12 per cent of total multimer density, respectively, P<0.001). Multimeric abnormalities were positively correlated with plasma vWF levels (r=0.51, P=0.0007) and negatively correlated with vWF biological activity (r=-0.54, P=0.004). Thus, decreased biological function is related to abnormalities in the multimeric structure of vWF, possibility reflecting extensive endothelial dysfunction in pulmonary hypertension.