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

Abstract

False positive (FP) viral marker results in blood donors continue to pose many challenges. Informing donors of FP results and subsequent deferral can result in stress and anxiety for donors and additional complexity and workload for blood services. Donor management strategies need to balance the requirement to minimise donor anxiety and inconvenience while maintaining sufficiency of supply. Decisions about how and when to inform donors of FP results and determine deferral periods can be difficult as FP results, while often transitory, can take up to several years to resolve. Additional complexities include the interpretation of indeterminate serological confirmatory testing without detectable viral RNA or non-discriminated NAT results with concomitant anti-HBc reactivity - both may be due to FP results, but the former may also represent past infection and the later may represent occult hepatitis B infection. In this review we discuss strategies to minimise indeterminate serological confirmatory results, possible donor deferral policies and the impact on donors when notified of FP results. We also provide some new data from Australia that address the challenge of interpreting non-discriminated NAT results with concomitant anti-HBc reactivity. Ultimately, the challenge is for each blood service to develop appropriate strategies for donor management, taking into account local information and requirements.

Excluding Occult Hepatitis B Infection before Assigning False-Positive Status to Non-Repeatable NAT Reactivity: Concerning Stolz et al. “Safe-Testing Algorithm for Individual-Donation Nucleic Acid Testing: 10 Years of Experience in a Low-Prevalence Country” [Transfus Med Hemother. 2019 Apr;46(2):104–10]

“…As reviewed by Kiely et al [2], there are at least two lines of evidence to support this. Firstly, the detection rate of anti-HBc is significantly higher in NRR/NDR donors compared to NAT non-reactive donors, for example, 12.2% in Ultrio NRR donors versus 6.0% in non-reactive donors (South Africa) [4], 13% Ultrio NDR and 57% Ultrio Plus NDR versus 6.8% in random donors (New Zealand) [3], and 7.6% Ultrio Plus NDR versus approximately 2.2% in non-reactive donors (Australia) [2]. Secondly, a proportion of these anti-HBc-positive donors are confirmed as OBI when retested using an alternative high-sensitivity NAT assay, or with additional replicates on the same assay [3, 5].…”

“…It has been well documented that a subset of donors with non-repeatable and/or non-discriminated reactivity (NDR) on ID-NAT, including in low-prevalence countries, represent possible OBI [2-4]. As reviewed by Kiely et al [2], there are at least two lines of evidence to support this.…”

“…It has been well documented that a subset of donors with non-repeatable and/or non-discriminated reactivity (NDR) on ID-NAT, including in low-prevalence countries, represent possible OBI [2-4]. As reviewed by Kiely et al [2], there are at least two lines of evidence to support this. Firstly, the detection rate of anti-HBc is significantly higher in NRR/NDR donors compared to NAT non-reactive donors, for example, 12.2% in Ultrio NRR donors versus 6.0% in non-reactive donors (South Africa) [4], 13% Ultrio NDR and 57% Ultrio Plus NDR versus 6.8% in random donors (New Zealand) [3], and 7.6% Ultrio Plus NDR versus approximately 2.2% in non-reactive donors (Australia) [2].…”

“…Additionally, as these donations were not tested for anti-HBc and therefore the prevalence is unknown among this group, it is unclear how an accurate assessment of OBI risk from NRR donations could be made. The algorithm presented by Stolz et al [1] would not be appropriate in Australia because of the risk of TT-HBV, despite a similarly low anti-HBc prevalence of approximately 2% among Australian and Swiss blood donors [2, 10]. We believe that anti-HBc testing for NAT NRR donations is an efficient and cost-effective way to help reduce the associated risk of OBI, and anti-HBc non-reactivity should be a minimum requirement prior to release of fresh blood components associated with NAT NRR results.…”

False‐positive viral marker results in blood donors and their unintended consequences: P. Kiely, V.C. Hoad, E.M. Wood

“…Kiely et al [1] elegantly describe the unintended consequences of false-positive infectious disease markers in blood donors for stakeholders.…”