Thrombin Generation Profile Using ST-Genesia after PEG-asparaginase in Pediatric Patients with Acute Lymphoblastic Leukemia

Abstract

Background: Venous thromboembolism (VTE) etiology in children with acute lymphoblastic leukemia (ALL) is multifactorial. The use of global assays of hemostasis as thrombin generation test (TGT) is useful to individualize VTE risk in adult patients. The aim of this prospective cohort study was to evaluate the usefulness of an automated TGT to evaluate VTE risk during ALL treatment in children. Methods: TGT (automated analyzer ST Genesia; ThromboScreen) and pro and anticoagulant plasma proteins were analyzed during ALL treatment in pediatric patients following LAL-SEHOP-PETHEMA-2013 guidelines. Results were compared with a series of pediatric normal controls and evaluated according to pegylated asparaginase PEG-ASP administration and to VTE risk factors. Results: The study included 67 patients: males n=35, B-ALL (n=60). None had a VTE during the evaluated period. Compared to healthy controls, normalized endogenous thrombin potential (N-ETP) ratio in patients was higher and ETP inhibition (ETP-inh) was lower, especially after PEG-ASP administration. Plasmatic protein C and protein S levels decreased after PEG-ASP administration, but antithrombin mean level did not. A bivariant analysis showed that ETP-inh was lower in patients >10-year-old (p=0.05) and in those with non-O blood type (p=0.005). A linear mixed model also showed a higher TGT prothrombotic profile in patients with inherited thrombophilia. Conclusions: TGT could be a biomarker of a high VTE risk in ALL pediatric patients. Patients > 10 years, of non-O blood group and with inherited thrombophilia were associated with a significantly higher thrombotic profile, and an increased profile was also observed after administration of PEG-ASP.