Sturzenegger M, Beer J H, Rihs F
Department of Neurology, University of Bern, Inselspital, Switzerland.
Stroke. 1995 Jan;26(1):63-9. doi: 10.1161/01.str.26.1.63.
The combined use of coumarin and low-dose aspirin appears to reduce the risk of systemic embolism at a low risk of bleeding. The remaining incidence of embolism of approximately 2%/y is still high. Methods for real-time detection of embolic events have not been used thus far to monitor the efficacy of therapeutic strategies. They might permit individually tailored, effective treatments.
The frequency of embolic signals in both middle cerebral arteries was monitored using a two-channel 2-MHz transcranial Doppler system. We examined five patients with mechanical prosthetic heart valves suffering from recurrent cerebral ischemic symptoms despite adequate anticoagulant therapy (international normalized ratio, 3.0 to 4.3). Measurements were performed on coumarin alone (four baseline values) and subsequent to the addition of intravenous (500 mg bolus) and oral (100 mg/d for 10 days) aspirin or intravenous (5000 IU bolus) heparin. The prothrombotic markers thrombin-antithrombin III complex, fibrinopeptide A, D-dimer, and platelet beta-thromboglobulin were measured simultaneously.
None of the combined drug regimens led to a significant reduction of the emboli count. The values of thrombin-antithrombin III complex, fibrinopeptide A, and D-dimer were already within normal limits with coumarin alone. The beta-thromboglobulin levels, however, were increased, and additional aspirin or heparin did not reduce them. There was no correlation between the emboli count and the prothrombotic markers or between the prothrombotic markers and the different drug regimens.
The rate of cerebral emboli measured with transcranial Doppler in the group of high-risk patients studied was not influenced by additional antiplatelet therapy. The emboli are likely to be composed at least in part of platelets, and their generation seems not dependent on thrombin or cyclooxygenase. There is an apparent discrepancy between the unchanged rate of emboli during Doppler monitoring found in this and other studies and the partial efficacy of combined treatment with coumarin and aspirin in clinical long-term studies. This may be explained by differences in the composition or size of the emboli.
香豆素与小剂量阿司匹林联合使用似乎能降低全身栓塞风险，且出血风险较低。然而，约2%/年的剩余栓塞发生率仍然较高。迄今为止，尚未使用实时检测栓塞事件的方法来监测治疗策略的疗效。这些方法可能有助于实现个体化的有效治疗。
使用双通道2兆赫经颅多普勒系统监测双侧大脑中动脉的栓塞信号频率。我们检查了5例机械人工心脏瓣膜患者，尽管进行了充分的抗凝治疗（国际标准化比值为3.0至4.3），仍出现复发性脑缺血症状。测量分别在单独使用香豆素时（四个基线值）以及添加静脉注射（500毫克推注）和口服（100毫克/天，共10天）阿司匹林或静脉注射（5000国际单位推注）肝素后进行。同时测量血栓前标志物凝血酶 - 抗凝血酶III复合物、纤维蛋白肽A、D - 二聚体和血小板β - 血栓球蛋白。
联合用药方案均未导致栓塞计数显著降低。单独使用香豆素时，凝血酶 - 抗凝血酶III复合物、纤维蛋白肽A和D - 二聚体的值已在正常范围内。然而，β - 血栓球蛋白水平升高，额外添加阿司匹林或肝素并未使其降低。栓塞计数与血栓前标志物之间或血栓前标志物与不同药物方案之间均无相关性。
在本研究的高危患者组中，经颅多普勒测量的脑栓塞发生率不受额外抗血小板治疗的影响。栓塞物可能至少部分由血小板组成，其形成似乎不依赖于凝血酶或环氧化酶。本研究及其他研究中多普勒监测期间栓塞发生率不变，与香豆素和阿司匹林联合治疗在临床长期研究中的部分疗效之间存在明显差异。这可能是由于栓塞物的组成或大小不同所致。
