Pegaspargase-associated cerebral venous sinus thrombosis: risk factors and anticoagulation management in pediatric...

Despite improving outcomes in pediatric acute lymphoblastic leukemia (ALL), pegaspargase (PEG-ASP) carries a risk of cerebral venous sinus thrombosis (CVST), for which optimal anticoagulation management in children remains undefined. This retrospective case series aimed to analyze the incidence, associated factors, and management outcomes of PEG-ASP-associated CVST in pediatric ALL patients. Among 741 ALL patients treated at a single center over a 3-year period, the incidence of PEG-ASP-associated CVST was 1.4% (11 cases).

Eleven pediatric ALL patients who developed PEG-ASP-associated CVST were stratified by disease severity [intensive care unit (ICU) admission vs. non-ICU] and anticoagulation duration (>3 vs. ≤3 months). ICU-admitted patients received significantly higher cumulative PEG-ASP doses (4,000 IU/m²) compared to ward-managed patients (2,250 IU/m²), and a strong positive correlation (r=0.75) was observed between cumulative PEG-ASP dose and disease severity. Extended anticoagulation (>3 months) was associated with improved laboratory parameters, including notably lower triglyceride and D-dimer levels at 8 weeks, along with increased antithrombin (AT)-III levels. All patients were managed conservatively with low-molecular-weight heparin without thrombectomy or discontinuation of PEG-ASP. Outcomes were excellent, with 90.9% survival, complete neurological recovery (modified Rankin Scale grade 0), and no cases of thrombosis recurrence or leukemia relapse.

The study highlights a significant association between cumulative PEG-ASP dose and CVST severity in this pediatric ALL cohort. The findings support the feasibility and safety of extended anticoagulation therapy alongside continued chemotherapy, without interrupting PEG-ASP treatment, leading to favorable clinical and neurological outcomes.