Effects of universal vs bedside leukoreductions on the alloimmunization to platelets and the platelet transfusion refractoriness

Mishima, Yuko; Tsuno, Nelson H.; Matsuhashi, Mika; Sato, Tomohiko; Ikeda, Toshiyuki; Watanabe‐Okochi, Naoko; Nagura, Yutaka; Sone, Satoru; Kurokawa, Mineo; Okazaki, Hitoshi

doi:10.1016/j.transci.2014.11.001

Cited by 22 publications

(13 citation statements)

References 40 publications

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“…Platelet transfusions can elicit a primary or boost a secondary alloimmune response, which may lead to refractoriness to subsequent random platelet transfusions and eventually even hindrance of curative therapies . Universal leukoreduction significantly reduced the frequency of alloimmunization, but a residual risk remains . Recently introduced pathogen‐inactivation techniques have been hypothesized to further reduce the risk of alloimmunization .…”

Section: Discussionmentioning

confidence: 99%

“…The Trial to Reduce Alloimmunization to Platelets (TRAP) revealed that both ultraviolet (UV)‐B illumination of nonleukoreduced PCs and leukoreduction reduce alloimmunization against HLA . Subsequent introduction of universal leukoreduction in most high‐income countries has resulted in a reduction of alloimmunization from 19% to 45% to 9% to 18%, and concomitant alloimmune refractoriness from 14% to 4% . By the introduction of pathogen inactivation techniques, UV illumination has become increasingly available.…”

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confidence: 99%

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The role of pathogen‐reduced platelet transfusions on HLA alloimmunization in hemato‐oncological patients

et al. 2018

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BACKGROUND: Platelet transfusions can induce alloimmunization against HLA antigens. The use of pathogen-reduced platelet concentrates (PCs) was suggested to reduce HLA alloimmunization and concomitant transfusion refractoriness. METHODS:This study investigated HLA alloimmunization in available samples from 448 hematooncological patients who were randomized for the Pathogen Reduction Evaluation and Predictive Analytical Rating Score (PREPAReS) trial to receive either untreated or pathogen-reduced PCs (Mirasol, Terumo BCT Inc.). Anti-HLA Class I and II antibodies were determined before the first platelet transfusion and weekly thereafter using multiplex assay with standard cutoffs to detect low-as well as high-level antibodies. ABBREVIATIONS: IQR = interquartile range; ITT = intention-totreat; NBGs = normalized background ratios; ORs = odds ratios; PCs = platelet concentrates; PP = per-protocol; PRA = panel reactivity; SD = standard deviation; UV = ultraviolet.From the

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

The role of pathogen‐reduced platelet transfusions on HLA alloimmunization in hemato‐oncological patients

et al. 2018

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“…The mother becomes sensitised by foetal platelet antigens that she lacks, and this may develop within few days to several months of the initial exposure to transfused blood cellular components. Transfused patients could develop platelet antibodies approximately 3-4 weeks after transfusion (Mishima et al, 2015). As expected, the development of these platelet-reactive antibodies can cause immune-mediated platelet destruction, which, in turn, results in different clinical conditions, such as platelet transfusion purpura (PTP), refractoriness to platelet transfusion (Kifel et al, 1987) and in case of pregnancy, neonatal alloimmune thrombocytopenia (NAITP).…”

mentioning

confidence: 82%

Gene frequency of human platelet alloantigens‐1 to ‐6 and ‐15 in Saudi blood donors

Al-Ouda

Albanyan

Gader

et al. 2016

Transfusion Medicine

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Studying the prevalence of HPA antigens in Saudi population will help in the understanding of its role in platelet-related disorders. It will also enable the blood bank to establish an HPA-based donor registry that will be a valuable source of compatible platelet-therapeutic products to alloimmunised patients. This will also enhance the safety and efficacy of platelet transfusion. This data obtained will form an addition to the existing body of literature in transfusion research.

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“…In this study, RNAi-mediated HLA class I silencing allowed the generation of a HLA-universal iPSC line with the capacity to serve as a cell source for low immunogenic cell products. PLT transfusion is a widespread therapeutic strategy to treat life-threatening conditions caused by severe and persistent thrombocytopenia due to prolonged BM aplasia or insufficient PLT function secondary to genetic disorders or malignancy (24). Despite the key role of PLTs in the maintenance of hemostasis, they were shown to regulate multiple processes such as angiogenesis, cell differentiation, cell migration, immune responses and tissue remodeling (25)(26)(27).…”

Section: Hla-universal Mks Generate Plts In a Refractoriness Mouse Modelmentioning

confidence: 99%

Generation of HLA-Universal iPSC-Derived Megakaryocytes and Platelets for Survival Under Refractoriness Conditions

Börger

Eicke

Wolf

et al. 2016

Mol Med

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Platelet (PLT) transfusion is indispensable to maintain homeostasis in thrombocytopenic patients. However, PLT transfusion refractoriness is a common life-threatening condition observed in multitransfused patients. The most frequent immune cause for PLT transfusion refractoriness is the presence of alloantibodies specific for human leukocyte antigen (HLA) class I epitopes. Here, we have silenced the expression of HLA class I to generate a stable HLA-universal induced pluripotent stem cell (iPSC) line that can be used as a renewable cell source for the generation of low immunogenic cell products. The expression of HLA class I was silenced by up to 82% and remained stable during iPSC cultivation. In this study, we have focused on the generation of megakaryocytes (MK) and PLTs from a HLA-universal iPSC source under feeder-and xeno-free conditions. On d 19, differentiation rates of MKs and PLTs with means of 58% and 76% were observed, respectively. HLA-universal iPSC-derived MKs showed polyploidy with DNA contents higher than 4n and formed proPLTs. Importantly, differentiated MKs remained silenced for HLA class I expression. HLA-universal MKs produced functional PLTs. Notably, iPSC-derived HLA-universal MKs were capable to escape antibody-mediated complement-and cellular-dependent cytotoxicity. Furthermore, HLA-universal MKs were able to produce PLTs after in vivo transfusion in a mouse model indicating that they might be used as an alternative to PLT transfusion. Thus, in vitro produced low immunogenic MKs and PLTs may become an alternative to PLT donation in PLT-based therapies and an important component in the management of severe alloimmunized patients.

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Effects of universal vs bedside leukoreductions on the alloimmunization to platelets and the platelet transfusion refractoriness

Cited by 22 publications

References 40 publications

The role of pathogen‐reduced platelet transfusions on HLA alloimmunization in hemato‐oncological patients

The role of pathogen‐reduced platelet transfusions on HLA alloimmunization in hemato‐oncological patients

Gene frequency of human platelet alloantigens‐1 to ‐6 and ‐15 in Saudi blood donors

Generation of HLA-Universal iPSC-Derived Megakaryocytes and Platelets for Survival Under Refractoriness Conditions

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