How effective is defibrotide in the treatment of hepatic veno-occlusive disease?

How effective is defibrotide in the treatment of hepatic veno-occlusive disease? Studies have shown that defibrotide exerts various biological functions mainly by affecting vascular endothelial cell response and platelet activity. Defibrinoside contains nucleic acid aptamers that interact with adenosine A1 and A2 receptors, thereby reducing the response of endothelial cells to injury and protecting vascular endothelium.

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.

In addition, defibrotide can also promote the release of prostaglandin I2 (PGI2) and prostaglandin E2 (PGE2), thereby causing blood vessel dilation, inhibiting platelet aggregation, and reducing ischemic damage. Studies have shown that defibrotide can significantly increase the expression of thrombin regulatory protein (TM) and tissue factor pathway inhibitors to produce anticoagulant effects.

The most common side effects (incidence ≥10% and independently causal) with defibrotide therapy are hypotension, diarrhea, vomiting, nausea, and epistaxis.

In a clinical trial, the incidence rate of grade 3-4 side effects related to defibrotide was 7%, mainly hypotension, pulmonary and gastrointestinal bleeding, and abdominal cramps. 4% of patients discontinued treatment due to side effects, and there were no reports of patient death directly caused by defibrotide administration. 

For some patients with leukemia and lymphoma, hematopoietic stem cell transplantation (HSCT) is the only hope to cure the disease and regain health. Hepatic veno-occlusive disease (HVOD) is one of the serious complications after hematopoietic stem cell transplantation (HSCT), and the mortality rate in patients with severe HVOD can be as high as 100%. The launch of defibrotide has brought new treatment hope to the majority of patients and has broad development and treatment prospects.