Clinical and molecular characterization of thrombocytosis in transient abnormal myelopoiesis

Transient abnormal myelopoiesis (TAM) is a distinctive hematological disorder in neonates with Down syndrome, driven by somatic GATA1 mutations that promote blast proliferation [ 1 , 2 ]. Although TAM typically resolves spontaneously, a subset of patients may progress to myeloid leukemia associated with Down syndrome (ML-DS) [ 3 , 4 , 5 , 6 ]. Clinically, TAM ranges from asymptomatic cases to severe disease with multiorgan dysfunction. While thrombocytopenia is well recognized in TAM, sporadic reports of thrombocytosis [ 7 , 8 ] indicate that platelet abnormalities may be more heterogeneous than previously appreciated. In some cohorts, platelet counts have approached 1000 × 10⁹/L [ 3 , 4 ]. Whether elevated counts increase thrombosis risk, define a distinct clinical subtype, or influence disease progression has not been systematically explored. To address this gap, we conducted a secondary analysis of the TAM-10 prospective cohort, stratified by platelet count at diagnosis. We hypothesized that thrombocytosis represents a clinically and biologically distinct TAM subgroup, reflecting potential differences in underlying pathophysiology. Detailed methods are provided in the Supplementary Methods.