What is the treatment for sinusoidal occlusive syndrome?

Treatment of Sinusoidal Obstruction Syndrome

Defibrotide is the only FDA-approved treatment for sinusoidal obstruction syndrome (SOS) with renal or pulmonary dysfunction following hematopoietic stem cell transplantation. 1

Understanding SOS

Sinusoidal obstruction syndrome, previously known as veno-occlusive disease (VOD), is characterized by damage to the sinusoidal endothelial cells of the liver, leading to:

• Loss of sinusoidal wall integrity
• Endothelium denudation
• Cell embolization toward central zones of hepatic lobules
• Sinusoidal congestive obstruction by outflow block
• Potential centrilobular hepatocellular necrosis 2

Treatment Algorithm

1. For SOS with Renal or Pulmonary Dysfunction After HSCT:

• First-line therapy: Defibrotide 6.25 mg/kg every 6 hours as a 2-hour intravenous infusion 1
  • Treat for a minimum of 21 days
  • If signs and symptoms persist after 21 days, continue treatment until resolution 1
  • Monitor for bleeding (major adverse effect) and hypersensitivity reactions 1

2. For SOS in Other Settings (Non-HSCT or Without Organ Dysfunction):

• Supportive care measures:
  • Fluid and sodium restriction
  • Diuretics for fluid overload
  • Paracentesis for tense ascites
  • Pain management
  • Oxygen supplementation if needed 2

3. For Severe SOS with Multi-Organ Failure:

• Defibrotide (as above)
• Intensive supportive care for organ dysfunction
• Consider liver transplantation in select cases of intractable disease 2

Risk Factors and Prevention

Major Risk Factors:

• Myeloablative conditioning regimens for HSCT
• Certain chemotherapeutic agents (busulfan, cyclophosphamide, melphalan)
• Total body or hepatic irradiation
• Pre-existing liver disease 2

Prevention Strategies:

• Defibrotide prophylaxis in high-risk patients undergoing HSCT 2
• Ursodeoxycholic acid may be considered for prevention 3
• Avoid hepatotoxic drugs when possible
• Reduce intensity of conditioning regimens in high-risk patients 2

Diagnostic Approach

Early diagnosis is crucial for effective treatment. Key diagnostic elements include:

1. Clinical criteria:

   • Weight gain due to fluid retention
   • Painful hepatomegaly
   • Jaundice (elevated bilirubin) 2

2. Imaging:

   • Doppler ultrasound to assess portal vein flow and signs of portal hypertension
   • MRI may show patchy signal enhancement 2

3. Liver biopsy (if feasible):

   • Transjugular approach preferred due to coagulopathy risk
   • Combined with hepatic venous pressure gradient measurement (>10 mmHg supports diagnosis) 2

Special Considerations

• Timing: SOS typically occurs within 20 days post-HSCT with cyclophosphamide regimens, but may occur later with other agents 2
• Severity grading: Mild (self-limiting), moderate (requiring treatment), severe (not resolving by day 100 despite treatment) 2
• Contraindications to defibrotide: Concomitant systemic anticoagulant or fibrinolytic therapy, hypersensitivity to defibrotide 1
• Drug interactions: Defibrotide may enhance the activity of antithrombotic/fibrinolytic drugs 1

Pitfalls to Avoid

1. Delayed diagnosis: Early recognition and treatment initiation are critical for improved outcomes
2. Misdiagnosis: Rule out other causes of liver dysfunction (e.g., GVHD, infection, drug toxicity)
3. Inadequate monitoring: Regular assessment of liver function, renal function, and respiratory status is essential
4. Inappropriate anticoagulation: Avoid systemic anticoagulants with defibrotide 1

Early intervention with defibrotide in patients with SOS, particularly those with organ dysfunction following HSCT, is crucial to prevent progression to multi-organ failure and improve survival outcomes.