University Department for Cardiac Surgery, Leipzig Heart Center, Helios Clinic, Leipzig, Germany.
MVZ Labor Dr. Reising-Ackermann und Kollegen, Center of Hemostasis, Leipzig, Germany.
J Thromb Haemost. 2021 May;19(5):1331-1341. doi: 10.1111/jth.15279. Epub 2021 Mar 28.
Non-surgical bleeding (NSB) is a major complication after left ventricular assist device (LVAD) implantation. It has been reported that non-physiological shear stress caused by LVADs could alter platelet receptor expression, which leads to bleeding disorders caused by coagulation dysfunctions.
Because bleeding diathesis could be multifactorial, we focused on the combined characterization of platelet receptor expression patterns and oxidative stress to compare patients with NSB and patients without coagulation disorder in a monocentric, prospective study.
Blood samples were obtained from LVAD patients with NSB (bleeder group, n = 19) and without NSB (non-bleeder group, n = 20). The platelet receptors platelet endothelial cell adhesion molecule-1 (PECAM-1), glycoprotein (GP)Ibα, P-selectin, CD63, and GPIIb/IIIa, as well as the production of intraplatelet reactive oxygen species (ROS) were quantified by flow cytometry. Aggregation capacity was evaluated by aggregometry.
The surface expression level of P-selectin and GPIbα on platelets was decreased in bleeders (P-selectin: 465 ± 72 U; GPIbα: 435 ± 41 U) compared to non-bleeders (P-selectin: 859 ± 115 U, P < .01; GPIbα: 570 ± 49 U, p = .04). Additionally, the mean fluorescence intensity of ADP-stimulated P-selectin and PECAM-1 expressing platelets were reduced in bleeders (P-selectin: 944 ± 84 U; PECAM-1: 6722 ± 419 U) compared to non-bleeders (P-selectin: 1269 ± 130 U, P = .04; PECAM-1: 8542 ± 665 U, P = .03). Bleeders showed a higher amount of ROS formation in platelets (88.0 ± 2.6%) than non-bleeders (81.5 ± 2.1%, P = .05).
These findings suggested that changes of three platelet receptors (GPIbα, P-selectin, and PECAM-1) and elevated oxidative stress may play a role in patients with bleeding complications following LVAD implantation. These results might help to explain the high incidence of spontaneous hemorrhage during LVAD support through an altered platelet function.
左心室辅助装置（LVAD）植入后非手术性出血（NSB）是一种主要并发症。据报道，LVAD 产生的非生理切变力会改变血小板受体的表达，从而导致凝血功能障碍引起的出血性疾病。
由于出血倾向可能是多因素的，我们专注于血小板受体表达模式和氧化应激的联合特征，以在一项单中心前瞻性研究中比较有 NSB 和无凝血障碍的患者。
从有 NSB（出血组，n=19）和无 NSB（非出血组，n=20）的 LVAD 患者中采集血样。通过流式细胞术定量测定血小板内皮细胞黏附分子-1（PECAM-1）、糖蛋白（GP）Ibα、P-选择素、CD63 和 GPIIb/IIIa 的血小板受体，以及血小板内活性氧物质（ROS）的产生。通过聚集度测定评估聚集能力。
与非出血者（P-选择素：859±115 U，P<.01；GP Ibα：570±49 U，p=0.04）相比，出血者的血小板表面 P-选择素和 GPIbα 表达水平降低（P-选择素：465±72 U，P<.01；GP Ibα：435±41 U）。此外，与非出血者（P-选择素：1269±130 U，P=0.04；PECAM-1：8542±665 U，P=0.03）相比，ADP 刺激的 P-选择素和 PECAM-1 表达血小板的平均荧光强度在出血者中降低（P-选择素：944±84 U；PECAM-1：6722±419 U）。出血者血小板中 ROS 形成量（88.0±2.6%）高于非出血者（81.5±2.1%，P=0.05）。
这些发现表明，三种血小板受体（GPIbα、P-选择素和 PECAM-1）的变化和氧化应激水平升高可能在 LVAD 植入后出血并发症患者中起作用。这些结果可能有助于通过改变血小板功能来解释 LVAD 支持期间自发性出血的高发生率。
