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Complement in Sickle Cell Disease: Are We Ready for Prime Time?

Authors Varelas C, Tampaki A, Sakellari I, Anagnostopoulos A, Gavriilaki E, Vlachaki E

Received 15 February 2021

Accepted for publication 11 March 2021

Published 23 March 2021 Volume 2021:12 Pages 177—187

DOI https://doi.org/10.2147/JBM.S287301

Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 2

Editor who approved publication: Dr Martin Bluth


Christos Varelas,1 Athina Tampaki,2 Ioanna Sakellari,1 &Agr;chilles Anagnostopoulos,1 Eleni Gavriilaki,1,* Efthymia Vlachaki2,*

1Hematology Department – BMT Unit, G. Papanicolaou Hospital, Thessaloniki, Greece; 2Adults Thalassemia Unit, 2nd Department of Internal Medicine, Hippokration Hospital, Thessaloniki, Greece

*These authors contributed equally to this work

Correspondence: Eleni Gavriilaki
Hematology Department - BMT Unit, G. Papanicolaou Hospital, Exochi, Thessaloniki, 57010, Greece
Email [email protected]

Abstract: Sickle cell disease (SCD) is a widely spread inherited hemoglobinopathy that includes a group of congenital hemolytic anemias, all characterized by the predominance of sickle hemoglobin (HbS). Its features are anemia, predisposal to bacterial infections and complications such as vaso-occlusive crisis (VOC) or delayed hemolytic transfusion reaction (DHTR), which lead to increased rate of morbidity and mortality even in the era of hydroxyurea. The interaction between sickle cells, neutrophils, platelets or endothelial cells in small vessels results in hemolysis and has been considered the disease’s main pathophysiological mechanism. Complement activation has been reported in small cohorts of SCD patients, but the governing mechanism has not been fully elucidated. This will be important to predict the patient group that would benefit from complement inhibition. Until now, eculizumab-mediated complement inhibition has shown beneficial effects in DHTR, with limited reports in patients with VOC. In the meantime, several innovative agents are under clinical development Our state-of-the-art review summarizes current data on 1) complement activation in SCD both in steady state and crisis, 2) underlying mechanisms of complement over-activation for the clinician in the context of SCD, 3) actions of hydroxyurea and new therapeutic approaches including indirect involvement in complement activation, and 4) novel paradigms in complement inhibition.

Keywords: sickle cell disease, complement system, eculizumab, complement inhibition

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