ABSTRACT NUMBER: ESOC2026A2200 HIGH–ALLELE BURDEN JAK2 V617F MUTATION AND EARLY STROKE RECURRENCE IN EMBOLIC STROKE OF UNDETERMINED SOURCE

Abstract Background and aims The JAK2 V617F mutation has been linked to thromboinflammatory cardiovascular disease, including ischemic stroke. With increasingly sensitive assays, JAK2 V617F can also be detected in individuals without overt myeloproliferative neoplasms and may be classified as clonal hematopoiesis of indeterminate potential (CHIP), but its clinical relevance at low allele burdens remains uncertain. Its role in embolic stroke of undetermined source (ESUS), particularly regarding early stroke recurrence, is unknown. We assessed the prevalence of JAK2 V617F and its association with early stroke recurrence, stratified by variant allele fraction (VAF). Methods We conducted a retrospective cohort study including 547 patients with a first ischemic stroke classified as ESUS, with no prior diagnosis of myeloproliferative neoplasm. JAK2 V617F was measured by allele-specific PCR (limit of detection 0.01%). Based on hematology-defined thresholds, JAK2 status was categorized as JAK2 V617F-negative (no detectable variant or VAF ≤ 0.1%), JAK2 V617F-CHIP (VAF 0.1–1.0%), or high-burden JAK2 V617F (VAF > 1.0%). Early stroke recurrence (ESR) was defined as a new cerebrovascular event within 3 months. Results JAK2 V617F positivity was 8.2% (45/547): 5.9% (32/547) CHIP and 2.4% (13/547) high-burden. ESR occurred in 13.0% (71/547), with rates of 12.0% (60/502) in JAK2 V617F-negative, 18.8% (6/32) in CHIP, and 38.5% (5/13) in high-burden groups (P = 0.0118). In multivariable logistic regression adjusted for age, sex, and baseline stroke severity, high-burden JAK2 V617F was associated with ESR (OR 3.64; 95% CI 1.12–11.85; P = 0.032). Conclusions JAK2 V617F was detected in 8.2% of ESUS patients. High allele burden (VAF > 1.0%) was associated with increased risk of ESR. Conflict of interest All authors: nothing to disclose.