False positive viral marker results in blood donors and their unintended consequences

Universal donor screening for the major transfusion relevant viruses, hepatitis B virus (HBV), human immunodeficiency virus types 1 and 2 (HIV-1/2) and hepatitis C virus (HCV) has contributed to the current very low risk of transmitting infectious diseases by transfusion. While contemporary blood donor screening assays have excellent specificity, defined as the probability of giving a negative result for donors without previous exposure to the virus in question, 100% specificity remains elusive. Therefore an inevitable, albeit unintended, consequence of blood donor serological screening is the generation of false positive results.

Just over 10 years ago, we reviewed the management of donors with false positive serological screening test results. Taking into account diagnostic and therapeutic developments since that time, the purpose of this review is, firstly, to review the potential causes of serological false positive results and strategies that can help to distinguish between false and ‘true’ positive serological results; secondly, to discuss some of the interpretative difficulties associated with nucleic acid testing (NAT); and thirdly, to describe the unintended consequences of false positive results for both blood services and blood donors for whom being informed of false positive results can have adverse psychological effects. Finally, we also discuss the challenges posed by atypical serology or NAT results for blood services and health care providers. In addition to summarizing and discussing information from a literature review, we have provided some examples and modelling based on data for Australian blood donors, particularly related to notifying and deferring donors with false positive serology results and determining when NAT reactivity may represent occult hepatitis B virus infection.

In this review, we have then summarized the potential causes of false positive serological results and how they may currently be distinguished from true positive results. We have highlighted the importance of recognizing that donors can be adversely affected when notified of false positive results due to stress and anxiety. However, donors with screening false positive results or NAT positive results without concomitant serological reactivity should be reassured that their results do not indicate current or past infection with the virus in question. NAT positive results with concomitant anti-HBc reactivity may represent an occult HBV infection and therefore additional testing and donor follow-up is required.

We suggest that ultimately, each blood service should develop its own strategies for the notification and deferral of donors with false positive results, taking into account the variable time taken for false positive results to resolve, the frequency of false positive results in its own donor population and the impact on sufficiency of supply due to the potential loss of donors and donations.

Finally, as donor screening technologies evolve and more jurisdictions extend screening to include a number of emerging infectious disease pathogens, we encourage blood services to analyse the performance of their assays, particularly the rate of false positive results, and publish their findings. These suggestions will provide valuable information which could be used as a basis for ongoing reviews and inform the development of improved donor notification and deferral strategies.

Vox Sanguinis 2018 Jul 4

False positive viral marker results in blood donors and their unintended consequences

Philip Kiely, Veronica C. Hoad, Erica M. Wood.