Department of Clinical Sciences and Advanced Medicine, University of Pennsylvania School of Veterinary Medicine, Philadelphia, Pennsylvania, USA.
Department of Pathology and Cell Biology, Columbia University Irving Medical Center - New York Presbyterian Hospital, New York, New York, USA.
Transfusion. 2021 Dec;61(12):3309-3319. doi: 10.1111/trf.16690. Epub 2021 Oct 11.
Transfusion of red blood cells (RBCs) stored for longer durations induces hemolysis and inflammatory cytokine production in murine and canine models. Despite immune system activation by stored RBCs, human randomized trials suggest that fresher RBC transfusions do not improve clinical outcomes. We hypothesized that underlying recipient hemolysis may affect cytokine responses to older RBC transfusions.
C57BL/6 mouse cohorts were infused with anti-TER119 antibody to induce hemolysis, rabbit anti-platelet antiserum to induce immune thrombocytopenia (ITP), or appropriate control antibodies. Two days later, mice were transfused with fresh or stored RBCs. Furthermore, in a prospective, randomized, blinded trial, 38 client-owned dogs with primary autoimmune hemolytic anemia (AIHA) and two dogs with ITP, requiring RBC transfusion, were enrolled and randomized to receive fresh (≤7 days) or old (≥21 days) stored RBC transfusions. Monocyte chemoattractant protein (MCP)-1 levels were assessed at defined times after transfusion.
Prior immune-mediated hemolysis blunted the MCP-1 response to stored RBC transfusion in mice (361 ± 111 pg/ml vs. 6836 ± 1528 pg/ml in mice with immune hemolysis vs. ITP, respectively; mean ± SD; p < .0001). Although hemolysis markers increased after transfusion of older RBCs, the cytokine response was also muted in dogs with AIHA. No differences in morbidity or mortality were evident comparing dogs randomized to fresh or old RBCs.
These data suggest that underlying hemolysis blunts inflammatory responses to old RBC transfusions. The canine data support randomized trial results suggesting a lack of clinical benefit with fresh RBC transfusions in subjects with underlying, baseline hemolysis.
在鼠类和犬类模型中，输注保存时间较长的红细胞（RBC）会引起溶血和炎症细胞因子的产生。尽管储存的 RBC 会激活免疫系统，但人类随机试验表明，输注更新鲜的 RBC 并不能改善临床结局。我们假设潜在的受体溶血可能会影响对较陈旧 RBC 输注的细胞因子反应。
C57BL/6 小鼠队列接受抗 TER119 抗体输注以诱导溶血，兔抗血小板抗血清以诱导免疫性血小板减少症（ITP），或给予适当的对照抗体。两天后，将新鲜或储存的 RBC 输注到小鼠体内。此外，在一项前瞻性、随机、盲法试验中，纳入了 38 例患有原发性自身免疫性溶血性贫血（AIHA）的患犬和 2 例患有 ITP 需接受 RBC 输注的犬，并将其随机分为输注新鲜（≤7 天）或陈旧（≥21 天）储存 RBC。在输血后规定的时间评估单核细胞趋化蛋白-1（MCP-1）水平。
先前的免疫介导性溶血使储存 RBC 输注后的 MCP-1 反应减弱（361±111pg/ml 与免疫性溶血与 ITP 的小鼠分别为 6836±1528pg/ml；均数±SD；p<0.0001）。尽管在输注陈旧 RBC 后溶血标志物增加，但 AIHA 犬的细胞因子反应也减弱。在比较随机分配至输注新鲜或陈旧 RBC 的犬时，未发现发病率或死亡率有差异。
这些数据表明，潜在的溶血会使陈旧 RBC 输注的炎症反应减弱。犬类数据支持随机试验结果，即在存在潜在的、基线性溶血的情况下，输注新鲜 RBC 并无临床获益。
