U1163, Laboratory of Cellular and Molecular Mechanisms of Hematological Disorders and Therapeutic Implications, INSERM, Université de Paris, Paris, France.
Laboratoire d'Excellence GR-Ex, Paris, France.
Blood. 2021 Apr 29;137(17):2285-2298. doi: 10.1182/blood.2020008563.
Permanent availability of red blood cells (RBCs) for transfusion depends on refrigerated storage, during which morphologically altered RBCs accumulate. Among these, a subpopulation of small RBCs, comprising type III echinocytes, spheroechinocytes, and spherocytes and defined as storage-induced microerythrocytes (SMEs), could be rapidly cleared from circulation posttransfusion. We quantified the proportion of SMEs in RBC concentrates from healthy human volunteers and assessed correlation with transfusion recovery, investigated the fate of SMEs upon perfusion through human spleen ex vivo, and explored where and how SMEs are cleared in a mouse model of blood storage and transfusion. In healthy human volunteers, high proportion of SMEs in long-stored RBC concentrates correlated with poor transfusion recovery. When perfused through human spleen, 15% and 61% of long-stored RBCs and SMEs were cleared in 70 minutes, respectively. High initial proportion of SMEs also correlated with high retention of RBCs by perfused human spleen. In the mouse model, SMEs accumulated during storage. Transfusion of long-stored RBCs resulted in reduced posttransfusion recovery, mostly due to SME clearance. After transfusion in mice, long-stored RBCs accumulated predominantly in spleen and were ingested mainly by splenic and hepatic macrophages. In macrophage-depleted mice, splenic accumulation and SME clearance were delayed, and transfusion recovery was improved. In healthy hosts, SMEs were cleared predominantly by macrophages in spleen and liver. When this well-demarcated subpopulation of altered RBCs was abundant in RBC concentrates, transfusion recovery was diminished. SME quantification has the potential to improve blood product quality assessment. This trial was registered at www.clinicaltrials.gov as #NCT02889133.
红细胞（RBC）的永久供应取决于冷藏储存，在此过程中会积累形态发生改变的 RBC。其中，一小部分 RBC 会变成小细胞，包括 III 型棘形红细胞、球形棘形红细胞和球形红细胞，被定义为储存诱导的微红细胞（SMEs），在输血后可迅速从循环中清除。我们定量了来自健康志愿者的 RBC 浓缩物中的 SMEs 比例，并评估了其与输血恢复的相关性，研究了 SMEs 在体外人类脾脏灌注时的命运，探索了 SMEs 在血库和输血的小鼠模型中被清除的位置和方式。在健康志愿者中，长期储存的 RBC 浓缩物中 SMEs 的高比例与输血恢复不良相关。当通过人类脾脏灌注时，分别有 15%和 61%的长期储存 RBC 和 SMEs 在 70 分钟内被清除。初始 SMEs 比例较高也与灌注的人类脾脏对 RBC 的高保留相关。在小鼠模型中，SMEs 在储存过程中积累。输注长期储存的 RBC 会导致输血后恢复减少，主要是由于 SMEs 的清除。在小鼠输血后，长期储存的 RBC 主要积聚在脾脏中，主要被脾脏和肝脏巨噬细胞吞噬。在巨噬细胞耗竭的小鼠中，脾脏积聚和 SME 清除延迟，输血恢复得到改善。在健康宿主中，SMEs 主要被脾脏和肝脏中的巨噬细胞清除。当 RBC 浓缩物中富含这种形态明确的改变 RBC 亚群时，输血恢复会降低。SME 定量有可能改善血液制品质量评估。该试验在 www.clinicaltrials.gov 上注册为 #NCT02889133。
