PB0292 - Thrombotic risk evaluation in pediatric patients with acute lymphoblastic leukemia using thrombin generation test

Background: Thromboembolism (TE) etiology in children with acute lymphoblastic leukemia (ALL) is multifactorial. It has been described that global assays of hemostasis as thrombin generation test (TGT) could be useful to individualize TE risk in this setting but scarce studies on this topic have been performed.

Aims: To identify individual TE risk in pediatric patients receiving chemotherapy during ALL treatment.

Methods: TGT (automated analyzer ST-Genesia; ThromboScreen) and pro and anti-anticoagulant plasma proteins were performed at different moments of treatment in ALL pediatric patients following SEHOP-PETHEMA-2013 treatment guideline. Normalized data were evaluated according to pegylated (PEG)-asparaginase administration and compared with a series of pediatric normal controls. Data were also evaluated according to the risk factors for TE previously described.

Results: A total of 67 patients (1-18 years) were included: boys n=35 (52%), B-ALL (n=60). Any patient had a TE during treatment. Normalized endogenous thrombin potential (N-ETP) ratio was statistically significant higher, and ETP inhibition was statistically significant lower than pediatric healthy controls (table 1), especially after PEG-asparaginase administration (figure 1A-1B). Plasmatic protein C (PC) and protein S (PS) levels were low at onset (figure 1C) and decreased after PEG-asparaginase administration. However, antithrombin (AT) mean does not decrease under 50% during treatment.
Regarding TE risk factors, a bivariant analysis showed that ETP inhibition was statistically significant lower in patients older than 10-year-old (49.29 versus 55.59; p=0.05) and, in those with non-O blood type (57.78 versus 50.08; p=0.005). A multivariable analysis corroborated the relationship between non-O group and values of ETP inhibition (p=0.006). Patients with inherited thrombophilia (n=7) had higher N-ETP and lower ETP-inhibition, but differences were not significant.

Conclusion(s): TGT results in our series suggest that ALL pediatric patients might have biomarkers suggestive of higher TE risk than normal controls, especially after PEG-asparaginase administration. Age older than 10-year-old and non-O group were related to higher TGT results.