Platelet morphological and functional abnormalities and their impact on clinical manifestations in pediatric patients with inherited platelet disorders

Abstract

This study investigated clinical features, bleeding severity, and platelet function in pediatric patients with inherited platelet disorders associated with an increased risk of hematologic malignancies: familial platelet disorder with predisposition to acute myeloid leukemia (FPD/AML), ANKRD26-related thrombocytopenia (ANKRD26-RT), and ETV6-related thrombocytopenia (ETV6-RT). Twenty-seven patients were evaluated using standardized bleeding scores and comprehensive platelet function assays. FPD/AML was associated with mild thrombocytopenia and defects in dense granule storage and release, procoagulant platelet formation, and calcium signaling. ANKRD26-RT showed moderate to severe thrombocytopenia, impaired aggregation, and altered activation-dependent platelet structural remodeling. ETV6-RT was characterized by variable bleeding severity, largely preserved aggregation, but impaired granule release, integrin activation, and cytoskeletal organization. Bleeding severity correlated with platelet function in FPD/AML and ANKRD26-RT, but with platelet count in ETV6-RT. These findings demonstrate distinct platelet phenotypes and highlight the added value of functional testing beyond platelet count in assessing bleeding risk. Standardized diagnostic approaches incorporating platelet function assays may improve individualized clinical management.

Dissertation ist gesperrt bis 13. März 2027 !