Development of a Severe von Willebrand Factor/ADAMTS13 Dysbalance During Orthotopic Liver Transplantation

Abstract

Patients with liver disease show profound changes in their hemostatic system, which may further change during liver transplantation. We previously demonstrated that highly elevated levels of the platelet adhesive protein von Willebrand factor (VWF) in patients with cirrhosis lead to an increased VWF-dependent platelet deposition under flow as compared to healthy controls. In this study we examined VWF parameters during the course of liver transplantation. We collected serial plasma samples from 20 patients undergoing liver transplantation in which we determined plasma levels of VWF and the VWF-cleaving protease ADAMTS13. Furthermore, we performed functional tests of VWF-dependent platelet adhesion. We found persistently elevated levels of VWF during and after liver transplantation. The capacity of VWF to interact with platelets normalized during the course of transplantation, and flow-mediated VWF-dependent platelet adhesion remained at levels far exceeding those observed in healthy individuals during and after transplantation. Plasma levels of ADAMTS13 dropped during transplantation, and in four patients levels below 10% of normal were observed after reperfusion. We observed the development of a hyperreactive primary hemostatic system, as evidenced by high levels of fully functional VWF and a temporary ADAMTS13 deficiency, during liver transplantation, and speculate that these changes contribute to postoperative thrombotic complications.

Rebalanced hemostasis in patients with liver disease: evidence and clinical consequences

“…49 Hepatic artery thrombosis after liver transplantation has long been considered a surgical complication, but recent laboratory and clinical data have implicated a role for hypercoagulation in the occurrence of these thrombotic events. [50][51][52][53] Intrahepatic thrombus formation has been demonstrated in patients with cirrhosis and also in patients with acute liver failure. 54,55 These microthrombi are believed to play a key role in progression of fibrosis as a result of local ischemia, a process referred to as parenchymal extinction.…”

Development of a Hypercoagulable Status in Patients Undergoing Off-Pump Lung Transplantation despite Prolonged Conventional Coagulation Tests

“…We have previously reported on the progressive changes in hemostatic function of patients undergoing a liver transplantation (6,7). In these studies, we have found that the coagulation/ anticoagulation equilibrium shifted toward "hypercoagulability" during the procedure.…”

Successful liver transplantation in a child with acute‐on‐chronic liver failure and acquired thrombotic thrombocytopenic purpura

“…In acquired TTP (aTTP), severe ADAMTS13 deficiency is due to circulating anti-ADAMTS13 autoantibodies, which act as functional inhibitors in most patients. 1-3 TTP has been described after liver transplantation (LT), [4][5][6][7][8][9] but this is, to the best of our knowledge, the first report in which aTTP is associated with pretransplant acute-on-chronic liver failure (ACLF) and no preoperative or perioperative thrombotic complications.…”

“…In the other cases reported to date, low ADAMTS13 activities were observed both before and after LT without any measurable inhibitors. [4][5][6][7][8][9] Cirrhosis is associated with impaired innate and acquired immune responses. 13,14 Although the mechanism is unclear, we hypothesize that dysimmunity due to cirrhosis, possibly exacerbated by Fusobacterium infection, might have triggered a misrouted immune response leading to the production of inhibitory anti-ADAMTS13 autoantibodies.…”