BACKGROUND AND METHODS It has been reported that C/T dimorphism at position 1418 of the thrombomodulin gene causes a cytosine (C) transition to thymidine (T), resulting in an alanine (A) to valine (V) substitution at amino acid position 455 (TM455). TM455 had been found not only in African American and American whites, but also in whites in The Netherlands and Sweden. Among these populations, t...

OBJECTIVE Immediate loss of thrombomodulin activity in the endothelium of vein grafts has been demonstrated during 90 min exposure to arterial circulation; this loss of activity is ascribed as an important cause of early thrombosis. Conventional ex vivo gene transfection after vein harvest cannot cover this acute period immediately after implantation. We have established a highly efficient non-...

Background Acute traumatic coagulopathy (ATC) identified in the first hour of trauma patients is associated with worse outcomes and increased risk of death [1]. Identification of critical coagulation pathways involved in ATC is important for future targeted drug discovery. Previous studies have demonstrated an activation of the thrombomodulin-protein C pathway during ATC [2]. We examined the ef...

Chemoselective conjugation of an azido-functionalized thrombomodulin to pancreatic islets was achieved by Staudinger ligation to a surface-bound bifunctional poly(ethylene glycol) linker. The presence of the tethered thrombomodulin resulted in a significant increase in the production of activated protein C with a reduction in islet-mediated thrombogenicity. This report highlights the potential ...

BACKGROUND Coagulopathy is present at admission in 25% of trauma patients, is associated with shock and a 5-fold increase in mortality. The coagulopathy has recently been associated with systemic activation of the protein C pathway. This study was designed to characterize the thrombotic, coagulant and fibrinolytic derangements of trauma-induced shock. METHODS This was a prospective cohort stu...

Studies have been carried out to investigate aspects of the structure of thrombomodulin, an endothelial cell glycoprotein that binds thrombin and accelerates both the thrombin-dependent activation of protein C and the inhibition of antithrombin III. We have determined the shape of SolulinTM, a soluble recombinant form of human thrombomodulin missing the transmembrane and cytoplasmic domains, by...

Protein C activation on the surface of the endothelium is critical to the negative regulation of blood coagulation. We now demonstrate that monoclonal antibodies that block protein C binding to the endothelial cell protein C receptor (EPCR) reduce protein C activation rates by the thrombin-thrombomodulin complex on endothelium, but that antibodies that bind to EPCR without blocking protein C bi...