Review article: the prothrombin time test as a measure of bleeding risk and prognosis in liver disease.
BACKGROUND
Prothrombin time (PT)-derived international normalized ratio (INR) is used to assess bleeding risk and prognosis in cirrhosis, and to guide management of associated coagulation disturbances. Recent studies cast doubt on the validity of the assumptions that form the basis for these applications.


OBJECTIVE
To review and critique the use of the PT-INR in cirrhosis.


METHODS
Search of the literature.


RESULTS
In cirrhosis, there is a decrease in both pro- and anti-coagulants. The PT-INR measures only the activity of procoagulants and fails to capture changes in anticoagulants. It is therefore not surprising that the PT does not predict the bleeding risk. The PT-INR provides a robust measure of liver function but recent data showed INR inter-laboratory variability in this setting. This is not surprising as the INR was validated to normalize results for patients on vitamin-K antagonists, not for cirrhosis. This limitation was not appreciated, but the INR is used to construct the model for end-stage liver disease score to prioritize patients for liver transplantation. Reports showed that model for end-stage liver disease is modified by the thromboplastin used for testing.


CONCLUSIONS
Alternate tests to predict bleeding risk should be developed. The potential for misuse of the PT-INR should drive the development of alternate algorithms for organ allocation.
Tripodi
A
A
Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, IRCCS Maggiore Hospital, Mangiagalli and Regina Elena Foundation, University of Milan, Milan, Italy. armando.tripodi@unimi.it
Caldwell
S H
SH
Hoffman
M
M
Trotter
J F
JF
Sanyal
A J
AJ
D006470:Hemorrhage / Q000175:diagnosis*; D006801:Humans; D019934:International Normalized Ratio / Q000592:standards*; D008103:Liver Cirrhosis / Q000097:blood / Q000175:diagnosis*; D011379:Prognosis; D011517:Prothrombin Time / Q000592:standards*; D012016:Reference Values; D012307:Risk Factors