Splenectomy revisited in Wiskott-Aldrich syndrome in the era of HSCT and gene therapy: a bridge, a rescue, or simply obsolete?

Wiskott-Aldrich syndrome (WAS) is a rare X-linked primary immunodeficiency caused by mutations in the WAS gene, classically presenting with microthrombocytopenia, eczema, and recurrent infections, with an incidence of approximately 1 per 100, 000 live births. At the mechanistic level, deficiency of the WAS protein (WASp) disrupts actin cytoskeleton remodeling across hematopoietic cells, impairing immune synapse formation, T-cell receptor signaling, natural killer cell cytotoxicity, B-cell activation, and dendritic cell migration. Concurrently, these cytoskeletal defects compromise megakaryocyte proplatelet formation, producing structurally fragile platelets that are rapidly cleared by the spleen and further targeted by immune-mediated destruction, culminating in thrombocytopenia. This pathophysiological basis explains the historical use of splenectomy to control life-threatening bleeding in refractory cases, as removal of the spleen reduces platelet sequestration and destruction, leading to reliable increases in platelet counts, often exceeding 150 × 10