Transcript Document

BSG Postgraduate Course
Birmingham 2006
Haematological and vascular
complications affecting the liver
Dominique-Charles Valla
Hôpital Beaujon, Clichy, France
Blood disorders affecting the liver
• Lymphoproliferative or
myeloproliferative diseases
Infiltration
• Activated Macrophages
Infiltration
Cytokine release
• Lymphoproliferative
diseases
Light chain
deposition
• Prothombotic disorders
Thrombosis
Prothrombotic Disorders
Involvement of hepatic vessels
• Portal venous thrombosis
large- or small-sized veins
• Hepatic venous thrombosis
large- or small-sized veins
• Any combination thereof
Secondary architectural changes
Vascular obstruction
Sinusoidal
dilatation
Atrophy
Hypertrophy
• central
• random
• macronodules
• micronodules
Fibrosis
• portal
• central
• sinusoidal
Prothrombotic disorders affecting hepatic vessels
Portal hypertension or Abnormal liver tests
• Extrahepatic portal vein thrombosis
Pylephlebitis and Portal cavernoma
• Hepatic vein/IVC thrombosis
Budd-Chiari syndrome
• Intrahepatic vascular obstruction
Hepatic veins or Portal veins
• Non-cirrhotic architectural changes
Prothrombotic Disorders
in BCS or PVT
BCS PVT
Myeloproliferative diseases %
Hereditary thrombophilias %
Antiphospholipid syndrome %
PNH %
60
30
35
15
35
15
5
0
Janssen, Blood 2000. Deltenre, Gut, 2001. Primignani, Hepatology 2005
Case history
• Healthy male patient, 39 year-old.
Enlarged spleen (6 cm) at routine examination
• AST/ALT
Normal
WBC
GGT & ALP 1.8xULN Platelets
Prothrombin 72%
RBC
Factor V
70%
Hematocrit
• No cause for chronic liver disease
9 000/fL
250 000/fL
4.2 106/fL
39%
• CT / US : Portal cavernoma.
• Grade III esophageal varices with red signs
• Needle biopsy: Normal liver
WBC
Platelets
Hematocrit
Prothrombin
Factor V
9 000/fL
250 000/fL
39%
72%
70%
Antithrombin N > 75%
Protein C N > 65%
Protein S N > 65%
Factor V Leiden
Factor II mutation
APL Ab/LA
70%
55%
62%
Absent
Present
Absent
How many causal factors
have been fully identified ?
WBC
Platelets
Hematocrit
Prothrombin
Factor V
9 000/fL
250 000/fL
39%
72%
70%
Antithrombin N > 75%
Protein C N > 65%
Protein S N > 65%
Factor V Leiden
Factor II mutation
APL Ab/LA
70%
55%
62%
Absent
Present
Absent
How many causal factors
have been fully identified ?
1
2
3
• F II gene mutation
•X
WBCC
Platelets
Hematocrit
Prothrombin
Factor V
9 000/fL
250 000/fL
39%
72%
70%
Antithrombin N > 75%
Protein C N > 65%
Protein S N > 65%
Factor V Leiden
Factor II mutation
APL Ab/LA
70%
55%
62%
Absent
Present
Absent
PVT - Coagulation inhibitors
Fisher. Gut 2000; 46:534
WBCC
Platelets
Hematocrit
Prothrombin
Factor V
9 000/fL
250 000/fL
39%
72%
70%
Antithrombin N > 75%
Protein C N > 65%
Protein S N > 65%
Factor V Leiden
Factor II mutation
APL Ab/LA
70%
55%
62%
Absent
Present
Absent
Combination of prothrombotic disorders
BCS
PVT
At least 2 disorders (%) 25-35% 10-20%
Myeloproliferative disease in 20-60%
of patients with hereditary thrombophilias
Denninger. Hepatology 2000. Janssen Blood 2000.
Primignani Hepatology 2005
WBCC
Platelets
Hematocrit
Prothrombin
Factor V
9 000/fL
250 000/fL
39%
72%
70%
Antithrombin N > 75%
Protein C N > 65%
Protein S N > 65%
Factor V Leiden
Factor II mutation
APL Ab/LA
70%
55%
62%
Absent
Present
Absent
BCS or PVT
Features of Myeloproliferative Disease
PPV
Δ Spleen > 5 cm
Platelets > 200 000/fL
Chait et al. Br J Haematol 2005
100%
Myeloproliferative diseases
Diagnostic criteria
•
•
•
•
Classical criteria (PVSG) %
Endogenous erythroid colonies %
Bone marrow biopsy %
V617F JAK2 mutation %
BCS PVT
10
60
60
60
0
30
30
30
James Nature 2005. Kralovics NEJM 2005. Baxter Lancet 2005. Levine Cancer Cell 2005.
Patel RK et al. ASH Dec 2005. Fabris FH et al. EASL 2006
• F II gene mutation
• Myeloproliferative disease
• Portal vein thrombosis
• Large oesophageal varices with
red signs
Would you recommend
permanent anticoagulation ?
YES - NO
Disease-specific Antithrombotic Therapies
• Myeloproliferative diseases
Hydroxyurea
 Low dose aspirin
 Anagrelide

Data still unclear for
venous thromboses
• Other acquired or inherited conditions
 Little
or no data
Cortelazzo NEJM 1995. Landolfi NEJM 2004. Eliott Br J Haematol 2004.
Crother Thromb Res 2004. Harrisson NEJM 2005
per 100 patients
per year
Chronic Portal Vein Thrombosis
Anticoagulation
yes
no
Anticoagulation
yes
no
17
6.0
p = 0.015
1.2
Thrombosis
p = 0.212
7
Bleeding
Condat et al. Gastroenterology 2001; 120:490
per 100 patients
per year
Chronic PVT – GI Bleeding
Prophylaxis
no
yes
24
17
Moderate/large-sized
varices
Condat et al. Gastroenterology 2001;120:490-497
Chronic portomesenteric
venous thrombosis
Hazard Ratio for Death
1.00
1.00
p=0.038
0.10
no
yes
Warfarine
p=0.030
0.28
yes
no
Beta-blockers
Orr et al. Hepatology 2005; 42: 212A (AASLD San Francisco 2005)
Acute Portal Vein Thrombosis
Recanalisation
83 %
75 %
Anticoagulation
Thrombolysis
(alone, n = 27)
(in situ, n = 20)
Condat.
Hepatology 2000
Holliingshead.
J Vasc Interv Radiol 2005
Acute Portal Vein Thrombosis
100
Major Bleeding
%
60%
5%
0
Anticoagulation
Thrombolysis
(alone, n = 27)
(in situ, n = 20)
Condat.
Hepatology 2000
Holliingshead.
J Vasc Interv Radiol 2005
Portal Vein Thrombosis
Current guidelines in Beaujon
Permanent prothrombotic disorder
→ Permanent anticoagulation
No contraindication
Prophylaxis for PHT-related bleeding
Anticoagulation for BCS
• Anticoagulation recommended to all
patients, in the absence of major
contraindication.
• Previous bleeding from portal hypertension
is not considered a major contraindication,
provided appropriate prophylaxis for
recurrent bleeding is initiated.
Janssen et al, J Hepatol 2003. de Franchis, J Hepatol 2005.
Conclusions
• Blood disorders are major causes of
vascular liver diseases.
• Atypical myeloproliferative diseases most
commonly implicated.
• Frequent combination of several causes.
• Permanent anticoagulation is generally
recommended once prophylaxis for portal
hypertensive bleeding has been instituted.