Serum cellular fibronectin and matrix metalloproteinase-9 as screening biomarkers for the prediction of parenchymal hematoma after thrombolytic therapy in acute ischemic stroke -: A multicenter confirmatory study
Serum cellular fibronectin and matrix metalloproteinase-9 as screening biomarkers for the prediction of parenchymal hematoma after thrombolytic therapy in acute ischemic stroke -: A multicenter confirmatory study
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DOI：
10.1161/strokeaha.106.481556
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发表时间：
2007-06-01
期刊：
影响因子：
8.3
通讯作者：
Davalos, Antoni
中科院分区：
文献类型：
--
作者：
Castellanos, Mar;Sobrino, Tomas;Davalos, Antoni
背景和目的--急性缺血性卒中患者接受组织型纤溶酶原激活剂（t-PA）治疗后，血浆细胞纤连蛋白（c-Fn）>= 3.6 μ g/mL和基质金属蛋白酶-9（MMP- 9）>= 140 ng/ mL的水平与脑实质血肿（PH）相关.在这项前瞻性研究中，我们试图验证这些生物标志物在更大范围内对PH的预测能力，方法-我们研究了134例根据SITS-MOST标准在症状发作后3小时内接受t-PA治疗的患者（中位输注时间，152分钟;中位国立卫生研究院卒中量表评分，14）。根据欧洲-澳大利亚急性卒中研究II对治疗后24至36小时进行的计算机断层扫描的定义，对出血性转化进行分类。相关的出血性转化定义为出血性梗死2型或任何PH。血清c-Fn和MMP- 9水平通过ELISA从治疗前获得的血液样本测定。结果-头颅计算机断层扫描显示出血性转化27例（20%），出血性梗死15例（2型8例），PH 12例（4例症状）。有相关出血性转化和PH的患者基线时血清c-Fn和MMP- 9水平显著高于无相关出血性转化和PH的患者（均P < 0.001）。c-Fn水平>= 3.6 μ g/ mL的PH的敏感性、特异性、阳性和阴性预测值分别为100%、60%、20%和100%，而MMP- 9水平>= 140 ng/ mL的相应值分别为92%、74%、26%和99%。当两种生物标志物均高于临界值时，特异性增加至87%，阳性预测值增加至41%. Conclusion-This前瞻性研究证实了c-Fn和MMP- 9在预测t-PA治疗患者PH中的高敏感性和阴性预测值，并保留了良好的特异性。快速分析方法的发展将证明这些生物标志物在常规临床实践中的适用性。
Background and Purpose - Plasma levels of cellular fibronectin ( c- Fn) >= 3.6 mu g/mL and of matrix metalloproteinase- 9 ( MMP- 9) >= 140 ng/ mL have been associated with parenchymal hematoma ( PH) after treatment with tissue- type plasminogen activator ( t- PA) in patients with acute ischemic stroke. In this prospective study, we sought to validate the predictive capacity of the preestablished cutoff values of these biomarkers for PH in a larger series of patients.Methods - We studied 134 patients treated with t- PA within 3 hours from symptom onset according to the SITS-MOST criteria ( median time to infusion, 152 minutes; median National Institutes of Health Stroke Scale score, 14) in 4 university hospitals. Hemorrhagic transformation was classified according to the European- Australasian Acute Stroke Study II definitions on computed tomography scans performed 24 to 36 hours after treatment. Relevant hemorrhagic transformation was defined as hemorrhagic infarction type 2 or any PH. Serum c- Fn and MMP- 9 levels were determined by an ELISA om blood samples obtained before treatment.Results - Cranial computed tomography showed hemorrhagic transformation in 27 patients ( 20%), hemorrhagic infarction in 15 ( type 2 in 8 patients), and PH in 12 patients ( symptomatic in 4). Serum c- Fn and MMP- 9 concentrations at baseline were significantly higher in patients with relevant hemorrhagic transformation and PH than in those without ( all P < 0.001). The sensitivity, specificity, and positive and negative predictive values for PH by c- Fn levels >= 3.6 mu g/ mL were 100%, 60%, 20%, and 100%, respectively, whereas corresponding values were 92%, 74%, 26%, and 99% for MMP- 9 levels >= 140 ng/ mL. When both biomarkers were at levels above the cutoff points, specificity increased to 87% and the positive predictive value increased to 41%.Conclusions - This prospective study confirmed the high sensitivity and negative predictive value, with retained good specificity, of c- Fn and MMP- 9 for the prediction of PH in patients treated with t- PA. Development of faster analytic methods will prove the applicability of these biomarkers in routine clinical practice.