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

Authors :
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
Source :
British journal of haematology [Br J Haematol] 2020 May; Vol. 189 (3), pp. 551-558. Date of Electronic Publication: 2020 Feb 21.
Publication Year :
2020

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).<br /> (© 2020 British Society for Haematology and John Wiley & Sons Ltd.)

Details

Language :
English
ISSN :
1365-2141
Volume :
189
Issue :
3
Database :
MEDLINE
Journal :
British journal of haematology
Publication Type :
Academic Journal
Accession number :
32086819
Full Text :
https://doi.org/10.1111/bjh.16385