Veno-occlusive disease: cytokines, genetics, and haemostasis.
Hepatic veno-occlusive disease (VOD) is a major cause of morbidity and mortality following high dose cytotoxic therapy for stem cell transplantation (SCT). Pre-existing liver damage, SCT-related therapy, and genetic polymorphisms all appear to increase the risk of developing VOD. Studies of biological markers during SCT suggest that cytokines, haemostasis, and hepatic drug metabolism via the glutathione pathway are all involved in the pathogenesis of VOD. Until recently, treatment options were limited and experimental therapies directed at the pathogenesis of the disease were mostly unsuccessful. However, Defibrotide, a relatively new agent that has modulatory effects on vascular endothelium, cytokine release, and haemostasis, has been used with some success in the management and prophylaxis of VOD. In the future, a better understanding of genetic polymorphisms and biological markers which may be important in the pathogenesis of VOD, may enable us to predict which patients are most likely to be affected.
Coppell
Jason A
JA
Haemophilia Centre and Haemostasis Unit, Royal Free Campus, Royal Free and University College Medical School, Pond Street, London NW3 2QG, UK. j.coppell@rfc.ucl.ac.uk
Brown
Simon A
SA
Perry
David J
DJ
D000818:Animals; D016207:Cytokines / Q000097:blood* / Q000235:genetics; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects; D006487:Hemostasis / Q000502:physiology*; D006504:Hepatic Veno-Occlusive Disease / Q000097:blood / Q000209:etiology* / Q000503:physiopathology; D006801:Humans; D008954:Models, Biological; D011110:Polymorphism, Genetic; D012307:Risk Factors
D016207:Cytokines