Pb2065: severe hemolysis of pnh patients associated with omicron infection in china

Topic: 12. Bone marrow failure syndromes incl. PNH - Clinical Background: Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, chronic hemolytic, multi-systemic disease with PIG-A mutation of hematopoietic stem cell. Deficiency of PIG-A gene blocks glycosylphosphatidylinositol (GPI) biosynthesis which anchors many proteins to cell membrane, such as CD55 and CD59. It leads to the vulnerability of PNH cell for complement attack and PNH patients primarily present hemolytic anemia, thrombosis. And COVID-19, which caused by a novel coronavirus with many variants including Alpha (B.1.1.7), Beta (B.1.351), Gamma (P.1), Delta (B.1.617.2) and Omicron (B.1.1529), induces hemolytic crises in PNH by activating complement and inflammatory storm. Aims: The purpose of this study is to describe severe hemolysis of PNH patients in China after Omicron infection and to better manage such patients. Methods: This study depicted demographic and clinical characteristics of 20 PNH patients with Omicron infection in China by prospective registration in the Chinese Eastern Collaboration Group of Anemia (ChiCTR2100050945), which was conducted by three centers: the First Affiliated Hospital with Nanjing Medical University (Nanjing, China), Funing People’s Hospital (Funing, China) and Wuxi People’s Hospital (Wuxi, China) from December 2022 to February 2023 (Table 1). All the patients hadn’t previously been administrated by complement inhibitors. Meanwhile we reviewed the hemolysis of 9 PNH patients with Omicron infection, who have been treated with complement inhibitors in the past from literature[1–5]. The severity of hemolysis was compared with which even happened most heavily in previous course in these patients by pairing test. Data of 5 patients who were treated by eculizumab were also analyzed by pairing test. Results: All of 20 patients were with high disease activity (HDA). 10 patients showed apparent hemoglobinuria and 10 presented with worsen fatigue and cytopenia. During this hemolytic process, there were no thromboembolic events. Two patients developed mild pulmonary hypertension (32mmHg and 35mmHg, respectively), while 5 patients’ glomerular filtration rate (GFR) declined (GFR＜60 ml/min/1.73m2). Unexpectedly, one patient with covid-19 infection complained acute renal injury and achieved hemodialysis. Compared with PNH patients who received complement inhibitors and experienced hemolysis after Omicron infection in the literature[1–5], level of lactate dehydrogenase (LDH) was higher in our group of patients (7.47×ULN vs 2.04×ULN, p＜0.001). Patients with previous complement inhibitor therapy has shown better tolerance to Omicron attacks. And in this group, the level of LDH (9.43×ULN vs 5.62×ULN, p=0.011) increased markedly than even happened since the diagnosis of PNH. (Table 1). 5 patients were administrated with eculizumab therapy (Table 2), red blood cell count (1.96×1012/L vs 2.45×1012/L, p=0.01), hemoglobin level (64 g/L vs 83 g/L, p=0.005) had improved and hemolysis was controlled (LDH, 13.53×ULN vs 3.38×ULN, p=0.028) (Table 1). The patients treated by eculizumab could not be vaccinated in advance for emergency use, but infection didn’t occur with the whole course of penicillin. Summary/Conclusion: The Omicron infection could induce severe hemolysis, cytopenia and organ function damage in PNH patients. Compared with hemolytic episodes in the past, the hemolysis induced by Omicron is more intense. Eculizumab could effectively improve the of hemolysis induced by Omicron infection in patients with PNH.Keywords: COVID-19, Paroxysmal nocturnal hemoglobinuria (PNH), Hemolysis