Management conference

Middle age man

with
nephrotic
syndrome,
ascitis and edema
Raika Jamali MD
Digestive Disease Research Center
Tehran University of Medical Sciences
 A 49 years old man with progressive
bilateral pedal edema and ascitis from 1
month ago.
History of DM for 4 years.

Three months ago during the evaluation

for excessive proteinuria inappropriate for
diabetic nephropathy ,prolongation of PT
was detected before kidney biopsy.
Viral markers requested and was referred
for liver function evaluation.
 EXAM
Vital signs were stable. No fever.
Mild anemia. Ichterus in sclera.
Parallel collaterals in chest and upper
abdomen which filled upward.
Tense ascitis. liver span 14 cm.
Moderate splenomegaly .
No signs of chronic liver disease.
Bilateral pedal edema.
 WBC=6500

AST=52
HB=10

ALT=43
PLT=245000
MCV=85
Bili T=5
Bili D=1.3
FBS=180 ALP=508
TG=200 PT(INR)=2.6
PTT=38
AFP =60,92 Albumin=2.2
Protein=5.2
 BUN=15
Cr=0.9
Uric Acid=4

U/A: 3+ protein
24 h urine protein: 7 gr /day
 HCV Ab=suspicious

HBs Ag=Neg
HBs Ab=positive
HBc Ab=positive

HBV DNA and HCV RNA Titer :

undetectable
 Ascitic fluid
RBC=20
WBC=70
Albumin=0.5

Cytology=negative for malignancy

 Sonography
Liver was enlarged with hetrogenous echo
pattern.
PV diameter 10 mm.
Severe ascitis.
Moderate splenomrgaly.
 Color Doppler sonography
IVC and suprahepatic veins were
occluded.
Portal vein was occluded with collaterals
in hilum.
Renal veins were thrombosed.
Splenic vein was patent.
 Activated protein C resistance: 221(120)
B2 micro globulin : 10 (0-3)
Anti cardiolipin Ab: normal
Anti phospholipids Ab: normal
Pr C: reduced
Pr S: reduced
Anti thrombin 3: normal
homocysteine: normal
Ham, sucrose test: normal
CD 55,59: normal
 Endoscopy
Fundal and esophageal varices were
seen.
Snake skin appearance in fundus and
body.
 mottled appearance to the underperfused liver with
collapsed portal veins,
ascites (small arrows)
extensive retroperitoneal varices (large arrow).
enlarged caudate lobe of the liver (large arrowhead)
the collapsed small IVC (small arrowhead).
 Follow Up
The patient was treated with diuretic and
concomitant albumin.
Several abdominal paracentesis were
performed.
Heparin started and switched to warfarin.
Proteinuria decreased during F/U.
Ascitis and edema is partially controlled
with diuretic.
Hypercoagulability states were checked
again which showed normal results.
 Budd-Chiari syndrome
more common in women
third or fourth decade
most common symptoms is ascites (84%)
and hepatomegaly (76%)
obstruction was in the hepatic veins (62%)
inferior vena cava (7%)
portal vein thrombosis (14%)
myeloproliferative disorder was present in
23% (polycythemia vera).
Major causes of the Budd-Chiari
syndrome
Myeloproliferative diseases
Malignancy (Hepatocellular carcinoma)
Infections and benign lesions of the liver
Oral contraceptives
Pregnancy
Hypercoagulable
Behcet's disease
Membranous webs of IVC
Idiopathic
 Acute (20%) :
(2% with fulminant hepatic failure)

Subacute (40%):
(having signs or symptoms for < 6 months
and no evidence of cirrhosis)

