Acute portal vein thrombosis: a concise review.
Until recently portal vein thrombosis was recognised late, usually with
portal hypertension. Therefore clinical features of acute portal vein
thrombosis are poorly defined in the literature. The proportion that
progress to chronic portal vein thrombosis and the influences of the
various treatments are not well known. Portal vein thrombosis is being
recognised with increasing frequency with ultrasonography. This is a
condition, which if not recognised early, leads to long-term sequelae.
Hence, clinicians dealing with acute emergencies should be aware of the
symptoms, signs and means of diagnosis. The surgical team may be
involved in the early care of these patients as non specific abdominal
symptoms are often the initial presentation. In this article, the existing
literature on acute portal vein thrombosis is briefly reviewed.
Portal vein thrombosis is a well-defined cause of portal vein obstruction.
It was first described in 1868 1. Normally portal vein constitutes two-third
of the total hepatic blood flow. Still occlusion of the portal vein by a
thrombus often does not produce an acute manifestation. The reasons
being a compensatory vasodilatation of the hepatic arterial system as also
the rapid development of tortuous collateral veins bypassing the blocked
portal vein
2-4
. These collateral veins eventually make up the cavernoma.
Collateral veins develop within the walls or at the periphery of the
structures adjacent to the obstructed portion of the portal vein: bile ducts,
gall bladder, pancreas, gastric antrum, and duodenum. The collateral veins
may alter the aspect of these structures at imaging and, occasionally, this
will lead to erroneous diagnoses of bile duct or pancreatic tumour,
pancreatitis or cholecystitis 5. As a result of arterial buffer response and
development of the cavernoma, total hepatic blood flow is only minimally
reduced. Portal pressure, however, is increased. The increase in portal
pressure can be viewed as a compensatory mechanism allowing portal
perfusion to be maintained through the collateral veins. Portal perfusion is
maintained at the expense of portal hypertension and, eventually,
gastrointestinal bleeding from varices. It is worth noting at this point that
ruptured varices may belong to the portosystemic collateral circulation (in
the oesophagus and the gastric fundus) or to the portal cavernoma (in the
gastric antrum and the duodenum) 5.
A cause for portal vein thrombosis can be identified in more than 85% of
cases
6-7
. Portal vein thromboses occur only when several factors are
combined 8. These factors comprise inherited or acquired prothrombotic
disorders, other thrombophilic factors and local factors. Inherited
prothrombotic disorders can be classified into two groups 2. The first one
includes the long identified deficiencies in protein C, in protein S and in
antithrombin. The prevalence of these anomalies in the general Caucasian
population is low (<0.04%) and the associated relative risk of thrombosis
in the heterozygous state is high (around 10). The second subgroup of
inherited disorders includes conditions, which were recently identified
like gene mutations in factor V Leiden (FVL) and factor II prothrombin.
These are associated with lower relative risk of thrombosis
being more prevalent in the general population (2%)
8-10
2-8
despite
. The acquired
thrombophilic disorders include malignancy, myeloproliferative disorders,
oral contraceptive pills, pregnancy and postpartum, antiphospholipid
syndrome and paroxysmal nocturnal haemogobinuria 11.
Local factors that precipitate portal vein thrombosis can be classified into
three categories. A first category refers to conditions characterised by
local inflammation and infection. Neonatal thrombosis is well
documented following omphalitis or umbilical vein cannulation
complicated by septic phlebitis. Other infectious processes that may lead
to portal vein thrombosis include portal pyaemia secondary to
appendicitis, biliary tract infection, post abdominal surgical sepsis,
amoebic colitis with hepatic abscess, acute necrotizing pancreatitis,
diverticulitis and septicaemia 4. A second category of local factors refers
to operations that, intentionally or not, involve injury to the portal venous
system. As a rule, this type of operation does not precipitate portal vein
thrombosis unless there is an associated prothrombotic state or portal
hypertension
12
. A third category refers to cancer of abdominal organs.
