In children with sickle cell disease (SCD), splenectomy is immediately beneficial for acute sequestration crises and hypersplenism (ASSC/HyS) but portends a long-term risk of asplenia-related complications. We retrieved peripheral and splenic red blood cells (RBCs) from 17 SCD children/teenagers undergoing partial splenectomy for ASSC/HyS, 12 adult subjects without RBC-related disease undergoing splenectomy (controls), five human spleens perfused ex vivo with Hb_SS- and Hb_AA-RBC, and quantified abnormal RBC by microscopy, spleen-mimetic RBC filtration, and adhesion assays. Spleens were analyzed by immunohistochemistry and transmission electron microscopy (TEM). In circulating blood of SCD and control subjects, dysmorphic (elongated/spherocytic) RBCs were <2%, while proportions of pocked-RBC were 4.3-fold higher in SCD children than in controls. Compared to controls, splenic RBCs were more frequently dysmorphic (29.3% vs. 0.4%), stiffer (42.2% vs. 12.4%), and adherent (206 vs. 22 adherent RBC/area) in SCD subjects. By TEM, both polymer-containing and homogenous RBC contributed to spleen congestion, resulting in 3.8-fold higher RBC population density in SCD spleens than in control spleens, predominantly in the cords. Perfused spleens with normal function displayed similar congestion and retention of dysmorphic RBC as SCD spleens. The population density of active macrophages was similar in SCD and control spleens, with a relative deficit in phagocytosis of polymer-containing RBC. Despite the existence of hyposplenism, splenectomy in SCD children removes an organ that still efficiently filters out potentially pathogenic altered RBC. Innovative treatments allowing fine-tuned reduction of RBC retention would alleviate spleen congestion, the major pathogenic process in ASSC/HyS, while preserving spleen protective functions for the future.

中文翻译：

---

尽管镰状细胞病患儿的脾功能障碍，但病原性红细胞的清除仍能维持


在患有镰状细胞病 （SCD） 的儿童中，脾切除术对急性隔离危象和脾功能亢进 （ASSC/HyS） 立即有益，但预示着无脾相关并发症的长期风险。我们从 17 例接受部分脾切除术的 SCD 儿童/青少年中检索了外周红细胞和脾红细胞 （RBC），12 例没有 RBC 相关疾病的成年受试者接受了脾切除术 （对照），5 个人脾脏离体灌注了 Hb_SS-和 Hb_AA-RBC，并通过显微镜、脾模拟红细胞滤过和粘附试验量化了异常红细胞。通过免疫组化和透射电子显微镜 （TEM） 分析脾脏。在 SCD 和对照受试者的循环血液中，畸形（细长/球形红细胞）红细胞为 <2%，而 SCD 儿童的麻点红细胞比例比对照组高 4.3 倍。与对照组相比，SCD 受试者的脾脏红细胞更频繁地变形 （29.3% vs. 0.4%） 、更坚硬 （42.2% vs. 12.4%） 和粘附性 （206 vs. 22 个粘附红细胞/面积）。通过 TEM，含聚合物和均质红细胞都会导致脾脏充血，导致 SCD 脾脏的 RBC 种群密度比对照脾高 3.8 倍，主要是在脊髓中。功能正常的灌注脾与 SCD 脾表现出相似的充血和畸形红细胞潴留。SCD 和对照脾脏中活性巨噬细胞的种群密度相似，含聚合物红细胞的吞噬作用相对不足。尽管存在脾功能减退症，但 SCD 儿童的脾切除术会切除一个器官，该器官仍然可以有效过滤掉可能致病性改变的红细胞。 允许微调减少红细胞滞留的创新疗法将缓解脾脏充血，这是 ASSC/HyS 的主要致病过程，同时保留脾脏的保护功能以备将来使用。