Mistakes in ... 2021 - 41

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Mistakes in... 2021
Mistakes in coagulation in liver disease and how to avoid them
Edoardo G. Giannini and Stephen H. Caldwell
Alteration of common coagulation tests and thrombocytopenia represent an integral part of
the clinical picture of patients with advanced chronic liver disease.1
Normalised Ratio for prothrombin time is part of the Model for End-stage Liver
Disease score, which is commonly used to assess prognosis and the need for
liver transplantation in patients with cirrhosis.2
Thrombocytopenia-being mainly related
to hypersplenism and decreased synthesis of thrombopoietin by the liver-can also be used
to identify the presence of portal hypertension and decreased liver function in patients with
chronic liver disease.3
In patients who have liver disease, altered coagulation parameters and thrombocytopenia
have long been considered a hallmark of an increased risk of bleeding and such patients are
generally believed to be 'anticoagulated'. However, recent advances in our understanding
actually suggest this belief is not correct.4-6
Indeed, there is evidence of an increased risk of
thrombotic events in these patients, despite the presence of a deranged International Normalised
Ratio and severe thrombocytopenia.7-9
Overall, the findings from several studies indicate that
anti- and procoagulant tendencies are still balanced in patients who have advanced liver disease,
though less robustly than in healthy individuals, and that they can be unbalanced in either
direction by perturbing events, such as infections or acute kidney injury.10-12
In these patients,
bleeding is generally portal-pressure-driven while inappropriate clotting is made evident by
peripheral venous thrombosis and especially by portal-mesenteric thrombosis.
Here we discuss some of the mistakes frequently made when managing patients who have
liver disease and findings of altered coagulation or thrombocytopenia. The discussion is based
on the best level of evidence available in the literature and expert consensus.
Mistake 1 Assuming spontaneous
bleeding is always associated with altered
coagulation parameters
Oesophageal variceal bleeding is one of
the most dreaded complications in patients
with advanced chronic liver disease, as it is
associated with substantial morbidity and an
increased risk of death.13
In patients with
cirrhosis, thrombocytopenia or an altered
prothrombin time can be used to noninvasively
predict the presence of varices, due to their
association with portal hypertension and
decreased liver function.14,15
These findings have
often led to the misconception that a decreased
platelet count or elevated International
Normalised Ratio (INR), per se, can be a cause
of oesophageal variceal bleeding, rather than
representing a proxy for more advanced liver
disease and increased portal pressure, thus
pinpointing patients at increased risk of bleeding.
The main parameters associated with risk
of bleeding from varices are, in fact, variceal
size, the presence of red signs on varices, and
decompensation of liver disease, while altered
© UEG 2021 Giannini and Caldwell.
Cite this article as: Giannini EG and Caldwell SH. Mistakes in
coagulation in liver disease and how to avoid them. UEG Education
2021; 21: 29-34.
Edoardo G. Giannini is a Professor in the Gastroenterology Unit,
Department of Internal Medicine, University of Genoa, IRCCS
coagulation has no direct correlation with this
clinical event.16
Moreover, apart from bleeding events being
a direct complication of the underlying liver
disease, the occurrence of spontaneous bleeding
in patients with cirrhosis is rare.17
In the largest
study to evaluate this issue in patients with
cirrhosis, any major or clinically relevant
non-major bleeding event-defined as having a
symptomatic presentation or requiring prompt
medical intervention-were uncommon, with
a reported annual significant bleeding rate of
5.5%.17
All in all, it is important to emphasize that
portal-hypertension-related bleeding represents
the preponderance of major bleeding events in
patients with cirrhosis. Alteration of common
coagulation parameters may be used to identify
those with more advanced liver disease in whom
bleeding prophylaxis-either with nonselective
beta-blockers or endoscopic treatment-is
crucial to improve survival independently of any
alteration in coagulation parameters.13
In this study, which also included patients
on anticoagulants, the annual rate of major
bleeding events was 3.6%, with more than 90%
being portal-hypertension-related, while the
annual rate of minor bleeding events was
1.9%, with the vast majority originating from
the gastrointestinal tract.17
Interestingly, no
association was identified between the
occurrence of bleeding events and platelet counts
or INR, but these events were rather related to
features of portosystemic shunting and increased
portal pressure, such as hepatic encephalopathy
and previous gastrointestinal bleeding.17
Ospedale Policlinico San Martino, Genoa, Italy. Stephen H. Caldwell
is a Professor and Director of Clinical Research in the Division of
Gastroenterology and Hepatology, at the University of Virginia,
Charlottesville, Virginia, USA.
Illustration: J. Shadwell.
Correspondence: egiannini@unige.it
Mistake 2 Believing an altered INR is
associated with an increased risk of
procedure-related bleeding
The prothrombin time (PT)-derived INR is
commonly used in clinical practice to determine
the adequacy of vitamin K antagonist (VKA)
treatment.18
Due to the nature of the test, which
includes calibration of the PT measuring system
with PT values of patients on VKA, its application
in any other setting is not appropriate.19
Patients with advanced liver disease, and
hence decreased liver synthetic capacity, produce
less procoagulant factors, as reflected by an
Conflicts of interest: Edoardo G. Giannini reports acting as a
consultant and serving on advisory boards for AbbVie, Bayer,
EISAI, Gilead Sciences, GSK, MSD, Roche, Shionogi and SOBI.
Stephen H. Caldwell reports receiving relevant research support
from DOVA, Shionogi and Daiichi.
Published online: October 1, 2021.
29
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