Immune thrombocytopenia in a patient with a rare ITGB3 missense variant of uncertain significance (VUS

Introduction Immune thrombocytopenia (ITP) is an acquired autoimmune disorder characterized by accelerated platelet destruction and impaired platelet production. In treatment-refractory cases, genetic testing may provide additional insight into baseline platelet counts and therapeutic targets. Method We evaluated the clinical course of a patient diagnosed with ITP in August 2021, reviewing medical history, therapeutic interventions, laboratory monitoring, bone marrow examination, and genetic testing. After identification of a rare ITGB3 missense variant of uncertain significance (VUS), a segregation analysis was initiated in the family. Results The patient experienced multiple relapses after corticosteroid tapering, transient responses to IVIG, and insufficient platelet stabilization with sequential trials of thrombopoietin receptor agonists (romiplostim, avatrombopag, eltrombopag) and fostamatinib. Bleeding symptoms (epistaxis, hematomas) persisted, while high-dose corticosteroids caused considerable adverse effects. Genetic testing revealed a heterozygous ITGB3(NM_000212.2):c.2131C>T,p.(Pro711Ser) variant, classified as VUS. Segregation analysis demonstrated that family members carrying this variant consistently showed higher mean platelet volume (MPV) and lower platelet counts in comparison non-carriers. This indicates that the variant is not causative of the patient’s severe thrombocytopenia (