TROMBOSI PORTAL EN LA CIRROSI: SIGNIFICAT I TRACTAMENT

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1 TROMBOSI PORTAL EN LA CIRROSI: SIGNIFICAT I TRACTAMENT Virginia Hernández Gea Barcelona Hepatic Hemodynamic Unit Liver Unit. Hospital Clinic. Barcelona. Octubre 2013

2 Balance of anti & prohemostatic drivers in chronic liver disease Tripodi A & Mannucci PM. NEJM 2011

3 Balance of anti & prohemostatic drivers in chronic liver disease Tripodi A & Mannucci PM. NEJM 2011

4 Balance of anti & prohemostatic drivers in chronic liver disease Tripodi A & Mannucci PM. NEJM 2011

5 Balance of anti & prohemostatic drivers in chronic liver disease Tripodi A & Mannucci PM. NEJM 2011

6 Balance of anti & prohemostatic drivers in chronic liver disease Tripodi A & Mannucci PM. NEJM 2011

7 Hemostasis in liver failure Caldwell SH et al. Hepatology 2006 Jairath V and Burroughs A. Gut 2013

8 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

9 Assessing the risk: Diagnostic Test of Coagulation Northup & caldwell. Clin gastro & hep. 2013

10 Cirrhosis and risk of thrombotic complications Improvement in imaging techniques allowed an easier detection PVT prevalence 1% of compensated cirrhosis 10 25% of patients awaiting OLT Risk of DVT/PE range from 0.5 to 1.87% Higher risk of systemic venous thromboembolism (99,444 pts and 496,872 controls ) Francoz et al. J Hepatol 2012; Sogaard et al. AJG 2009

11 Factors contributing to PVT in Cirrhosis Endothelial injury/ dysfunction Incidence of PVT at 1 year (%) <15 cm/s >15 cm/s Virchow s triad Maximal PBF velocity only variable independently associated with development of PVT Hypercoagulative state Hereditary or other acquired prothrombotic disorders Local factors Venous stasis of the PV owe to liver s architectural derangement Amitrano. Hepatol. 2000; Amitrano. J Hepatol. 2004; Zocco. J Hepatol 2009

12 Factors contributing to PVT in Cirrhosis 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 cirrhosis Amitrano J Hepatol Thrombophilic disorders Detected in 69.5% of cirrhotic patients with PVT May influence the duration of anticoagulation Amitrano Hepatology 2000

13 Clinical Manifestations Silent presentation in around 50% cases (routine US Doppler for HCC screening) 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

14 Diagnosis US Doppler Angio CT Angio MRI High sensitivity and specificity Evaluation of extension Operator dependent Entire visualization of the portal venous system Patient and operator independent Availability Radiation (CT) US Doppler the first choice technique for thrombosis detection Confirm and evaluate extension with Angio CT or Angio MRI

15 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?

16 Impact of PVT on Liver Transplantation Patients waiting list: No PVT (n=45,573) PVT (n=957) (2,1%) No differences in mortality Transplant Recipients No PVT (n=21,394) PVT (n=897) (4%) Worse outcome after LT more benefit from transplantation less benefit from transplantation Patients with cirrhosis and PVT despite not having an increased mortality while in the waiting list have a worse outcome after transplant Englesbe MJ et al. Liver Transplant 2010

17 Impact of PVT on Liver 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

18 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 Grades PVT Grade 1: Minimally or partially thrombosed PV(<50%) Grade 2: >50% occlusion of the PV Grade 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)

19 PVT evolution in patients not receiving anticoagulation Progression / Spontaneous recanalization Francoz (2005) (n=10, all partial) 5 Senzolo (2012) (n=21, 14 partial) Luca (2012) (n=42, all partial) Progression Recanalization / *Improvement in Luca s study

20 Anticoagulation Complete Rec. 100 Partial Rec. No Response 75 33% at 6 month Rx Author/Year Number of Pts Rx Francoz/ LMWH VKA Amitrano/ LMWH Senzolo/ LMWH Delgado/ LMWH/LMWH VKA/VKA Delayed initiation of anticoagulation was the only factor associated with no recanalization

21 Clinical Events During Anticoagulation Therapy 55 patients 13 patients had 23 liver related clinical events p= Variceal Bleeding n=6 Ascites n=8 15 Hepatic Encephalopathy n=5 SBP n=2 HCC n= /33 15% 8/22 27% 0 Recanalization Partial/complete No Recanalization Delgado et al. Clin Gastroenterol Hepatol 2012

22 Anticoagulation in Cirrhosis. Complications 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 anemia b 1 VB 1 Cereb Hemorrhage 1 heparin induced thrombocitopenia In 10 pts: 6 VB; 5 Non VB Platelet < Bleed predictive factor No Mortality related to Anticoagulation

23 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 months 5 of 13 patients (38.5%) rethrombosed 1.3 months after Amitrano et al Delgado et al. 2012

24 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 but suboptimal monitoring using INR. No RCTs New antithrombotic agents Direct action on antithrombin or in Factor Xa Better option?

25 TIPS in Patients with Cirrhosis and PVT It is difficult to estimate the real applicability of TIPS in the management of PVT in cirrhosis Senzolo pts TIPS Feasibility (%) Van Ha 2006 Perarnau pts 34 pts Han pts Luca pts 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 Feasibility reduced portal cavernoma complete PV occlusion no patent intrahepatic PV branches

26 Thrombolysis in Patients with Cirrhosis and PVT Anecdotic reports with systemic/local administration of different thrombolytic agents Thrombolytic therapy may be useful but severe complications may occur 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

27 PVT in Cirrhosis. Treatment Recommendations Recent or evident progression of thrombosis Anticoagulation Stable old thrombus or Portal Cavernoma Is the spleno SMV junction patent and is the patient a possible LT candidate? Yes No Evaluation at 3 6 months with Imaging study Is there a thrombophilic disorder? Yes No Routine follow up Progression of Thrombosis Improvement or Stabilization of PVT Careful Imaging follow up Consider TIPS Consider Anticoagulation for life or until LT Progression of Thrombosis TIPS should also be considered in patients with concomitant severe complications of portal hypertension such as variceal bleeding or refractory ascites

28 THANKS

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