Hepatocellular carcinoma, often seen in association with cirrhosis, and
pancreatic carcinoma comprise the majority of cases
1, 13
. Cancer can lead
to thrombosis of the portal venous system through a combination of
prothrombogenic changes, tumour invasion, and a compression or
constriction effect from tumour mass 3, 14.
To sum up, general thrombophilic factors should be investigated, even
when a local factor for portal vein thrombosis is evident. Conversely, a
local factor should be investigated even when a systemic thrombophilic
factor is obvious 5. The discussion about the causative factors would not
be complete without considering cirrhosis. Cirrhosis has been long
considered a major cause of portal vein thrombosis in adults. The reported
prevalence of portal vein thrombosis in cirrhotic patients varies widely
from 0.6% to 26%
12, 15,16
. The pathogenesis of portal vein thrombosis in
patients with cirrhosis is uncertain, although it has been suggested that
decreased portal blood flow and the presence of periportal lymphangitis
and fibrosis in these patients promote the formation of thrombus 17.
The natural history of portal vein thrombosis is not known because in all
reported cohorts of patients, some form of therapy was used for portal
hypertension or thrombophilia. The rarity of the condition has not allowed
controlled therapeutic trials to be conducted 18. The main complications of
portal vein thrombosis are intestinal ischaemia and chronic portal
hypertension. Intestinal ischaemic occurs when thrombosis extends to the
mesenteric venules. When the ischaemic is prolonged for several days,
intestinal infarction may follow. It is invariably fatal without prompt
surgical intervention
4, 19
. Portal hypertension develops when there is no
repermeation of the portal vein
18
. The proportion that progress to portal
hypertension is not known. The overall prognosis for patients with nonacute portal vein thrombosis in the absence of cirrhosis or malignancy is
good. The overall mortality from several studies has been less than 10% in
this group 4, 20. The mortality in patients with acute portal vein thrombosis
was approximately 50% in the past
13
. The mortality rate has gradually
diminished over the years because of the advent of effective antibiotics,
early surgical intervention and use of anticoagulants 21-23.
The clinical course of patients with non-tumourous, non-cirrhotic portal
vein thrombosis is complicated with recurrent gastrointestinal bleeding
and thrombosis. A recent study found the incidence of gastrointestinal
bleeding was 12.5 per 100 patient years. The size of oesophageal varices
was the main independent predictive factor for bleeding. The incidence
rate of thrombotic events was almost half of that of bleeding, but
significantly the lethality of thrombosis was higher than that of
gastrointestinal bleeding. The main independent predictive factor for
recurrent thrombosis was an underlying documented prothrombotic
condition 18.
Four distinct clinical pictures can be observed with portal vein thrombosis
4
. First, there is the classic group of patients presenting with complications
of portal hypertension. Haematemesis from rupture of varices is the most
frequent presentation. The bleed is well tolerated with mortality of less
than 5% 18, 20. Clinical examination reveals splenomegaly in most patients.
Laboratory tests are mostly unremarkable. The second group consists of
cirrhotic patients with portal vein thrombosis. Variceal haemorrhage is
poorly tolerated in this group. Further abnormal liver function tests and
intractable ascites are often present. The third group consists of patients
with intra abdominal malignancy. These patients do not survive long
enough to develop the sequelae of portal hypertension. Patients usually
have ascites, anorexia and weight loss. The fourth group of patients
present with acute portal vein thrombosis. Diagnosis needs a high index of
suspicion and very often radiologist is usually the first physician to
suggest the diagnosis on the basis of imaging findings. The patients
usually have abdominal pain. Ascites may occur transiently immediately
after the thrombotic event 6, 24, 26. Patients may have abdominal tenderness
6, 25, 26
. Other common complaints of patients with portal vein thrombosis
include nausea, vomiting, anorexia, weight loss, diarrhoea and abdominal
distension
4,6,26
. Further abnormal liver function tests are common with
acute portal vein thrombosis, probably secondary to portal pyaemia 28.
