Worrisome finding or false alarm?
In an accompanying editorial, Steven Greenberg, MD, PhD, with the department of neurology, Harvard Medical School, Boston, said there are “good reasons to treat the possibility of CAA transmission via blood transfusion seriously – and good reasons to remain skeptical, at least for the present.”
“Powerful” arguments in support of the findings include the robust study methodology and the “striking” similarity in results from the two registries, which argues against a chance finding. Another is the negative control with ischemic stroke as the outcome, which argues against unsuspected confounding-causing associations with all types of stroke, Dr. Greenberg noted.
Arguments for remaining “unconvinced” of the association center on the weakness of evidence for a plausible biological mechanism for the finding, he points out. Another is the short-time course of ICHs after blood transfusion, which is “quite challenging to explain,” Dr. Greenberg said. Nearly half of the ICHs among blood recipients occurred within 5 years of transfusion, which is “dramatically” faster than the 30- to 40-year interval reported between neurosurgical exposure to cadaveric tissue and first ICH, he added.
Another related “mechanistic reservation” is the plausibility that a transmissible species of amyloid-beta could travel from blood to brain in sufficient quantities to trigger advanced CAA or Alzheimer disease pathology, he wrote.
He added the current study leaves him “squarely at the corner of anxiety and skepticism.”
With more than 10 million units of blood transfused in the United States each year, even a modest increase in risk for future brain hemorrhages or dementia conferred by “an uncommon – but as of now undetectable – donor trait would represent a substantial public health concern,” Dr. Greenberg wrote.
“From the standpoint of scientific plausibility, however, even this well-conducted analysis is at risk of representing a false alarm,” he cautioned.
Looking ahead, Dr. Greenberg said one clear direction is independent replication, ideally with datasets in which donor and recipient dementia can be reliably ascertained to assess the possibility of Alzheimer’s disease as well as CAA transmissibility.
“The other challenge is for experimental biologists to consider the alternative possibility of transfusion-related acceleration of downstream steps in the CAA-ICH pathway, such as the vessel remodeling by which amyloid beta–laden vessels proceed to rupture and bleed.”
“The current study is not yet a reason for alarm, certainly not a reason to avoid otherwise indicated blood transfusion, but it is a strong call for more scientific digging,” Dr. Greenberg concluded.
The study was funded by grants from the Karolinska Institute, the Swedish Research Council, and Region Stockholm. Dr. Zhao and Dr. Greenberg report no relevant financial relationships.
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