Hepatic veno-occlusive disease after hematopoietic stem cell transplantation: update on defibrotide and other current investigational therapies

Successful treatment of sinusoidal obstructive syndrome after hematopoietic stem cell transplantation with recombinant human soluble thrombomodulin

“…4 Other promising new agents for SOS include defibrotide, a mixture of singlestranded polydeoxyribonucleotides that possesses local antithrombotic, anti-ischemic and anti-inflammatory activities. 5 In multiinstitutional phase II trials involving patients with severe SOS, defibrotide produced 100-day survival rates of 35-45%, compared to 10-20% for best available therapy. 5,6 Recombinant human soluble thrombomodulin (rTM) is composed of the active, extracellular domain of thrombomodulin, 7 and inactivates coagulation by binding to thrombin.…”

“…5 In multiinstitutional phase II trials involving patients with severe SOS, defibrotide produced 100-day survival rates of 35-45%, compared to 10-20% for best available therapy. 5,6 Recombinant human soluble thrombomodulin (rTM) is composed of the active, extracellular domain of thrombomodulin, 7 and inactivates coagulation by binding to thrombin. In addition, the thrombin-rTM complex activates protein C to produce activated protein C, which in the presence of protein S inactivates factors VIIIa and Va, thereby inhibiting further thrombin formation.…”

Defibrotide for Prevention and Treatment of Veno-Occlusive Disease in Adults: Single-Center Experience

“…This agent seems to have a protective effect against endothelial cell injury by increasing fibrinolysis and reducing procoagulant activity yet without an increase in bleeding events [3][4][5]. In support of these observations, several studies focused attention on the use of defibrotide as a potentially effective and reliable agent for preventing and treating VOD [6,7].…”

“…High risk population for the development of VOD were identified according to the following risk factors: 1) patient-related factors: preexisting hepatic disease, previous treatment including prior abdominal irradiation or use of gemtuzumab ozogamicin, viral hepatitis in both donor and recipient, iron overload in patients with β thalassaemia major, older transplant recipient age, poor performance status, advanced malignancy at the time of transplantation; 2) transplantationrelated factors: second myeloablative transplant, donor-recipient HLA disparity, use of busulfan conditioning regimen particularly in combination with cyclophosphamide [6,21,22].…”

Fatal intracranial hemorrhage following administration of recombinant thrombomodulin in a patient after cord blood transplantation

“…Although DIC is characterized by the widespread activation of coagulation, occlusion of the hepatic veins with endothelial damage predominantly contributes to the pathogenesis of SOS. 8 Considering that rTM inhibits thrombosis in the hepatic veins, rTM seems to be promising for the treatment of SOS. However, bleeding risk of rTM might be substantial in patients with SOS, as these patients are usually thrombocytopenic and their coagulation functions are impaired.…”