Effect of a New Antithrombotic Agent (Defibrotide) in Acute Renal Failure Due to Thrombotic Microangiopathy

Abstract

8 patients with thrombotic microangiopathy were treated with a new antilfcrombotic agent, defibrotide. This drug displays considerable fibrinolytic and antithrombotic activity, and induces generation and release of a prostacyclin-like substance from vascular tissue. At admission all patients presented severe renal involvement and coagulation abnormäÄies. Neurological manifestations were present in 6. Defibrotide admiu&tration was followed by recovery of renal function in 6, disappearance of neurological Symptoms and coagulation abnormalities in all p9l!ajits. The use of defibrotide was not associated with side effects. On the basis of the results obtained in these patients, we suggest that defibrotide might be considered as a valuable drug in the management of patients with thrombotic microangiopathy.

Multi-institutional use of defibrotide in 88 patients after stem cell transplantation with severe veno-occlusive disease and multisystem organ failure: response without significant toxicity in a high-risk population and factors predictive of outcome

“…The observation that decreases in both actual and mean creatinine were especially important in predicting better outcome is of great interest and may have relevance to the favorable renovascular effects seen with DF treatment in other disease states. 25,36 This finding is also consistent with the notion that hepatorenal dysfunction is fundamental to the morbidity and mortality associated with severe VOD. 5,32,35 It is of note that in the 29 patients who did not respond and in whom autopsy was carried out, 7 did not have VOD, with GVHD predominating as the alternate diagnosis.…”

“…14,31 This finding is also consistent with the experience reported in treating patients with severe hemolytic uremic syndrome and thrombotic thrombocytopenic purpura in whom no serious side effects were seen and reflects the extensive experience with DF in aged individuals with peripheral vascular disease where its safety profile was well established in a placebocontrolled phase III trial. 36,37 The use of DF as a novel approach in the treatment of severe VOD was originally based on its unique pharmacologic characteristics and its lack of systemic anticoagulant activity. 29 Recent in vitro work has demonstrated DF's selective effects on small vessels compared with large vessels, with a reduction in PAI-1 release and a protective action seen in a lipopolysaccharide-stimulated, microvessel-derived endothelial cell model.…”

Defibrotide for the treatment of hepatic veno‐occlusive disease: results of the European compassionate‐use study

“…preparations and can be given orally or parenterally (Palmer et al, 1993). It has been studied in various vascular disorders, including peripheral vascular disease (Ferrari et al, 1994) and chemotherapy-related haemolytic uraemic syndrome (HUS)/thrombotic thrombocytopenia purpura (TTP) (Bonomini et al, 1985), and appears to be well tolerated with no serious side-effects. A study comparing DF with heparin for post-surgical deep vein thrombosis (DVT) prophylaxis demonstrated a reduced incidence of bleeding episodes in the DF-treated patients (Battistel & De Rosa, 1988).…”

Defibrotide Is Antithrombotic and Thrombolytic against Rabbit Venous Thrombosis

“…results]. High levels of FDPS were normalized in both animals [1] and man [10], The thrombolytic activity of D, demonstrated in this experi mental model, could be attributed to D's pro fibrinolytic activity [9] and to increases in tis sue plasminogen activator [8] and PGH pro duction [7],…”