Glanzmann Thrombasthenia (GT) is an inherited bleeding disorder of poor platelet function secondary to a defect in platelet membrane glycoprotein IIb/IIIa (GPIIb/IIIa). Patients with GT may develop anti-platelet antibodies including anti-GPIIb/IIIa which can lead to severe refractory thrombocytopenia and life-threatening bleeding, management of which is challenging. We report successful use of imlifidase, a novel IgG protease enzyme, as part of a multimodal approach for management of severe platelet refractoriness and alloimmunization in a child with GT and primary graft failure following hematopoietic stem cell transplant (HSCT). The patient had no detectable anti-platelet alloantibodies following imlifidase, and underwent a second HSCT.