Transfusion-transmissible agent linked to some types of spontaneous ICH: JAMA

In an exploratory analysis of patients who received RBC (red blood cell) transfusions, the researchers found that patients who underwent transfusion with RBCs from donors who later developed multiple spontaneous ICHs were at an elevated risk of spontaneous ICH. The analysis included 759 858 patients in Sweden and 329 512 patients in Denmark with a median follow-up of 5.8 years and 6.1 years, respectively.

The study findings published in the Journal of the American Medical Association (JAMA) suggest a transfusion-transmissible agent linked with some types of spontaneous ICH. The researchers add that the findings may be susceptible to residual confounding and selection bias and note the need for further research to investigate if transfusion transmission of cerebral amyloid angiopathy might explain this association.

Recent reports have indicated that cerebral amyloid angiopathy (CAA), a common cause of multiple spontaneous ICHs, may be transmissible through parenteral injection of contaminated cadaveric pituitary hormone in humans.

Under the assumption that at least some observed intracerebral haemorrhages are due to underlying CAA, Jingcheng Zhao, Karolinska Institutet, Stockholm, Sweden, and colleagues hypothesized that transfusion transmission of CAA may manifest through an increased risk of spontaneous ICH among transfusion recipients exposed to blood from a donor with spontaneous ICH.

To probe this hypothesis, they examined the association between spontaneous ICH occurrence in blood donors and their recipients using a nationwide cohort in Sweden and a validation in a nationwide cohort in Denmark.

The researchers determined receipt of RCBC transfusions from blood donors who subsequently developed (1) a single spontaneous ICH, (2) multiple spontaneous ICHs, or (3) no spontaneous ICH.

The study led to the following findings:

• Patients who underwent transfusion with RBC units from donors who developed multiple spontaneous ICHs had a significantly higher risk of a single spontaneous ICH themselves, compared with patients receiving transfusions from donors who did not develop spontaneous ICH, in both the Swedish cohort (unadjusted incidence rate [IR], 3.16 versus 1.12 per 1000 person-years; adjusted hazard ratio [HR], 2.73) and the Danish cohort (unadjusted IR, 2.82 versus 1.09 per 1000 person-years; adjusted HR, 2.32).
• No significant difference was found for patients receiving transfusions from donors who developed a single spontaneous ICH in the Swedish cohort (unadjusted IR, 1.35 versus 1.12 per 1000 person-years; adjusted HR, 1.06) nor the Danish cohort (unadjusted IR, 1.36 vs 1.09 per 1000 person-years; adjusted HR, 1.06), nor for ischemic stroke as a negative control outcome.

"The findings indicate a transfusion-transmissible agent associated with some types of spontaneous ICH, but findings may be susceptible to selection bias and residual confounding, and further research is needed to understand the potential underlying mechanism," the researchers concluded.