Hepatic veno-occlusive disease, also called sinusoidal obstruction syndrome (VOD/SOS), is a severe complication which usually occurs due to conditioning regimens used for hematopoietic stem cell transplantation (HSCT). It is characterized by hepatomegaly, hyperbilirubinemia, ascites and right upper quadrant pain and usually develops within the first 20-30 days after transplant. It is accepted to be a result of endothelium and hepatocyte damage caused by chemotherapy and radiotherapy of the conditioning regimen.

Current studies suggest that the primary site of toxic injury is the hepatocyte, subsequently followed by damage to the central veins in zone 3 of the hepatic acinus and sinusoidal endothelial cells. Early changes include fibrin deposition, venous occlusion, progressive venous micro-thrombosis and sinusoidal occlusion. These changes lead to severe clinical problems including portal hypertension, hepatorenal syndrome and hepatocellular necrosis, which may ultimately result in multiorgan dysfunction (MOD) and death. Previously, the Baltimore and Seattle criteria were used for VOD/SOS diagnosis; however, the limitations of these criteria for VOD/SOS diagnosis (especially in anicteric children and those who have symptom onset after 21 days), led to establishment of the EBMT (European Society for Blood and Marrow Transplantation) 2017 VOD/SOS criteria which evaluates pediatric and adult patients separately. The EBMT 2017 criteria is comprised of laboratory and clinical findings such as transfusion-resistant thrombocytopenia, unexplained weight gain, hepatomegaly, ascites and elevation in bilirubin levels. Despite the advantages brought by this criteria, it is still difficult to diagnose VOD/SOS.

Several approaches to prevent its development of VOD/SOS were put forth, including individualized dosing of chemotherapy, reduction of the intensity of the conditioning regimens, close monitoring of the levels of busulfan and cyclophosphamide and also reducing their use. Prostaglandin E1 and tissue-plasminogen activator with or without concurrent heparin have been explored in VOD/SOS treatment; however, these approaches have shown little success, as is the case with supportive treatments. Defibrotide (DF) emerged as the most promising medication for both prophylaxis and treatment in patients with VOD/SOS. DF is a single-stranded polydeoxyribonucleotide with anti-inflammatory, anti-ischemic, anti-thrombotic, and thrombolytic properties in addition to its protective effects on endothelial cells. DF is approved for adult and pediatric patients with VOD/SOS with renal or pulmonary dysfunction after HSCT in the United States, and for severe VOD/SOS post-HSCT in patients aged >1 month in the European Union. In addition, several studies have examined DF prophylaxis can reduce the incidence of VOD/SOS in high-risk patients. Although the literature is unanimous for the use of DF in patients diagnosed with VOD/SOS, its use as a prophylactic agent has not been approved; even though many studies have reported reduced VOD/SOS incidence and severity with DF prophylaxis.