Portal vein thrombosis: scenarios and principles of treatment

1. Portal vein thrombosis:
scenarios and principles of treatment
Andrea De Gottardi, Hepatology, Inselspital,
University of Berne

2. First things first
venous thrombus formation
→endothelial dysfunction or
injury
→hemodynamic changes
→hypercoagulability
(Rudolf Virchow 1821 – 1902)

3. Outline
The scenarios of portal vein thrombosis
→Anatomical brush-up
→Acute (with or without cirrhosis)
→Chronic
→Local factors
→General factors
→Localisation
→Extension
→Degree of obstruction
→Complications
→Principles of treatment

4. Clinical case: history and examination
43 year-old man presenting with diffuse
abdominal pain and vomiting for 2 days
one episode of diarrhea, chills, but no
fever
his daughter had fever, nausea and
vomiting
reduced general conditions, T 37.3°C,
BP 130/85 mmHg, HR 99/min
diffuse abdominal tenderness on
palpation, reduced peristaltic sounds

5. Clinical case: laboratory
Haematology
white blood cells 14.4 G/L
hemoglobin 144 G/L
thrombocytes 82 G/L
Biochemistry
C reactive protein 143 mg/L
creatinine 66 uM
bilirubin 27 uM
glucose 6.9 mM
ALT 17 U/L
alcaline phosphatase 65 U/L

6. Anatomy of the portal system
Pressure gradient to hepatic veins:
< 6 mmHg = normal
≥ 6 mmHg = portal hypertension
≥ 10 mmHg = clinically relevant PHT
Blood flow:
750 – 1500 mL/min
Velocity:
10-15 cm/s
spleno-mesenteric
confluence

7. Clinical case: images

8. Clinical case: images

9. Clinical case: images

10. Acute PVT
Definition
• Sudden formation of a thrombus within the
portal vein
• Can involve a variable portion of the
mesenteric veins and/or the splenic vein
• Occlusion can be complete or it can be
partial

11. Acute PVT
Degree and extension of occlusion
short partial
long partial
long complete
short complete

12. Acute PVT
Symptoms
• no symptoms
• abdominal or lumbar pain of sudden onset or
progressing over a few days
• abdomen might be moderately distended by ileus,
but without any other features of intestinal obstruction
• ascites, bloody diarrhea (suggesting infarction)
• acute septic PVT = acute pylephlebitis
provided there is no extension of the thrombus to
mesenteric venous arches, all manifestations of
acute PVT are completely reversible
Condat, Nat Clin Pract Gastroenterol Hepatol, 2006
Hoekstra, Neth J Med, 2009
Primignani, Dig Liver Dis, 2009

13. Acute PVT
Laboratory
• marked systemic inflammatory response
• liver function is preserved (compensatory
increase of hepatic arterial blood flow)
• acidosis and renal or respiratory dysfunction
are also suggestive of intestinal infarction
Condat, Nat Clin Pract Gastroenterol Hepatol, 2006
Hoekstra, Neth J Med, 2009
Primignani, Dig Liver Dis, 2009

14. Acute PVT
Imaging
Abdominal ultrasound:
- hyperechoic intraportal material
- absence of portal flow, no Doppler signal
CT-scan:
- contrast enhanced (portal phase, evaluation
of the extension of the thrombosis)

15. Acute PVT
General factors
Primignani, Dig Liver Dis, 2010. Plessier, Hepatology, 2010. Leebeek, Neth J med, 2012
FACTOR PREVALENCE %
JAK2 V617F mutated MPD 17-53
Anti-phospholipid syndrome 1-11
Paroxysmal nocturnal hemoglobinuria 0-9
Hyperhomocystinemia 11-15
Factor V Leiden 3-9
Prothrombin mutation G20210A 2-22
Protein C deficiency 1-9
Protein S deficiency 0-7
Oral contraceptive 0-4
Pregnancy and post-partum 7-44

16. James, Nature, 2005
JAK2 V617F mutation

17. FACTOR PREVALENCE %
Abdominal inflammatory lesions
7-34
- diverticulitis, appendicitis, pancreatitis
- inflammatory bowel disease
- CMV infection/hepatitis
- abdominal abcess
Abdominal surgery/trauma
3-45
- splenectomy, gastrectomy, cholecystectomy, LT
Abdominal cancer
Acute PVT
Local factors
Primignani, Dig Liver Dis, 2010. Plessier, Hepatology, 2010. Leebeek, Neth J med, 2012

18. Chronic PVT
Definition
the obstructed portal vein is replaced by a
network of hepatopetal collateral veins
connecting the patent portion of the vein
upstream from the thrombus to the patent
portion downstream

19. Cavernous transformation
Zhang, World J Gastroenterol, 2011
Cavernoma may be identified as soon as 15-30 days after the
onset with abdominal symptoms

20. Chronic PVT
Consequences
With occlusion of the trunk of the portal vein, antral,
duodenal and biliary veins are markedly enlarged.
This enlargement can produce compression and
deformation of large bile ducts = portal
cholangiopathy or portal biliopathy.
Complete occlusion of the portal vein trunk is virtually
always associated with portal hypertension and the
development of portosystemic collaterals.

