What is the effect of defibrination?

Defibrotide is currently recognized as the most promising new drug for the treatment of hepatic veno-occlusive disease (HVOD) after hematopoietic stem cell transplantation (HSCT). Based on its anticoagulant, fibrinolysis-promoting, and anti-inflammatory effects, Richardson et al. first explored its application in the treatment of HVOD after HSCT. This study included 19 sHVOD patients. The dosage of Defibrotide is 5~60 mg/kg per day, intravenous infusion, and the median use time is 15 days (2-61 days). The results showed that 42% of patients achieved complete remission (CR), and the overall survival (os) rate 100 days after transplantation reached 32%, and patients could tolerate defibrination well. Since then, multiple clinical trials have confirmed the effectiveness of Defibrotide in the treatment of HVOD.

Defibrotide is an adenosine receptor agonist with multiple effects. The adenosine A1/A2 receptors of endothelial cells are involved in the regulation of endothelial cells and the response of endothelial cells to injury. Defibrotide can act on these receptors to produce a variety of downstream effects. Defibrotide can also reduce the expression of cell adhesion molecules on the surface of endothelial cells, thereby reducing the adhesion of leukocytes to vascular endothelial cells and reducing the inflammatory damage of endothelial cells.

A large series of prospective clinical studies included 305 patients with HVOD after HSCT, with a median age of 16 years (0.1-70 years), including 220 patients with sHVOD. The therapeutic dose of Defibrotide is 25 mg/kg per day by intravenous infusion. Preliminary results show that: the complete response (CR) rate is 30%, and the overall survival (OS) rate 100 days after transplantation is 50%; the CR rate of sHVOD patients is 26%, and the OS rate 100 days after transplantation is 45%; the CR rate of non-sHVOD patients is 39%, and the OS rate 100 days after transplantation is 65%. The CR rates of pediatric and adult patients were 33% and 26%, respectively (P=0.187), and the OS rates 100 days after transplantation were 56% and 44%, respectively (P=0.0277).

The above is the therapeutic effect of defibrotide. If you have any other questions, please feel free to consult a medical companion.