Intracerebral Hemorrhage Among Blood Donors and Their Transfusion Recipients

Abstract

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

Objective: To determine whether spontaneous ICH in blood donors after blood donation is associated with development of spontaneous ICH in transfusion recipients.

Design, setting, and participants: Exploratory retrospective cohort study using nationwide blood bank and health register data from Sweden (main cohort) and Denmark (validation cohort) and including all 1 089 370 patients aged 5 to 80 years recorded to have received a red blood cell transfusion from January 1, 1970 (Sweden), or January 1, 1980 (Denmark), until December 31, 2017.

Exposures: Receipt of red blood cell transfusions from blood donors who subsequently developed (1) a single spontaneous ICH, (2) multiple spontaneous ICHs, or (3) no spontaneous ICH.

Main outcomes and measures: Spontaneous ICH in transfusion recipients; ischemic stroke was a negative control outcome.

Results: A total of 759 858 patients from Sweden (median age, 65 [IQR, 48-73] years; 59% female) and 329 512 from Denmark (median age, 64 [IQR, 50-73] years; 58% female) were included, with a median follow-up of 5.8 (IQR, 1.4-12.5) years and 6.1 (IQR, 1.5-11.6) years, respectively. Patients who underwent transfusion with red blood cell 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 vs 1.12 per 1000 person-years; adjusted hazard ratio [HR], 2.73; 95% CI, 1.72-4.35; P < .001) and the Danish cohort (unadjusted IR, 2.82 vs 1.09 per 1000 person-years; adjusted HR, 2.32; 95% CI, 1.04-5.19; P = .04). 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 vs 1.12 per 1000 person-years; adjusted HR, 1.06; 95% CI, 0.84-1.36; P = .62) nor the Danish cohort (unadjusted IR, 1.36 vs 1.09 per 1000 person-years; adjusted HR, 1.06; 95% CI, 0.70-1.60; P = .73), nor for ischemic stroke as a negative control outcome.

Conclusions and relevance: In an exploratory analysis of patients who received red blood cell transfusions, patients who underwent transfusion with red blood cells from donors who later developed multiple spontaneous ICHs were at significantly increased risk of spontaneous ICH themselves. This may suggest a transfusion-transmissible agent associated with some types of spontaneous ICH, although the findings may be susceptible to selection bias and residual confounding, and further research is needed to investigate if transfusion transmission of cerebral amyloid angiopathy might explain this association.

Figure 1.. Adjusted Hazard Ratios for Development of Spontaneous Intracerebral Hemorrhage (sICH) From the Main and Sensitivity Analyses Using a 180-Day Exposure Assessment Window

^aExcluding hospital episodes with another primary diagnosis. ^bAs a negative control, the exposure is transfusions from blood donors who develop sICH, and the outcome is the first ischemic stroke in patients who underwent transfusion. ^cAs a negative control, the exposure is transfusions from blood donors who develop ischemic stroke, and the outcome is the first ischemic stroke in patients who underwent transfusion. ^dThe exposure is transfusions from blood donors who develop no sICH, single sICH, or single sICH and dementia. The outcome is the first sICH in patients who underwent transfusion.

Figure 2.. Cumulative Incidence of Single Spontaneous Intracerebral Hemorrhage (sICH) Using a 180-Day Exposure Assessment Window (Main Swedish Cohort)

In this analysis only, a matched cohort with 3 controls per exposed patient was used for computational efficiency, which resulted in a lower number of patients at risk than in the complete cohort. Median follow-up was 8.3 (IQR, 1.8-19.4) years for transfusion recipients from blood donors with multiple sICHs, 7.1 (IQR, 1.8-16.3) years for transfusion recipients from blood donors with a single sICH, and 7.6 (IQR, 2.0-16.8) years for transfusion recipients from blood donors with no sICH.