21. Portal cholangiopathy
Llop, Gut, 2011
Symptomatic portal cholangiopathy develops in 19% after 5 years

22. Chronic PVT
Complications
Portal hypertension
- formation of esophageal or gastric varices
- the occurrence of ascites or encephalopathy in patients with
chronic PVT is uncommon
Portal cholangiopathy
- it mimics the bead-like appearance of primary sclerosing
cholangitis
- It is much more commonly seen on biliary tract imaging than
with clinical or laboratory features of biliary disease.
- A tumor-like cavernoma can be confused with carcinoma of
the main bile duct.

23. PVT in cirrhosis
PVT occurs rarely in early cirrhosis
High prevalence in patients on transplant WL (5-26%)
Severe liver disease ⇆ aggravates ⇆ PVT
Decreased portal flow velocity (<10 cm/s)
Coagulation inbalance and role of thrombocytopenia
and hyperfibrinolysis
Changes in portal endothelial cells
Plessier, J Hepatol, 2012. Francoz, J Hepatol, 2012. Zocco, J Hepatol, 2009. Rijken, Throm Hemost, 2012

24. PVT in cirrhosis
Virchow’s triad (1)
La Mura, Gut, 2011
Endothelial dysfunction in the hepatic vascular bed

25. PVT in cirrhosis
Virchow’s triad (2&3)
Lisman, J Hepatol, 2010
Hepatic vascular resistance is increased and
consequently portal flow velocity is decreased or even
inversed (hepatofugal).
Cirrhosis is characterized by a hemostatic rebalance.

26. Principles of treatment
Goals of treatment
ACUTE PVT
• To recanalize the obstructed veins, which
will prevent intestinal infarction and portal
hypertension
• To treat or avoid infection
• Recanalisation of the portal vein virtually
never occurs without treatment

27. Treatment options
Anticoagulation for acute PVT
Recanalization can be expected until the 6th/12th month of anticoagulation
portal 39%, splenic 80%, mesenteric 73%
(Condat, Hepatology, 2000. Plessier, Hepatology, 2010)
Optimal duration of anticoagulation
from 3 months to long-term (prothrombotic conditions)
In patients with DVT, a lack of complete recanalization indicates a high
risk of recurrence after cessation of anticoagulation therapy.
Is this also true for patients with acute PVT?
Bleeding under anticoagulation occurs in 9%, however
without related mortality

28. Treatment options
Anticoagulation for acute PVT
Unfractionated heparin or low molecular weight heparin represent the
mainstay of initial therapy.
Vitamin K antagonists are generally used after recovery from the acute
event. Very few data on DOACs.
Thrombolysis
• Transhepatic or transjugular route
• Limited number of patients,
but
• Recanalisation rate similar to those achieved with anticoagulation
• Major procedure-related bleeding in up to 50%

29. Treatment options
Other treatment modalities for acute PVT
Antibiotics
are indicated with chills and positive blood cultures
Surgical intestinal resection
when clinical and radiological features indicate that a
patient has (or may have) intestinal infarction
Surgical thrombectomy
Recanalisation is obtained in 30% of the patients and
recurrence of PVT is frequent

30. Principles of treatment

31. Principles of treatment

32. Treatment options
Aim: to prevent recurrence or extension of thrombosis
Anticoagulation for chronic PVT
Risk of GI bleeding and severity not increased
(Condat, Gastroenterology, 2001, Kitchens, J Thromb Thrombolysis, 2007)
Should be discussed in patients with a prothrombotic
condition
(De Franchis, Baveno V, J Hepatol, 2010)

33. Prevention of PVT in cirrhosis
Dashed line: controls Continuous line: enoxaparin-treated patients
Villa, Gastroenterology, 2012

34. TAKE HOME MESSAGES
Recurrence or extension should be avoided by
treating local or systemic factors
Recanalisation should be the aim of
anticoagulation or invasive procedures if indicated
PVT should be correctly diagnosed

35. Further reading
EASL Clinical Practice Guidelines:
Vascular liver diseases 2015
J. Hepatol. In preparation
AASLD Practice Guidelines:
Vascular disorders of the liver
Hepatology, 2010