PORTAL VEIN THROMBOSIS;
ANTICOAGULANT ?YES AND NO
Dr.
MOHAMMED EMAM
Prof. tropical medicine and Hepatology
ZAGAZIG UNIVERSITY 2011
CIRRHOSIS
PVT
in cirrhosis
• has rarely been the subject of detailed
evaluation and thus many questions
remain unanswered regarding its
clinical course, prognosis and optimal
management.
• Indeed, although a consensus
concerning non cirrhotic extra-hepatic
PVT has been published, no such
consensus exists for PVT with
cirrhosis.
AIM OF THIS SERIES
• we explore the different aspects of PVT in cirrhosis
in terms of prevalence, pathogenesis, clinical
course, prognosis and management.
• We focus in particular on the unresolved issues,
which are often the critical problems clinicians
encounter in their everyday practice.
• We try to provide answers to these problems on the
basis of available literature.
• Finally, we propose a possible research agenda to
address these unresolved issues.
Key points
• Portal vein thrombosis (PVT) is being
recognized with increasing frequency
with the use of ultrasonography.
• Reduced portal blood flow caused by
hepatic parenchymal disease and
abdominal sepsis (I .e, infectious or
ascending thrombophlebitis) are the
major causes
Key points
• PVT occurs in up to 25% of patients with
advanced cirrhosis.
• . There are several clinical implications of
PVT, including worsening of portal
hypertension, onset of refractory ascites,
increased occurrence of encephalopathy,
and increased complications related to organ
transplantation
Pathophysiology
• The portal vein forms at the junction of the
splenic vein and the superior mesenteric
vein behind the pancreatic head.
• It can become thrombosed or obstructed at
any point along its course.
• In cirrhosis and hepatic malignancies, the
thromboses usually begin intrahepatically
and spread to the extrahepatic portal vein.
Pathophysiology
• In most other etiologies, the
thromboses usually start at the site of
origin of the portal vein. Occasionally,
thrombosis of the splenic vein
propagates to the portal vein, most
often resulting from an adjacent
inflammatory process such as chronic
pancreatitis
The prevalence
• Being 11-28%.
• Operator experience or different patient
and ⁄ or disease characteristics may
explain these differences.
• Also different means of diagnosis as
angiography or surgery, influence the
prevalence
Etiology
• Etiology of liver disease has an
influence on prevalence,
• 3.6% in primary sclerosing cholangitis,
• 8% in primary biliary cirrhosis,
• 16% in alcoholic and HBV-related
cirrhosis
• 35% in HCC
The true prevalence
• The true prevalence of PVT in cirrhosis might
be greater, as intrahepatic thrombosis
is more difficult to diagnose and may not be
looked for unless the main portal vein shows
thrombosis.
• Moreover, in an autopsy study, portal vein
intimal fibrosis was found in 36% of the
livers examined, but most of this portal vein
disease would not have been clinically
detectable with available ultrasound
techniques
Prevalence
• Amongst all cases of PVT,
cirrhosis is the underlying cause in
22–28%.
When HCC patients are excluded,
studies based on ultrasound have
reported a prevalence of 10–25%,
The severity of cirrhosis
• Finally, the risk of PVT is
independently associated with the
severity of cirrhosis.
• with worsening indices of
coagulation, there is more
thrombosis.
CAUSES& CLASSIFICATION
• Portal vein thrombosis (PVT) is encountered
in a variety of clinical settings such as
myelo-proliferative diseases, cirrhosis,
cancer or infection.
• Its clinical presentation, prognosis and
management vary substantially according to
etiology.
• It can be classified as acute or chronic, extraor intra-hepatic, occlusive or non-occlusive
and progressive or self-resolving
S
CLINICAL PRESENTATION
• Patients with these conditions
may present with acute or sub
acute intestinal angina.
• In late stages, patients may
have variceal bleeding.
CLINICAL
• As current imaging techniques allow
detection of asymptomatic PVT during
routine ultrasonographic examination,
more patients with cirrhosis are
diagnosed with PVT.
*The presence of PVT can exclude a
patient from transplant listing, or
negatively impact on post
transplantation survival..