To sum up, diagnosis should be suspected in many different situations:
abdominal pain, abdominal sepsis, and gastrointestinal bleeding due to
portal hypertension or fortuitous finding of portal hypertension. The next
step, once there is clinical suspicion of portal vein thrombosis is an
appropriate radiologic approach to confirm the diagnosis. A duplex or
colour Doppler-ultrasound is an appropriate first investigation. If the
ultrasound study is non diagnostic, then MR is the procedure of choice. If
MR is not available, dynamic contrast CT may be performed. If noninvasive tests are unsatisfactory, angiography should be performed 4.
The next step following diagnosis should be to try to determine when
thrombosis developed. Thrombosis can be considered recent when a
thrombus is visible within the lumen of the portal vein and when there are
no or minimal portoportal or portosystemic collateral veins. Computed
tomography is most useful in this regard because spontaneous high
luminal high density prior to any contrast medium injection indicates a
thrombus dating back to less than 10 days. Conversely demonstration of a
well-developed cavernoma usually indicates an old thrombosis.
The third step in management should be an investigation of the factors
favouring or precipitating thrombosis. The purpose of this investigation is
to identify a condition amenable to treatment. Investigation of the local
factors is based mainly on abdominal computed tomography with contrast
medium injection. It can be completed by endoscopic ultrasound in some
cases. Barium X-ray studies and endoscopy rarely uncover an intestinal
5
disease that was not clinically evident
. Investigation of general
thrombophilic factors must be extensive because an association of several
factors is the rule rather than an exception 27.
The treatment issues must be considered separately for acute and old
portal vein thrombosis. In the treatment of acute portal vein thrombosis,
the issue of anticoagulation is a central one. To what extent spontaneous
repermeation can be expected is not known. Current experience suggests
that spontaneous repermeation is possible but uncommon, whereas
complete or extensive repermeation can be achieved with anticoagulant
therapy in 50- 80% of patients
23,28,29,30
. The minimum duration of
anticoagulation used in these studies was three months. Repermeation
prevents ischaemic intestinal injury in the short term and extra hepatic
portal hypertension in long term. The duration of anticoagulation should
be given for at least 6 months, and then be continued if an underlying
thrombophilia has been demonstrated or be stopped in other cases. Is there
a place for aggressive therapeutic procedures such as thrombolytic agents,
or transjugular intrahepatic portosystemic stent shunt placement coupled
with fibrinolysis for portal vein thrombosis of recent onset? Current data
are insufficient to evaluate the benefit/risk ratio of these procedures 5.
The treatment of patients with old portal vein thrombosis is focussed on
the control of acute bleeding episodes and attempts to prevent recurrent
variceal haemorrhage. The available uncontrolled data indicate that the
measures that are of established efficacy in patients with cirrhosis, namely
propanolol and endoscopy therapy can be applied to patients with portal
vein thrombosis 31, 32. However, there is a matter of concern about the use
of vasoconstrictive agents in acute GI bleeds. Theoretically the profound
decrease in splanchnic blood flow induced by bleeding and by the
therapeutic vasoconstrictive agents might trigger recurrence or favour the
extension of thrombosis in the portal venous system and precipitate
intestinal ischaemia 5. Evidence on the benefit of anticoagulation and
thrombolytic therapy in patients with chronic portal vein thrombosis with
or without cirrhosis is lacking, and therefore cannot be recommended in
such cases
chronic
11
. A recent study
portal
vein
18
reported that anticoagulant therapy in
thrombosis
increased
neither
the
risk
of
gastrointestinal bleeding nor the severity of bleeding. There were no
deaths due to bleeding on anticoagulant therapy. The study further showed
that recurrent thrombosis was efficiently prevented. However, further
experience is
needed,
before advocating indiscriminate use of
anticoagulant agents in patients with old portal vein thrombosis.
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