Peters Anna L, Vlaar Alexander P J, van Bruggen Robin, de Korte Dirk, Meijers Joost C M, Nieuwland Rienk, Juffermans Nicole P
Laboratory of Experimental Intensive Care and Anesthesia, Amsterdam, The Netherlands.
Department of Intensive Care, Amsterdam, The Netherlands.
Transfusion. 2018 Jun;58(6):1486-1493. doi: 10.1111/trf.14607. Epub 2018 Mar 25.
Red blood cell (RBC) transfusion has been related to thromboembolic events. Microvesicles in the RBC product may support coagulation because they have procoagulant effects in vitro. We investigated whether transfusion of RBCs containing extracellular vesicles promotes coagulation in human recipients. As transfusion is mostly administered to ill patients, we used a model of endotoxemia.
Eighteen healthy volunteers were randomized to receive either saline or fresh (2 days stored) or stored autologous (35 days stored) RBC transfusion (Dutch Trial Register: NTR4455). Two hours after infusion of lipopolysaccharide (LPS, from Escherichia coli, 2 ng/kg body weight), subjects received either saline or fresh or stored RBCs. Blood was sampled every 2 hours up to 8 hours after LPS infusion. Vesicles were measured with a flow cytometer (A50-Micro, Apogee Flow Systems).
LPS resulted in increased thrombin generation compared to baseline. During storage, the total number of extracellular vesicles increased from 1.4 × 10 /mL (interquartile range [IQR], 8.3 × 10 -1.9 × 10 /mL) in the fresh product to 1.7 × 10 /mL (IQR, 7.9 × 10 -2.3 × 10 /mL; p < 0.01) in the stored product (p < 0.001). Vesicles appeared to be mostly RBC derived.
After transfusion, extracellular vesicles from stored RBC products, but not from fresh products, could be detected in the circulation of healthy volunteers. However, infusion of stored RBC extracellular vesicles did not augment thrombin generation compared to endotoxemic controls. Also, levels of d-dimer and thrombin-antithrombin complex were unaffected. In conclusion, transfusion of autologous RBCs containing high levels of extracellular vesicles does not enhance coagulation in human volunteers with endotoxemia.
红细胞（RBC）输血与血栓栓塞事件有关。红细胞制品中的微泡可能会促进凝血，因为它们在体外具有促凝作用。我们研究了输注含有细胞外囊泡的红细胞是否会促进人类受血者的凝血。由于输血大多用于患病患者，我们使用了内毒素血症模型。
18名健康志愿者被随机分为接受生理盐水、新鲜（储存2天）或储存自体（储存35天）红细胞输血组（荷兰试验注册：NTR4455）。在输注脂多糖（LPS，来自大肠杆菌，2 ng/kg体重）2小时后，受试者接受生理盐水、新鲜或储存的红细胞。在输注LPS后长达8小时内，每2小时采集一次血液样本。使用流式细胞仪（A50-Micro，Apogee Flow Systems）测量囊泡。
与基线相比，LPS导致凝血酶生成增加。在储存过程中，新鲜制品中细胞外囊泡的总数从1.4×10⁶/mL（四分位间距[IQR]，8.3×10⁵ - 1.9×10⁶/mL）增加到储存制品中的1.7×10⁶/mL（IQR，7.9×10⁵ - 2.3×10⁶/mL；p < 0.01）（p < 0.001）。囊泡似乎大多源自红细胞。
输血后，在健康志愿者的循环系统中可检测到储存红细胞制品中的细胞外囊泡，但新鲜制品中的未检测到。然而，与内毒素血症对照组相比，输注储存红细胞的细胞外囊泡并未增加凝血酶生成。此外，D-二聚体和凝血酶-抗凝血酶复合物水平未受影响。总之，输注含有高水平细胞外囊泡的自体红细胞不会增强内毒素血症人类志愿者的凝血功能。
