A novel strategy for the screening for platelet refractoriness: prospects and limitations

Over the last decades the progressive increase in platelet use has coincided with increasingly aggressive myelosuppressive therapy for malignancies or allogeneic hematopoietic stem cell transplantation. The US National Marrow Donor Program predicts a doubling in allogeneic transplants between 2010 and 2015 (1). More than three million Brazilian donors were registered in the Bone Marrow Donors Worldwide program by 2010 (2). Together, it is anticipated that there will be a continuing growth in the number of allogeneic transfusions. Although platelets were identified over 100 year ago, data accumulated from the last ten years has provided a boost of novel information on platelet biology, and hope for the development of therapy to improve platelet production and survival (3,4). Current data suggest that platelets emerge from the tips of the proplatelet extension of mature megakaryocytes, and individual platelets may be capable of dividing in the circulation (3). The identification of thrombopoietin, the primary cytokine required for normal numbers of marrow megakaryocytes and circulating platelets, resulted in the generation of its recombinant derivatives, now used to minimize the duration of thrombocytopenia. Interleukin-11 the only US Federal Food and Drug Agency (FDA) approved drug to treat thrombocytopenia has a limited effect on platelet numbers after intensive myelosuppression. Other cell-based therapies, such as the generation of megakaryocytes and the use of human embryonic/mature pluripotent hematopoietic precursors, raise the possibility of a future supply of platelets (1). To date, the platelet products available for transfusion are based on platelet concentrates from whole blood or platelet apheresis. The main complication in the use of platelets is the development of alloantibodies that precludes the improvement of severe thrombocytopenia, which is associated with increased morbidity and mortality (5,6). Platelet transfusion refractoriness (PTR) is characterized by the lack of adequate post-transfusional platelet increments, with the underlying mechanisms being due to immune and non-immune pathologies (4,6). The latter comprises the large majority (~70-80%) of PTR cases. Platelet alloimmunization is the result of both the donor product transfused and the immune status of the recipient. Platelets express a number of antigens that have been shown to influence post-transfusion counts and platelet survival; these include ABO, human leukocyte antigens (HLA) and human platelet antigens (HPA). Primary immunization against HLA-antigens, which are also expressed in other cells, is caused mostly by contaminating leukocytes in platelet products; HPA-specific immunization is less frequent. The management of alloimmune PTR is clinically challenging and without consensus on the ideal …