Andersson Linnea I, Sandgren Per, Sjöström Dick J, Mohlin Camilla, Hägerström Kim, Tjernberg Ivar, Mollnes Tom Eirik, Nilsson Per H
Department of Chemistry and Biomedicine, Linnaeus University, Kalmar, Sweden.
Center for Hematology and Regenerative Medicine (HERM), Karolinska Institutet, Stockholm, Sweden.
Platelets. 2025 Dec;36(1):2513298. doi: 10.1080/09537104.2025.2513298. Epub 2025 Jun 25.
Platelet storage is associated with storage lesions, including platelet morphological changes and a gradual functional loss. We investigated the impact of complement C3 inhibition on complement activation and platelet storage lesions in clinical platelet concentrates. Platelet concentrates ( = 8) were prepared in PAS-E and stored for seven days at 22°C. Each concentrate was split in two, with the C3 inhibitor compstatin Cp40 added to one part, and the other serving as the control. Complement and platelet activation markers, platelet function, and metabolic measures were analyzed every second day. Cp40 significantly reduced C3bc and sC5b-9 levels, but not C4c, indicating inhibition of complement activation at the level of C3. However, Cp40 did not affect platelet-specific or metabolic measures. Surface expression of CD62P and NAP-2 release increased significantly over the storage time, whereas CD63 expression and PF4 and TSP-1 release remained stable. Platelet responses to TRAP-6 mediated PAR-1 activation and U46619 mediated TXAR stimulation decreased over time, recorded as CD62P and CD63 expression and release of soluble factors. No drop in platelet count was observed, and metabolic markers remained within their critical limits. While C3 inhibition effectively reduced complement activation in stored platelet concentrates, it did not mitigate platelet storage lesions.
血小板储存与储存损伤有关，包括血小板形态变化和功能逐渐丧失。我们研究了补体C3抑制对临床血小板浓缩物中补体激活和血小板储存损伤的影响。在PAS-E中制备血小板浓缩物（n = 8），并在22°C下储存7天。将每个浓缩物分成两部分，其中一部分加入C3抑制剂compstatin Cp40，另一部分作为对照。每隔一天分析补体和血小板激活标志物、血小板功能和代谢指标。Cp40显著降低了C3bc和sC5b-9水平，但未降低C4c水平，表明在C3水平抑制了补体激活。然而，Cp40并未影响血小板特异性指标或代谢指标。在储存期间，CD62P的表面表达和NAP-2的释放显著增加，而CD63的表达以及PF4和TSP-1的释放保持稳定。随着时间的推移，血小板对TRAP-6介导的PAR-1激活和U46619介导的TXAR刺激的反应降低，表现为CD62P和CD63的表达以及可溶性因子的释放。未观察到血小板计数下降，代谢标志物仍在其临界范围内。虽然C3抑制有效降低了储存血小板浓缩物中的补体激活，但并未减轻血小板储存损伤。
