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  • Title: A pilot trial of complement inhibition using eculizumab to overcome platelet transfusion refractoriness in human leukocyte antigen allo-immunized patients.
    Author: Vo P, Purev E, West KA, McDuffee E, Worthy T, Cook L, Hawks G, Wells B, Shalabi R, Flegel WA, Adams SD, Reger R, Aue G, Tian X, Childs R.
    Journal: Br J Haematol; 2020 May; 189(3):551-558. PubMed ID: 32086819.
    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).
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