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Haematological and vascular complications affecting the liver

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 Activated Macrophages

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Haematological and vascular complications affecting the liver

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  1. BSG Postgraduate Course Birmingham 2006 Haematological and vascular complications affecting the liver Dominique-Charles Valla Hôpital Beaujon, Clichy, France

  2. Blood disorders affecting the liver • Lymphoproliferative or myeloproliferative diseases • Activated Macrophages • Lymphoproliferative diseases • Prothombotic disorders Infiltration Infiltration Cytokine release Light chain deposition Thrombosis

  3. Prothrombotic DisordersInvolvement of hepatic vessels • Portal venous thrombosis large- or small-sized veins • Hepatic venous thrombosis large- or small-sized veins • Any combination thereof

  4. Secondary architectural changes Vascular obstruction Atrophy Hypertrophy Sinusoidal dilatation Fibrosis • portal • central • sinusoidal • central • random • macronodules • micronodules

  5. Prothrombotic disorders affecting hepatic vessels Portal hypertension or Abnormal liver tests • Extrahepatic portal vein thrombosis Pylephlebitis andPortal cavernoma • Hepatic vein/IVC thrombosis Budd-Chiari syndrome • Intrahepatic vascular obstruction Hepatic veins or Portal veins • Non-cirrhotic architectural changes

  6. Prothrombotic Disorders in BCS or PVT BCS PVT Myeloproliferative diseases % Hereditary thrombophilias % Antiphospholipid syndrome % PNH % 60 30 35 35 15 15 5 0 Janssen, Blood 2000. Deltenre, Gut, 2001. Primignani, Hepatology 2005

  7. Case history • Healthy male patient, 39 year-old. • Enlarged spleen (6 cm) at routine examination • AST/ALT Normal WBC 9 000/fL • GGT & ALP 1.8xULN Platelets 250 000/fL Prothrombin 72% RBC 4.2 106/fL • Factor V 70% Hematocrit 39% • No cause for chronic liver disease • CT / US : Portal cavernoma. • Grade III esophageal varices with red signs • Needle biopsy: Normal liver

  8. WBC 9 000/fL Platelets 250 000/fL Hematocrit 39% Prothrombin 72% Factor V 70% Antithrombin N > 75% 70% Protein C N > 65% 55% Protein S N > 65% 62% Factor V Leiden Absent Factor II mutation Present APL Ab/LA Absent

  9. How many causal factors have been fully identified ?

  10. WBC 9 000/fL Platelets 250 000/fL Hematocrit 39% Prothrombin 72% Factor V 70% Antithrombin N > 75% 70% Protein C N > 65% 55% Protein S N > 65% 62% Factor V Leiden Absent Factor II mutation Present APL Ab/LA Absent

  11. 1 • F II gene mutation • X 2 3 How many causal factors have been fully identified ?

  12. WBCC 9 000/fL Platelets 250 000/fL Hematocrit 39% Prothrombin 72% Factor V 70% Antithrombin N > 75% 70% Protein C N > 65% 55% Protein S N > 65% 62% Factor V Leiden Absent Factor II mutation Present APL Ab/LA Absent

  13. PVT - Coagulation inhibitors Fisher. Gut 2000; 46:534

  14. WBCC 9 000/fL Platelets 250 000/fL Hematocrit 39% Prothrombin 72% Factor V 70% Antithrombin N > 75% 70% Protein C N > 65% 55% Protein S N > 65% 62% Factor V Leiden Absent Factor II mutation Present APL Ab/LA Absent

  15. 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

  16. WBCC 9 000/fL Platelets 250 000/fL Hematocrit 39% Prothrombin 72% Factor V 70% Antithrombin N > 75% 70% Protein C N > 65% 55% Protein S N > 65% 62% Factor V Leiden Absent Factor II mutation Present APL Ab/LA Absent

  17. BCS or PVTFeatures of Myeloproliferative Disease PPV Δ Spleen > 5 cm Platelets > 200 000/fL 100% Chait et al. Br J Haematol 2005

  18. Myeloproliferative diseases Diagnostic criteria BCS PVT • Classical criteria (PVSG) % 10 0 • Endogenous erythroid colonies % 60 30 • Bone marrow biopsy % 60 30 • V617F JAK2 mutation % 60 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

  19. F II gene mutation • Myeloproliferative disease • Portal vein thrombosis • Large oesophageal varices with red signs

  20. Would you recommend permanent anticoagulation ? YES -NO

  21. Disease-specific Antithrombotic Therapies • Myeloproliferative diseases • Hydroxyurea • Low dose aspirin • Anagrelide • Other acquired or inherited conditions • Little or no data Data still unclear for venous thromboses Cortelazzo NEJM 1995. Landolfi NEJM 2004. Eliott Br J Haematol 2004. Crother Thromb Res 2004. Harrisson NEJM 2005

  22. Chronic Portal Vein Thrombosis Anticoagulation Anticoagulation yes yes no no 17 6.0 p = 0.212 per 100 patients per year p = 0.015 7 1.2 Bleeding Thrombosis Condat et al. Gastroenterology 2001; 120:490

  23. Chronic PVT – GI Bleeding Prophylaxis no yes 24 17 per 100 patients per year Moderate/large-sized varices Condat et al. Gastroenterology 2001;120:490-497

  24. Chronic portomesenteric venous thrombosis Hazard Ratio for Death 1.00 1.00 p=0.030 p=0.038 0.28 0.10 yes no no yes Beta-blockers Warfarine Orr et al. Hepatology 2005; 42: 212A (AASLD San Francisco 2005)

  25. Acute Portal Vein Thrombosis Recanalisation 83% 75 % Thrombolysis (in situ, n = 20) Anticoagulation (alone, n = 27) Condat. Hepatology 2000 Holliingshead. J Vasc Interv Radiol 2005

  26. Acute Portal Vein Thrombosis 100 Major Bleeding % 60% 5% 0 Thrombolysis (in situ, n = 20) Anticoagulation (alone, n = 27) Condat. Hepatology 2000 Holliingshead. J Vasc Interv Radiol 2005

  27. PortalVeinThrombosisCurrent guidelines in Beaujon Permanent prothrombotic disorder → Permanent anticoagulation No contraindication Prophylaxis for PHT-related bleeding

  28. 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.

  29. 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.

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