Influence of two different Escherichia coli asparaginase preparations on fibrinolytic proteins in childhood ALL

University Children's Hospital, Munster, Germany.

BACKGROUND. Alterations in hemostasis have frequently been observed in patients with leukemia, and thrombotic events are well documented in patients receiving L-asparaginase (ASP) as a single agent or in combination with vincristine, prednisone (sometimes complemented by an anthracycline). The present study was designed to evaluate prospectively fibrinolytic parameters in leukemic children receiving different E. coli ASP preparations (Kyowa ASP, n = 20; Bayer ASP, n = 20), and to relate changes in the fibrinolytic system to serum ASP activity. MATERIALS AND METHODS. Blood samples for coagulation studies were obtained together with serum samples for pharmacokinetic monitoring in the same venipuncture (before the first and 6th-7th doses of ASP). RESULTS. Patients receiving Kyowa ASP showed significantly (0.0001) enhanced ASP-activity compared to children treated with the Bayer preparation. Significantly decreased values of fibrinogen (p < 0.001), plasminogen (p < 0.0002) and alpha 2-antiplasmin (p < 0.0003) were found in the Kyowa group, along with significantly enhanced thrombin generation (F1 + 2; p < 0.001), t-P (p < 0.01) and D-dimer levels (p < 0.05). In contrast, PAI 1 activity demonstrated no significant difference in the two E. coli ASP administered. CONCLUSIONS. Changes in fibrinogen, plasminogen, alpha 2-antiplasmin and D-dimer are clearly associated with ASP activity during the course of ASP administration in children with ALL.