We describe here the alteration of thrombin specificity induced by its interaction with glycocalicin. Glycocalicin is the external part of platelet glycoprotein Ib alpha (GPIb alpha) and contains binding sites for von Willebrand factor and thrombin. Taking advantage of its solubility, we have used glycocalicin in competition assays on various thrombin activities. Glycocalicin did not inhibit ch...

Inflammatory cytokines promote the activation of coagulation through the induction of tissue factor, downregulation of thrombomodulin and upregulation of plasminogen activator inhibitor. In addition to these mechanisms, infections can trigger the release of extracellular traps from leukocytes consisting of DNA and histones. Tissue injury results in release of nucleosomes. Either of these histon...

BACKGROUND No single anticoagulant has been proven effective for sepsis-associated disseminated intravascular coagulation (DIC). Thus, the concomitant use of antithrombin concentrate and recombinant thrombomodulin has been conceived. This observational study was conducted to investigate the efficacy and safety of this combination therapy. METHODS A total of 510 septic DIC patients who receive...

Single-stranded DNA molecules containing a 15-nucleotide consensus sequence have been reported to inhibit thrombin activity. The mechanism of the inhibition was studied using a consensus 15-mer oligonucleotide and two recombinant mutant thrombins: the anion-binding exosite mutant thrombin R70E, and thrombin K154A, in which the mutation was located in a surface loop outside of the exosite. The c...

BACKGROUND The basic mechanisms of thromboembolism in cyanotic congenital heart disease (CCHD) have not been well clarified. P-selectin on the platelets reflects platelet activation. Thrombomodulin is a critical cofactor for thrombin-mediated activation of protein C and reflects the anticoagulant activity of the endothelium. The present study was performed to evaluate whether platelet activatio...

Absence of the blood coagulation inhibitor thrombomodulin (Thbd) from trophoblast cells of the mouse placenta causes a fatal arrest of placental morphogenesis. The pathogenesis of placental failure requires tissue factor, yet is not associated with increased thrombosis and persists in the absence of fibrinogen. Here, we examine the role of alternative targets of coagulation that might contribut...

BACKGROUND Although plasma endothelin concentrations are elevated in patients with pulmonary hypertension, the precise sites of endothelin production have not been defined. We investigated the endothelin production in the pulmonary circulation of patients with mitral stenosis and its effects on pulmonary vascular tone. METHODS AND RESULTS We measured plasma concentrations of endothelin-1, ang...

Activation of protein C by thrombin is stimulated by the endothelial cell cofactor thrombomodulin. The structural regions of thrombomodulin necessary for cofactor activity have been localized to the fourth through sixth epidermal growth factor (EGF)-like domains. The fourth EGF-like domain is unnecessary for high affinity thrombin binding, but is required for cofactor activity. To identify esse...

OBJECTIVE To investigate a novel marker of oxidative stress in patients with congestive heart failure (CHF). PATIENTS 15 patients with mild CHF, 15 patients with severe CHF with acute exacerbation, and 15 control subjects. MAIN OUTCOME MEASURES Measurement of urinary 15-F2t-isoprostane, plasma brain natriuretic peptide (BNP), serum interleukin 6 (IL-6), and serum thrombomodulin concentratio...

Absence of the blood coagulation inhibitor thrombomodulin (Thbd) from trophoblast cells of the mouse placenta causes a fatal arrest of placental morphogenesis. The pathogenesis of placental failure requires tissue factor, yet is not associated with increased thrombosis and persists in the absence of fibrinogen. Here, we examine the role of alternative targets of coagulation that might contribut...