trombosi portal en la cirrosi: significat i tractament · 2013. 10. 11. · cirrhosis and risk of...
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TROMBOSI PORTAL EN LA CIRROSI: SIGNIFICAT I TRACTAMENT
Virginia Hernández‐Gea
Barcelona Hepatic Hemodynamic Unit
Liver Unit. Hospital Clinic. Barcelona. Octubre 2013
Tripodi A & Mannucci PM. NEJM 2011
Balance of anti & prohemostatic drivers in chronic liver disease
Tripodi A & Mannucci PM. NEJM 2011
Balance of anti & prohemostatic drivers in chronic liver disease
Tripodi A & Mannucci PM. NEJM 2011
Balance of anti & prohemostatic drivers in chronic liver disease
Tripodi A & Mannucci PM. NEJM 2011
Balance of anti & prohemostatic drivers in chronic liver disease
Tripodi A & Mannucci PM. NEJM 2011
Balance of anti & prohemostatic drivers in chronic liver disease
Caldwell SH et al. Hepatology 2006
Hemostasis in liver failure
Jairath V and Burroughs A. Gut 2013
Thrombin generation & inhibition
Plasma from patients with cirrhosis generates as much thrombin (the final enzyme of coagulation) as plasma from healthy subjects
Tripodi A & Mannucci PM. NEJM 2011
Northup & caldwell. Clin gastro & hep. 2013
Assessing the risk: Diagnostic Test of Coagulation
Cirrhosis and risk of thrombotic complications
PVT prevalence1% of compensated cirrhosis10‐25% of patients awaiting OLT
Risk of DVT/PErange from 0.5 to 1.87%
Higher risk of systemic venous thromboembolism
Francoz et al. J Hepatol 2012; Sogaard et al. AJG 2009
(99,444 pts and
496,872 controls )
Improvement in imaging techniques allowed an easier detection
Factors contributing to PVT in Cirrhosis
Virchow’s triad
Endothelial injury/dysfunction
Hypercoagulative state
Local factors
Hereditary or other acquired prothrombotic disorders
Amitrano. Hepatol. 2000; Amitrano. J Hepatol. 2004; Zocco. J Hepatol 2009Incide
nce of PVT
at 1
year (%
)
0
10
20
30
40
50
>15 cm/s<15 cm/s
Maximal PBF velocity only variable independently associated with
development of PVT
Venous stasis of the PV owe to liver’s architectural derangement
Patients with more advanced liver disease have a higher rate of developing PVT
1 % in compensated cirrhosis
8% to 25% of patients with Child B–C cirrhosisAmitrano J Hepatol. 2004
Thrombophilic disordersDetected in 69.5% of cirrhotic patients with PVTMay influence the duration of anticoagulation
Amitrano Hepatology 2000
Factors contributing to PVT in Cirrhosis
Clinical Manifestations
79 patients with Liver Cirrhosis and PVT at diagnosis
• 43% Asymptomatic (Routine US for HCC screening)• 39% portal hypertension related gastrointestinal bleeding• 18% acute abdominal pain (10 intestinal infarction)
Amitrano et al. J Hepatol 2004
Silent presentation in around 50% cases (routine US‐Doppler for HCC screening)
Diagnosis
US‐Doppler Angio‐CT Angio‐MRI
Entire visualization of the portal venous systemPatient and operator independent
Availability Radiation (CT)
High sensitivity and specificity
Evaluation of extensionOperator dependent
US‐Doppler the first choice technique for thrombosis detectionConfirm and evaluate extension with Angio‐CT or Angio‐MRI
Should We Treat PVT in Cirrhosis Once Developed?
•Is PVT the consequence of an advanced liver disease?
•Does PVT cause further deterioration of the clinical condition or does it appear when liver is decompensated?
•What’s the hemodinamyc impact of PV T in advanced cirrhosis and hyperdinamic circulation ?
•Does spontaneous regression really happen?
•Does it impact liver transplantation?
Englesbe MJ et al. Liver Transplant 2010
Impact of PVT on Liver Transplantation
Patients waiting list:No PVT (n=45,573) PVT (n=957) (2,1%)No differences in mortality
Patients with cirrhosis and PVT despite not having an increased mortality while in the waiting‐list have a worse outcome after transplant
Transplant Recipients
No PVT (n=21,394) PVT (n=897) (4%)Worse outcome after LT
more benefit from transplantation less benefit from transplantation
Occlusive PVT – Complicates the liver transplant operation
– Is associated with a significantly higher post‐transplant mortality rate
– Preventing the development of severe forms of PVT impact outcome in potential OLT candidates
Impact of PVT on Liver Transplantation
(n=24)
(n=716)
(Grd 2:n=23 Grd 3:n=6;Grd 4:n=10)
Grade 1 PVT patients do as well as non‐PVT patients
Grades 2–4 patients have higher perioperative complications and reduced long‐term survival
Impact of PVT on Liver Transplantation
Grades PVTGrade 1: Minimally or partially thrombosed PV(<50%)Grade 2: >50% occlusion of the PVGrade 3: Complete thrombosis of both PV and proximal SMV.Grade 4: Complete thrombosis of the PV and proximal as well as distal SMV
With increased experience in LTx in patients with PVT , outcome has improved 5‐year survival rate > 60% ( even in severe forms of PVT)
0
60
5
71
45 48
0
10
20
30
40
50
60
70
80
Francoz (2005)(n=10, all partial)
Senzolo (2012)(n=21, 14 partial)
Luca (2012)(n=42, all partial)
Recanalization / *Improvement in Luca’s studyProgression
PVT evolution in patients not receiving anticoagulation
Progression / Spontaneous recanalization
Anticoagulation
Complete Rec.
