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, 8, 105-113

Defibrotide in the Treatment of Hepatic Veno-Occlusive Disease


Defibrotide in the Treatment of Hepatic Veno-Occlusive Disease

Alessandro Fulgenzi et al. Hepat Med.


Hepatic veno-occlusive disease (VOD), also known as sinusoidal obstruction syndrome (SOS), represents the most frequent complication in patients in early phase following hematopoietic stem-cell transplantation (HSCT). In its severe form, VOD/SOS can be associated with multiorgan failure and with a mortality rate >80% by day +100. Defibrotide (DF) (a mixture of 90% single-stranded phosphodiester oligonucleotides and 10% double-stranded phosphodiester oligonucleotides derived from controlled depolarization of porcine intestinal mucosal DNA) has been proposed for the treatment of SOS due to its ability to restore thrombo-fibrinolytic balance and protect endothelial cells. The present review highlights why the mechanisms of action of DF allow its successful use in the prevention and treatment of SOS following HSCT.

Keywords: defibrotide; hematopoietic stem-cell transplantation; hepatic veno-occlusive disease.

Conflict of interest statement

The authors report no conflicts of interest in this work.


Figure 1
Figure 1
Effects of defibrotide on hepatic sinusoidal endothelium. (A) Normal sinusoid. (B) Endothelial cells are damaged by radiation and chemotherapeutic treatment carried out before HSCT. Endothelial cell activation promotes, through the expression of endothelial molecules (VCAM-1, ICAM-1), the binding and diapedesis of monocytes expressing LFA-1. The increased permeability of endothelium permits the flow of red blood cells to the space of Disse, with loss of Kupffer cells, and increased recruitment of monocytes. Activation of coagulation pathway following endothelial release of von Willebrand factor favors vessel obstruction, and hepatocyte necrosis occurs. (C) Treatment with defibrotide abrogates endothelial activation and preserves sinusoidal blood flow function by favoring (+) and inhibiting (−) the release of some mediators. Abbreviations: HSCT, hematopoietic stem-cell transplantation; VCAM-1, vascular cell adhesion molecule 1; ICAM-1, intracellular cell adhesion molecule 1; LFA-1, lymphocyte function-associated antigen 1; NO, nitric oxide; PGE2, prostaglandin E2; PGI2, prostacyclin 2; tPA, tissue plasminogen activator; TNFα, tumor necrosis factor alpha; PAI, plasminogen activator inhibitor-1.

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