Endothelial dysfunction associated with chronic intravascular coagulation in secondary pulmonary hypertension

Altered endothelial anti-thrombotic properties have been observed in primary and secondary pulmonary hypertension. In the Eisenmenger syndrome, correlations of these abnormalities with the clinical status and occurrence of chronic intravascular coagulation (CIC) have not been confirmed. The purpose of this study was to investigate whether the occurrence of CIC, as determined by circulating levels of D-dimer is associated with changes in endothelial markers in Eisenmenger patients; and to identify variables that correlate with the severity of clinical presentation. Twenty-one patients were enrolled (ages, 4-52 years). Plasma levels of D-dimer, tissue plasminogen activator (t-PA), thrombomodulin, and von Willebrand factor antigen (vWF:Ag) were measured with enzyme-linked immunosorbent assay. Univariate and multivariate analyses were used to differentiate patients with stable (group 1, N = 12) from those with unstable disease (group 2, N=9). Increased t-PA (p<0.0001) and vWF:Ag (p=0.001) and decreased thrombomodulin (p<0.0001) were associated with increased D-dimer levels (p=0.0201) in patients. Group 2 had a higher prevalence of affected women (p=0.0242), lower arterial oxygen saturation, and higher t-PA levels compared with group 1 (p<0.0001, discriminant analysis). t-PA and vWF:Ag correlated positively in group 2 (r=0.71, p=0.0309), but not in group 1 (r=0.25, p=NS). Two patients in group 2 but none in group 1 had episodes of pulmonary arterial thrombosis. Endothelial dysfunction is associated with evidence of CIC and correlates to some extent with the severity of symptoms in these patients.