Intracerebral Hemorrhage Among Blood Donors and Their Transfusion Recipients

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Intracerebral Hemorrhage Among Blood Donors and Their Transfusion Recipients

Jingcheng Zhao, MD, PhD¹; Klaus Rostgaard, MSc^2,3; Elsa Lauwers, PhD⁴; et al Torsten Dahlén, MD, PhD^1,5; Sisse Rye Ostrowski, MD, PhD, DMSc^6,7; Christian Erikstrup, MD, PhD^8,9; Ole Birger Pedersen, MD, PhD^7,10; Bart de Strooper, MD, PhD^4,11,12; Robin Lemmens, MD, PhD^4,11,13; Henrik Hjalgrim, MD, PhD, DMSc^2,3,7,14; Gustaf Edgren, MD, PhD^1,15

Author Affiliations

JAMA. 2023;330(10):941-950. doi:10.1001/jama.2023.14445

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Editorial

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• Editorial
  Blood Transfusion and Brain Amyloidosis
  Steven M. Greenberg, MD, PhD
  JAMA

Full Text

Key Points

Question  Is there an association between the occurrence of spontaneous intracerebral hemorrhage among blood donors and the risk of spontaneous intracerebral hemorrhage in patients who receive a transfusion with their blood?

Findings  In this exploratory retrospective cohort study, which included 759 858 patients in Sweden and 329 512 patients in Denmark, receiving red blood cell transfusions from donors who later developed multiple spontaneous intracerebral hemorrhages was significantly associated with an increased risk of developing spontaneous intracerebral hemorrhage compared with receiving a transfusion from donors without subsequent intracerebral hemorrhage (hazard ratios, 2.73 and 2.32 in the Swedish and Danish cohorts, respectively).

Meaning  The findings suggest a transfusion-transmissible agent associated with some types of spontaneous intracerebral hemorrhage, but findings may be susceptible to selection bias and residual confounding, and further research is required to understand the potential underlying mechanism.

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.