The association and functional relevance of genetic variation in low‐to‐medium‐affinity Fc‐gamma receptors with clinical platelet transfusion refractoriness

Abstract

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 alloantibodies. 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 (FcγRs). Genetic variation in FcγRs is associated with susceptibility to immune thrombocytopenia, in which autoantibodies against platelets cause thrombocytopenia. Objectives:We hypothesized that genetic variation in FcγRs may also influence PLT refractoriness in allo-immunized patients and could help in identifying the patients at risk. How to cite this article: Nagelkerke SQ, Porcelijn L, Geissler J, et al. The association and functional relevance of genetic variation in low-to-medium-affinity Fc-gamma receptors with clinical platelet transfusion refractoriness.

Avatrombopag for the salvage treatment of platelet transfusion refractoriness

“… 34 The main mechanism of PTR treatment using steroids and IVIG is their binding to FcR on the platelet surface to reduce macrophage–phagocytosis thrombocytopenia. 19 , 20 The refractory PTR patients enrolled in our research did not respond to steroid or IVIG treatment. Therefore, the activation of Fc-mediated phagocytosis of macrophages by anti-HLA antibodies may not be the critical mechanism in these patients.…”

“…Recent studies suggest that the immune factors may include Fc receptor (FcR)-mediated enhancement of phagocytosis and T cell-mediated immune imbalance, which may further lead to megakaryopoiesis and thrombopoiesis destruction. 16 – 18 FcR-mediated enhancement of phagocytosis-induced PTR can be treated with IVIG and steroids 19 , 20 ; yet, no recognized treatment scheme for PTR mediated by T cell dysregulation is currently available.…”

Analysis of FCGR3A-p.176Val variants in women with recurrent pregnancy loss and the association with CD16a expression and anti-HLA antibody status

“…Healthy women: a cohort of 164 Dutch healthy female donors from Sanquin Amsterdam, that gave written consent and were genotyped for the FCGR3A polymorphism in the context of a previous study 54 .…”

“…The group of 164 healthy females, was genotyped in a previous study by a FCGR-specific multiplex ligationdependent probe amplification (MLPA) assay (MRC-Holland, Amsterdam, The Netherlands) 54 . To ensure that both typing methods yielded comparable genotypic results, 5 women with of the current RPL cohort were genotyped by SBT and also by MLPA and this resulted in the same typing.…”