Fator von Willebrand e disfunçäo endotelial pulmonar. Implicaçöes prognósticas / von Willebrand factor and pulmonary vascular endothelial cell dysfunction. Prognostic implications

OBJETIVO - Avaliar alteraçöes quantitativas e estruturais do fator von Willebrand (fvW) circulante em 40 pacientes com hipertensäo pulmonar pré-capilar e verificar possíveis implicaçöes prognósticas dos resultados iniciais, em um ano de seguimento. MÉTODOS - A atividade antigênica plasmática do fator von Willebrand (vWF:Ag) foi analisada por imunoeletroforese. A concentraçäo de multímeros de baixo peso molecular em relaçäo...

Decreased biological activity is related to abnormal multimeric structure of von Willebrand factor in pulmonary hypertension

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.

Plasma anticoagulant system in patients with pulmonary hypertension

Adults with pulmonary hypertension and polycythemia (N=22) have low levels of plasma antithrombin III (84 ñ 18 vs 98 ñ 13½ for controls, N=35, P<0.005) and protein C (66ñ21 vs 125 ñ 30%, N 8, P<0.0002 but normal levels of total protein S. Data are reported as means ñ SD and percent normal values obtained for pooled plasma from normal healthy adults. Children with the same disorder (N = 6) also had low protein C levels (66 ñ 16 vs 85 ñ 5½, P < 0.025). Total protein S was normal for children, but free protein S was decreased (66 ñ 13 vs 91 ñ 23,, P < 0.02). Since the levels observed in these patients are above those reported for congenital deficiencies, the reduction in plasma levels of anticoagulant proteins may be the result of cronic intravascular coagulation. Furthermore, normal levels of plasminogen and fibrin degradation products suggested a localized disorder or an acquired decrease in fibronolytic activity