Soluble thrombomodulin--a marker of reperfusion injury after orthotopic liver transplantation.

Thrombomodulin is an endothelial cell membrane protein that is released into the blood in soluble forms (soluble thrombomodulin [sTM]) in response to endothelial cell damage. We evaluated intraoperative sTM as a marker of reperfusion injury in 29 liver transplant recipients using an ELISA. Preoperative sTM levels were significantly elevated, as compared with healthy control subjects (75 +/- 61 ng/ml vs. 17 +/- 10 ng/ml; 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 after reperfusion (P < 0.001). Post-reperfusion sTM levels correlate significantly with the early liver enzyme release (aspartate transaminase) (P < 0.001). Patients with pronounced reperfusion injury (postreperfusion arterial sTM > 138 ng/ml, n = 16) present significantly higher maximum 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 graft, since patients with pronounced reperfusion injury present significantly higher sTM levels in the hepatic vein 3 min after reperfusion compared with the portal vein (P < 0.001) and artery (P = 0.025), respectively. In patients with higher reperfusion injury, we found significantly more adherent intrasinusoidal granulocytes in the liver biopsy taken 1 hr after reperfusion (P = 0.006), indicating an interrelation of endothelial damage and the important phenomenon of "leukocyte sticking" in reperfusion injury. Thus the postreperfusion increase of sTM as a marker of reperfusion injury correlates with the early liver enzyme release and the accumulation of intrasinusoidal granulocytes.