Mayo Clinic and Foundation for Education and Research, Rochester, Minnesota, USA.
Thromb Haemost. 2011 Jul;106(1):75-82. doi: 10.1160/TH10-11-0765. Epub 2011 Jun 9.
Nearly 15% of patients with non-valvular atrial fibrillation (NVAF) have left atrial appendage thrombus (LAAT) by transesophageal echocardiography (TEE) and yet the annual stroke rate averages 5%. The aim of this study was to identify variables influencing embolic propensity of LAAT. Platelet RNA was extracted from platelet-rich regions within formalin-fixed, paraffin-embedded specimens obtained from NVAF patients during cardiac surgery (26 LAAT from 23 patients) or peripheral embolectomy (51 thrombi from 41 patients). Platelet RNA was also assessed from whole blood from 40 NVAF patients. Expression of six platelet-predominate genes: H2A histone family, A1 domain of factor XIII, integrin α₂bβ₃; glycoprotein IX, platelet factor 4, glycoprotein Ib, was performed using TaqMan MGB-probe based quantitative real-time polymerase chain reaction. Platelet factor XIII subunit A gene expression was significantly lower in embolised compared to non-embolised thrombi as determined by normalised cycle threshold values (4.0 ± 1.2 v 2.8 ± 1.8, p=0.02). Expression of other genes did not differ by embolic status. In conclusion, RNA extracted from formalin-fixed, paraffin-embedded platelet-rich tissues can be used for analysis of platelet-predominate gene expression. Variable factor XIII gene expression in thrombi generated during NVAF may in part explain the propensity to embolisation.
将近 15%的非瓣膜性心房颤动 (NVAF) 患者通过经食管超声心动图 (TEE) 检查有左心耳血栓 (LAAT),但每年的中风发生率平均为 5%。本研究旨在确定影响 LAAT 栓塞倾向的变量。从心脏手术期间 (23 例患者的 26 个 LAAT) 或外周血栓切除术 (41 例患者的 51 个血栓) 获得的福尔马林固定、石蜡包埋标本中的富含血小板区域提取血小板 RNA。还从 40 名 NVAF 患者的全血中评估了血小板 RNA。使用 TaqMan MGB 探针基于定量实时聚合酶链反应 (PCR) 检测六个血小板优势基因的表达:组蛋白家族 H2A、因子 XIII A1 域、整合素 α₂bβ₃、糖蛋白 IX、血小板因子 4、糖蛋白 Ib。通过标准化循环阈值值确定,与非栓塞性血栓相比,栓塞性血栓中血小板 XIII 亚单位 A 基因的表达明显降低 (4.0 ± 1.2 v 2.8 ± 1.8,p=0.02)。其他基因的表达不受栓塞状态的影响。总之,从福尔马林固定、石蜡包埋的富含血小板组织中提取的 RNA 可用于分析血小板优势基因的表达。NVAF 期间产生的血栓中可变的因子 XIII 基因表达可能部分解释了栓塞倾向。