INHIBITION OF HYPERCOAGULATION BY ANTITHROMBIN SUBSTITUTION IN ESCHERICHIA-COLI L-ASPARAGINASE-TREATED CHILDREN

Acquired deficiency of antithrombin (AT), which in some patients could lead to thrombosis, has been a serious side effect of protocols which incorporate E. coli L-asparaginase (ASP) for the treatment of acute l ymphoblastic leukaemia (ALL). In a longitudinal, prospective, non-rand omized study children with ALL (n = 27) were treated according to the protocol ALL-BFM-90. During the induction phase using prednisone, vinc ristine, daunorubicin and ASP, AT substitution was performed in 15/27 patients, when their plasma concentration decreased below 60% of norma l with a concomitant increase of D-dimer formation. After the administ ration of the AT concentrate the patients, plasma concentration of AT increased and remained elevated after 18, 48 and 72 h. In addition, th e plasma concentration of enhanced thrombin generation, D-dimer format ion and plasminogen activator inhibitor 1 decreased towards normal lev els. Although the observed laboratory findings may serve as evidence f or a possible clinical benefit of AT substitution during ASP treatment , further randomized studies are requested to evaluate whether the use of prophylactic AT administration could reduce the incidence of throm boembolic events in childhood acute leukaemia.