Steroid-refractory graft-versus-host disease causes significant morbidity and mortality after allogeneic stem cell transplantation. The pathomechanism of steroid resistance is currently not understood, but it has been suggested that endothelial cell dysfunction plays a role. Endothelial thrombomodulin was quantified along with histological markers of epithelial damage and cytotoxic T cells in c...

BACKGROUND AND PURPOSE Atrial fibrillation is the most important risk factor for cardioembolic stroke. Thrombi form in the left atrial appendage rather than in the right. The causes of this different thrombogenicity are not well-understood. The goal herein was to compare the activation of the anticoagulant protein C and the thrombomodulin and endothelial protein C receptor/activated protein C r...

TAFI (thrombin-activatable fibrinolysis inhibitor) is a recently discovered plasma protein that can be activated by thrombin-catalyzed proteolysis to a carboxypeptidase B-like enzyme that inhibits fibrinolysis. This work shows that the thrombin-thrombomodulin complex, rather than free thrombin, is the most likely physiologic activator. Thrombomodulin increases the catalytic efficiency of the re...

BACKGROUND Thrombotic thrombocytopenic purpura (TTP) is a rare vascular disorder of unknown etiology. There is evidence to support the hypothesis that platelets and endothelium play a pivotal pathogenetic role. Immunological assays for plasma thrombomodulin and P-selectin levels have recently been made available and they allow simple evaluation of endothelial damage and endothelial/platelet act...

The activity of the coagulation system is regulated, in part, by the interaction of thrombin with the endothelial cell receptor thrombomodulin with subsequent generation of activated protein C and suppression of thrombin production. Our previous investigation demonstrated that ablation of the thrombomodulin gene in mice causes embryonic lethality before the assembly of a functional cardiovascul...

BACKGROUND Altered plasma levels of protein C, thrombomodulin, and the endothelial protein C receptor are associated with poor clinical outcomes in patients with acute respiratory distress syndrome (ARDS). We hypothesized that common variants in these genes would be associated with mortality as well as ventilator-free and organ failure-free days in patients with ARDS. METHODS We genotyped lin...

The endothelium appears to play an important role in the regulation of intravascular coagulation. Thrombomodulin is one of the anticoagulant substances that is expressed by endothelial cells. The influence of age and illness on the thrombomodulin-protein C system was studied prospectively in 80 cardiac surgery patients. Patients > 70 yr old (n = 20) were compared with patients < 50 yr (n = 20) ...

BACKGROUND The antithrombogenic properties of venous endothelium may be attenuated when vein is implanted in the arterial circulation. Such changes may facilitate thrombosis, which is the final common pathway for saphenous vein arterial bypass graft occlusion. METHODS AND RESULTS Using human saphenous vein in a validated ex vivo flow circuit, we investigated (1) the possibility that arterial ...

Coagulation is initiated by the binding of factor VIIa to tissue factor, with resultant limited factor IX and X activation and thrombin production. Owing to the feedback inhibition of the factor VIIa/tissue factor complex by tissue factor pathway inhibitor (TFPI), additional factor X activation and thrombin generation must proceed through a pathway involving factors VIII, IX, and XI. Experiment...

Background—Thrombomodulin is an anticoagulant expressed during endothelial activation and damage. To address the potential role of allelic variants of thrombomodulin gene in the pathogenesis of cardiovascular diseases, we analyzed in a prospective follow-up study 8 single-nucleotide polymorphisms (SNPs) across the thrombomodulin locus, covering all common ( 5%) haplotypes. Methods and Results—T...