Mistakes in ... 2021 - 43

ueg education
Mistakes in... 2021
receptor agonists, in order to decrease the
likelihood of bleeding in the case of high-risk
procedures.6,42-44
for a procoagulant balance.52
The results of pragmatic studies
designed to identify whether proactively
increasing platelet counts, by any means, before
a procedure might be associated with an actual
decrease in the risk of bleeding, compared with a
reactive wait-and-see strategy that involves blood
product administration only in the case of
bleeding, are eagerly awaited. In the meantime,
the recommendation to maintain a platelet
count above 50x109
/L still holds true in patients
undergoing high-risk procedures, or low-risk
procedures if the occurence of bleeding may be
catastrophic (e.g. intercranial) or cannot be
managed by local haemostasis.
Mistake 4 Assuming that altered
coagulation parameters in patients with
cirrhosis have the same clinical relevance
regardless of whether they have stable
disease or acute-on-chronic liver failure.
Acute-on-chronic liver failure (AoCLF) is a
complex syndrome that can develop in patients
who have cirrhosis, with acute liver disease
decompensation and concomitant failure of
different organs.45
AoCLF can develop in both
compensated and previously decompensated
cirrhotic patients, and can be triggered by various
superimposed factors, among which the most
common precipitating factor, at least in Western
countries, is bacterial infection.46
In particular,
the CANONIC study showed that spontaneous
bacterial peritonitis was by far the most
frequent precipitating infectious trigger for the
development of AoCLF.47
Moreover, AoCLF is
characterized by the development of an intense
systemic inflammatory response and a marked
increase in proinflammatory cytokines that
are deemed responsible for both liver disease
derangement and the several extrahepatic
manifestations of the disease.48
AoCLF is a clinically demanding complication,
with a substantially increased risk of death,
and patients often have a profoundly altered
and highly unstable coagulation balance, with a
greater risk of either spontaneous or procedurerelated
bleeding, as well as development of
macro- and microvascular thrombosis.49-51
Indeed, patients with AoCLF may have a
profound perturbation in the fibrinolytic
equilibrium, and a variable tendency towards
profibrinolytic activity or hypofibrinolysis has
been described, which may lead to bleeding or
thrombosis in the individual patient.50,51
All in
all, these patients tend to have abnormal clot
formation with a varied clot lysis time, and are
characterized by marked hypofibrinogenaemia,
suggesting bleeding diathesis. Moreover,
despite often having a prolonged INR, patients
have elevated factor VIII and decreased
antithrombin III levels, which potentially account
On the clinical side,
the net result of such altered coagulation is
represented by the occurrence of bleeding,
observed in up to 67% of AoCLF patients, or the
formation of intraparenchymal microthrombi
that can contribute to liver dysfunction and other
organ failures, or even macrovascular thrombosis
that might precipitate or follow AoCLF.53,54
A retrospective study showed that patients
with AoCLF have a threefold higher incidence of
bleeding after paracentesis compared with
controls. In addition, when AoCLF patients were
propensity score-matched for severity of liver
disease with patients who had decompensated
cirrhosis, no differences were observed in platelet
counts and INR between those who experienced
post-procedural bleeding and those who
did not. The only parameter predictive of
haemorrhagic complications after paracentesis
in AoCLF patients was hypofibrinogenaemia.55
On
the other hand, another study observed that the
plasma levels of individual fibrinolytic proteins
were unable to identify those patients who
exhibited a hypo- or hyperfibrinolytic tendency,
with patients showing marked variability in clot
lysis times; patients with AoCLF and sepsis had
the highest clot lysis time and plasminogen
activator inhibitor type 1 levels, with
non-survivors having significantly higher clot
lysis times.51
This last finding encourages
speculation that such coagulation alterations
might be involved in the development of
intraorgan microthrombosis, leading to organ
dysfunction and liver parenchymal extinction
with organ atrophy.
From a practical point of view, patients
with AoCLF are a heterogeneous group and
common coagulation test results are not a
solid reflection of their coagulative status, or of
potential responses when the coagulation
process is challenged, for instance, after
invasive procedures. Despite identifying an
hypocoagulable profile, global coagulation
assays results in AoCLF patients have been
described not to associate with bleeding
episodes related or unrelated to portal
hypertension, although these results are not
consistent with those of another study in which
deranged thromboelastograhy results were
predictive of bleeding.50,53
Thus, these findings emphasize once again
how unreliable common coagulation tests are in
this complex population, and how their alteration
may not portray the actual bleeding or thrombotic
risk in these patients. In clinical practice, the use
of global coagulation assays, such as viscoelastic
tests (e.g. ROTEM® [Instrumentation Laboratory]
or TEG® [Haemonetics Corporation]), may be
indicated to assess the coagulation balance and
the need for blood product supplementation,
or of anticoagulation, in the individual patient,
despite some shortcomings when used to predict
outcome in the AoCLF population as a whole.
Mistake 5 Treating portal vein thrombosis in
patients with cirrhosis too conservatively
Portal vein thrombosis (PVT) is a common
finding in patients with chronic liver disease.
As cancer-related PVT and PVT in non-cirrhotic
patients are distinct enough from benign PVT in
cirrhosis to warrant separate consideration, the
following discussion focuses on non-HCC-related
PVT in patients with cirrhosis.56,57
PVT in cirrhosis is often discovered
incidentally, but it can be symptomatic in ~50%
of patients, manifesting as pain, exacerbation
of fluid retention and sometimes with portal
hypertensive bleeding.56,57
PVT may further be
described based on the extent of the thrombus,
in terms of whether the thrombus is occlusive,
partial or mural and whether it extends into
portal vein branches and the mesenteric
and/or splenic veins.57
Deciding whether to treat a patient with
anticoagulants or to observe them is
challenging and depends on multiple individual
considerations. If symptoms are present and
suspected to be related to the PVT, this obviously
favours therapy. On the other hand, the decision
to treat has to be balanced against the
bleeding risk (usually assessed endoscopically
and potentially managed by prophylactic banding
of varices) and, perhaps more importantly, against
the fall risk, which may be difficult to assess but is
probably related, at least in part, to the patient's
frailty.58
One of the clearest indications to treat PVT
is among patients awaiting liver transplantation,
as a patent portal vein allows for avoidance of
complicated vascular anastomoses.59
The optimal duration of therapy is also unclear
as recurrence after stopping therapy appears to
be common. Indeed, recurrence can be as
high as 38.5% following discontinuation of
anticoagulants in patients with previously
known PVT who had achieved complete
recanalization.60,61
This probably reflects
persistence of the underlying risks for PVT
associated with cirrhosis-endothelial injury
from the underlying liver disease, slow venous
flow in liver fibrosis and cirrhosis-related
hypercoagulability.4
The persistent constellation
of risks for PVT in cirrhosis represents the key
elements of Virchow's triad-stasis, endothelial
injury and hypercoagulable blood.
One final consideration is the possible role
of prophylactic anticoagulation in the setting
of these significant risk factors. In a provocative
study, which has yet to be confirmed or
refuted, Villa et al. demonstrated a decreased
incidence of PVT, a remarkable reduction in
decompensation and improved survival in
patients with compensated cirrhosis who received
a trial of prophylactic low-molecular-weight
heparin (LMWH) that was conducted over 2 years
(1 year of active therapy).62
The study was
controlled but small and unblinded, but
31
Mistakes in ... 2021

Table of Contents for the Digital Edition of Mistakes in ... 2021
