Long-term Behavior of Endothelial and Coagulation Markers in Eisenmenger Syndrome

Abstract

The long-term behavior of endothelial markers was studied in patients with Eisenmenger syndrome who were subjected to conventional therapy (no vasodilators) and observed for 18 months. Biochemical markers were analyzed comparatively in patients with class II or III symptoms (group 1, n=10) and patients with class IV symptoms (group 2, n=7). Plasma von Willebrand factor antigen (vWF: Ag), thrombomodulin, tissue-type plasminogen activator (t-PA) and its inhibitor (PAI-1), and D-dimer were determined by immunoenzymatic assay at baseline, and at 6, 12, and 18 months. At baseline, the main clinical difference between groups was a decreased peripheral oxygen saturation in group 2 versus group 1 (77±5% and 86±4%, respectively, p=0.001). Basal vWF: Ag and t-PA were increased and thrombomodulin was decreased in both groups in comparison with controls (p<0.0001), while D-dimer was increased in group 2 only (p=0.0003). In response to treatment, there was a decrease in vWF: Ag in both groups (19% and 23%, respectively in groups 1 and 2, at 18 months vs. baseline, p<0.0001) and t-PA in group 1 (38% vs. baseline, p=0.0485). Plasma vWF: Ag tended to be higher in group 2 in comparison with group 1 during the whole follow-up. Levels of PAI-1 greater than 38.4 ng/mL (upper 90% limit for normals) and D-dimer greater than 500 ng/mL were detected in individual patients (both groups) during the follow-up period. Thrombomodulin remained decreased in both groups. Thus, severity of symptoms in the Eisenmenger syndrome appears to correlate with low oxygen saturation and higher vWF: Ag levels. Improvement of endothelial dysfunction may occur in response to treatment, although increased risk for thrombosis persists, in view of residual abnormalities.

Patients with Pulmonary Hypertension Related to Congenital Systemic-to-Pulmonary Shunts are Characterized by Inflammation Involving Endothelial Cell Activation and Platelet-mediated Inflammation

“…The elevated vWF levels in PAH‐CSPS denote an activated endothelium in these individuals as described by others 3,4,15,16 . Furthermore, it has previously been reported that PAH‐CSPS patients are characterized by increased plasma levels of tissue‐type plasminogen activator and decreased levels of thrombomodulin, suggesting an inflammatory and procoagulant state of the endothelium in these patients.…”

“…The elevated vWF levels in PAH-CSPS denote an activated endothelium in these individuals as described by others. 3,4,15,16 Furthermore, it has previously been reported that PAH-CSPS patients are characterized by increased plasma levels of tissuetype plasminogen activator and decreased levels of thrombomodulin, suggesting an inflammatory and procoagulant state of the endothelium in these patients. In the present study, we extend these findings by showing that the elevated levels of vWF in patients with PAH-CSPS are accompanied by a marked rise in plasma levels of sCD40L, primarily reflecting platelet-mediated inflammation.…”

“…Thrombus formation secondary to endothelial cell dysfunction, platelet activation, erythrocytosis, and impaired fibrinolysis also seem to be important pathogenic features in PAH-CSPS. 3,4 The idea that cytokines, chemokines, and perivascular inflammatory cell infiltrates contribute to disease progression has recently also received support, regarding both idiopathic and associated forms of PAH. 5,6 Elevated circulating levels of inflammatory cytokines and enhanced pulmonary expression of several chemokines have been found in patients with PAH.…”

“…Endothelial activation followed by increased proliferation and migration of pulmonary vascular smooth muscle cells is a pathophysiological keystone in all forms of PAH. Thrombus formation secondary to endothelial cell dysfunction, platelet activation, erythrocytosis, and impaired fibrinolysis also seem to be important pathogenic features in PAH‐CSPS 3,4 …”

Paediatric and congenital heart disease in South America: an overview

“…Also, patients born in places at high altitudes have a higher prevalence of PDAs and develop severe pulmonary hypertension early on in the course of the natural history. Extensive local research in this field has provided some interesting observations about endothelial and coagulation abnormalities and vascular remodelling 899091929394959697. The benefits of haemodilution in these patients can be marked 98.…”