A scoping review of grey zone use for transfusion-transmitted infection screening among blood donors

Screening for transfusion-transmitted infections (TTIs) among blood donors is done using qualitative screening assays. Screening values that are close to cut-off values lie in the uncertainty zone, often denoted as the grey zone (GZ). This scoping review evaluated studies that have assessed the GZ reactivity by supplementary tests and its consequences.

Studies evaluating GZ or indeterminate or inconclusive results for TTI screening among blood donors were searched using PubMed, Scopus and Google Scholar databases. Full text for the included articles was reviewed and analysed for study characteristics, TTI screening and GZ reactivity. This included GZ range, repeat or confirmatory testing, follow-up of such donors, effect on donor deferral and collected blood units.

A total of 16 studies were included. GZ was evaluated for human immunodeficiency virus (HIV), hepatitis B virus (HBV), hepatitis C virus (HCV), syphilis, Chagas disease and human T-lymphotropic virus (HTLV). GZ values ranged from 0.5 to 1.2 times sample to cut-off (S/CO) values in different studies. The protocol for repeat/confirmatory testing was also heterogeneous. During repeat testing, many donors were found to be reactive or repeat GZ reactive. In confirmatory assays, the majority were negative, but many were positive or indeterminate. The protocol for donor follow-up and deferral protocols also varied significantly among different centres.

GZ evaluation showed a small yet significant risk of TTI from samples identified within the GZ range. There is further need for follow-up studies to establish TTI risk from repeat reactive or indeterminate samples, which will help in establishing uniform protocols for GZ samples.