Partial Rec.
No Response
Author/YearNumber of PtsRx
Francoz/200519
LMWH VKA
Amitrano/201028
LMWH
Senzolo/201233LMWH
0
25
50
75
100
33% at 6 month Rx
Delgado/201255
LMWH/LMWH VKA/VKA
Delayed initiation of anticoagulation was the only factor associated with no recanalization
Delgado et al. Clin Gastroenterol Hepatol 2012
0
5
10
15
20
25
30
8/22
27%
5/33
15%
RecanalizationPartial/complete
No Recanalization
p=0.1
Clinical Events During Anticoagulation Therapy
55 patients13 patients had 23 liver‐related
clinical events
• Variceal Bleeding n=6
• Ascites n=8
• Hepatic Encephalopathy n=5
• SBP n=2
• HCC n=2
Anticoagulation in Cirrhosis. Complications
No Mortality related to Anticoagulation
Deep Venous Thrombosis or Pulmonary Embolism
17 Patients
‐14 pts bleeding (85%); 6 Severe (35%)‐Anticoagulation was stopped in 14 pts in < 6m
Garcia‐Fuster 2008
Portal Vein Thrombosis
Francoz/2005 n=19 Amitrano/2010 n=28 Senzolo/2012 n=33 Delgado/2012 n=55
1 Post‐EBL bleeding 2 PHG anemiab
1 VB1 Cereb Hemorrhage1 heparin induced thrombocitopenia
In 10 pts: 6 VB; 5 Non‐VB
Platelet < 50.000 Bleed predictive factor
What shoud be do if recanalization is achieved?
Pathophysiological mechanisms leading to the development of thrombosis remain
Optimal length of anticoagulation?
Should it be maintained indefinitely to prevent rethrombosis?
Risk of rethrombosis after stopping anticoagulation
3/11 (27%) patients rethrombosis at 1, 4, and 24 monthsAmitrano et al. 2010
5 of 13 patients (38.5%) rethrombosed 1.3 months after Delgado et al. 2012
Anticoagulation agent in cirrhosis. LMWH or VKA?
LMWH VKA
Requires antithrombin(reduced in cirrhosis)1‐2 daily injections
Do not need monitoring Safer than VKA?
Decrease the anticoagulants protein C and S already reduced in cirrhosis
INR aimed at interval 2.0‐3.0 but suboptimal monitoring
using INR.
No RCTsNew antithrombotic agents
Direct action on antithrombin or in Factor Xa Better option?
TIPS in Patients with Cirrhosis and PVT
0102030405060708090
100TIPS Feasibility (%)
Senzolo 200625 pts
Van Ha 200615 pts
Perarnau 201034 pts
Han 201157 pts
Luca 201170 pts
Feasibility reducedportal cavernomacomplete PV occlusion no patent intrahepatic PV branches
TIPS was indicated to treat severe complications of portal hypertension and not PVT itself
The number of patients in whom TIPS was not considered because of the presence of PVT is unknown
It is difficult to estimate the real applicability of TIPS in the management of PVT in cirrhosis
Anecdotic reports with systemic/local administration of different thrombolytic agents
Thrombolytic therapy may be useful but severe complications may occur
Thrombolysis in Patients with Cirrhosis and PVT
A pilot study in 9 patients with cirrhosis and PVT:suggests that systemic thrombolysis with low dose r‐tPA could be effective in obtaining recanalization (45% partial and 45% complete recanalization) with no major side effects
De Santis. Dig Liv Dis 2010
Recent or evident progression of thrombosis
Anticoagulation
Evaluation at 3‐6 months with Imaging study
Progression of Thrombosis
Consider TIPS
Stable old thrombus or Portal Cavernoma
Is the spleno‐SMV junction patent and is the patient a possible LT candidate?
No
Routine follow‐up
Yes
Is there a thrombophilic disorder?
No
Careful Imaging follow‐up
Yes
Progression of Thrombosis
Improvement or Stabilization of PVT
Consider Anticoagulation for
life or until LT
PVT in Cirrhosis. Treatment Recommendations
TIPS should also be considered in patients with concomitant severe complications of portal hypertension such as variceal bleeding or refractory ascites
THANKS
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