Sama Snigdha, Cho Sunjoo, Rehni Ashish K, Jy Wenche, Dave Kunjan R
Department of Neurology, Peritz Scheinberg Cerebral Vascular Disease Research Laboratories, University of Miami Miller School of Medicine, 1600 NW 10th Ave RMSB #7046, Miami, FL, 33136, USA.
The Wallace H. Coulter Platelet Laboratory, Division of Hematology/Oncology, Department of Medicine, University of Miami Miller School of Medicine, Miami, FL, USA.
Pharmacol Rep. 2025 Apr;77(2):508-516. doi: 10.1007/s43440-024-00688-0. Epub 2025 Jan 8.
Current therapies to treat excessive bleeding are associated with significant complications, which may outweigh their benefits. Red blood cell-derived microparticles (RMPs) are a promising hemostatic agent. Previous studies demonstrated that they reduce bleeding in animal models, correct coagulation defects in patient blood, and have an excellent safety profile. However, their exact mechanism of action is not known. We investigated the potential role of RMPs on primary and secondary hemostasis.
To evaluate the effects of RMPs, prepared using high-pressure extrusion, on primary hemostasis, we employed platelet aggregometry with platelet inhibitors, eptifibatide, and ticagrelor, with and without RMPs. To evaluate their effects on secondary hemostasis, we employed thromboelastography with plasma deficient in factors VII, VIII, IX, XI, and XII with and without RMPs.
We found that RMPs significantly increased collagen-induced platelet aggregation. However, there were no significant differences with and without RMP in the presence of the platelet inhibitors, indicating that RMPs may work through these receptors, either directly or indirectly. For secondary hemostasis, RMPs significantly decreased clotting times for plasma deficient in factors VII, VIII, IX, and XI but not in XII.
Our results indicate that RMPs enhance primary hemostasis and both pathways of secondary hemostasis.
目前用于治疗出血过多的疗法会引发严重并发症，其风险可能超过益处。红细胞衍生的微粒（RMPs）是一种很有前景的止血剂。先前的研究表明，它们可减少动物模型中的出血，纠正患者血液中的凝血缺陷，且具有出色的安全性。然而，其确切作用机制尚不清楚。我们研究了RMPs在初级和次级止血中的潜在作用。
为评估采用高压挤压制备的RMPs对初级止血的影响，我们使用血小板聚集测定法，加入或不加入RMPs，并使用血小板抑制剂依替巴肽和替格瑞洛。为评估其对次级止血的影响，我们采用血栓弹性描记法，加入或不加入RMPs，并使用缺乏凝血因子VII、VIII、IX、XI和XII的血浆。
我们发现RMPs显著增加了胶原诱导的血小板聚集。然而，在存在血小板抑制剂的情况下，加入和未加入RMPs并无显著差异，这表明RMPs可能直接或间接通过这些受体发挥作用。对于次级止血，RMPs显著缩短了缺乏凝血因子VII、VIII、IX和XI但不缺乏XII的血浆的凝血时间。
我们的结果表明，RMPs可增强初级止血以及次级止血的两条途径。
