Boshkos Mitchell C, Fives Kaila R, Phrathep Davong D, Healey Kevin D, Patel Miten
Internal Medicine, Lake Erie College of Osteopathic Medicine, Bradenton, USA.
College of Medicine, Lake Erie College of Osteopathic Medicine, Bradenton, USA.
Cureus. 2023 Mar 16;15(3):e36240. doi: 10.7759/cureus.36240. eCollection 2023 Mar.
Breakthrough hemolysis (BTH) is the return of hemolytic disease resulting in an overall increase in complement activation in a patient being treated for paroxysmal nocturnal hemoglobinuria (PNH) with complement inhibitors (CI). BTH after COVID-19 vaccination has only been reported in PNH patients treated with the traditional C5 CI eculizumab and ravulizumab. We report on a new association of BTH in a newly COVID-19 vaccinated, previously stable PNH patient treated with pegcetacoplan, a C3 CI. The patient is a 29-year-old female diagnosed with PNH in 2017 and was started on eculizumab but was switched to pegcetacoplan in 2021 after continuing to exhibit symptomatic hemolysis. Subsequently, the patient returned to PNH remission serologically and symptomatically until her first COVID-19 vaccination. Since then, her lactate dehydrogenase (LDH) and hemoglobin counts have not fully returned to previous baseline levels, with significant exacerbations after her second COVID-19 vaccine and de novo COVID-19 infection. As of May 2022, the patient requires packed red blood cell transfusions every two to three months and has undergone a bone marrow transplant evaluation. This case study suggests that the administration of the upstream C3 CI, pegcetacoplan, is associated with active extravascular hemolysis in the setting of COVID-19 vaccinations and active COVID-19 infection. The pathophysiology of this hemolysis is unclear as hemolysis could be related to the underlying complement factor deficiency or amplification of complement factors causing extravascular hemolysis. There are conflicting reports in the literature regarding the mechanism by which COVID-19 vaccination and infection cause BTH in PNH patients, regardless of the choice of CI treatment. Bringing awareness to this case of BTH secondary to COVID-19 in a PNH patient treated with pegcetacoplan can further warrant the investigation of the role of COVID-19 in complement disruption and its role in BTH.
突破性溶血（BTH）是指在使用补体抑制剂（CI）治疗阵发性夜间血红蛋白尿（PNH）的患者中，溶血性疾病复发，导致补体激活总体增加。新冠病毒疫苗接种后发生的BTH仅在接受传统C5 CI依库珠单抗和ravulizumab治疗的PNH患者中有所报道。我们报告了一例新的BTH关联病例，该病例为一名新接种新冠病毒疫苗、此前病情稳定的PNH患者，其接受的是C3 CI聚乙二醇化阿巴西普治疗。患者为一名29岁女性，2017年被诊断为PNH，开始使用依库珠单抗治疗，但在持续出现症状性溶血后，于2021年改用聚乙二醇化阿巴西普。随后，患者在血清学和症状方面均恢复至PNH缓解状态，直至她首次接种新冠病毒疫苗。从那时起，她的乳酸脱氢酶（LDH）和血红蛋白计数一直未完全恢复到先前的基线水平，在第二次接种新冠病毒疫苗和新发新冠病毒感染后病情显著加重。截至2022年5月，该患者每两到三个月需要输注浓缩红细胞，并已接受了骨髓移植评估。本病例研究表明，在新冠病毒疫苗接种和活动性新冠病毒感染的情况下，上游C3 CI聚乙二醇化阿巴西普的使用与活动性血管外溶血有关。这种溶血的病理生理学尚不清楚，因为溶血可能与潜在的补体因子缺乏或导致血管外溶血的补体因子放大有关。无论CI治疗的选择如何，文献中关于新冠病毒疫苗接种和感染导致PNH患者发生BTH的机制存在相互矛盾的报道。提高对该例接受聚乙二醇化阿巴西普治疗的PNH患者继发于新冠病毒的BTH病例的认识，可进一步促使人们研究新冠病毒在补体破坏中的作用及其在BTH中的作用。
