Carboxypeptidase U (TAFIa) decreases the efficacy of thrombolytic therapy in ischemic stroke patients
Carboxypeptidase U (TAFIa) decreases the efficacy of thrombolytic therapy in ischemic stroke patients
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DOI：
10.1016/j.clineuro.2008.09.002
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发表时间：
2009-02-01
影响因子：
1.9
通讯作者：
De Deyn, Peter P.
中科院分区：
文献类型：
--
作者：
Brouns, Raf;Heylen, Evelien;De Deyn, Peter P.
导言：溶栓治疗改善了急性缺血性中风患者的临床结果，但受到症状性颅内出血和不可预测的治疗反应的影响。目的：探讨前CPU激活程度与脑梗塞溶栓疗效和安全性的关系。方法：对12例接受静脉溶栓和动脉溶栓治疗的脑梗塞患者，分别于溶栓前、溶栓中和溶栓后不同时间采静脉血。用高效液相色谱法测定ProCPU和羧基肽酶U(CPU，Tafia)的血浆浓度。计算溶栓期间的最大CPU活性(CPUmax)和ProCPU消耗百分比。通过临床症状、再通、最终脑梗塞体积、溶栓所致颅内出血和死亡率的变化来评估溶栓治疗的有效性和安全性。结果：未发现CPUmax或proCPU消耗与患者或卒中特征相关。然而，CPUmax与临床缺陷的演变和实现再钙化有关。ProCPU消耗与脑出血风险、死亡率和最终脑梗塞体积有关。结论：无论患者和卒中特征如何，在缺血性卒中溶栓治疗中，CPUmax和ProCPU消耗是影响疗效和安全性的指标。进一步评估这些参数的临床适用性和进一步研究CPU抑制剂在溶栓治疗中作为辅助治疗的潜在作用可能是有价值的。(C)2008爱思唯尔B.V.保留所有权利。
Introduction: Thrombolytic therapy improves clinical outcome in patients with acute ischemic stroke but is compromised by symptomatic intracranial hemorrhage and an unpredictable therapeutic response. In vitro and in vivo data suggest that activation of procarboxypeptidase U (proCPU) inhibits fibrinolysis.Aims: To investigate whether the extent of proCPU activation is related to efficacy and safety of thrombolytic therapy in ischemic stroke patients.Methods: In twelve patients with ischemic stroke who were treated with intravenous (n = 7) or intra-arterial (n = 5) thrombolysis, venous blood samples were taken at different time points before, during and after thrombolytic therapy. ProCPU and carboxypeptidase U (CPU, TAFIa) plasma concentrations were determined by HPLC. The maximal CPU activity (CPUmax) and the percentage of proCPU consumption during thrombolytic therapy were calculated. The efficacy and safety of the thrombolytic therapy were assessed by evolution of the clinical deficit, recanalisation, final infarct volume, thrombolysis-induced intracranial hemorrhage and mortality.Results: No correlations between CPUmax, or proCPU consumption and patient or stroke characteristics were found. However, CPUmax is associated with evolution of the clinical deficit and achieved recanalisation. ProCPU consumption is related to the risk of intracranial hemorrhage, mortality and final infarct volume.Conclusions: Irrespective of patient and stroke characteristics, CPUmax and proCPU consumption during thrombolytic treatment for ischemic stroke are parameters for therapeutic efficacy and safety. Further evaluation of the clinical applicability of these parameters and further investigation of the potential role for CPU inhibitors as adjunctive therapeutics during thrombolytic treatment may be of value. (c) 2008 Elsevier B.V. All rights reserved.