Platelet transfusion refractoriness (PTR) can be defined as the less increment of platelet count than expected after platelets transfusion, which is a challenging and expensive problem often observed in platelet-transfusion-dependent patients. Although PTR occurs most frequently due to non-immune causes, a significant minority is still caused by immune factors. The most important factor in immune dependent PTR is alloimmunization against Class I human leukocyte antigens (HLAs) or human platelet antigens (HPAs). The compatible platelets can be provided to immune-mediated patients using platelet crossmatching, HLA matching, and antibody specificity testing. These measures-aimed to eliminate donor-specific HLA antibodies will lead to the improved clinical management of PTR patients, caused by severe alloimmunization.