Antithrombin treatment of severe hepatic veno-occlusive disease in children with cancer

Hepatic veno-occlusive disease (VOD) is a well-known complication of chemot herapy in Wilms tumor patients, particularly young children. Although this complication resolves uneventfully in most patients, fatal cases have been reported. Severe VOD after transplantation has a high mortality rate rangin g from 45% to 98%. New hemostatic therapeutic strategies have significantly improved the prognosis of VOD. Chemotherapy-related VOD in Wilms tumor usu ally has a good prognosis. We describe two patients with Wilms tumor and on e with acute lymphoblastic leukemia, who developed severe veno-occlusive di sease of the liver according to the Baltimore criteria while undergoing che motherapy; the symptoms were hepatomegaly, ascites, hyperbilirubinemia, wei ght gain and, in one patient, short-term lethargy. Elevated LDH levels of 8 72 to 12,000 U/l were observed in our patients. All patients had thrombocyt openia between 29,000 and 40,000/mu l and decreased antithrombin (AT) and p rotein C levels; two patients had gastrointestinal bleeding. All patients d eveloped a coagulopathy because of severe hepatic dysfunction. Two patients received low-dose heparin at the onset of VOD. The thrombolytic therapy wa s rapidly changed to AT supplementation (20-80 IU/kg bw 2x per day) without heparin when thrombocytes were very low or gastrointestinal bleeding occur red. Resolution of VOD was observed in all patients receiving AT alone. The chemotherapy was discontinued in a patient with accidental actinomycin D o verdosage in view of the severity of symptoms. The remaining two patients r eceived chemotherapy according to the therapy protocol after restitution. A ll patients survived without sequelae with a median follow-up of 28 months (range 8-48 months). Conclusion Hepatic veno-occlusive disease is a rare but increasingly recogn ized complication in pediatric cancer patients receiving conventional chemo therapy. AT supplementation constitutes a good alternative treatment of sev ere VOD in comparison with other thrombolytic therapies, particularly in pa tients at high risk of bleeding.