去纤苷(Defibrotide)的作用及治疗效果？

Author: Medicalhalo

Release time: 2025-10-19 11:44:20

Defibrotide has multiple effects, such as anticoagulation, promotion of fibrinolysis, anti-inflammatory, etc. Defibrotide is the first drug approved by the U.S. FDA to treat severe hepatic venous occlusion. It has remarkable efficacy and patients can use the drug correctly under the guidance of a doctor.

Defibrotide drug introduction

It is the sodium salt of a mixture of single-stranded oligodeoxyribonucleotides derived from porcine mucosal DNA. It has been shown to have antithrombotic, anti-inflammatory and anti-ischemic properties. Defibrotide is available as intravenous and intramuscular preparations, and as an oral preparation for long-term use.

Existing data indicate that defibrotide is a well-tolerated drug with little or no anticoagulant activity and is readily available in parenteral and oral formulations.

Drug effects

In vitro evidence shows that defibrotide can repair the thrombus-fibrinolytic balance in the vascular endothelium and has a certain protective effect on the vascular endothelium. Defibrotide has been shown to significantly reduce veno-occlusive disease (VOD)-related mortality and resolve VOD-related symptoms with a manageable safety profile.

Defibrotide has demonstrated a protective effect on myocardial ischemia in different experimental models and successfully prevented several ischemic features, such as myocardial contracture, loss of high-energy substrates, decreased sensitivity of β-adrenergic receptors, and decreased infarction-related blood flow.

Similar protective effects were observed during hepatic and renal ischemia and in different types of experimental shock. The mechanisms underlying the anti-ischemic properties of defibrotide have been studied in experimental and human pharmacological studies. This substance has been shown to regulate arachidonic acid metabolism by enhancing the production and release of prostacyclin and prostaglandin E2 in tissues and whole blood, and inhibiting the production of leukotriene B4 in leukocytes.

In addition, the activation of polymorphonuclear leukocytes and their incorporation into thrombi by defibrotide has been described.

Therapeutic effect

Hepatic veno-occlusive disease (VOD), also known as sinusoidal obstruction syndrome (SOS), in a phase 2 study, Defibrotide showed good efficacy in treating liver VOD/SOS with MOF. This Phase 3 study investigated the safety and efficacy of defibrotide in patients with established hepatic VOD/SOS and advanced MOF.

Patients taking 25 mg/kg of defibrotide daily were compared with 32 historical controls from the medical records of 6867 HSCT patients. Baseline characteristics were well balanced between groups. The primary endpoint was survival +100 days after HSCT.

The observed rate was 38.2% in the Defibrotide group and 25% in the control group (estimated difference, 23%; 95.1% confidence interval, using propensity-adjusted analysis). The observed +100 days were 25.5% in the Defibrotide group and 12.5% in the control group.

Defibrotide is generally well tolerated and its toxicity is controllable. Defibrotide was associated with significant improvements in +100-day survival and CR rates.

In addition, another trial confirmed the safety and efficacy of defibrotide in the treatment of VOD/SOS in adult and pediatric HCT patients, with complete response rates ranging from 25.5% to 76% and +100-day overall survival rates ranging from 35% to 64%. The British Committee for Standards in Hematology/British Society for Blood and Marrow Transplantation guidelines recommend defibrotide prophylaxis in pediatric and adult HCT patients with risk factors for VOD/SOS. The toxicity of Defibrotide is controllable, and the incidence of grade 3-4 adverse reactions is low.

Side effects

Common symptoms during defibrotide treatment include hypotension, nausea and epistaxis, diarrhea, and vomiting.

Methods for dealing with side effects

1. Hypotension:

Patients should pay attention to diet control. They should not eat too much at each meal. They should add more protein-rich foods, such as lean meat, eggs and milk, etc. to control their emotions and avoid being overly excited. It is also necessary to appropriately strengthen exercise, improve physical fitness, and improve the regulatory functions of nerves and blood vessels.

2. Nausea and nosebleeds:

Patients can take symptomatic treatment under the guidance of a doctor. Antiemetics, such as metoclopramide tablets, can be used when nausea occurs, and measures such as compression and nasal packing can be used to stop bleeding when nose bleeding occurs.

3. Diarrhea:

Diarrhea can lead to the loss of a large amount of water and electrolytes. You need to drink more water during diarrhea to avoid dehydration. You can also choose oral rehydration salt solution. During diarrhea, you should eat small meals frequently and avoid eating large amounts. It is recommended to choose foods that are easy to digest, low in fat and low in fiber, and avoid irritating foods.

If diarrhea symptoms are severe, antidiarrheal drugs, such as montmorillonite powder, can be used under the guidance of a doctor. When using antidiarrheal drugs, you should pay attention to the dosage and duration of use, and it is best to use them under the guidance of a doctor.

Contraindications

1. Systemic anticoagulation or fibrinolytic therapy:

Defibrotide (Defibrotide) cannot be administered at the same time as systemic anticoagulation or fibrinolytic therapy to avoid an increased risk of bleeding.

2. Allergy:

Patients known to be allergic to Defibrotide or any of its excipients should be strictly prohibited from using it, otherwise the patient may suffer allergic reactions, including urticaria, rash and angioedema.

Summary

Defibrotide can play anti-inflammatory, anticoagulant and other effects, and has significant curative effect. It is recommended that patients strictly follow the doctor's instructions when taking medication, consult a doctor before taking medication, and must not use it privately to avoid improper use of medication that may harm their health.