Kumar Monisha, Cao Wenjing, McDaniel Jenny K, Pham Huy P, Raju Dheeraj, Nawalinski Kelsey, Frangos Suzanne, Kung David, Zager Eric, Kasner Scott E, Levine Joshua M, Zheng X Long
X. Long Zheng, MD, PhD, Division of Laboratory Medicine, Department of Pathology, The University of Alabama at Birmingham, 619 19th Street South, Birmingham, AL 35249, USA, E-mail:
Thromb Haemost. 2017 Apr 3;117(4):691-699. doi: 10.1160/TH16-11-0834. Epub 2017 Jan 19.
Increased von Willebrand factor (VWF) and reduced ADAMTS13 activity are associated with arterial thrombosis. This may also be the culprit mechanism implicated in delayed cerebral ischaemia after aneurysmal subarachnoid haemorrhage (SAH). It was our objective to determine plasma VWF and ADAMTS13 in patients with SAH and healthy subjects; and to explore the levels of those markers and outcome after SAH. Forty consecutive patients were enrolled between September 2007 and April 2014 in a pilot study. Plasma samples were collected from SAH patients on post-bleed day (PBD) 0, 1, 3, 5, 7 and 10 and healthy controls. VWF antigen (VWFAg) and VWF activity (VWFAc) were determined by enzyme-linked immunoassay and collagen binding assay, respectively. ADAMTS13 activity was determined by the cleavage of a fluorescent substrate. Univariate descriptive statistics and cluster analyses were performed based on outcomes in the group with SAH only. Mean age of SAH patients was 52.4 years (26-84 years) and 30 (75 %) were women. 12/40 (30 %) had a high Hunt and Hess grade (IV-V) and 25 (62.5 %) were treated with coil embolisation. Plasma VWFAg and VWFAc were significantly higher in SAH patients than those in healthy subjects on each PBD (p<0.0001). Concurrently, plasma ADAMTS13 activity in SAH patients was significantly lower than that in healthy subjects (p<0.0001). Among those with SAH, cluster analysis demonstrated that patients with higher VWFAg and VWFAc and/or lower ADAMTS13 activity might be at risk of increased mortality. In conclusion, the relative deficiency of plasma ADAMTS13 activity in SAH patients may associate with worse outcome.
血管性血友病因子（VWF）升高和ADAMTS13活性降低与动脉血栓形成有关。这也可能是动脉瘤性蛛网膜下腔出血（SAH）后迟发性脑缺血的潜在机制。我们的目的是测定SAH患者和健康受试者的血浆VWF和ADAMTS13；并探讨这些标志物的水平与SAH后的预后。在2007年9月至2014年4月期间的一项初步研究中，连续纳入了40例患者。在出血后第0、1、3、5、7和10天从SAH患者以及健康对照者中采集血浆样本。分别通过酶联免疫测定法和胶原结合测定法测定VWF抗原（VWFAg）和VWF活性（VWFAc）。通过荧光底物的裂解来测定ADAMTS13活性。仅基于SAH组的预后进行单变量描述性统计和聚类分析。SAH患者的平均年龄为52.4岁（26 - 84岁），30例（75%）为女性。12/40（30%）具有较高的Hunt和Hess分级（IV - V级），25例（62.5%）接受了弹簧圈栓塞治疗。在每个出血后天数（PBD），SAH患者的血浆VWFAg和VWFAc均显著高于健康受试者（p<0.0001）。同时，SAH患者的血浆ADAMTS13活性显著低于健康受试者（p<0.0001）。在SAH患者中，聚类分析表明，VWFAg和VWFAc较高和/或ADAMTS13活性较低的患者可能有死亡风险增加。总之，SAH患者血浆ADAMTS13活性相对不足可能与较差的预后相关。
