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A pilot trial of complement inhibition using eculizumab to overcome platelet transfusion refractoriness in human leukocyte antigen allo-immunized patients.

ABSTRACT: Heavily transfused patients frequently develop human leukocyte antigen (HLA) allo-immunization resulting in platelet transfusion refractoriness and a high risk for life-threatening thrombocytopenia. Data suggest complement activation leading to the destruction of platelets bound by HLA allo-antibodies may play a pathophysiologic role in platelet refractoriness. Here we conducted a pilot trial to investigate the use of eculizumab, a monoclonal antibody that binds and inhibits C5 complement, to treat platelet transfusion refractoriness in allo-immunized patients with severe thrombocytopenia. A single eculizumab infusion was administered to 10 eligible patients, with four (40%) patients overcoming platelet refractories assessed measuring the corrected platelet count increment (CCI) 10-60 min and 18-24 h post transfusion. Responding patients had a reduction in the requirement for subsequent platelet transfusions and had higher post-transfusion platelet increments for 14 days following eculizumab administration. Remarkably, three of the four responders met CCI criteria for response despite receiving HLA-incompatible platelets. Our results suggest that eculizumab has the ability to overcome platelet transfusion refractoriness in patients with broad HLA allo-immunization. This study establishes proof of principle that complement inhibition can treat platelet transfusion refractoriness, laying the foundation for a large multicentre trial to assess the overall efficacy of this approach (ClinicalTrials.gov, identifier: NCT02298933).

SUBMITTER: Vo P

PROVIDER: S-EPMC7192788 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Platelet transfusion refractoriness (PTR) is common in patients with hematology and oncology and is becoming an important barrier in the treatment of thrombocytopenia and hemorrhage. Bibliometrics is an effective method for identifying existing research achievements, important breakthroughs, current research hotspots, and future development trends in any given field. In recent years, research on PTR has received increasing attention, but a bibliometric analysis of this field has not yet been reported. In this study, we applied bibliometrics to analyze the existing literature on PTR research over the past 17 years. On November 1, 2021, we began a publications analysis of PTR research using the Science Citation Index Expanded of the Web of Science Core Collection with collection dates from 2004 to 2021. This research aimed to summarize the state of PTR research using Bibliometrix to identify connections between different elements (i.e., authors, institutions, countries, journals, references, and keywords) using VOS viewer analyses to visualize key topics and trends in PTR research using Cite Space and gCLUTO. The results of all 310 studies showed that the annual number of publications focused on PTR is steadily increasing, with the United States of America and Japan making significant contributions. We noted that the research group led by Dr. Sherrill J. Slichter was prominent in this field, while Estcourt Lise may become the most influential newcomer. Transfusion was the most popular journal, and Blood was the most cited journal. Using various analyses, including co-cited analysis, historiography analysis, citation burst analysis, and factorial analysis, we pointed out and discussed contributing publications. According to occurrence analysis, co-word biclustering analysis, landform map, thematic evolution, and thematic map, we believe that "activation," "p-selection," "CD36 deficiency," "gene-frequencies," "CD109," "HPA-1," and "beta (3) integrin" may become new trends in PTR research. The outcome of our bibliometric analyses has, for the first time, revealed profound insights into the current state and trends in PTR research. The systematic analysis provided by our study clearly demonstrates the field's significant advancements to all researchers who are interested in a quick and comprehensive introduction to the field.

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A pilot trial of complement inhibition using eculizumab to overcome platelet transfusion refractoriness in human leukocyte antigen allo-immunized patients.

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