Transient PVT
• Transient PVT is also being recognized
with increasing frequency, partly
because of the great increase in the
use of ultrasonography in the
evaluation of patients with abdominal
inflammation such as appendicitis.
Hypercoagulable syndromes can lead
to portomesenteric and splenic vein
thrombosis.
Pathophysiology
• Recently, our understanding of coagulopathy
in cirrhosis has changed, and cirrhosis is
no longer considered to be a
hypocoagulable state.
• What happens is that in the setting of
hepatic synthetic impairment, both pro- and
anticoagulant proteins are reduced to a
similar degree.
• The net result is haemostatic balance that in
normal circumstances is compensated, with
no tendency for bleeding or thrombosis
Thrombotic potential
• Moreover, rather than a bleeding risk
(excluding portal hypertension-related
bleeding) in cirrhosis, various clinical
studies as well as a recent in vitro one
support a thrombotic potential.
• Three recent independent studies have been
published specifically evaluating the
prevalence of deep vein thrombosis (DVT)
and pulmonary embolism (PE) in patients
with cirrhosis
• the incidence of DVT or PE ranged from 0.5%
to 1.87% across the different studies
Thrombotic potential
• even patients with cirrhosis and a
prolonged PT receiving antithrombotic
drugs can develop a thrombosis.
• decreased hepatic synthetic function
as reflected by albumin levels was
associated with the risk of DVT ⁄ PE,
suggesting a greater tendency to
thrombosis the more severe the liver
disease
Thrombotic potential
• The ratio of the two most powerful pro- and
anti-coagulants operating in plasma, factor
VIII and protein C respectively, showed a
balance strongly in favour of factor VIII,
which indicates hypercoagulability.
• Importantly, concentrations of factor VIII, a
potent pro-coagulant involved in thrombin
generation, increased progressively with
worsening Child-Pugh grade and score (from
Child class A to C)
Virchow’s triad
• Thrombosis risk is substantial when
• any of the components of Virchow’s triad i.e.
venous stasis, endothelial injury and
hypercoagulability is present.
• In cirrhosis, stasis in the portal vein is
favored by the relative splanchnic
vasodilatation and is further aggravated by
the liver architectural derangement that
decreases portal flow
Virchow’s triad
• Moreover, a thrombophilic genotype has been
reported in 69.5% of patients with cirrhosis and PVT.
• high levels of factor VIII were independently
associated with non cirrhotic and cirrhotic PVT
• The role of anticardiolipin antibodies remains
controversial.
• Finally,, endotoxaemia emerged as a potential
mechanism.
• Thrombin generation correlated with
platelet number,
when thrombocytopenia was severe
thrombin generation impaired.
• INR in liver disease probably overestimates
the bleeding risk as the international
sensitivity index used is determined by
means of plasma from patients on vitamin K
antagonists
Optimal management of portal
vein thrombosis
• in cirrhosis is currently not addressed
in any consensus publication.
• Treatment strategies most often include
the use of anticoagulation,
• while thrombectomy and transjugular
intrahepatic portosystemic shunts are
considered second-line option
Intervention
• The development of PVT can
precipitate the need for emergency
endoscopy for sclerotherapy of varices,
transjugular intrahepatic portosystemic
shunt (TIPS) creation, surgical
portocaval shunt creation, transjugular
or transhepatic portomesenteric
thrombolysis and thrombectomy, or
even resection of ischemic bowel or
liver transplantation.
November 15, 2011 (San
Francisco, California)
• A new treatment regimen with the lowmolecular-weight heparin enoxaparin
reduced the incidence of portal vein
thrombosis (PVT), leading to fewer
events of clinical decompensation and
enhanced survival in patients with
advanced cirrhosis, according to data
presented at The Liver Meeting 2011:
American Association for the Study of
Liver Diseases 62nd Annual Meeting
Management
• Optimal management of PVT in
cirrhosis is currently not
addressed in any consensus
publication, including the recent
practice guidelines on vascular
disorders of the liver
Management
• Treatment strategies that are
published most often include the
use of anticoagulation, while
thrombectomy and transjugular
intrahepatic portosystemic shunts
(TIPS) are considered as secondline options.
Anticoagulation
• Its goal is not necessarily recanalization, but
prevention of further thrombosis with
extension to the superior mesenteric vein
(SMV).
