Sinusoidal obstruction syndrome (SOS), also known as veno-occlusive disease (VOD), is a serious condition affecting the liver’s small blood vessels, called sinusoids. It often arises after exposure to certain drugs or toxins. The mechanism involves damage to the specialized endothelial cells lining these vessels. When injured, these cells swell and detach, leading to partial or complete obstruction of blood flow. This blockage impedes blood passage through the liver, resulting in congestion and reduced oxygen and nutrient supply to liver cells, ultimately impairing liver function.
Causes and Risk Factors
The primary cause of sinusoidal obstruction syndrome is often high-dose chemotherapy and/or radiation therapy given as part of a conditioning regimen before a hematopoietic stem cell transplant (HSCT). This intensive treatment aims to prepare the body for the new stem cells, but it can inadvertently damage the liver’s blood vessels. The incidence of SOS in patients undergoing HSCT can vary, ranging from about 5% to over 60%, depending on the specific regimen and patient factors.
Other factors can also lead to SOS, including certain targeted cancer drugs. For instance, oxaliplatin and 5-fluorouracil, commonly used in chemotherapy, have been significantly associated with severe forms of the syndrome. Exposure to pyrrolizidine alkaloids, natural toxins found in some herbal teas, supplements, and honey, can also cause SOS. High-dose radiation directed at the liver for other medical reasons is another potential trigger.
Several factors increase an individual’s susceptibility to developing SOS. Patients with pre-existing liver conditions, those undergoing an allogeneic (donor) stem cell transplant compared to an autologous (self) transplant, and individuals receiving specific high-dose chemotherapy agents are at higher risk. Younger age, a lower overall health status (Karnofsky performance scale score), and a history of hepatitis B or C also contribute to an elevated risk.
Symptoms and Clinical Presentation
Symptoms of sinusoidal obstruction syndrome often appear rapidly within the first few weeks following a triggering event like a stem cell transplant. A common initial sign is unexplained, rapid weight gain, often exceeding 2% or 5% of baseline body weight, due to fluid retention. This fluid accumulation can also lead to ascites (fluid in the abdomen) and discomfort.
Individuals may also experience a tender and enlarged liver, medically termed hepatomegaly, which can be accompanied by upper right abdominal pain. This engorgement occurs as blood backs up due to the obstruction of its small vessels. Another hallmark symptom is jaundice, a yellowish discoloration of the skin and eyes, resulting from the liver’s impaired ability to process bilirubin. These symptoms usually emerge within the first 20 days post-transplant, with a peak around day 12, though some cases can have a later onset.
Diagnosis and Severity Staging
Diagnosing sinusoidal obstruction syndrome involves observing clinical signs and performing specific medical tests. Doctors rely on established criteria, such as the modified Seattle or Baltimore criteria, to confirm a diagnosis. These criteria typically require a total serum bilirubin level above 2 mg/dL, alongside two or more symptoms like an enlarged liver (hepatomegaly), right upper quadrant pain, or unexplained weight gain greater than 2% of baseline. These signs usually appear within 20 days after a stem cell transplant.
Blood tests are used to measure bilirubin levels and other indicators of liver injury, such as elevated liver enzymes. Imaging techniques, particularly Doppler ultrasound, are also valuable. This type of ultrasound can visualize blood flow within the liver and may show altered or reversed flow in the portal vein, strongly supporting the diagnosis by indicating obstructed outflow.
Once SOS is diagnosed, its severity is staged to guide treatment decisions and predict the disease course. Severity is commonly classified as mild, moderate, or severe, sometimes extending to very severe, using established criteria. This staging helps medical teams anticipate the patient’s prognosis and determine the intensity of treatment needed. Mild cases may resolve with supportive care, while severe forms, particularly those involving multi-organ dysfunction such such as kidney or pulmonary problems, carry a higher risk and necessitate more aggressive management.
Treatment and Management
Managing sinusoidal obstruction syndrome involves a two-pronged approach: supportive care and specific medical therapy. Supportive care forms the foundation of treatment, focusing on alleviating symptoms and preventing further complications. This includes careful management of fluid balance, using diuretics to control rapid weight gain and reduce fluid accumulation like ascites. Pain management is also an important aspect of supportive care.
For more severe cases of SOS, a specific medication called defibrotide is available. Defibrotide is the only FDA-approved drug for treating severe SOS, particularly with kidney or pulmonary dysfunction, after stem cell transplantation in both adults and children. This medication works to restore the balance of blood clotting and dissolving systems at the endothelial cell level, helping to protect damaged liver sinusoids and improve blood flow.
Clinical trials supporting its approval showed improved survival rates in patients receiving defibrotide. The recommended intravenous dosage is 6.25 mg/kg every six hours, administered for at least 21 days, or until the condition resolves, up to 60 days.
In very severe instances where patients do not respond to standard treatments, more invasive procedures may be considered. These can include a transjugular intrahepatic portosystemic shunt (TIPS), which helps decompress the portal venous system and reduce fluid buildup. In rare circumstances, liver transplantation might also be explored as a therapeutic option. These interventions are reserved for patients with severe prognoses.