Human Leukocyte Antigen Alloimmunization and Alloimmune Platelet Refractoriness

Despite significant advancements in the production of platelet products, storage, and transfusion, transfusion refractoriness remains a significant clinical problem, affecting up to 14% of hematological patients receiving platelet transfusions. Human leukocyte antigen (HLA) alloimmunization is a major cause of immune platelet refractoriness, and its rate can be significantly reduced by implementation of leukoreduction. Despite promising preclinical results, pathogen reduction does not reduce HLA alloimmunization. Patients with HLA alloimmune refractoriness are usually managed with HLA-selected platelet transfusions. In this review, we describe the pathophysiology of HLA alloimmunization and alloimmune refractoriness, as well as options to prevent and treat these transfusion complications. We discuss the evidence supporting these options and point out the outstanding gaps. Finally, we review the possible future directions for prevention and treatment of alloimmune refractoriness. •Platelet refractoriness is a significant complication of platelet transfusions.•HLA alloimmunization is the most common reason of immune refractoriness and can be mitigated by leukoreduction of red blood cell and platelet products.•HLA alloimmune refractoriness is managed with HLA-selected platelet transfusions.•Future options to prevent and treat HLA alloimmune refractoriness include low HLA antigen expression or HLA-universal platelets.