How do I interpret transfusion transmissible infectious disease testing in a low-risk donor population?

Abstract

Background: Blood donors represent a unique population. Pre-donation screening questions, donor self-deferral, and temporary deferral and re-testing of repeat reactive donors result in lower prevalence of infectious disease compared to the general population. Prevalence directly affects the clinical performance of assay systems apart from the analytical sensitivity and specificity of the assay.

Study design and methods: It is important that blood operators understand what situations frequently elicit false reactive and false nonreactive cases, and how to mitigate the effect of these.

Results: False reactive transmissible disease assays are seen more frequently in low-prevalence populations due to a reduced positive predictive value, whereas false nonreactives may be derived from failures in quality control (control failures, temperature and humidity deviations), pathophysiology in the donor, or how specimens are processed and tested (e.g., pooling). Reactive screening results require confirmation testing to differentiate between true infection and false reactive interpretation, and result in either temporary or permanent donor deferral (for false reactive or confirmed screens respectively). Complete validation or verification of laboratory assays can mitigate these donor impacts and help laboratorians understand how assays function in their local environments.

Discussion: Here we describe how blood donor screening assays are characterized prior to use, explore possible contributors to false reactive and nonreactive results, and the importance of tracking and monitoring infectious disease positivity rates. Two case examples: one for serology and one for molecular testing demonstrate how common errors in laboratory testing can be mitigated.

Keywords: laboratory testing; testing in low prevalence populations; transfusion transmittable disease; validation; verification.