Hepatic Veno-Occlusive Disease following Hematopoietic Stem Cell Transplantation

Abstract

The clinical syndrome of hepatic veno-occlusive disease (VOD) is one of the most common and serious complications following hematopoietic stem cell transplantation (SCT). High-dose chemotherapy or chemoradiation therapy in the context of autologous and allogeneic SCT can profoundly injure sinusoidal endothelium and hepatocytes within zone 3 of the liver acinus, producing the clinical syndrome of hepatomegaly and/or right upper quadrant pain with jaundice and fluid retention, typically manifest as weight gain. The incidence is variable and ranges from 10 to 60%. Mild to moderate disease is characterized by eventual complete resolution. In contrast, severe disease frequently results in multiorgan failure and death. The purpose of this review is to discuss the pathophysiology and clinical features of VOD, and the current status and future directions of research for both prevention and treatment.

Defibrotide reduces procoagulant activity and increases fibrinolytic properties of endothelial cells

“…5 VOD develops in 10-60% of patients undergoing allogeneic transplantation, but has also been described in autologous and syngeneic transplants. 6 Established severe VOD is associated with a mortality rate of about 100% at day +100 after stem cell transplantation. 6 Treatment of this complication with DF has resulted in a response rate of 35-43%.…”

“…6 Established severe VOD is associated with a mortality rate of about 100% at day +100 after stem cell transplantation. 6 Treatment of this complication with DF has resulted in a response rate of 35-43%. [7][8][9] VOD is characterized by endothelial cell (EC) injury, inflammation and fibrosis leading to occlusion of small hepatic venules.…”

“…The endothelial damage, caused by chemo-and radiotherapy regimens, represents the initial event, which leads to platelet and coagulative material (fibrinogen and Factor VIII) deposition in the subendothelium of the hepatic sinusoids and venules. 6 Commonly, in malignant disease, the vascular endothelium is exposed to the insults of the different antitumor treatments (ie, chemo-, radio-and hormone therapies) and to inflammatory molecules released by tumor cells and leukocytes. 10 As well documented these insults may exert a thrombogenic role.…”

“…14,15 In this context, it is important to consider that ECs from different sites can react differently and the microcirculation of peripheral organs may play a crucial role in the pathogenesis of microangiopathies and tissue damage associated with malignancy and stem cell transplantation. 6,16,17 DF therapy is effective in resolving VOD, a condition characterized by elevated endothelial toxicity. 6 There are few and incomplete studies on the effects of DF on the hemostatic properties of EC derived from large vessels, 18,19 and no information at all on DF effect on EC derived from the microvasculature.…”

“…6,16,17 DF therapy is effective in resolving VOD, a condition characterized by elevated endothelial toxicity. 6 There are few and incomplete studies on the effects of DF on the hemostatic properties of EC derived from large vessels, 18,19 and no information at all on DF effect on EC derived from the microvasculature.…”