Case 5: A Minipool-Negative Donation That Wasn't Negative
A 41-year-old repeat male donor makes his 12th donation - a whole blood collection - at a community blood center. He denies risk factors and his ALT is normal. Results: HBsAg nonreactive (S/CO 0.2), total anti-HBc reactive (S/CO 8.4), anti-HBs reactive at 45 mIU/mL, and minipool HBV DNA nonreactive. Because the minipool NAT was nonreactive, the platelet component was released and transfused 3 days later to a 62-year-old man with AML who is neutropenic and on chemotherapy. Two days after release, individual-donation NAT on the retention sample is reactive, and the discriminatory HBV assay confirms HBV DNA at 45 IU/mL. A red cell unit from the same donation is still in inventory.
1. Interpret the serologic and NAT pattern. What is the diagnosis, and how confident are you?
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The markers only make sense together:
- HBsAg nonreactive - no detectable surface antigen.
- Total anti-HBc reactive - anti-HBc is not produced by vaccination, so this indicates natural infection at some point. It cannot be explained by an HBV vaccine history.
- Anti-HBs reactive at 45 mIU/mL - could be vaccine-derived or infection-derived; it is protective for the donor but does not exclude viremia.
- HBV DNA reactive at 45 IU/mL on individual-donation NAT after a nonreactive minipool.
This is occult hepatitis B infection (OBI): HBsAg-negative with low-level HBV DNA, usually below 200 IU/mL.
The minipool NAT was falsely negative because pooling diluted a viral load sitting near the limit of detection - precisely why some centers test every donation individually. Confirm on a second sample (repeat HBsAg, anti-HBc, and HBV DNA) before permanent deferral, but a reactive anti-HBc with confirmed HBV DNA is not a false positive.
2. What happens to the red cell unit still in inventory, and what must be done about the platelet recipient?
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Red cell unit: quarantine and discard. It came from a donor now shown to be HBV DNA-positive; it is not suitable for transfusion at any price, and there is no 'release with a warning' option.
Platelet recipient: he has already been transfused and is immunocompromised (AML, neutropenic, on chemotherapy) - the highest-risk recipient for transfusion-transmitted HBV.
- Notify the hospital transfusion service and his physician in writing.
- Test him for HBsAg, total anti-HBc, anti-HBs, and HBV DNA at baseline; if negative, repeat at roughly 3 and 6 months.
- His physician should assess for hepatitis (ALT, symptoms) and consider prophylaxis or early antiviral treatment. HBV can be transmitted by components that were HBsAg-negative, so a negative HBsAg alone does not reassure.
- Involve the blood center medical director in the notification, and complete the facility's lookback and deviation documentation. Because release followed a negative minipool result, this is most likely a lookback notification rather than a release error - but say so explicitly in the record.
3. What should be done about the donor and about his previous 11 donations?
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The donor
- Permanently defer him from all future donations, whole blood and apheresis.
- Notify him confidentially, with counseling, that he carries hepatitis B, and refer him to a physician for evaluation of chronic HBV (HBeAg status, quantitative DNA, liver enzymes, imaging). His anti-HBs at 45 mIU/mL and low DNA level suggest a low-risk carrier state, but infectivity to a transfusion recipient is not zero.
- Enter the permanent deferral and the results into the donor record so that a future registration is rejected at the record-review step, not after collection.
Previous donations
- Run a lookback per your center's procedure. His prior donations were HBsAg-negative, anti-HBc-negative, and NAT-nonreactive, which makes transmission unlikely, but the identification of a now-positive repeat donor triggers review of prior collections.
- Notify the consignees and, through them, the recipients, so their physicians can decide about testing.
- Close the loop: document the lookback outcome, and use the case as a validation review of your NAT pooling strategy if the center relies on minipools.