Geiser T, Sturzenegger M, Genewein U, Haeberli A, Beer J H
Department of Internal Medicine, University Hospital, Bern, Switzerland.
Stroke. 1998 Sep;29(9):1770-7. doi: 10.1161/01.str.29.9.1770.
Cerebrovascular events (CVE) in patients with prosthetic heart valves (PHV) have remained a severe and frequent complication despite oral anticoagulation with or without aspirin. We studied the possible pathophysiological involvement of platelet-derived microparticles (PMP) as a contributing factor for the increased incidence of CVE in patients with PHV.
We compared in a retrospective, case-control study the clinical outcome after the implantation of the PHV with several different independent morphological and functional methods, including simultaneous transcranial Doppler monitoring of both middle cerebral arteries, PMP detection by flow cytometry with use of platelet-specific antibodies, coagulation markers, and determination of the procoagulant activity by Russell's viper venom time, a phospholipid-dependent coagulation assay.
Eight of 26 patients with PHV had 9 CVE during 136 person-years of observation. Transcranial Doppler monitoring revealed an increased frequency of microembolic signals recorded over a 30-minute period in patients with CVE (75+/-25; median, 55; range, 27 to 248) compared with those without CVE (23+/-12; median, 7; range, 0 to 153; P<0.05) or with control subjects (0; P<0.001). Flow cytometry analysis showed increased levels of PMP in patients with compared to those without CVE (4.1+/-0.6% versus 2.4+/-0.4% of all fluorescence-positive events gated; P<0.05). Increased procoagulant activity was documented by the shortened Russell's viper venom time expressed as an increased level of platelet equivalents per microliter of plasma in patients compared with control subjects (+24.7+/-14.9%; P<0.01). Subgroup analysis revealed that patients with CVE had a higher excess of platelet equivalents per microliter of plasma than patients without CVE in relation to the controls (+68.7+/-36.7%; P<0.05). Mildly elevated thrombin-antithrombin III complexes (2.9+/-0.7; median, 2.3; normal, <2.0 microg/L) suggested incompletely suppressed thrombin formation, and fibrin generation (fibrinopeptide A) was in the upper normal range (2.1+/-0.2; median, 1.8; normal, <2.0 ng/mL), despite adequate anticoagulation (INR=3.6+/-0.1).
Our data show increased microembolic signals, platelet microparticles, and procoagulant activity in symptomatic patients with PHV and provide a potential pathophysiological explanation of CVE.
尽管使用口服抗凝剂（无论是否联合阿司匹林），人工心脏瓣膜（PHV）患者的脑血管事件（CVE）仍然是一种严重且常见的并发症。我们研究了血小板衍生微粒（PMP）作为PHV患者CVE发生率增加的一个促成因素可能的病理生理作用。
在一项回顾性病例对照研究中，我们采用几种不同的独立形态学和功能方法比较了PHV植入后的临床结局，包括同时经颅多普勒监测双侧大脑中动脉、使用血小板特异性抗体通过流式细胞术检测PMP、凝血标志物以及通过罗素蝰蛇毒时间（一种磷脂依赖性凝血试验）测定促凝活性。
26例PHV患者中有8例在136人年的观察期内发生了9次CVE。经颅多普勒监测显示，与无CVE的患者（23±12；中位数，7；范围，0至153；P<0.05）或对照组（0；P<0.001）相比，CVE患者在30分钟内记录到的微栓塞信号频率增加（75±25；中位数，55；范围，27至248）。流式细胞术分析显示，与无CVE的患者相比，CVE患者的PMP水平升高（所有荧光阳性事件门控中分别为4.1±0.6%和2.4±0.4%；P<0.05）。与对照组相比，患者的罗素蝰蛇毒时间缩短，以每微升血浆中血小板当量水平升高表示促凝活性增加（+24.7±14.9%；P<0.01）。亚组分析显示，与无CVE的患者相比，CVE患者每微升血浆中的血小板当量相对于对照组更高（+68.7±36.7%；P<0.05）。凝血酶 - 抗凝血酶III复合物轻度升高（2.9±0.7；中位数，2.3；正常，<2.0μg/L）提示凝血酶形成未被完全抑制，尽管抗凝充分（国际标准化比值[INR]=3.6±0.1），纤维蛋白生成（纤维蛋白肽A）仍处于正常上限范围（2.1±0.2；中位数，1.8；正常，<2.0ng/mL）。
我们的数据显示有症状的PHV患者的微栓塞信号、血小板微粒和促凝活性增加，并为CVE提供了潜在的病理生理学解释。
