title: Early intervention with antithrombin III therapy to prevent progression of hepatic venoocclusive disease.
abstract: Venoocclusive disease (VOD) is the most frequent cause of early nonrelapse mortality among patients receiving high-dose chemoradiotherapy and hematopoietic stem cell transplantation. Endothelial injury of sinusoids and hepatic veins following chemotherapy is considered the initial event in the development of VOD. Activation of the coagulation cascade and inflammatory processes following endothelial injury results in a hypercoagulable state and a localized consumption of the natural anticoagulants, antithrombin III, protein C and protein S. The resultant coagulopathy can lead to multiorgan dysfunction and death. The objective was to retrospectively study the largest series of patients that has received antithrombin III for the treatment of VOD following hematopoietic stem cell transplantation. A total of 48 patients were diagnosed with VOD post hematopoietic stem cell transplantation (median age, 39 years; range, 1-69 years); 38 of the 48 received a nonradiation-based conditioning regimen and 21 of 48 received a transplant from an unrelated donor. Treatment was primarily directed at early intervention rather than prophylactic therapy to correct the antithrombin III deficiency associated with VOD. We attempted to achieve antithrombin III levels greater than 120%. There was no significant treatment-related morbidity. The overall 100-day mortality for the treatment cohort was 17%, with 10% for the mild/moderate group and 39% for the severe group, respectively. In conclusion, the encouraging results of this study suggest that this antithrombin III treatment should be further considered in patients with severe VOD.
authors.affiliation: University of Michigan Comprehensive Cancer Center, School of Medicine, University of Michigan, Ann Arbor, MI 48109, USA. Edwardpe@umich.edu
authors.forename: Edward
authors.initials: E
authors.lastname: Peres
authors.forename: Polly
authors.initials: P
authors.lastname: Kintzel
authors.forename: Roger
authors.initials: R
authors.lastname: Dansey
authors.forename: Roy
authors.initials: R
authors.lastname: Baynes
authors.forename: Muneer
authors.initials: M
authors.lastname: Abidi
authors.forename: Jared
authors.initials: J
authors.lastname: Klein
authors.forename: Rami B
authors.initials: RB
authors.lastname: Ibrahim
authors.forename: Esteban
authors.initials: E
authors.lastname: Abella
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000925:Anticoagulants / Q000627:therapeutic use*; D000990:Antithrombin III / Q000627:therapeutic use*; D020152:Antithrombin III Deficiency / Q000188:drug therapy* / Q000209:etiology; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D006504:Hepatic Veno-Occlusive Disease / Q000188:drug therapy* / Q000209:etiology; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D016019:Survival Analysis
chemical_list: D000925:Anticoagulants; D000990:Antithrombin III