Defibrotide Therapy for Thrombophlebitis -Controlled Clinical Trial

Abstract

Deep venous thrombosis is a common disease with significant danger of both acute and chronic complications. Widely accepted therapies are based on anticoagulant (heparin and/or anticoagulant agents) or early fibrinolytic therapy. All these therapies frequently have severe side effects. Defibrotide is a new drug with antithrombotic and profibrinolytic activities but without anticoagulant activity and major side effects. To evaluate the efficacy of this drug against acute thrombophlebitis, we treated a group of 10 patients with 200 mg defibrotide intravenously three times a day for 15 days. Fibrinolysis parameters were monitored every other day. The indices of venous function by strain-gauge plethysmography and venous occlusion were evaluated every 7 days.The drug induced a significant improvement in plethysmographic indices and a significant profibrinolytic activity. Defibrotide-treated patients showed a fast disappearance of clinical and instrumental signs of thrombophlebitis. No side effects were reported during the study.

The use of defibrotide in blood and marrow transplantation

“…In an early clinical study in 10 patients with thrombophlebitis, defibrotide 200 mg administered IV 3 times daily for 15 days significantly improved leg blood pressure measures and profibrinolytic activity, with rapid disappearance of symptoms. 35 A later trial randomized 288 patients (159 completed the study) with chronic venous insufficiency resulting from deep vein thrombosis (DVT) and/or reflux (chronic deep vein insufficiency) to oral defibrotide 800 mg/d or matching placebo for 1 year. 36 Defibrotide significantly reduced mean ankle circumference (P , .01), mean scores for pain (P 5 .05), and the number of thrombotic events such as DVT (2 events with defibrotide vs 10 with placebo; P 5 .04).…”

Diagnosis and Treatment of VOD/SOS After Allogeneic Hematopoietic Stem Cell Transplantation

“…Moreover, defibrotide acts as an antithrombotic and profibrinolytic drug; it reduces platelet adhesion and activation, without systemic anticoagulant effects, by means of inhibition of PAI-1, thrombin, and leukocyte adhesion process (via inhibition of P-selectin expression), and also decreases vascular permeability and apoptosis due to calcineurin inhibitors and chemotherapy, without interfering with antitumor effect of cytotoxic drugs (85). Because of the capacity of defibrotide to protect endothelium from toxic, inflammatory, and ischemic damage, its potential therapeutic use has been tested, some decades ago, in several vascular disorders such as thrombophlebitis (86,87), in postsurgery deep vein thrombosis prophylaxis (88,89), and peripheral arterial diseases (90) with significant benefits. It has been used, even in a pivotal way, in acute myocardial infarction (91), in postthrombolysis reocclusion of coronary (92), ischemic damage of the liver (93), diabetic microangiopathy, and Reynaud phenomenon (94).…”