Defibrotide, marketed under names like Defitelio, is a medication classified as a single-stranded oligonucleotide. It is derived through a purification process from the intestinal mucosa of pigs. This substance serves as a therapeutic agent, specifically developed to address a severe medical condition affecting the liver.
Treating a Critical Complication
Defibrotide is primarily used to treat hepatic veno-occlusive disease (VOD), also known as sinusoidal obstruction syndrome (SOS). This life-threatening condition involves the obstruction of small veins and sinusoids within the liver. VOD/SOS often arises as a serious complication following high-dose chemotherapy, especially before hematopoietic stem cell transplantation (HSCT).
The underlying cause of VOD/SOS is thought to be injury to the endothelial cells that line the hepatic sinusoids and central venules, leading to inflammation and clotting. This damage can result in blockages that impede blood flow through the liver. The reduced blood flow causes pressure to build up, leading to symptoms such as jaundice, tender liver enlargement, and fluid accumulation in the abdomen, known as ascites, along with rapid weight gain.
VOD/SOS can range in severity, but severe cases, especially those accompanied by multi-organ failure involving kidney or lung dysfunction, are associated with a very high mortality rate, often exceeding 80% if left untreated. Defibrotide has received approval for this indication in both the European Union and the United States, offering a therapeutic option for patients facing this challenging complication.
How Defibrotide Works
Defibrotide’s mechanism of action involves restoring normal blood flow in the liver and mitigating VOD/SOS damage. A primary function of defibrotide is its protective effect on endothelial cells, the specialized cells that line the inside of blood vessels. It helps to reduce their activation and dysfunction, which are central to VOD/SOS development.
The medication also promotes fibrinolysis, a natural process in the body responsible for breaking down blood clots. By increasing fibrinolytic activity, defibrotide aids in dissolving the clots that obstruct the small blood vessels in the liver, thereby improving blood flow. This action helps to counteract the procoagulant state often seen in VOD/SOS.
Defibrotide also exhibits anti-inflammatory properties. It reduces the release of inflammatory mediators and possesses antioxidant effects, which lessens the inflammatory response and oxidative stress that contribute to endothelial cell damage in the liver. These combined actions of endothelial protection, clot breakdown, and inflammation reduction work together to restore the balance of blood clotting and improve liver function in affected patients.
Receiving Defibrotide Treatment
Defibrotide is typically administered as an intravenous infusion. The recommended dosage is generally 25 mg per kilogram of body weight per day, often given in four divided doses, each infused over two hours. This medication is indicated for adults and children older than one month who develop severe VOD/SOS, particularly after hematopoietic stem cell transplantation or with kidney or lung dysfunction.
The usual duration of defibrotide treatment is a minimum of 21 days, though it may continue longer until the signs and symptoms of VOD/SOS resolve or the patient is discharged from the hospital. Patients receiving this treatment require close monitoring by healthcare professionals in a hospital setting.
During treatment, medical staff monitor patients for changes in their condition, including signs of bleeding or allergic reactions. Regular assessments of blood parameters, such as hemoglobin levels and platelet counts, are also conducted. The goal is to achieve complete resolution of VOD/SOS symptoms and improve patient survival rates.