The Association And Functional Relevance Of Genetic Variation In Low-To-Medium-Affinity Fc-Gamma Receptors With Clinical Platelet Transfusion Refractoriness

Background Inadequate responses to platelet transfusions (i.e., platelet transfusion refractoriness [PLT refractoriness]) are a serious problem. Multiple factors contribute to low yields upon platelet transfusion, among which are platelet-reactive allo-antibodies. Platelet-reactive allo-antibodies occur in up to 30% of patients receiving multiple transfusions, and presumably lead to rapid destruction of the transfused platelets via receptors for IgG, the Fc-gamma receptors (Fc gamma Rs). Genetic variation in Fc gamma Rs is associated with susceptibility to immune thrombocytopenia, in which autoantibodies against platelets cause thrombocytopenia. Objectives We hypothesized that genetic variation in Fc gamma Rs may also influence PLT refractoriness in allo-immunized patients and could help in identifying the patients at risk. Patients/Methods Patients with severe PLT refractoriness for whom diagnostic testing for allo-immunization was requested in the period of 2005 to 2013 were retrospectively included. A case-control study was performed comparing patients in whom platelet-reactive antibodies were detected (n = 181) with ethnically matched healthy controls (n = 180) to determine differences in all known functional copy number variations and single nucleotide polymorphisms in Fc gamma Rs. Results and Conclusions None of the tested Fc gamma R genetic variations seemed associated with the development of severe PLT refractoriness. In contrast to observations in immune thrombocytopenia, genetic variation in Fc gamma Rs does not seem to influence the chance to develop PLT refractoriness. Our results do not support determination of Fc gamma R genetic background as a means to identify patients most at risk for PLT refractoriness.