A review and opinion piece published in The Lancet and led by UCL (University College London) and UCLH researchers discusses the possibility that blood transfusions may inadvertently transmit harmful brain proteins, and whether additional safety measures are warranted as a precaution whilst further research is conducted to better understand these potential risks.
Professor John Collinge said: "Blood transfusions are important and save many lives. However, to ensure that they are as safe as they can possibly be, it's important that we thoroughly investigate any potential risks."
Understanding the potential risks and the evidence behind it
The authors consider the evidence for transmission of amyloid-beta, a protein associated with two diseases: Alzheimer's disease, a type of dementia, and cerebral amyloid angiopathy (CAA), which causes brain haemorrhages (strokes caused by bleeding).
Professor Collinge and colleagues review the evidence available on whether amyloid-beta pathology could potentially be transmitted through blood transfusions. The researchers point to a large Scandinavian epidemiological study, published in 2023*, which found that recipients of blood from donors who later developed multiple brain bleeds (a marker of CAA) had a higher risk of brain bleeds themselves. While these findings do not prove causation, the authors of the new Lancet article say the findings raise questions about the possible transmission of amyloid-beta and CAA through blood transfusion.
The reason for considering this possibility is that the amyloid-beta has already been acquired as an inadvertent consequence of historical medical treatments. Iatrogenic, or medically acquired, CAA was first described in living patients by a team at UCL**; these patients developed brain bleeds caused by CAA at an unusually young age, having had childhood procedures using transplants of cadaveric dura mater (the tough protective tissue that surrounds the brain and spinal cord) three or four decades earlier. Cases of iatrogenic CAA have now been reported by centres all over the world.
In 2024, Professor Collinge and colleagues published a paper*** describing five patients with acquired (iatrogenic) Alzheimer's disease, which developed decades after childhood treatment with a type of human growth hormone extracted from the glands of deceased individuals (cadaveric pituitary-derived human growth hormone, or c-hGH).
These patients had developed dementia symptoms at an unusually young age, having been treated with c-hGH three or four decades earlier. Earlier this year, the researchers published a paper**** describing another patient with iatrogenic Alzheimer's disease, with early onset dementia following childhood c-hGH treatment, this time with unequivocal autopsy confirmation of Alzheimer's disease.
Cases of iatrogenic CAA and iatrogenic Alzheimer's disease show that, in rare circumstances, amyloid-beta has been transmitted via these discontinued historical medical treatments (in the UK, use of cadaveric dura was stopped in 1992, c-hGH in 1985).
However, the potential risks from contemporary medical procedures have not yet been fully evaluated, in part because of significant technological challenges in developing good tests for amyloid-beta infectivity.
Lessons learned from the Infected Blood Inquiry
In the new paper, the scientists discuss the UK Infected Blood Inquiry report, published in 2024; this investigated how thousands of people in the UK were infected with HIV and hepatitis C through contaminated blood and blood products, and concluded that the infections and resulting harm were largely avoidable.
The inquiry noted how the UK was much more effective in handling the risk of variant Creutzfeldt-Jakob disease (CJD), another disease caused by harmful proteins (prions), by acting quickly and pre-emptively to filter out white blood cells in donated blood to reduce risk.
This action was taken when the risk was only theoretical, based on the principle that "no evidence of harm is not evidence of no harm", in contrast to the slower responses to risks associated with HIV and hepatitis C, where action was not taken until scientists had clearer evidence.
Professor Collinge concluded: "The Infected Blood Inquiry provides a cautionary tale in waiting for absolute certainty before making decisions on patient safety. We also think it's important to be open and transparent about possible risks of amyloid-beta transmission, so that we can proactively mitigate any potential risk to patients."
*Evidence that brain bleeds might be transmissible by blood transfusion (2023) https://jamanetwork.com/journals/jama/fullarticle/2809417
** https://www.ucl.ac.uk/brain-sciences/news/2019/feb/cerebral-amyloid-angiopathy-caa-may-be-caused-prions
*** https://www.ucl.ac.uk/news/2024/jan/alzheimers-disease-acquired-historic-medical-treatments
**** https://jamanetwork.com/journals/jamaneurology/fullarticle/2847009
