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Effect of disease and chemotherapy on hemostasis in children with acute lymphoid leukemia
L G Mitchell1, J M Halton, P A Vegh
1Department of Pediatrics, McMaster University, Hamilton, Ontario, Canada.
Insights
Disease and chemotherapy significantly alter coagulation proteins in children with acute lymphoid leukemia (ALL). L-asparaginase alone decreased most proteins, while combination therapy effects varied.
Area of Science:
- Hematology
- Pediatric Oncology
- Hemostasis
Background:
- Acute lymphoid leukemia (ALL) is a pediatric cancer affecting blood.
- The hemostatic system involves complex interactions of proteins regulating blood clotting.
- Understanding treatment effects on hemostasis is crucial for managing ALL patients.
Purpose of the Study:
- To investigate the impact of ALL disease and chemotherapy on the hemostatic system in children.
- To analyze changes in plasma levels of 21 hemostatic proteins during ALL treatment.
Main Methods:
- Prospective study of newly diagnosed pediatric ALL patients.
- Plasma samples collected at four key time points: diagnosis, L-asparaginase monotherapy, post-induction, and post-consolidation.
- Quantification of 21 hemostatic proteins and thrombin generation potential.
Main Results:
- ALL diagnosis altered levels of multiple coagulation factors, with increases in factors VIII, IX, von Willebrand, alpha 2-macroglobulin, and protein S, and decreases in protein C, prekallikrein, and factors XIIIA/XIIIS.
- L-asparaginase monotherapy reduced concentrations of 11 proteins, notably antithrombin III.
- Multiagent chemotherapy (without L-asparaginase) generally increased protein levels; however, consolidation therapy (with weekly L-asparaginase) led to decreased protein concentrations compared to baseline.
Conclusions:
- Both ALL disease and combination chemotherapy, with or without L-asparaginase, significantly affect plasma coagulation protein concentrations.
- In vitro thrombin generation capacity remains unimpaired in pediatric ALL patients.
- L-asparaginase monotherapy profoundly decreases most hemostatic proteins, with antithrombin III being most affected.
Purpose:
We sought to determine the effect of disease and combination chemotherapy on the hemostatic system in children with acute lymphoid leukemia (ALL).
Patients And Methods:
We conducted a prospective study of children newly diagnosed with ALL. Plasma samples were obtained at four time points: at diagnosis before therapy, 5 days after administration of L-asparaginase alone, after the remission induction program, and at completion of the consolidation phase. Plasma levels of 21 hemostatic proteins were measured. The amount of thrombin generated following activation with an APTT reagent was quantitated.
Results:
At diagnosis there were significant elevations in factors VIII, IX, von Willebrand, alpha 2-macroglobulin and protein S. In contrast, there were significant reductions in protein C, prekallikrein, and factors XIIIA and XIIIS. L-asparaginase treatment alone decreased concentrations of 11 proteins, with antithrombin III being affected to the greatest extent. After multiagent chemotherapy, not including L-asparaginase, concentrations of most proteins increased to or above baseline. At completion of consolidation therapy, which included weekly L-asparaginase administration, concentrations of most proteins were decreased compared with baseline values. The amount of thrombin generated following activation with an APTT reagent was similar to adults.
Conclusion:
Plasma concentrations of coagulation proteins are affected by disease (ALL) alone and by combination chemotherapy with or without L-asparaginase. There is no impairment of in vitro capacity to generate thrombin. L-asparaginase alone caused a decrease in almost all proteins; however, ATIII was affected to the greatest extent.