去纤维钠适用于肝小静脉闭塞病的治疗

Hepatic veno-occlusive disease (HVOD), also known as sinusoidal obstruction syndrome, is a non-thrombotic obstruction of the hepatic circulation, accompanied by centrilobular sinusoidal fibrosis and fibrotic stenosis or occlusion of common hepatic venules. Clinical manifestations include liver enlargement, pain, ascites, etc., and more than half of the patients can recover. 20% of patients die of liver failure, and a few patients develop cirrhosis and portal hypertension. On October 22, 2013, (Defibrotide Sodium) was approved for marketing by the European Union as the first treatment for severe hepatic veno-occlusive disease in adults and children undergoing hematopoietic stem cell transplantation.

On March 30, 2016, the U.S. Food and Drug Administration (FDA) approved defibrotide (defibrotide sodium) for the treatment of hepatic veno-occlusive disease (VOD) caused by hematopoietic stem cell transplantation in adults and children with renal and pulmonary dysfunction. Defibrotide is the first and only drug for the treatment of severe hepatic veno-occlusive disease.

The mechanism of action of defibrinoside (defibrotide sodium) has not been fully elucidated. In vitro, defibrotide (sodium defibrination) enhances the enzymatic activity of plasmin that hydrolyzes fibrin clots. Studies evaluating the pharmacological effects of defibrotide (sodium defibrotide) on endothelial cells (ECs) were primarily conducted in human microvascular endothelial cell lines. In vitro, defibrotide (defibrotide) 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 (sodium defibrotide) protects ECs from damage caused by chemotherapy, tumor necrosis factor-alpha (TNF-alpha), serum starvation, and perfusion.

In clinical trials, heparin was used to prevent diseases such as hepatic venous occlusion while greatly increasing the risk of bleeding. However, defibrotide (defibrotide sodium) alone or in combination with heparin has a very low incidence of side effects and has achieved a good effect in preventing HVOD. In a phase III multi-center randomized clinical trial completed in Europe, a total of 356 stem cell transplant patients were recruited. The incidence of hepatic vein occlusion 30 days after transplantation was compared. It was found that 2 of 180 patients in the defibrotide group developed hepatic vein occlusion, accounting for 12%; 35 of 176 patients in the control group developed hepatic vein occlusion, accounting for 20%. It can be seen that the therapeutic effect of (defibrinated sodium) is still good.

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