Performance Evaluation of the Sysmex 'RBC Defect Workflow Optimisation' Flag for the Detection of Haemoglobinopathies...

Haemoglobinopathies are among the most common inherited disorders worldwide. Early detection of heterozygous carriers remains essential for appropriate diagnosis and counselling. The Sysmex 'RBC Defect Workflow Optimisation' (RWO) flag is a recently introduced automated tool designed to identify red cell abnormalities suggestive of heterozygous haemoglobinopathies (HGB HTZ), sickle cell disease (SCD), and iron deficiency anaemia (IDA). This study evaluated the diagnostic performance of the RWO flag in routine practice.

Over 6 months (March-August 2025), 405 samples flagged by RWO (HGB HTZ, SCD, IDA) were prospectively evaluated, and positive predictive values (PPVs) were calculated. In addition, a retrospective analysis of the RWO HGB HTZ, SCD flag was performed on 122 consecutive haemoglobin analyses to assess diagnostic accuracy metrics. Finally, the HGB HTZ β-thalassaemia flag was compared with an external discriminant index, %MicroRBC/%HypoHe ratio (cut-off of 3.7).

Prospectively, the Sysmex RWO flag demonstrated PPVs of 81.9% for HGB HTZ, 68.7% for IDA, and 100% for SCD (n = 1). For IDA, PPV increased when analysis was restricted to different exclusion criteria. Retrospective sensitivity for HGB HTZ and SCD was only 25.0%, further clarified in this study. Diagnostic performance of the HGB HTZ β-thalassaemia flag was broadly comparable to that of the %MicroRBC/%HypoHe ratio.

The Sysmex RWO flag represents a feasible and effective screening tool for heterozygous haemoglobinopathies and sickle cell disease in routine clinical practice. Despite modest retrospective sensitivity, its high predictive value and workflow efficiency support its use as a trigger for targeted haemoglobin analysis in everyday laboratory diagnostics.