Chronic (40%):
(having signs or symptoms for > 6 months
with evidence of cirrhosis)
 Acute
most commonly in women (during
pregnancy )
pain and hepatomegaly
Jaundice and ascites develop rapidly
Liver function can deteriorate quickly,
leading to hepatic encephalopathy
DDx: ischemic, viral, malignant/infiltrative,
and toxic hepatitis
 Subacute and chronic disease
clinical manifestations depend upon the
extent of occlusion, and the recruitment of
collateral circulation.
Chronic occlusion of the hepatic veins
may be associated with hypertrophy of the
caudate lobe.
This cause compression of the
intrahepatic portion of the IVC, leading to
lower extremity edema
 cirrhosis may develop in the chronically
congested liver, resulting in portal
hypertension
encephalopathy is infrequent
Hepatopulmonary syndrome (28%)
liver biochemical tests are usually mildly
abnormal
 DIAGNOSIS
Chronic or subacute Budd-Chiari syndrome
should be considered in unexplained liver
dysfunction, particularly if ascites is a
principal feature, or if risk factors for Budd-
Chiari syndrome exist.
Clinical:
Splenomegaly, venous collaterals
Edema of the lower extremities suggests
occlusion of the inferior vena cava
Signs of right-sided congestive heart failure
(such as jugular venous distension)
 Acute : hepatomegaly, RUQ pain, ascites

Accuracy of noninvasive imaging

modalities depends upon:
duration of disease,
location of the clot.

Portal vein thrombosis limits therapeutic

options and has a poor prognosis
 Doppler ultrasonography
Screening test
hepatomegaly,
splenomegaly,
ascites,
intraabdominal collaterals,
caudate lobe hypertrophy,
atrophy of other hepatic lobes,
compression of IVC
Thickening, irregularity, stenosis, or dilation
of the walls of the hepatic veins
Abnormal flow in the major hepatic veins or
IVC
 CT scan
Delayed or absent filling of the three major
hepatic veins
Patchy flea-bitten appearance of the liver
Rapid clearance of dye from the caudate
lobe
Narrowing and/or lack of opacification of
the inferior vena cava
 Magnetic resonance imaging
typical distorted "comma-shaped" intrahepatic
collaterals
unremarkable ultrasound examination but in
whom the suspicion is high
Venography
Gold standard for diagnosis
plan therapeutic interventions .
Determine pressure gradient above and below
the entrance of the hepatic veins into the
inferior vena cava
 Accurately define the extent or
characteristics of the hepatic venous flow

Compression of the intrahepatic IVC,

leads to sluggish flow in hepatic veins.
As a result, the hepatic veins can be
undetectable during ultrasound Doppler
studies, although they may be patent and
amenable to therapy
 Liver biopsy
Can be diagnostic in the acute or
subacute form
Features include centrizonal congestion,
necrosis, and hemorrhage
Cirrhosis may be present in the chronic
form
Determine prognosis and guide therapy
Cirrhotics are less likely to benefit from
revascularization procedures
 thrombotic process in Budd-Chiari syndrome
may not involve all the hepatic veins.
Thus, the distribution of the typical pathologic
findings may be focal or patchy. As a result,
some patients require biopsy of both the right
and the left lobes of the liver.
laparoscopic approach may be better suited

Perfom Bx when there is confusion regarding

the diagnosis and plan treatment accordingly
 TREATMENT
Prevent the propagation of the clot
Decompress the congested liver
Prevent complications (malnutrition, portal
hypertension)
_________________________________
Medical treatment (supportive care,
anticoagulation, thrombolysis),
Radiologic procedures (angioplasty,
TIPS,)
Surgical intervention (shunting procedures
, transplantation).
 Medical therapy
Diuretics and a low sodium diet
large-volume paracenteses
Improve nutritional status
Underlying cause should be investigated
Myeloproliferative disorder may benefit
from treatment with aspirin and
hydroxyurea
 Anticoagulation alone is unlikely to lead to
sufficient recanalization of occluded
vessels to avoid the progression of liver
disease.
A trend for a benefit of anticoagulation on
survival in less severe disease.
Medical therapy :
1) Chronic or subacute Budd-Chiari
syndrome with well compensated liver
disease at the time of presentation.
2) When other types of therapy are not
feasible
 Risk of anticoagulation should also be
considered, especially in patients who
present with bleeding complications

Patients receiving only medical therapy

should be monitored closely for disease
progression (liver biopsies annually )and
portal hypertension complications (looking
for varices)
 Thrombolytic therapy
In acute form which blood clots are
younger than three to four weeks

