去纤苷（defiteli）作用及功效

On March 30, 2016, the FDA approved defibrotide sodium/defiteli for the treatment of adult and pediatric patients with hepatic veno-occlusive disease (VOD), also known as sinusoidal obstruction syndrome (SOS), renal or pulmonary dysfunction following hematopoietic stem cell transplantation (HSCT).

Hepatic veno-occlusive disease (HVOD) mainly manifests as enditis and fibrosis in small veins such as the central lobular veins and sublobular veins of the liver, leading to lumen stenosis, extensive occlusion, and even liver cell necrosis and fibrosis. It is one of the serious complications after hematopoietic stem cell transplantation (HSCT). The mortality rate of patients with severe HVOD can be as high as 100%. Defibrotide (defiteli) is a single-stranded oligonucleotide mixture that has anti-thrombotic and fibrinolytic effects. In recent years, multiple clinical research results have shown that defiteli is a safe and effective drug for preventing and treating HVOD after HSCT.

The mechanism of action of defibrotide has not been fully elucidated. In vitro, defibrinoside enhances the enzymatic activity of plasmin, which hydrolyzes fibrin clots. Studies evaluating the pharmacological effects of defibrotide on endothelial cells (ECs) have been primarily conducted in human microvascular endothelial cell lines.

In vitro, defiteli increases tissue plasminogen activator (t-PA) and thrombomodulin expression and decreases von Willebrand factor (vWF) and plasminogen activator inhibitor-1 (PAI-1) expression, thereby reducing EC activation and increasing EC-mediated fibrinolysis. Defibrotide protects ECs from chemotherapy, tumor necrosis factor-α (TNF-α), serum starvation, and perfusion-induced injury.

In clinical trials, the use of defibrotide significantly reduced disease progression, and the 100-day survival rate of patients was effectively improved. Defibrotide was also granted orphan drug designation by the FDA.