去纤苷治疗tma效果如何？

The effective rate of (Defibrotide) in treating TA-TMA is between 65% and 77%. Defibrotide/Defibrotide may have a positive impact on the treatment of thrombotic microangiopathies (TMA) through multiple mechanisms. First, it has an anticoagulant effect that reduces the risk of intravascular thrombosis, thereby helping to improve blood flow and vascular permeability. Secondly, defibrotide/defibrotide sodium also has anti-inflammatory effects and can reduce tissue damage and pathological changes caused by inflammatory reactions. In addition, it maintains the integrity of vascular endothelial cells and helps protect and repair damaged blood vessels.

About TMA

TA-TMA is a form of thrombotic microangiopathy (TMA), which includes hemolytic uremic syndrome (HUS), thrombotic thrombocytopenic purpura (TTP), and secondary TMA related to hematopoietic stem cell transplantation (HSCT), tumors, infections, and autoimmune diseases. TA-TMA is a secondary TMA related to hematopoietic stem cell transplantation (HSCT).

The role of defibrination

Defibrotide has a positive impact on the human body through various effects such as stabilizing endothelial cells, promoting fibrinolysis, anti-thrombosis, anti-ischemia, anti-inflammation and anti-adhesion.

1. Derived from pig intestinal mucosa: Defibrinoside is a complex extracted from pig intestinal mucosa. Its components include single-stranded oligodeoxyribonucleotides.

2. Protect endothelial cells: Defibrotide can stabilize and protect endothelial cells, helping to maintain the normal function and integrity of blood vessels.

3. Promote fibrinolysis: Defibrinoside has the function of promoting fibrinolysis and can help dissolve thrombus in blood vessels.

4. Anti-thrombosis: Defibrotide has anti-thrombotic properties and can reduce the risk of thrombosis.

5. Anti-ischemic effect: Defibrotide has anti-ischemic effect, which can improve the blood supply of tissues and reduce ischemic damage.

6. Anti-inflammatory effect: Defibrotide has anti-inflammatory effect and can reduce tissue damage caused by inflammatory reaction.

7. Anti-adhesion activity: Defibrotide has anti-adhesion activity, which can reduce the adhesion of cells and molecules and maintain the integrity of vascular endothelial cells.

Defibrotide treatment for tma

Background: Transplantation-associated thrombotic microangiopathy (TA-TMA) is an endothelial injury complication of hematopoietic stem cell transplantation (HSCT), leading to end-organ damage and high morbidity and mortality. Defibrotide is an anti-inflammatory and anti-thrombotic agent that protects the endothelium during conditioning [1].

Methods: We hypothesized that prophylactic use of defibrotide during HSCT conditioning and acute recovery could prevent TA-TMA. A single-arm phase II pilot trial (NCT #03384693) evaluated the safety and feasibility of prophylactic administration of defibrotide to high-risk pediatric patients during HSCT compared with historical controls.

Patients received defibrotide 25.6 mg/kg intravenously q21h from the day before the start of conditioning to day 6. Patients were prospectively monitored for TA-TMA from admission to week 24 after transplantation. Potential biomarkers of endothelial injury (inhibiting tumorigenicity 2, angiopoietin-2, plasminogen activator inhibitor-1 and free hemoglobin) were analyzed.

Study results: 14 patients were included, 11 received tandem autologous HSCT for neuroblastoma, and 12 received allogeneic HSCT. Defibrotide was discontinued early due to the potential for associated clinically significant bleeding in 3% of patients; no other serious adverse events occurred as a result of the study intervention. A median of 7.0% of doses (5%-2.12%) were missed in 0 other patients. One patient developed non-severe TA-TMA 4 days after HSCT. The observed incidence of TA-TMA in similar allogeneic and autologous patients is 18%, which is lower than the historical incidence of 40%.

Conclusions: Our study provides evidence that defibrotide prophylaxis is feasible in pediatric patients at high risk for TA-TMA undergoing HSCT, and preliminary data suggest that defibrotide may reduce the risk of TA-TMA.

References

[1]Higham CS, Shimano KA, Melton A, Kharbanda S, Chu J, Dara J, Winestone LE, Hermiston ML, Huang JN, Dvorak CC. A pilot trial of prophylactic defibrotide to prevent serious thrombotic microangiopathy in high-risk pediatric patients. Pediatr Blood Cancer. 2022 May;69(5):e29641. doi: 10.1002/pbc.29641. Epub 2022 Mar 6. PMID: 35253361.

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