Bleeding disorder, platelet-type, 24

An inherited platelet-type bleeding disorder caused by heterozygous variants in the ITGB3 gene that alter integrin alpha-IIb/beta-3 inside-out and outside-in signaling, resulting in defective platelet production and function. Affected individuals present with congenital macrothrombocytopenia, comprising mild to moderate thrombocytopenia, giant platelets and platelet anisocytosis, together with variable mucocutaneous bleeding. Functional studies show reduced integrin alpha-IIb/beta-3 expression or impaired activation, decreased platelet aggregation in response to physiologic agonists, and impaired platelet spreading on fibrinogen.