A-341 Impact of PlGF Assay Imprecision on sFlt-1/PlGF Ratio Interpretation in Preeclampsia Risk Assessment

Background Preeclampsia remains a challenge in OB/GYN care, as current management largely relies on symptom monitoring and laboratory tests with limited diagnostic accuracy. Once diagnosed, the only effective treatment is delivery of the infant. The discovery of angiogenic biomarkers imbalance—as reflected by an increased sFlt-1/PlGF ratio—has led to the development of more specific diagnostic tools. While European guidelines have endorsed sFlt-1/PlGF-based testing for many years, adoption in the US has been delayed, partly due to the absence of an FDA-approved assay. In May 2023, the FDA cleared the sFlt-1/PlGF ratio assay on the ThermoFisher B·R·A·H·M·S KRYPTOR platform, yet its clinical uptake remains limited. In this study, we evaluated the analytical precision of the sFlt-1 and PlGF assays, and particularly the impact of PlGF imprecision on sFlt-1/PlGF ratio interpretation and its clinical reliability in preeclampsia risk assessment. This study presents our practical experience with the aim to optimize laboratory practices and facilitate the clinical implementation of the sFlt-1/PlGF testing. Methods sFlt-1 and PlGF were measured on the KRYPTOR instrument using a homogeneous sandwich fluoroimmunoassay. Between-day precision was assessed using three levels of commercial QC materials, and analyzed over a three-month span. Patient-based QC pools were measured for PlGF once perday for 9 non-consecutive days and the results were compared to those of the commercial QC materials. 180 samples obtained from 161 hospitalized pregnant women were analyzed to assess the relationship between PlGF levels and the sFlt-1/PlGF ratio. Results The sFlt-1 assay demonstrated good precision (CV ∼3.0%) across all QC levels, while the PlGF assay exhibited higher imprecision as compared to the manufacturer’s claims, particularly at low QC levels (CV 7.7%-11.3%). Long-term QC monitoring revealed a downward drift in PlGF values, with improved stability after reagent lot changes. Patient-based QC pools showed similar swings and patterns compared to the QC materials during the same 9-day time frame. Importantly, despite higher imprecision at lower PlGF levels (23.1-34.7 pg/mL), the clinical interpretation of the sFlt-1/PlGF ratio remained robust, as low PlGF consistently correlated with ratios well above the critical cut-off of 40. Conclusion Despite the suboptimal precision observed at low QC levels and potential drifts in PlGF results, the sFlt-1/PlGF ratio remains a reliable tool for preeclampsia risk assessment. Our study highlights the need for critical evaluation of analytical performance beyond FDA approval, and the importance of assessing the potential impact of assay imprecision on patient care for individual biomarkers.