Normal to increased thrombin generation in patients undergoing liver transplantation despite prolonged conventional coagulation tests.
OBJECTIVE
Patients with liver disease often show substantial changes in their hemostatic system, which may aggravate further during liver transplantation. Recently, thrombin generation in patients with stable disease was shown to be indistinguishable from controls provided thrombomodulin, the natural activator of the anticoagulant protein C system, was added to the plasma. These results indicated that the hemostatic balance is preserved in patients with liver disease, despite conventional coagulation tests suggest otherwise.


METHODS
Here we examined thrombin generation profiles in serial plasma samples taken from ten consecutive patients undergoing liver transplantation.


RESULTS
At all time points, the endogenous thrombin potential (ETP) was slightly lower compared to healthy volunteers, despite substantially prolonged PT and APTT values. However, when thrombin generation was tested in the presence of thrombomodulin, the ETP was equal to or even higher than that in healthy subjects. In fact, thrombin generation was hardly affected by thrombomodulin, while thrombin generation in healthy subjects decreased profoundly upon the addition of thrombomodulin. In patients undergoing liver transplantation, efficient thrombin generation in the presence of thrombomodulin may be explained by decreased levels of protein C, S, and antithrombin, and by elevated levels of FVIII.


CONCLUSIONS
Thrombin generation in patients undergoing liver transplantation is equal or even superior to thrombin generation in healthy volunteers when tested in the presence of exogenous thrombomodulin. These results support the recently advocated restrictive use of plasma during liver transplantation and warrants further study of the prophylactic use of anticoagulants to reduce thromboembolic complications after transplantation.
Lisman
Ton
T
Surgical Research Laboratory, Department of Surgery, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands. j.a.lisman@chir.umcg.nl
Bakhtiari
Kamran
K
Pereboom
Ilona T A
IT
Hendriks
Herman G D
HG
Meijers
Joost C M
JC
Porte
Robert J
RJ
D000328:Adult; D001780:Blood Coagulation Tests / Q000379:methods*; D016022:Case-Control Studies; D015209:Cholangitis, Sclerosing / Q000378:metabolism / Q000601:surgery; D005169:Factor VIII / Q000378:metabolism; D005260:Female; D006526:Hepatitis C / Q000378:metabolism / Q000601:surgery; D006801:Humans; D008103:Liver Cirrhosis / Q000378:metabolism / Q000601:surgery; D008107:Liver Diseases / Q000378:metabolism* / Q000601:surgery*; D016031:Liver Transplantation / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D011517:Prothrombin Time; D013917:Thrombin / Q000378:metabolism*; D018180:Thrombomodulin / Q000097:blood; D013925:Thromboplastin / Q000378:metabolism; D013997:Time Factors
D018180:Thrombomodulin; D005169:Factor VIII; D013925:Thromboplastin; D013917:Thrombin