Sinusoidal Obstruction Syndrome
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Direct answer
Sinusoidal obstruction syndrome, also called hepatic veno-occlusive disease, is injury to the endothelium of hepatic sinusoids and central venules, causing painful hepatomegaly, ascites and jaundice. It follows high-dose conditioning chemotherapy before haematopoietic stem cell transplant, and it can also result from pyrrolizidine alkaloids in some herbal teas. Defibrotide is the agent used in severe disease, and reversed portal venous flow on Doppler ultrasound supports the diagnosis.
What you must remember
- Mechanism: endothelial injury to sinusoids and central venules leads to fibrin deposition, obstruction of outflow and congestion.
- Transplant setting: high-dose busulfan-based conditioning is the classic cause, and gemtuzumab ozogamicin is also associated.
- Non-transplant cause: pyrrolizidine alkaloids from certain plants and herbal teas cause the same syndrome in patients who have not had a transplant.
- Clinical triad: painful hepatomegaly, ascites and rapid weight gain, often with jaundice, and severe cases progress to multi-organ failure.
- Diagnostic criteria: Baltimore criteria need bilirubin of 2 mg/dL or more within 21 days of transplant plus two of hepatomegaly, ascites and weight gain; the modified Seattle criteria need any two of bilirubin, painful hepatomegaly and weight gain.
- Doppler: reversed portal venous flow, where flow moves away from the liver, supports the diagnosis.
- Defibrotide: an oligonucleotide with antithrombotic and endothelial-protective actions, used for severe hepatic veno-occlusive disease.
- Prophylaxis: ursodeoxycholic acid and low-dose heparin have been used in high-risk patients in some centres, though the evidence is variable.
A man with ascites three weeks after transplant
A 34-year-old man, sixteen days after a busulfan-based transplant, develops rapid weight gain, painful hepatomegaly, ascites and a raised bilirubin. The question is whether this is sinusoidal obstruction or another post-transplant complication.
- Recognise the time window: Symptoms in the first few weeks after conditioning, with a classic drug exposure, point to sinusoidal obstruction rather than an isolated infection.
- Apply the criteria: A bilirubin of 2 mg/dL or more, together with two of hepatomegaly, ascites and weight gain, meets the Baltimore criteria.
- Confirm with Doppler: Reversed portal venous flow and gallbladder wall thickening support the diagnosis, and they are checked with the liver ultrasound.
- Exclude the mimics: Sepsis, graft-versus-host disease, drug toxicity and transplant-associated thrombotic microangiopathy must be considered, since each can look similar.
- Start defibrotide: Defibrotide is given in severe disease, and it is the agent most often used for established sinusoidal obstruction.
- Manage fluid and the kidneys carefully: Fluid balance is monitored closely and diuretics are used cautiously, because renal failure and multi-organ dysfunction carry high mortality.
Where the examiner tests the transplant link
Most errors come from failing to link the syndrome to its cause and to its timing.
- Trap: attributing post-transplant jaundice to hepatitis or sepsis alone Correct: sinusoidal obstruction must be considered when painful hepatomegaly, ascites and weight gain appear in the first weeks after conditioning.
- Trap: treating hepatic veno-occlusive disease with diuretics alone Correct: ascites is managed with cautious diuresis, but defibrotide is the drug aimed at the endothelial injury.
- Trap: dismissing herbal teas as harmless in unexplained hepatic veno-occlusive disease Correct: pyrrolizidine alkaloids cause the same syndrome without transplant, so an exposure history is essential.
Frequently asked questions
What is the mechanism of sinusoidal obstruction syndrome?
Sinusoidal obstruction syndrome is caused by injury to the endothelium of hepatic sinusoids and central venules, which leads to subendothelial oedema, fibrin deposition and obstruction of venous outflow. The resulting congestion produces painful hepatomegaly, ascites and jaundice.
Which drugs are classically associated with hepatic veno-occlusive disease?
Busulfan-based conditioning before haematopoietic stem cell transplant and gemtuzumab ozogamicin are the classic drugs associated with sinusoidal obstruction syndrome. Pyrrolizidine alkaloids from certain plants and herbal teas cause the same syndrome in patients who have not had a transplant.
What is defibrotide used for in sinusoidal obstruction syndrome?
Defibrotide is an oligonucleotide used to treat severe sinusoidal obstruction syndrome after haematopoietic stem cell transplant, and it is approved for this use in many countries. It acts on the endothelium with antithrombotic and endothelial-protective effects.
Which Doppler finding supports sinusoidal obstruction syndrome?
Reversal of portal venous flow on Doppler ultrasound supports sinusoidal obstruction syndrome, because the obstructed sinusoids push flow away from the liver. Gallbladder wall thickening and ascites add supportive evidence in the same clinical setting.
How is hepatic veno-occlusive disease diagnosed after transplant?
Hepatic veno-occlusive disease is diagnosed clinically using transplant criteria, such as the Baltimore criteria of a bilirubin of 2 mg/dL or more with two of hepatomegaly, ascites and weight gain. Doppler ultrasound, along with exclusion of sepsis, graft-versus-host disease and drug toxicity, supports the diagnosis.