These ex vivo pharmacodynamic findings support the anticoagulant activity of LMWH and dabigatran in children with ALL, whereas apixaban and rivaroxaban showed minimal anticoagulant effect in thrombin generation assays; the clinical efficacy of dabigatran should be further investigated in prospective in vivo studies.
The study prospectively assessed the ex vivo effects of four anticoagulants on thrombin generation in 67 pediatric patients with ALL compared with healthy controls.
Low-molecular-weight heparin retained its anticoagulant activity in children with ALL both before and after asparaginase therapy, similar to healthy controls.
The direct factor Xa inhibitors apixaban and rivaroxaban showed minimal anticoagulant effect in samples from children with ALL compared with controls.
Dabigatran, an oral direct thrombin inhibitor, showed substantial anticoagulant activity in children with ALL before and after asparaginase therapy, comparable to controls.
The authors conclude that the ex vivo data support the anticoagulant activity of LMWH and dabigatran in this population and that dabigatran's clinical efficacy needs to be confirmed in vivo.
The study was motivated by the lack of consensus on anticoagulant prevention or treatment of VTE in pediatric ALL and the limited study of DOACs there.
Children with acute lymphoblastic leukemia (ALL) are at risk of dangerous blood clots, especially during treatment with asparaginase. There is no agreed approach to preventing or treating these clots, and newer oral blood thinners (DOACs) have not been well studied in this group. This study tested how four blood thinners worked in blood samples from 67 children with ALL, compared with healthy controls, using a lab test called thrombin generation that measures how well blood can form clots. Blood thinners were added to the samples in the lab, before and after the children received asparaginase. The injectable blood thinner low-molecular-weight heparin worked as well as in healthy controls both times. Dabigatran, an oral drug that blocks thrombin directly, also showed strong effects comparable to controls. In contrast, apixaban and rivaroxaban, which act on a different clotting factor (factor Xa), had only a small effect in the children's samples (a 7%-13% reduction versus 48%-59% in controls). This research suggests that dabigatran and low-molecular-weight heparin may be better suited than apixaban or rivaroxaban for this population. However, these were laboratory tests on blood samples, not trials of patients taking the drugs. The authors state that dabigatran's real-world effectiveness and safety in children with ALL would need to be confirmed in prospective studies in patients.
Leader A, Wolach O, Gavrieli B, Elitzur S, Spronk H, Nagy M, et al.. (2026). Ex Vivo Thrombin Generation Assessment of Four Anticoagulants in Children with Acute Lymphoblastic Leukemia.. Pediatric hematology and oncology. https://doi.org/10.1080/08880018.2026.2750854