Do not use thrombolytic agents in:

patients who have extensive clot involving
the IVC
or a clot of unknown age.
 Radiologic treatment
Angioplasty
Stenting
Transjugular intrahepatic portosystemic
shunt
 Surgical therapy
Restore hepatic venous drainage using
shunt surgery
Because of the availability of TIPS, few
vascular surgeons routinely perform shunt
surgery.
Underlying cause of the thrombotic
diathesis should be identified and treated
prior to considering shunt surgery.
Unlikely to be beneficial in patients who
have cirrhosis, Such patients are best
managed with liver transplantation.
 survival following shunt surgery depends upon
the extent of liver damage prior to surgery, and
the continued patency of the shunt

Maintenance of shunt patency often requires

anticoagulation

deterioration in patients following shunt surgery

should be investigated by angiography to
determine whether the shunt has thrombosed,
which may be corrected by angioplasty.
 Liver transplantation
who are not candidates for radiologic or surgical
decompression
or who have decompensated cirrhosis

protein S, protein C, or antithrombin III

deficiency may also be cured of their clotting
tendency by liver transplantation,
Survival following OLT depends upon the
underlying cause of the Budd-Chiari syndrome
and the patients condition at the time of the
transplant
Budd-Chiari syndrome during
nephrotic relapse in a patient
with resistance to activated
protein C clotting inhibitor

Am J Kidney Dis.
 It has long been known that patients with
nephrotic syndrome have a hypercoagulable
state, which explains the association between
nephrotic syndrome, renal vein thrombosis, and
thromboembolism.
However, the Budd-Chiari syndrome has never
been reported in nephrotic patients.

This is the first report of such an association

that, most likely, depended on a primary
resistance to activated protein C
 Budd-Chiari syndrome and
inferior vena cava thrombosis
in a nephrotic child.

Pediatr Nephrol.
 We observed Budd-Chiari syndrome in a
boy aged 2 years 6 months with nephrotic
syndrome due to hepatic vein and inferior
vena cava thrombosis, confirmed by
Doppler imaging.
Normal values of the routine hemostatic
parameters proved that they are of little
predictive value for the thrombotic state.
 Immediate heparin infusion was initiated.
High doses of heparin up to 59 IU/kg per
hour were required for efficient
anticoagulation.
A remission of the nephrotic syndrome
was achieved with vincristine.
Oral anticoagulation with a vitamin K
antagonist was continued for 6 months.
Doppler imaging then indicated full re-
establishment of the blood flow through
the affected vessels.
 The favorable outcome was due to the
immediate heparin infusion and prompt
remission of the nephrotic syndrome.

Doppler imaging was an important tool for

non-invasive diagnosis and follow-up.
 Thromboembolic
complications in children with
nephrotic syndrome in
Bulgaria (1974-1996).

Pediatr Nephrol.
 Over a period of 22 years, 447 children with
nephrotic syndrome (NS) have been
retrospectively studied for clinically apparent
thromboembolic complications (TEC).
The incidence of TEC is 2% (9/447).
TEC were predominantly venous (81%
venous vs. 19% arterial).
The most commonly affected vessels were
deep leg veins, IVC, SVC, mesenteric
artery, and hepatic veins (Budd-Chiari
syndrome).
 Etiology based prevalence of
Budd-Chiari syndrome in
eastern India

J Assoc Physicians India.

 Idiopathic membranous obstruction and
stricture of IVC are the commonest cause
of BCS in the eastern part of India.
Hepatocellular carcinoma is also a
common cause, presenting in the fulminant
form.
Ultrasonography may be a helpful
screening test for BCS,
IVC and hepatic vein catheterisation is
essential for a complete work up of these
patients.
Budd-Chiari syndrome--a
case report

Nepal Med Coll J.

 A 21year old male presented with abdominal
pain for 2 months and abdominal distension
and swelling of lower limbs for 1 month.
US showed coarse echotexture of liver and
intraluminal filling defect of IVC
Confirmation of diagnosis was done by
inferior venacavography.
The patient had nephrotic syndrome as the
risk factor for thrombosis.
The patient underwent portocaval shunt with
significant symptomatic relief.