title: Inhibition of hypercoagulation by antithrombin substitution in E. coli L-asparaginase-treated children.
abstract: Acquired deficiency of antithrombin (AT), which in some patients could lead to thrombosis, has been a serious side effect of protocols which incorporate E. coli L-asparaginase (ASP) for the treatment of acute lymphoblastic leukaemia (ALL). In a longitudinal, prospective, non-randomized study children with ALL (n=27) were treated according to the protocol ALL-BFM-90. During the induction phase using prednisone, vincristine, daunorubicin and ASP, AT substitution was performed in 15/27 patients, when their plasma concentration decreased below 60% of normal with a concomitant increase of D-dimer formation. After the administration of the AT concentrate the patients, plasma concentration of AT increased and remained elevated after 18, 48, and 72 h. In addition, the plasma concentration of enhanced thrombin generation, D-dimer formation and plasminogen activator inhibitor 1 decreased towards normal levels. Although the observed laboratory findings may serve as evidence for a possible clinical benefit of AT substitution during ASP treatment, further randomized studies are requested to evaluate whether the use of prophylactic AT administration could reduce the incidence of thromboembolic events in childhood acute leukaemia.
authors.affiliation: Department of Paediatrics, University Hospital, Münster, Germany.
authors.forename: U
authors.initials: U
authors.lastname: Nowak-Göttl
authors.forename: N
authors.initials: N
authors.lastname: Kuhn
authors.forename: J E
authors.initials: JE
authors.lastname: Wolff
authors.forename: J
authors.initials: J
authors.lastname: Boos
authors.forename: B
authors.initials: B
authors.lastname: Kehrel
authors.forename: B
authors.initials: B
authors.lastname: Rath
authors.forename: H
authors.initials: H
authors.lastname: Jürgens
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000990:Antithrombin III / Q000032:analysis / Q000378:metabolism / Q000627:therapeutic use*; D001215:Asparaginase / Q000009:adverse effects*; D002648:Child; D003630:Daunorubicin / Q000008:administration & dosage; D004926:Escherichia coli; D006801:Humans; D008137:Longitudinal Studies; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000097:blood / Q000188:drug therapy*; D011241:Prednisone / Q000008:administration & dosage; D011446:Prospective Studies; D018709:Statistics, Nonparametric; D013997:Time Factors; D014750:Vincristine / Q000008:administration & dosage
chemical_list: D000970:Antineoplastic Agents; D017395:Plasminogen Activator Inhibitor 1; D014750:Vincristine; D000990:Antithrombin III; D001215:Asparaginase; D011241:Prednisone; D003630:Daunorubicin