Refractoriness for platelet transfusion is mostly due to clinical factors but may also be caused by alloimmunization. Use of leukocyte-depleted blood cells for transfusions of patients with hematological diseases has reduced if not eliminated HLA-alloimmunization. HLA-antibodies reduce the survival time of incompatible platelets complicating seriously the platelet transfusion support in at least 5% of patients. If consecutive transfusions of HLA matched platelets also fail without identifiable clinical causes, HPA-alloimmunization may have occurred. Platelets from donors phenotyped for both HLA and HPA may produce good platelet count increments and allow optimal treatment of the basic disease despite broad spectrum alloimmunization. Additional cross-matching of phenotyped platelets with patient serum may be needed to circumvent platelet-specific antibodies of unknown specificity.