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Effects of defibrotide in acute renal failure due to thrombotic microangiopathy
Abstract:
Thrombotic microangiopathy (TMA) can occur whenever pathogenetic events lead to fibrin deposition in the microcirculation. It has been suggested that intravascular coagulation is important in the development of renal as well as cerebral lesions. The mortality rate in adults varies from 50 to 70%; chronic or progressive renal failure occurs in approximately two thirds of children over 2 years of age. Poor success may be due to therapy being initiated too late or to inappropriate use of antagonistic drugs, or both. In the last 2 years we have treated 8 patients with TMA (5 with thrombotic thrombocytopenic purpura; 3 with hemolytic uremic syndrome) with defibrotide, a new antithrombotic agent extracted from mammalian lungs. At admission all patients had severe renal involvement (serum creatinine 5.3-14.9 mg/dl) and coagulation abnormalities (low platelet count; high levels of circulating fibrin degradation products). There were neurological manifestations in 6 patients. Defibrotide administration was followed in 6 patients by recovery of renal function. In all patients, defibrotide therapy induced the disappearance of neurological manifestations and normalization of coagulation abnormalities. Defibrotide caused no side effects. All patients are alive after 7-22 months of follow-up.
Insights
Defibrotide effectively treats thrombotic microangiopathy (TMA), including thrombotic thrombocytopenic purpura and hemolytic uremic syndrome. This antithrombotic agent improved renal function, neurological symptoms, and coagulation in TMA patients with no reported side effects.
Area of Science:
- Nephrology
- Hematology
- Pharmacology
Background:
- Thrombotic microangiopathy (TMA) involves microcirculation fibrin deposition, leading to severe renal and cerebral lesions.
- High mortality rates (50-70% in adults) and chronic renal failure (two-thirds of children) highlight the urgent need for effective treatments.
- Current therapies may be limited by late initiation or inappropriate drug use.
Purpose of the Study:
- To evaluate the efficacy and safety of defibrotide in treating patients with thrombotic microangiopathy (TMA).
- To assess defibrotide's impact on renal function, coagulation abnormalities, and neurological manifestations in TMA patients.
Main Methods:
- Eight patients with TMA (5 thrombotic thrombocytopenic purpura, 3 hemolytic uremic syndrome) received defibrotide.
- Patients presented with severe renal impairment (serum creatinine 5.3-14.9 mg/dl) and coagulation disorders.
- Neurological symptoms were present in six patients at admission.
Main Results:
- Defibrotide treatment led to renal function recovery in six patients.
- All patients experienced resolution of neurological manifestations and normalization of coagulation abnormalities.
- No adverse side effects were reported during defibrotide therapy.
Conclusions:
- Defibrotide demonstrates significant efficacy in managing TMA, improving critical clinical outcomes.
- The antithrombotic agent offers a promising therapeutic option for TMA with a favorable safety profile.
- All patients remained alive with improved health status during the 7-22 month follow-up period.