Quantitative analysis of beta-2 transferrin via Hydrasys 2 ^Scan Focusing (Sebia) for the detection of CSF leaks – feasibility and measurement uncertainty

Abstract Objectives A CSF leak is a serious medical disorder that potentially leads to life-threatening conditions like meningitis. One analytical method to detect such CSF leaks is the measurement of beta-2 transferrin in human bodily fluids via Hydrasys 2 Scan Focusing (Sebia). While the default mode of beta-2 transferrin analysis is qualitative, a quantitative approach based on densitometric scanning is also feasible. For the later, the manufacturer provides an “aid for interpretation”, but no information on precision or reliability of the quantitative methodology is given. Methods In this study, we provide a first estimate of the precision of the quantitative beta-2 transferrin measurement and assess its impact on the applied cut-off values. To do so, we performed several serial measurements of various bodily fluids with the Hydrasys 2 Scan Focusing (Sebia), applied the quantitative approach and calculated the corresponding coefficients of variation (CVs) for the relevant transferrin fractions and the resulting asialo/disialo transferrin ratio (a/d-ratio). Results The obtained CVs ranged from moderate 6.4 % to concerning 25.2 % for the a/d-ratio, resulting in critical distance estimates of up to 0.7 around the proposed cut-off value of 1. The CVs for the asialo- and disialo-transferrin fractions increased rapidly for fraction areas below approximately 5 %. Conclusions Due to its potentially high CVs and subsequent uncertainty in defining reliable positive or negative results, the quantitative densitometric measurement of beta-2 transferrin should be interpreted with utmost caution and laboratories are advised to conduct their own validation when using this method.