Prophylactic administration of human HPA-1a–specific antibodies protects against FNAIT in mice. In FNAIT, HPA-1a–positive fetal platelets enter the maternal circulation, resulting in maternal alloimmunization characterized by the development of pathogenic HPA-1a alloantibodies. These antibodies cross the placenta and destroy the fetal platelets, causing thrombocytopenia and bleeding symptoms in the fetus or newborn (right side). Prophylactic administration of RLYB211 (polyclonal antibody) or RLYB212 (monoclonal antibody) rapidly clears HPA-1a–positive platelets and prevents maternal alloimmunization (development of pathogenic HPA-1a alloantibodies) and subsequent onset of FNAIT in an alloantigen-specific FNAIT mouse model (left side). This provides support for use of a similar approach to prevent FNAIT in humans. Figure was created with BioRender.com.