title: Effect of glucocorticoids, E. coli- and Erwinia L-asparaginase on hemostatic proteins in children with acute lymphoblastic leukemia.
abstract: BACKGROUND
  The concentrations of plasma hemostatic proteins were analyzed prospectively in 42 children with acute lymphoblastic leukemia (ALL), treated according to the protocol ALL-BFM-90.
  
  
  METHODS
  Treatment included glucocorticosteroids (GC), E. coli L-asparaginase (Asparaginase, Medac) or Erwinia L-asparaginase (Erwinase, Speywood), vincristine, anthracyclines and intrathecal methotrexate. The analysis of hemostatic proteins was performed during induction and re-induction therapy.
  
  
  RESULTS
  At diagnosis, the plasma concentrations of fibrinogen, antithrombin III (AT), plasminogen and protein C were within normal limits, whereas the von Willebrand factor antigen (vWF:Ag) was elevated. After eight days of mono-therapy with GC the concentration of fibrinogen decreased to 59%, vWF:Ag decreased to 67%, AT increased to 124%, protein C increased to 201% of the initial value (mean all p < or = 0.01), while the concentration of plasminogen remained unchanged. During the re-induction phase, the concentrations of the hemostatic proteins, with exception of vWF:Ag, altered in a similar way in response to GC as observed during the induction phase. Administration of two doses of E. coli L-asparaginase (10,000 U/m2) during the induction therapy led to a significant decrease of AT (123 +/- 24 to 63 +/- 15%/mL), protein C (168 +/- 34 to 87 +/- 19%/mL), plasminogen (94 +/- 21 to 41 +/- 12%/mL) and fibrinogen (148 +/- 59 to 79 +/- 30 mg/dL, p < or = 0.01 for all parameters). In contrast, administration of two doses of Erwinia L-asparaginase (10,000 U/m2) during re-induction therapy did not lead to change in the concentration of AT, protein C or plasminogen, and the decrease in fibrinogen (162 +/- 17 to 121 +/- 24 mg/dL) was less pronounced.
  
  
  CONCLUSIONS
  Our results indicate that GC and E. coli L-asparaginase, in particular, induce hemostatic alterations which have implications on our understanding of thrombotic and hemorrhagic events during the treatment of ALL in children.
authors.affiliation: Universitäts-Kinderklinik, Freiburg, Germany.
authors.forename: V
authors.initials: V
authors.lastname: Mall
authors.forename: K B
authors.initials: KB
authors.lastname: Thomas
authors.forename: S
authors.initials: S
authors.lastname: Sauter
authors.forename: C M
authors.initials: CM
authors.lastname: Niemeyer
authors.forename: A H
authors.initials: AH
authors.lastname: Sutor
mesh_terms: D000293:Adolescent; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects*; D001215:Asparaginase / Q000009:adverse effects*; D001779:Blood Coagulation Factors / Q000187:drug effects* / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D004347:Drug Interactions; D004885:Erwinia / Q000201:enzymology; D004926:Escherichia coli / Q000201:enzymology; D005260:Female; D005938:Glucocorticoids / Q000009:adverse effects*; D006487:Hemostasis / Q000187:drug effects; D006801:Humans; D007223:Infant; D008297:Male; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000097:blood* / Q000188:drug therapy*; D011446:Prospective Studies; D012074:Remission Induction
chemical_list: D001779:Blood Coagulation Factors; D005938:Glucocorticoids; D001215:Asparaginase