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), treated according to the protocol ALL-BFM-90. Procedure: 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 ≤ 0.01), while the concentration of plasminogen remained unchanged. During the reinduction 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 ≤ 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.