Elevated Pre- and Postoperative ROTEM™ Clot Lysis Indices Indicate Reduced Clot Retraction and Increased Mortality in Patients Undergoing Liver Transplantation

Abstract

Background: The ROTEM™ clot lysis index, describing the decrease in firmness of a clot with time, predicts mortality in various settings. The variability of the clot lysis index in surgical procedures and the involved pathophysiological mechanisms are unknown. We therefore compared pre- and postoperative clot lysis indices in liver transplantation (LTX) procedures, determined the eventual association with mortality, and investigated the mechanisms underlying decreased clot lysis index using inhibitors of fibrinolysis and clot retraction, respectively. Methods: In this retrospective cohort study, data on pre- and post-transplant ROTEM™ findings as obtained with EXTEM (tissue factor activation), INTEM (intrinsic system activation), FIBTEM (extrinsic system activation and inhibition of clot retraction), APTEM (extrinsic system activation and fibrinolysis inhibition), conventional laboratory coagulation tests, blood loss, transfusion of blood products, and outcome were registered. Results: Pre-transplant clot lysis indices showed a broad distribution ranging from 75% to 99% independent of the activator used (EXTEM, INTEM). During the surgical procedure, median clot lysis index values markedly increased from 92% to 97% (EXTEM) and 93% to 98% (INTEM), respectively (p < 0.0001 each). Aprotinin had no effect on either pre- or postsurgical clot lysis indices. Inhibition of platelet clot retraction with cytochalasin D (FIBTEM) markedly increased the preoperative clot lysis index. High pre- and post-transplantation clot lysis indices were associated with increased mortality irrespective of the activator used (EXTEM, INTEM) and the inhibition of fibrinolysis (APTEM). Inhibition of clot retraction (FIBTEM) abolished the association of clot lysis index with mortality in both pre- and post-transplantation samples. Conclusion: Both pre- and postoperative ROTEM™ clot lysis indices predict mortality in patients following liver transplantation. Inhibitor experiments reveal that the clot lysis index is not an indicator of fibrinolysis, but indicates platelet clot retraction. The marked increase of clot lysis index during liver transplantation is caused by a decrease in clot retraction with eventual consequences for clot stability, retraction of wound margins, and reperfusion of vessels in case of thrombosis.