From the Departments of Neurology (J.-W.C., M.J.L., G.-M.K., C.-S.C., O.Y.B.).
Hemato-oncology (M.-J.A.).
Stroke. 2018 May;49(5):1282-1285. doi: 10.1161/STROKEAHA.118.020995. Epub 2018 Apr 2.
Coagulopathy is an important cause of stroke in cancer patients. However, underlying mechanisms and clinical factors related to coagulopathy remain unclear. We hypothesized that certain characteristics of cancer affect coagulopathy in patients with lung cancer and ischemic stroke.
Consecutive patients with active lung cancer and acute ischemic stroke were prospectively studied. Volume and pattern of acute brain infarcts and plasma levels of circulating tumor extracellular vesicles (EVs) were measured using flow cytometry. In vitro experiments investigated the pathophysiological mechanisms underlying cancer-associated coagulopathy.
Of 114 patients, 95 (83.3%) had an adenocarcinoma cell type and 95 (83.3%) had distant metastasis. Acute brain infarct volumes were larger and circulating EV levels were higher in patients with an adenocarcinoma cell type than in those with other cell types. The presence of metastasis was not associated with infarct volume or circulating EV levels. Coagulation assays demonstrated dose-dependent shorter clotting times after treatment with EVs from adenocarcinoma cell lines than with the use of EVs from squamous cell carcinoma. These findings were confirmed by coagulation assays using circulating EVs from patients with adenocarcinoma and stroke and from those with conventional stroke mechanisms.
Our findings indicate that cancer cell type is associated with circulating EV levels and coagulopathy in patients with lung cancer and stroke.
凝血功能障碍是癌症患者发生中风的一个重要原因。然而，与凝血功能障碍相关的潜在机制和临床因素仍不清楚。我们假设某些癌症特征会影响肺癌合并缺血性中风患者的凝血功能障碍。
连续前瞻性研究了患有活动性肺癌和急性缺血性中风的患者。使用流式细胞术测量急性脑梗死的体积和模式以及循环肿瘤细胞外囊泡（EVs）的血浆水平。体外实验研究了癌症相关凝血功能障碍的病理生理机制。
在 114 名患者中，95 名（83.3%）为腺癌细胞类型，95 名（83.3%）有远处转移。与其他细胞类型相比，腺癌患者的急性脑梗死体积较大，循环 EV 水平较高。转移的存在与梗死体积或循环 EV 水平无关。凝血检测表明，用腺癌细胞系的 EV 处理后，凝血时间明显缩短，呈剂量依赖性，而用鳞癌的 EV 处理则没有这种情况。这些发现通过使用腺癌合并中风患者和常规中风机制患者的循环 EV 进行的凝血检测得到了证实。
我们的研究结果表明，癌症细胞类型与肺癌合并中风患者的循环 EV 水平和凝血功能障碍有关。
