Department of Medicine, Solna, Clinical Epidemiology Division, Karolinska Institutet, Stockholm, Sweden.
Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark.
JAMA. 2023 Sep 12;330(10):941-950. doi: 10.1001/jama.2023.14445.
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.
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.
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.
Spontaneous ICH in transfusion recipients; ischemic stroke was a negative control outcome.
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.
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.
最近有报告表明，脑淀粉样血管病是导致多发自发性脑出血（ICH）的常见原因，在人类中，通过注射污染的尸体垂体激素进行的胃肠道外给药可能具有传染性。
确定献血者在献血后发生自发性脑出血是否与输血受血者发生自发性脑出血有关。
设计、地点和参与者：这是一项使用来自瑞典（主要队列）和丹麦（验证队列）的全国性血库和健康登记数据进行的探索性回顾性队列研究，包括从 1970 年 1 月 1 日（瑞典）或 1980 年 1 月 1 日（丹麦）开始接受过红细胞输血的所有年龄在 5 至 80 岁之间的 1089370 例患者，直至 2017 年 12 月 31 日。
接受随后（1）单发自发性 ICH、（2）多发自发性 ICH 或（3）无自发性 ICH 的献血者的红细胞输血。
输血受血者的自发性 ICH；缺血性脑卒中为阴性对照结果。
共纳入了来自瑞典的 759858 例患者（中位年龄 65[IQR，48-73]岁；59%为女性）和来自丹麦的 329512 例患者（中位年龄 64[IQR，50-73]岁；58%为女性），中位随访时间分别为 5.8（IQR，1.4-12.5）年和 6.1（IQR，1.5-11.6）年。与接受未发生自发性 ICH 的供者输血的患者相比，接受来自多发自发性 ICH 供者输血的患者自身发生单发自发性 ICH 的风险显著更高，这在瑞典队列中（未校正发病率[IR]，3.16 比 1.12/1000人年；校正后的危险比[HR]，2.73；95%CI，1.72-4.35；P<0.001）和丹麦队列中（未校正 IR，2.82 比 1.09/1000人年；校正 HR，2.32；95%CI，1.04-5.19；P=0.04）均如此。在瑞典队列中，接受来自单发自发性 ICH 供者输血的患者未发现明显差异（未校正 IR，1.35 比 1.12/1000人年；校正 HR，1.06；95%CI，0.84-1.36；P=0.62），在丹麦队列中也未发现差异（未校正 IR，1.36 比 1.09/1000人年；校正 HR，1.06；95%CI，0.70-1.60；P=0.73），缺血性脑卒中作为阴性对照结果也未发现差异。
在对接受红细胞输血的患者进行的一项探索性分析中，接受来自后来发生多发自发性 ICH 的供者的输血的患者自身发生自发性 ICH 的风险显著增加。这可能表明存在与某些类型自发性 ICH 相关的输血传播性病原体，尽管这些发现可能易受选择偏倚和残余混杂因素的影响，需要进一步研究以调查脑淀粉样血管病的输血传播是否可以解释这种关联。
