Defibrotide: a review on clinical use and future development

Larocca, Alessandra; Cavallo, Federica; Magarotto, Valeria; Rossi, Davide; Boccadoro, Mario; Palumbo, Antônio

doi:10.1517/14712598.8.8.1201

Cited by 6 publications

(2 citation statements)

References 64 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Multiple myeloma is a malignant plasma cell disorder characterized by the accumulation of clonal plasma cells in the bone marrow, presence of a monoclonal immunoglobulin in serum and/or urine, and by evidence of end-organ damage including hypercalcemia, renal insufficiency, anemia, or lytic bone lesions. 19 Even with advances in therapeutic approaches, the disease remains incurable and is characterized by frequent relapses and fatal progression. However, the combination of novel biologically active agents with old chemotherapy shows promising results and changes the scenario of this disease.…”

Section: Discussionmentioning

confidence: 99%

Defibrotide Blunts the Prothrombotic Effect of Thalidomide on Endothelial Cells

Echart¹,

Somaini²,

Distaso³

et al. 2011

Clin Appl Thromb Hemost

View full text Add to dashboard Cite

Patients with multiple myeloma (MM) are at relatively high risk of developing thromboembolic events such deep venous thrombosis (DVT) where thalidomide therapy has been identified to increase this risk. Defibrotide (DF), a polydisperse oligonucleotide, showed previously to counteract the alterations in endothelial cells (ECs) induced by lipopolysaccharide. It prompts us to investigate the impact of thalidomide on ECs and whether DF modulates changes in fibrinolysis induced by thalidomide. In this in vitro study, MM by itself alters the profibrinolytic potential of ECs decreasing the tissue plasminogen activator (t-PA) and increasing the plasminogen activator inhibitor 1 (PAI-1) levels which is potentiated by thalidomide. Defibrotide was able to counteract these effects. Additionally, DF upregulated the t-PA and downregulated PAI-1 gene expression modulated by thalidomide. Defibrotide also protects ECs from thalidomide-mediated cell death without interfering with its antitumor effects. These findings support DF clinical use for the prevention of DVT induced by immunomodulatory drugs.

show abstract

Section: Discussionmentioning

confidence: 99%

Defibrotide Blunts the Prothrombotic Effect of Thalidomide on Endothelial Cells

Echart¹,

Somaini²,

Distaso³

et al. 2011

Clin Appl Thromb Hemost

View full text Add to dashboard Cite

show abstract

“…Debido a este escaso arsenal terapéutico, se ha prestado una especial atención al defibrótido, fármaco que estimula la síntesis de la trombomodulina, aumenta el tPA endógeno y disminuye el inhibidor del activador del plasminógeno tipo I, con poca actividad anticoagulante 71 . Este agente se ha mostrado capaz de lograr una solución completa en más del 50% de los casos de EVOH grave, incluyendo aquellos con fallo multiorgánico, y de reducir significativamente la mortalidad por esta causa en el día +100 del TPH, todo ello sin toxicidad digna de mención 18,72,73 .…”

Section: Tratamientounclassified