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蝙蝠葛苏林对脑静脉血栓形成患者抗血栓系统的影响:作用机制的线索。

Effects of batroxobin on the antithrombotic system in patients with cerebral venous thrombosis: Clues to mechanisms.

机构信息

Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing, China.

Department of China-America Institute of Neuroscience, Xuanwu Hospital, Capital Medical University, Beijing, China.

出版信息

CNS Neurosci Ther. 2024 Aug;30(8):e14861. doi: 10.1111/cns.14861.

Abstract

BACKGROUND AND PURPOSE

More evidence supports the benefits of batroxobin combined with anticoagulation in correcting acute cerebral venous thrombosis (CVT). The dynamic fluctuations of peripheral blood platelets, fibrinolysis, and coagulation biomarkers during this therapy were analyzed.

METHODS

We investigated batroxobin's effects on the antithrombotic system under two regimens. The pretreatment group included patients on anticoagulants for at least 1 week before starting batroxobin. The simultaneous treatment group began both treatments upon admission. The control group received only anticoagulation. Batroxobin was given on alternate days at doses of 10BU, 5BU, and 5BU, totaling three doses. Anticoagulation was continuous. Baseline data were T0; the next day after each batroxobin dose was T1, T2, and T3. Data from these four time points was analyzed.

RESULTS

The time-point paired sample T-test results of the pretreatment group [n = 60; mean age (SD), 43.3(16.5); 38 (63.35%) women] showed that batroxobin significantly inhibited ADP-induced platelet aggregation rate (T1-T0: p = 0.015; T2-T0: p = 0.025; T3-T0: p = 0.013), decreased fibrinogen level (T1-T0: p < 0.001; T2-T0: p < 0.001; T3-T0: p < 0.001), and increased D-dimer (T1-T0:p < 0.001; T2-T0: p < 0.001; T3-T0: p < 0.001), TT (T1-T0:p = 0.046; T2-T0: p = 0.003; T3-T0: p < 0.001), and APTT (T1-T0:p = 0.021; T2-T0: p = 0.012; T3-T0: p = 0.026). Compared to the control group, the simultaneous treatment group showed significantly higher TT (T2: p = 0.002; T3: p = 0.004) and D-dimer (T1: p < 0.001; T2: p < 0.001; T3: p < 0.001) values, while fibrinogen (T2: p < 0.001; T3: p < 0.001) levels were significantly lower. Using batroxobin can alleviate the amplitude of changes in coagulation indicators other than TT caused by anticoagulants. The above conclusions are consistent with the results of repeated measurement data analysis.

CONCLUSIONS

Batroxobin can significantly inhibit ADP-induced platelet aggregation rate, increase D-dimer, decrease fibrinogen, and prolong TT and APTT in the presence of anticoagulant agents. Using batroxobin can reduce the amplitude of changes in coagulation indicators caused by anticoagulants. These results reveal the potential mechanism of batroxobin combined with anticoagulation in the safe and effective treatment of CVT.

摘要

背景与目的

越来越多的证据支持巴曲酶联合抗凝治疗急性脑静脉血栓形成(CVT)的益处。本研究分析了在此治疗过程中外周血血小板、纤溶和凝血生物标志物的动态变化。

方法

我们研究了巴曲酶在两种方案下对抗栓系统的影响。预处理组患者在开始使用巴曲酶前至少接受抗凝治疗 1 周。同时治疗组入院后同时开始两种治疗。对照组仅接受抗凝治疗。巴曲酶隔天给予 10BU、5BU 和 5BU,共 3 剂。抗凝治疗持续进行。基线数据为 T0;巴曲酶每次剂量后的第二天分别为 T1、T2 和 T3。分析这四个时间点的数据。

结果

预处理组(n=60;平均年龄[标准差],43.3[16.5];38 名[63.35%]女性)的时间点配对样本 T 检验结果表明,巴曲酶显著抑制 ADP 诱导的血小板聚集率(T1-T0:p=0.015;T2-T0:p=0.025;T3-T0:p=0.013),降低纤维蛋白原水平(T1-T0:p<0.001;T2-T0:p<0.001;T3-T0:p<0.001),增加 D-二聚体(T1-T0:p<0.001;T2-T0:p<0.001;T3-T0:p<0.001)、TT(T1-T0:p=0.046;T2-T0:p=0.003;T3-T0:p<0.001)和 APTT(T1-T0:p=0.021;T2-T0:p=0.012;T3-T0:p=0.026)。与对照组相比,同时治疗组 TT(T2:p=0.002;T3:p=0.004)和 D-二聚体(T1:p<0.001;T2:p<0.001;T3:p<0.001)值明显更高,而纤维蛋白原(T2:p<0.001;T3:p<0.001)水平明显更低。使用巴曲酶可以减轻抗凝药物引起的 TT 以外的凝血指标变化幅度。上述结论与重复测量数据分析的结果一致。

结论

巴曲酶在抗凝药物存在的情况下,可显著抑制 ADP 诱导的血小板聚集率,增加 D-二聚体,降低纤维蛋白原,延长 TT 和 APTT。使用巴曲酶可以减少抗凝药物引起的凝血指标变化幅度。这些结果揭示了巴曲酶联合抗凝治疗在 CVT 安全有效的治疗中的潜在机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7421/11298196/7e68b9f200f0/CNS-30-e14861-g002.jpg

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