Eculizumab for complement mediated thrombotic microangiopathy in sickle cell disease.

• Type of Material: Article
• Authors: Satheesh Chonat, Emory University; Sara Graciaa, Aflac Cancer and Blood Disorders Center; H. Stella Shin, Emory University; Joanna G. Newton, Emory University; Maa-Ohui Quarmyne, Emory University; Jeanne Boudreaux, Emory University; Amy Tang, Emory University; Patricia E. Zerra, Emory University; Margo R. Rollins, Emory University; Cassandra D. Josephson, Emory University; Clark Brown, Emory University; Clinton H. Joiner, Emory University; Ross M. Fasano, Emory University; Sean R. Stowell, Emory University
• Language: English
• Date: 2020-12-01
• Publisher: Ferrata Storti Foundation
• Publication Version: Final Published Version
• Copyright Statement: © 2020 Ferrata Storti Foundation
• License: Creative Commons Attribution-NonCommercial 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.3324/haematol.2020.262006
• Title of Journal or Parent Work: Haematologica
• Volume: 105
• Issue: 12
• Start Page: 2887
• End Page: 2891
• Grant/Funding Information: No funding was used to conduct this study.
• Keywords: L-glutamine; crizanlizumab; voxelotor; premature death; hemolysis; vaso-occlusive pain crisis episodes; hemoglobin; hydroxyurea; pain; comorbidity; sickle cell disease
• Research Categories: Chemistry, Pharmaceutical; Biology, Genetics

Abstract

Despite being the first genetic disease described, sickle cell disease (SCD) continues to afflict patients with immense pain, significant comorbidities and premature death. SCD has only recently benefited from new interventions with L-glutamine (2017), voxelotor (2019) and crizanlizumab (2019) representing the first Food and Drug Administration approved medications for SCD since hydroxyurea in 1997. These interventions have demonstrated some ability to reduce vaso-occlusive pain crisis episodes, improve hemoglobin (HGB), or reduce markers of hemolysis and have largely been used as preventative care measures. While these and additional approaches, such as hematopoietic stem cell transplant and gene therapy, can improve SCD care, many patients with SCD continue to suffer from severe acute SCD complications that can result in organ damage and early death.1,2 Unfortunately, in these situations, supportive care remains the primary approach to alleviate complications. The lack of more targeted approaches in part reflects an incomplete understanding of the pathophysiology and accompanying pharmacological targets that could specifically mitigate acute disease complications. We present a summary of three cases of children with SCD who developed significant acute complications that demonstrate underlying complement-mediated thrombotic microangiopathy (CM-TMA). These cases include a delayed hemolytic transfusion reaction (DHTR), vasoocclusive crisis (VOC) and drug-induced immune hemolytic anemia (DIIHA).