A-362 Impact of lot-to-lot variation in absolute neutrophil count measured by a point-of-care device in patients receiving clozapine treatment

Abstract Background Clozapine is the antipsychotic of choice in the treatment of patients with schizophrenia that are resistant to other therapeutics or at high risk of recurrent suicidal behavior. However, use of clozapine is associated with hematological adverse events, including neutropenia and agranulocytosis, requiring regular monitoring of absolute neutrophil count (ANC). The CSAN® Pronto™ is a point-of-care device that uses image-based technology to measure WBC and ANC in capillary or venous whole blood. ANC results for patients on clozapine are classified for treatment safety as green (greater than or equal to 2.0 x10^9/L), yellow (1.5-1.9 x10^9/L), or red (less than 1.5 x10^9/L). It is recommended to repeat all yellow and red flags, and immediately discontinue treatment if the result is confirmed as <1.5 x10^9/L. The objective of this study was to evaluate the impact of lot-to-lot variation on ANC results. Methods Retrospective patient data were extracted since implementation of the Pronto device at a community hospital (2023/10/01 to 2024/11/01). Distribution of ANC results, frequency of green, yellow, and red flags, and rate and concordance of repeated results were determined across four separate different test strip lots. Patient comparisons between a laboratory analyzer (Sysmex XN-20) and Pronto device were completed for each lot. Correlation and bias relative to the laboratory method were assessed through regression and Bland-Altman statistics, respectively. Performance was compared to allowable performance limits of ±20% for results greater than or equal to 4.0 x10^9/L or ±0.6 x10^9/L for results less than 4.0 x10^9/L relative to the laboratory analyzer. Results A total of 522 patient results across lots were extracted with ANC means ranging from 3.5 to 4.5 x10^9/L. Percentage of results with yellow or red alerts varied markedly with lot number (yellow: 4.4 to 10.2%, red: 2.2 to 7.8%). Reclassification rates among repeated samples was 65%. Of discordant results (N=20), 11 had one sample with a red flag interpretation (<1.5 x10^9/L) and the other with a yellow or green flag (>1.5 x10^9/L). Patient comparisons between the Pronto device and laboratory method for ANC demonstrated good correlation across lots (R: 0.933 to 0.997, N=9-17 per lot). Mean ANC bias relative to the laboratory demonstrated lot-specific shifts and ranged from -0.8 to 0.6 x10^9/L. Across lots, percentage of samples within allowable performance limits ranged from 64.7 to 88.9%. The lot with the largest negative bias also demonstrated the highest red alert rate and repeat rate in real-time patient data. Conclusion Patients receiving clozapine treatment require monitoring of ANC. Point-of-care measurement offers significant advantages in this population, including rapid clinical decision-making and reduced risk of attrition. Our study combines patient-level data with laboratory method comparisons to highlight the impact of lot variation of the Pronto device on patient results. This variation could lead to downstream consequences on patient care, including increased rates of repeated blood draw and changes in management. These findings emphasize the need for additional quality metrics and provider education in the use of the Pronto device for measurement of ANC in individuals on clozapine treatment.