• The recent American Association for the
Study of Liver Disease (AASLD) practice
guidelines on liver vascular disorders
supporting anticoagulation in acute PVT, as
recanalization may occur in up to 80% of
cases
Anticoagulation
• However, anticoagulation is more
complex in the setting of cirrhosis.,
• First anticoagulation in patients with
esophageal Varices, especially when
the risk of rupture risk is high, could
further exacerbate a variceal bleeding
should it occur.
The risk to benefit
• The risk to benefit ratio of anticoagulation
was though to be unfavourable in cirrhosis if
there are medium or large oesophageal
varices.
• The proportion of patients with partial or
complete recanalization was significantly
higher in those who received anticoagulation
(8 ⁄ 19) compared with those who did not
The risk to benefit
• No anticoagulation-related complications
were noted and no patient had to stop
treatment.
• Patients with complete PVT at the time of
liver transplantation had significantly lower
survival after transplant. This suggests that
at least in patients with cirrhosis and PVT
listed for liver transplantation
anticoagulation should be used
The risk to benefit
• the use of coumarin anticoagulants increase
the INR and ‘artificially’ increase the MELD
score, an alternative score that excludes INR
(MELDXI) has been proposed for patients on
anticoagulation listed for transplantation
• An attractive alternative to oral
anticoagulants could be the use of lowmolecular weight heparin, the dosing of
which is weight-based and screening
therefore is not necessary
• A second study reported complete
response in 75% of patients by
using enoxaparin with no serious
side effects.
• . It is important that enoxaparin
was given for a prolonged period
of 6–17 months.68
Varices&ulcers
• If anticoagulation is to be
used, varices should be
eradicated by ligation and
any ulcers healed before
anticoagulation is started.
Beta blocker or endoscopic?
• A theoretical advantage of endoscopic
therapy over nonselective beta-blockers
could be argue for, as the latter might further
reduce splanchnic blood flow and thus cause
further portal vein stasis and thrombus
extension.
• Eradication of varices through ligation might
be a safer choice, but iatrogenic bleeding is
possible with ligation.
Radiological interventions
• Radiological interventions can be used
in PVT to repermeate the vessel even
percutaneously in acute forms through
the chest wall or by using TIPS when
concomitant portal hypertensive
complications or cirrhosis is present
• The use of TIPS is a feasible option
• combined mechanical thrombectomy with
intraportal thrombolysis.
Therapeutic algorithm
• when PVT is first diagnosed,
• 1- an attempt at evaluating the time interval from
•
•
•
•
appearance is made.
2- Endoscopic screening for varices takes place.
3-Anticoagulation using standard therapeutic
dose is considered in all patients with acute onset of
PVT and in patients with recent onset (<6 months) in
whom repermeation is more likely.
4-High-risk oesophageal varices are banded
before initiation of anticoagulation
5- reduction in coagulation dose is advocated when
platelet count is very low
Follow up
• After the first 6 months of
anticoagulation, even if repermeation is
not accomplished, prophylactic
anticoagulation is continued in patients
with underlying thrombophilic
conditions or in patients who are likely
candidates for liver transplantation in
the future, to avoid thrombosis
extension in the splanchnic vessels.
Longstanding PVT
• When PVT is longstanding and there is
cavernous transformation of the portal
vein, prophylactic anticoagulation is
reserved only in patients who have
thrombophilic conditions and ⁄ or high
risk of thrombus extension into the
SMV
Radiological interventions
• Radiological interventions
(i.e. TIPS and thrombectomy) are used
in patients who have already had
bleeding or intractable Ascites or when
thrombosis has extended despite
adequate anticoagulation
Conclusions
• Portal vein thrombosis in cirrhosis has
many unresolved issues, which are
often the critical problems clinicians
encounter in their everyday practice.
• We propose a possible research
agenda to address these unresolved
issues.
Conclusions
• Anticoagulant appears to be safe in
most cirrhotic patients.
• Thrombus extension appears to be
prevented in most patients.
• Recanalization can occurs in 40% of
patients.
• Anticoagulant should be considered in
cirrhotic with PVT when portal
hypertension is controlled.
• Thank you
Dr-MOHAMMED EMAM