title: Antithrombin treatment of severe hepatic veno-occlusive disease in children with cancer.
abstract: Hepatic veno-occlusive disease (VOD) is a well-known complication of chemotherapy 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 ranging from 45% to 98%. New hemostatic therapeutic strategies have significantly improved the prognosis of VOD. Chemotherapy-related VOD in Wilms tumor usually has a good prognosis. We describe two patients with Wilms tumor and one with acute lymphoblastic leukemia, who developed severe veno-occlusive disease of the liver according to the Baltimore criteria while undergoing chemotherapy; the symptoms were hepatomegaly, ascites, hyperbilirubinemia, weight gain and, in one patient, short-term lethargy. Elevated LDH levels of 872 to 12,000 U/l were observed in our patients. All patients had thrombocytopenia between 29,000 and 40,000/microl and decreased antithrombin (AT) and protein C levels; two patients had gastrointestinal bleeding. All patients developed a coagulopathy because of severe hepatic dysfunction. Two patients received low-dose heparin at the onset of VOD. The thrombolytic therapy was rapidly changed to AT supplementation (20-80 IU/kg bw 2x per day) without heparin when thrombocytes were very low or gastrointestinal bleeding occurred. Resolution of VOD was observed in all patients receiving AT alone. The chemotherapy was discontinued in a patient with accidental actinomycin D overdosage in view of the severity of symptoms. The remaining two patients received chemotherapy according to the therapy protocol after restitution. All patients survived without sequelae with a median follow-up of 28 months (range 8-48 months).
  
  
  CONCLUSIONS
  Hepatic veno-occlusive disease is a rare but increasingly recognized complication in pediatric cancer patients receiving conventional chemotherapy. AT supplementation constitutes a good alternative treatment of severe VOD in comparison with other thrombolytic therapies, particularly in patients at high risk of bleeding.
authors.affiliation: Department of Pediatrics, University of Aachen (RWTH), Germany. rmertens@post.klinikum.rwth-aachen.de
authors.forename: R
authors.initials: R
authors.lastname: Mertens
authors.forename: H
authors.initials: H
authors.lastname: Brost
authors.forename: B
authors.initials: B
authors.lastname: Granzen
authors.forename: U
authors.initials: U
authors.lastname: Nowak-Göttl
mesh_terms: D000970:Antineoplastic Agents / Q000009:adverse effects; D000990:Antithrombin III / Q000627:therapeutic use*; D005260:Female; D006504:Hepatic Veno-Occlusive Disease / Q000188:drug therapy* / Q000209:etiology; D006801:Humans; D007223:Infant; D008297:Male; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000150:complications* / Q000188:drug therapy; D009396:Wilms Tumor / Q000150:complications* / Q000188:drug therapy
chemical_list: D000970:Antineoplastic Agents; D000990:Antithrombin III