Development of a severe von Willebrand factor/ADAMTS13 dysbalance during orthotopic liver transplantation.
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.
Surgical Research Laboratory, Section of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
I T A
IT
Pereboom
J
J
Adelmeijer
Y
Y
van Leeuwen
H G D
HG
Hendriks
R J
RJ
Porte
T
T
Lisman
D051722:ADAM Proteins / Q000097:blood* / Q000172:deficiency; D000071120:ADAMTS13 Protein; D000328:Adult; D000368:Aged; D007611:Aprotinin / Q000627:therapeutic use; D006801:Humans; D008107:Liver Diseases / Q000145:classification / Q000601:surgery; D016031:Liver Transplantation / Q000009:adverse effects*; D008875:Middle Aged; D010919:Placebos; D010973:Platelet Adhesiveness; D011183:Postoperative Complications / Q000097:blood; D012086:Reoperation / Q000009:adverse effects; D014361:Trypsin Inhibitors / Q000627:therapeutic use; D014841:von Willebrand Factor / Q000378:metabolism*
D010919:Placebos; D014361:Trypsin Inhibitors; D014841:von Willebrand Factor; D007611:Aprotinin; D051722:ADAM Proteins; D000071120:ADAMTS13 Protein; C099604:ADAMTS13 protein, human