What are the possible causes of hepatic portal vein thrombosis?

Causes of Hepatic Portal Vein Thrombosis

Portal vein thrombosis (PVT) is most commonly caused by liver cirrhosis, malignancies, and prothrombotic disorders, with the etiology often being multifactorial requiring both local and systemic risk factors. 1

Local Risk Factors

• Liver cirrhosis: The most common cause of PVT, accounting for over half of cases, especially in advanced liver disease with decreased portal flow velocity 1
• Malignancies:
  • Hepatocellular carcinoma (present in 20-35% of HCC patients at diagnosis) 1
  • Other abdominal malignancies (pancreatic carcinoma, extrahepatic solid organ tumors) 1
• Focal inflammatory conditions:
  • Pancreatitis 1
  • Inflammatory bowel disease (Crohn's disease, ulcerative colitis) 1
  • Diverticulitis and appendicitis 1
  • Cholecystitis 1
  • Intra-abdominal infections and abscesses 1
• Surgical and traumatic causes:
  • Splenectomy (particularly high risk) 1
  • Abdominal surgery (hepatic, biliary, bariatric procedures) 1
  • Liver transplantation 1
  • Abdominal trauma 1
  • Surgical portosystemic shunting and TIPS procedures 1
• Neonatal/pediatric specific factors:
  • Omphalitis (umbilical infection) 1
  • Umbilical vein catheterization 1

Systemic Risk Factors

Inherited Thrombophilias

• Factor V Leiden mutation: 4-11 fold increased risk of BCS and 2-fold risk of PVT 1
• Prothrombin G20210A gene mutation: 4-5 fold increased risk of PVT, more common in PVT than BCS 1
• Natural anticoagulant deficiencies:
  • Antithrombin deficiency (0-5% in PVT) 1
  • Protein C deficiency 1
  • Protein S deficiency 1

Acquired Thrombophilias

• Myeloproliferative neoplasms (MPNs): Present in 21-49% of patients with PVT, particularly important in non-cirrhotic PVT 1
  • JAK2 V617F mutation (positive in 16-29% of PVT cases) 1
• Antiphospholipid syndrome: Anticardiolipin antibodies present in 5-15% of PVT cases 1
• Paroxysmal nocturnal hemoglobinuria: More commonly associated with BCS (9-19%) than PVT (0-2%) 1
• Hormonal factors:
  • Oral contraceptive use (present in up to 44% of PVT cases) 1
  • Pregnancy 1
• Other systemic conditions:
  • Behçet's disease (especially in Mediterranean regions) 1
  • Autoimmune disorders 1
  • Cytomegalovirus infections 1

Geographic Variations

• Western countries: Myeloproliferative disorders and inherited thrombophilias are more common causes 1
• Asian countries: Higher prevalence of:
  • Behçet's disease 1
  • Inferior vena cava webs (membranous obstruction) 1
  • Hydatid cysts 1

Multifactorial Nature

• In 46% of BCS and 10% of PVT patients, two or more prothrombotic factors are present 1
• In PVT patients with a local risk factor, a prothrombotic factor was found in 36% of cases 1
• Over 60% of patients with inherited thrombophilia and PVT have an additional risk factor 1

Special Considerations

• Decreased portal flow velocity (below 15 cm/s) is a significant risk factor for PVT development in cirrhotic patients 1
• Non-selective beta-blockers may increase PVT risk in cirrhotic patients, though this association may be confounded by the presence of more severe portal hypertension in these patients 1
• Obesity, metabolic syndrome, and NASH cirrhosis are emerging as independent risk factors for PVT 1