PMID- 32086819
OWN - NLM
STAT- MEDLINE
DCOM- 20210201
LR  - 20221005
IS  - 1365-2141 (Electronic)
IS  - 0007-1048 (Print)
IS  - 0007-1048 (Linking)
VI  - 189
IP  - 3
DP  - 2020 May
TI  - A pilot trial of complement inhibition using eculizumab to overcome platelet 
      transfusion refractoriness in human leukocyte antigen allo-immunized patients.
PG  - 551-558
LID - 10.1111/bjh.16385 [doi]
AB  - 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).
CI  - (c) 2020 British Society for Haematology and John Wiley & Sons Ltd.
FAU - Vo, Phuong
AU  - Vo P
AUID- ORCID: 0000-0002-0823-0244
AD  - Hematology Branch, National Heart, Lung and Blood Institute, National Institutes 
      of Health, Bethesda, MD, USA.
FAU - Purev, Enkhtsetseg
AU  - Purev E
AD  - University of Colorado, Denver, CO, USA.
FAU - West, Kamille A
AU  - West KA
AUID- ORCID: 0000-0001-8152-804X
AD  - Department of Transfusion Medicine, NIH Clinical Center, National Institutes of 
      Health, Bethesda, MD, USA.
FAU - McDuffee, Emily
AU  - McDuffee E
AD  - Hematology Branch, National Heart, Lung and Blood Institute, National Institutes 
      of Health, Bethesda, MD, USA.
FAU - Worthy, Tatyana
AU  - Worthy T
AD  - Hematology Branch, National Heart, Lung and Blood Institute, National Institutes 
      of Health, Bethesda, MD, USA.
FAU - Cook, Lisa
AU  - Cook L
AD  - Hematology Branch, National Heart, Lung and Blood Institute, National Institutes 
      of Health, Bethesda, MD, USA.
FAU - Hawks, Geri
AU  - Hawks G
AD  - Hematology Branch, National Heart, Lung and Blood Institute, National Institutes 
      of Health, Bethesda, MD, USA.
FAU - Wells, Brian
AU  - Wells B
AD  - Hematology Branch, National Heart, Lung and Blood Institute, National Institutes 
      of Health, Bethesda, MD, USA.
FAU - Shalabi, Reem
AU  - Shalabi R
AD  - Hematology Branch, National Heart, Lung and Blood Institute, National Institutes 
      of Health, Bethesda, MD, USA.
FAU - Flegel, Willy A
AU  - Flegel WA
AD  - Department of Transfusion Medicine, NIH Clinical Center, National Institutes of 
      Health, Bethesda, MD, USA.
FAU - Adams, Sharon D
AU  - Adams SD
AD  - Department of Transfusion Medicine, NIH Clinical Center, National Institutes of 
      Health, Bethesda, MD, USA.
FAU - Reger, Robert
AU  - Reger R
AD  - Hematology Branch, National Heart, Lung and Blood Institute, National Institutes 
      of Health, Bethesda, MD, USA.
FAU - Aue, Georg
AU  - Aue G
AD  - Hematology Branch, National Heart, Lung and Blood Institute, National Institutes 
      of Health, Bethesda, MD, USA.
FAU - Tian, Xin
AU  - Tian X
AD  - Office of Biostatistics Research, National Heart, Lung and Blood Institute, 
      National Institutes of Health, Bethesda, MD, USA.
FAU - Childs, Richard
AU  - Childs R
AD  - Hematology Branch, National Heart, Lung and Blood Institute, National Institutes 
      of Health, Bethesda, MD, USA.
LA  - eng
SI  - ClinicalTrials.gov/NCT02298933
GR  - National Institutes of Health in Bethesda/International
GR  - United States Public Health Service Commissioned Corps/International
GR  - Intramural Research Program of the National Heart, Lung and Blood 
      Institute/International
GR  - Z99 CL999999/ImNIH/Intramural NIH HHS/United States
GR  - CL/CLC NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Intramural
PT  - Research Support, U.S. Gov't, P.H.S.
DEP - 20200221
PL  - England
TA  - Br J Haematol
JT  - British journal of haematology
JID - 0372544
RN  - 0 (Antibodies, Monoclonal, Humanized)
RN  - 0 (HLA Antigens)
RN  - A3ULP0F556 (eculizumab)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Aged
MH  - Antibodies, Monoclonal, Humanized/pharmacology/*therapeutic use
MH  - Female
MH  - HLA Antigens/*immunology
MH  - Humans
MH  - Immunization/*methods
MH  - Male
MH  - Middle Aged
MH  - Pilot Projects
MH  - Platelet Transfusion/*methods
MH  - Young Adult
PMC - PMC7192788
MID - NIHMS1565920
COIS- Conflict of interest disclosure The authors declare no competing financial 
      interests.
EDAT- 2020/02/23 06:00
MHDA- 2021/02/02 06:00
PMCR- 2021/05/01
CRDT- 2020/02/23 06:00
PHST- 2019/07/24 00:00 [received]
PHST- 2019/10/11 00:00 [accepted]
PHST- 2020/02/23 06:00 [pubmed]
PHST- 2021/02/02 06:00 [medline]
PHST- 2020/02/23 06:00 [entrez]
PHST- 2021/05/01 00:00 [pmc-release]
AID - 10.1111/bjh.16385 [doi]
PST - ppublish
SO  - Br J Haematol. 2020 May;189(3):551-558. doi: 10.1111/bjh.16385. Epub 2020 Feb 21.