Summary
Alterations in haemostasis are frequently observed in children with acute lymphoblastic
leukemia (ALL). It was the objective of this study to analyse age-related disturbances
in coagulation and fibrinolysis parameters during the induction phase of the anti-leukemic
treatment. Sixty-four children were classified by age into three groups (1–5, 6–10,
11–16 years), and studied during induction treatment of ALL including four weeks of
dexamethasone, followed by two weeks tapering of dexamethasone during which 6,000
IU/m2 native L-Asparaginase (total 4 doses) was administered intravenously twice weekly.
Blood samples were collected immediately before each L-Asparaginase infusion to analyze
procoagulant (fibrinogen, factor [F] II, FV, FVII, F IX, F X) and anticoagulant factors
(antithrombin [AT], protein C, protein S), parameters of thrombin generation (F1+2,
TAT) and fibrinolysis (α2-antiplasmin, plasminogen, PA P , D-dimer). Children were
in a hypercoagulable state after four weeks of dexamethasone due to upregulation of
coagulation parameters. Upregulation was highest in the two youngest age groups. During
L-Asparaginase treatment the 11– to 16-year- olds showed lower values in procoagulant
and, even more, in anticoagulant factor levels compared to the younger children. Activation
markers of thrombin generation and fibrinolysis did not change over time during the
study period. Decreased synthesis of α2-antiplasmin and plasminogen during L-Asparaginase
treatment resulted in less potential of clot lysis by plasmin in children older than
11 years of age. In conclusion, a more severe decline of anticoagulant and fibrinolytic
parameters in children between 11 and 16 years of age underline that these children
are at higher risk of thrombosis during ALL induction treatment.
Keywords
ALL - developmental haemostasis - L-Asparaginase
