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 37.3C, 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 (