Normal to increased thrombin generation in patients undergoing liver transplantation despite prolonged conventional coagulation tests

Lisman, Ton; Bakhtiari, Kamran; Pereboom, Ilona T.A.; Hendriks, Herman G.D.; Meijers, Joost C.M.; Porte, Robert J.

doi:10.1016/j.jhep.2009.12.001

« Previous Next »Journal of Hepatology
Volume 52, Issue 3 , Pages 355-361, March 2010

Normal to increased thrombin generation in patients undergoing liver transplantation despite prolonged conventional coagulation tests

Ton Lisman
- Surgical Research Laboratory, Department of Surgery, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
- Section of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
- Corresponding author. Address: Surgical Research Laboratory, Department of Surgery, University Medical Center Groningen, BA44, University of Groningen, P.O. Box 30.001, 9700 RB Groningen, The Netherlands. Tel.: +31 50 361 9028; fax: +31 50 363 2796.
- These authors contributed equally.
Kamran Bakhtiari
- Department of Experimental Vascular Medicine, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands
- These authors contributed equally.
Ilona T.A. Pereboom
- Surgical Research Laboratory, Department of Surgery, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
- Section of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
Herman G.D. Hendriks
- Department of Anesthesiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
Joost C.M. Meijers
- Department of Experimental Vascular Medicine, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands
- These authors contributed equally.
Robert J. Porte
- Section of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
- These authors contributed equally.

Received 20 July 2009; received in revised form 25 August 2009; accepted 21 October 2009. published online 24 December 2009.

Background & Aims

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.

Abbreviations: APTT, activated partial thromboplastin time, PT, prothrombin time, CAT, calibrated automated thrombinography, ETP, endogenous thrombin potential, HCC, hepatocellular carcinoma, TM, thrombomodulin