del Zoppo Gregory J, Levy David E, Wasiewski Warren W, Pancioli Arthur M, Demchuk Andrew M, Trammel James, Demaerschalk Bart M, Kaste Markku, Albers Gregory W, Ringelstein Eric B
Harborview Medical Center, University of Washington, Seattle, WA 98104, USA.
Stroke. 2009 May;40(5):1687-91. doi: 10.1161/STROKEAHA.108.527804. Epub 2009 Mar 19.
Epidemiological studies have found strong correlations between elevated plasma fibrinogen levels and both ischemic stroke incidence and stroke mortality. Little is known about the influence of fibrinogen levels on functional stroke outcome.
Placebo data from the Stroke Treatment with Ancrod Trial (STAT) and European Stroke Treatment with Ancrod Trial (ESTAT) were analyzed. Fibrinogen levels were determined within 3 hours (STAT) or 6 hours (ESTAT) of stroke onset and at preset intervals throughout 5 days of intravenous infusions. Barthel Index scores at 90 days quantified functional outcomes. The association between initial fibrinogen levels and functional outcomes was evaluated using a multiple logistic regression analysis.
Fibrinogen levels increased gradually over the first 24 hours from a pretreatment median value of 340 mg/dL to a 24-hour median value of 376 mg/dL. In a univariate analysis, the proportion of patients with good functional outcome decreased with increasing quartiles of initial fibrinogen levels in both STAT (36.0% to 26.2%) and ESTAT (53.8% to 24.8%). In a multifactorial analysis, the same trend was observed. Patients with initial fibrinogen levels <450 mg/dL had better outcomes in both studies; the difference (42.0% versus 21.6%) was significant in ESTAT (P=0.0006), even when corrected for age and initial stroke severity.
The independent association of higher initial fibrinogen levels with poor outcome needs to be verified using a larger acute stroke dataset. Even in the present small populations, the apparent association of these 2 variables suggests that treatments designed to reduce fibrinogen levels could potentially be important in treating acute ischemic stroke.
流行病学研究发现，血浆纤维蛋白原水平升高与缺血性脑卒中发病率及脑卒中死亡率之间存在密切关联。关于纤维蛋白原水平对脑卒中功能结局的影响，目前所知甚少。
对安克洛酶治疗卒中试验（STAT）和欧洲安克洛酶治疗卒中试验（ESTAT）的安慰剂数据进行分析。在卒中发作后3小时（STAT）或6小时（ESTAT）内以及静脉输注的5天内按预设间隔测定纤维蛋白原水平。90天时的巴氏指数评分量化功能结局。采用多元逻辑回归分析评估初始纤维蛋白原水平与功能结局之间的关联。
纤维蛋白原水平在最初24小时内从治疗前的中位数340mg/dL逐渐升高至24小时的中位数376mg/dL。在单因素分析中，STAT（36.0%至26.2%）和ESTAT（53.8%至24.8%）中，功能结局良好的患者比例均随初始纤维蛋白原水平四分位数的增加而降低。在多因素分析中，观察到相同趋势。在两项研究中，初始纤维蛋白原水平<450mg/dL的患者结局更好；即使校正年龄和初始卒中严重程度后，ESTAT中的差异（42.0%对21.6%）仍具有显著性（P=0.0006）。
需要使用更大的急性卒中数据集来验证较高的初始纤维蛋白原水平与不良结局之间的独立关联。即使在目前的小样本中，这两个变量之间明显的关联表明，旨在降低纤维蛋白原水平的治疗方法可能对急性缺血性卒中的治疗具有重要意义。
