The Role of Red Blood Cell Lifespan Testing in the Evaluation of Patients with Paroxysmal Nocturnal Hemoglobinuria

Objective To explore the role of red blood cell(RBC) lifespan testing in the evaluation of patients with paroxysmal nocturnal hemoglobinuria (PNH). Methods The endogenous breath carbon monoxide (CO) test was used to detect the RBC lifespan of PNH patient with the treatment of crovalimab（ Roche） or iptacopan（ Novartis.），for comparison of different hemolysis indices in the assessment of patients' condition. Results Nine patients have been enrolled in the study at our centre from June to December 2021, 4 with the treatment of crovalimab and 5 with iptacopan. The median lifespan in the untreated patients was 17 (range 12-38) days, median hemoglobin(Hb) 83(69-94) g/l, median lactic dehydrogenase（LDH）590.8(446.1-935.5)U/L, median PNH clones 96.0(33.2-99.9)%. By 6 months post-treatment, 8 patients achieved hematologic improvement without breakthrough hemolysis. In all patients, LDH levels decreased rapidly and stabilized at lower levels after starting treatment. But the degree of Hb recovery varied，median 60(20-85)g/L. Analyzing the correlation between different hemolytic indices (LDH, RBC lifespan, total bilirubin, indirect bilirubin, etc.) and Hb changes, RBC lifespan showed good correlation（P=0.002，R=0.867）. In the crovalimab group, three patients presented with a positive Coombs test and the negative patient didn't obtain hematologic improvement. No patients with a positive Coombs test were seen in the iptacopan group. Conclusion Different (upstream/downstream) complement inhibitors have different effects on the condition of PNH patients, and different indicators can reflect different results; LDH responds to intravascular hemolysis, and red blood cell lifespan also quantifies extravascular hemolysis, and is applied to monitor hemolysis. The application of RBC lifespan testing can provide an accurate scientific basis for the assessment of PNH conditions.

Keywords: red blood cell lifespa, paroxysmal nocturnal hemoglobinuria ,red blood cell lifespan,lactic dehydrogenase