Abstract • 141

Background: Elevated plasma concentrations of endogenous thrombin generation markers such as thrombin-antithrombin complexes (TAT) have been reported in children with ALL both at onset and during treatment, related or not to thrombotic events. Recently, several inherited thrombotic risk factors have been identified: factor V Leiden mutation (F-V Leiden), prothrombin gene mutation, MTHFR gene mutation, and glycoprotein IIIa gene mutation. The aim of this study was to evaluate the effects of ALL immunophenotypic subgroups and the above mentioned risk factors on TAT levels. Material and Methods We evaluated 18 children (11M, 7F) aged 1 to 15 years (mean 6) with ALL (10 common, 5 T- and 3 pre-B types) and an age matched control group. In all patients the above mentioned prothrombin polymorphisms were studied together with TAT levels at onset and after 5-6 doses of L-asparaginase (MEDAC). Statistical evaluation: data were expressed as mean +/- SD and analysed by Student's t-test and both factorial and repeated measurements ANOVA. Results: No patient had F-V Leiden or prothrombin mutation. 12 patients were heterozygous and 2 homozygous for the MTHFR mutation and only 5 patients were heterozygous for the glycoprotein IIIa mutation. TAT levels were significantly higher in pts both at onset (13.94 +/9.81) and after MEDAC (17.29 +/-12.01) with respect to controls (4 +/- 1) (both p<0.001). TAT levels after MEDAC were not significantly higher than at onset (p=NS). Factorial ANOVA: at presentation there was a significant effect of ALL immunophenotypic subgroups on TAT levels (p<0.05) and no effect of inherited thrombotic risk factors. Repeated measurements of ANOVA: the variation of TAT levels during treatment were influenced significantly only by the ALL immunophenotypic subgroups (p < 0.01). Conclusions: Immunophenotypic subgroups have a major effect on thrombin generation in children with ALL with respect to inherited thrombotic risk factors. Research supported by a grant from MURST 60%.