Pediatric patients with acute lymphoblastic leukemia (ALL) are at highest risk of venous thromboembolism (VTE) during the induction phase of treatment (IT). These events are not predictable by conventional coagulation assays.
To investigate the utility of global coagulation assays (GCA) for assessing the hemostatic state in children with ALL during IT.
We included children with ALL (n=15) and healthy controls (n=15). Analyses were performed at different time points during IT of the AIEOP-BFM protocols. In addition to prothrombotic biomarkers, natural anticoagulants proteins and in vivo thrombin generation (TG) markers, ex vivo TG was measured using the gold-standard Calibrated-Automated-Thrombogram method (CAT), the automated-ST Genesia (STG), and Thrombodynamics-analyzer (TD). The latter also provided measurement of fibrin clot formation (FCF).
Differently from conventional coagulation assays and in vivo TG markers, ex vivo GCA, detected increasing prothrombotic changes during IT. Particularly, TG measured with TD as expressed by endogenous thrombin potential (ETP) was significantly elevated already at d8-12 (p<0.01) and continued to increase during IT as compared to prior to treatment beginning, indicating a very early shift towards a procoagulant state. A similar pattern was observed for the rate of FCF (V:p<0.01 at d8-12). Remarkably, in patients developing thrombotic complications (n=5), both GCA, STG and TD, showed a significantly higher ETP very early (already at d8-12, p<0.05), well before clinical manifestation.
GCA capture prothrombotic changes early during IT in ALL pediatric patients. If confirmed, this approach will allow tailoring thromboprophylaxis in children with ALL at highest risk for VTE.