THROMBOMODULIN - A MARKER FOR ENDOTHELIAL DAMAGE DURING ORTHOTOPIC LIVER-TRANSPLANTATION

Thrombomodulin is a surface protein of vascular endothelial cells. A s maller form of thrombomodulin in blood and urine, the soluble ((s))thr ombomodulin, appears to be derived from injured endothelial cells or t o be proteolytically cleaved from thrombomodulin by proteases. Several in vitro and in vivo studies have suggested (s)thrombomodulin as a ma rker of endothelial damage. In orthotopic liver transplantation, plate let and leukocyte activation as well as prothrombin activation are sus pected of being caused by damaged endothelial cells in the graft liver . We determined (s)thrombomodulin antigen as well as thrombin-antithro mbin III complexes, protein C, and antithrombin II activities in the c ourse of 23 orthotopic liver transplantations. Samples were taken at 7 different time-points intraoperatively, as well as out of the perfusa te released from the graft liver vein during the flushing procedure wi th arterial blood prior to the opening of the hepatocaval anastomosis. Levels of (s)thrombomodulin antigen and thrombin-antithrombin III com plexes showed a significant increase with reperfusion of the graft liv er and levels in the perfusate were higher (both: P = 0.0001) than the corresponding systemic levels. In parallel, antithrombin III decrease d significantly with reperfusion and perfusate levels of antithrombin III and protein C activities were lower in the systemic circulation (b oth: P = 0.0001). In conclusion, high levels of a (s)thrombomodulin an tigen in the early reperfusion phase and in the perfusate strongly ind icate endothelial damage to the graft liver vascular bed, paralleled a nd followed by signs of prothrombin activation. (C) 1994 Wiley-Liss, I nc.