SOLUBLE THROMBOMODULIN - A MARKER OF REPERFUSION INJURY AFTER ORTHOTOPIC LIVER-TRANSPLANTATION

Thrombomodulin is an endothelial cell membrane protein that is release d into the blood in soluble forms (soluble thrombomodulin [sTM]) in re sponse to endothelial cell damage. We evaluated intraoperative sTM as a marker of reperfusion injury in 29 liver transplant recipients using an ELISA. Preoperative sTM level were significantly elevated, as comp ared with healthy control subjects (75 +/- 61 ng/ml vs. 17 +/- 10 ng/m l; P < 0,001) and remain unchanged at the end of the anhepatic phase ( 58 +/- 40 ng/ml). There is an increase to 194 +/- 182 ng/ml 3 min afte r reperfusion (P < 0.001), Postreperfusion sTM levels correlate signif icantly with the early liver enzyme release (aspartate transaminase) ( P < 0,001), Patients with pronounced reperfusion injury (postreperfusi on arterial sTM > 138 ng/ml, n = 16) present significantly higher maxi mum aspartate transaminase levels within the first 24 postoperative hr , as compared with patients with less reperfusion injury (arterial sTM < 138 ng/ml, n = 12) (P = 0,001), Released sTM is derived from the gr aft, since patients with pronounced reperfusion injury present signifi cantly higher sTM levels in the hepatic vein 3 min after reperfusion c ompared with the portal vein (P < 0,001) and artery (P = 0,025), respe ctively, In patients with higher reperfusion injury, we found signific antly more adherent intrasinusoidal granulocytes in the liver biopsy t aken 1 hr after reperfusion (P = 0,006), indicating an interrelation o f endothelial damage and the important phenomenon of ''leukocyte stick ing'' in reperfusion injury, Thus the postreperfusion increase of sTM as a marker of reperfusion injury correlates with the early liver enzy me release and the accumulation of intrasinusoidal granulocytes.