Effect of glucocorticoids, E. coli- and Erwinia L-asparaginase on hemostatic proteins in children with acute lymphoblastic leukemia

Background: The concentrations of plasma hemostatic proteins were analyzed prospectively in 42 children with acute lymphoblastic leukemia (ALL), treat ed according to the protocol ALL-BFM-90. Procedure: Treatment included glucocorticosteroids (GC), E.coli L-asparagin ase (Asparaginase(R), Medac) or Erwinia L-asparaginase (Erwinase(R), Speywo od), vincristine, anthracyclines and intrathecal methotrexate. The analysis of hemostatic proteins was performed during induction and re-induction the rapy. Results: At diagnosis, the plasma concentrations of fibrinogen, antithrombi n III (AT), plasminogen and protein C were within normal limits, whereas th e 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 th e initial value (mean all p less than or equal to 0.01), while the concentr ation of plasminogen remained unchanged. During the reinduction phase, the concentrations of the hemostatic proteins, with exception of vWF:Ag, altere d 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/m(2)) duri ng 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 le ss than or equal to 0.01 for all parameters). In contrast, administration o f two doses of Erwinia L-asparaginase (10,000 U/m(2)) during re-induction t herapy did not lead to change in the concentration of AT, protein C or plas minogen, and the decrease in fibrinogen (162 +/- 17 to 121 +/- 24 mg/dL) wa s less pronounced. Conclusions: Our results indicate that GC and E.coli L-asparaginase, in par ticular, induce hemostatic alterations which have implications on our under standing of thrombotic and hemorrhagic events during the treatment of ALL i n children.