Changes in indicators of cerebral metabolic stress following treatment with voxelotor in children and adolescents with sickle cell anemia

EJHaem Pub Date : 2024-08-27 DOI:10.1002/jha2.1001
Andrew M. Heitzer, Ping Zou, Jason Hodges, Clark Brown, Mark Davis, Sandy Dixon, Robert J. Ogg, Jeremie Estepp, Jane S Hankins, Ranganatha Sitaram, Clifford M. Takemoto
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Abstract

Voxelotor is a small molecule that reduces the polymerization of sickle hemoglobin by increasing its affinity for oxygen. In patients with sickle cell anemia, it has been postulated that increasing hemoglobin-oxygen affinity could limit oxygen offloading from hemoglobin, causing an increase in cerebral metabolic stress. To investigate this hypothetical concern, we used multimodal brain imaging to define the effects of voxelotor on cerebral blood flow and oxygen extraction. We followed four patients for 2–5 months during and/or after voxelotor therapy. This study showed no observable increase in cerebral blood flow or oxygen extraction fraction during treatment.

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镰状细胞性贫血患儿和青少年接受伏洛托治疗后脑代谢压力指标的变化
Voxelotor 是一种小分子,可通过增加镰状血红蛋白对氧的亲和力来减少其聚合。据推测,在镰状细胞贫血患者中,增加血红蛋白与氧的亲和力可能会限制血红蛋白的氧卸载,从而导致脑代谢压力增加。为了探究这一假设性问题,我们使用多模态脑成像技术来确定体视显微镜对脑血流和氧萃取的影响。我们对四名患者进行了为期 2-5 个月的体位治疗期间和/或治疗后随访。研究结果表明,在治疗期间,脑血流量和氧萃取率均无明显增加。
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