Abstract：
Regular measurement of fibrinogen as dose guidance in catheter directed thrombolysis (CDT) for acute limb ischaemia (ALI) has recently been dropped from European guidelines based on inconsistent literature. This study aimed to determine whether low fibrinogen levels and high activated partial thromboplastin time (APTT) are associated with an increased major bleeding risk during CDT.
All consecutive patients treated with CDT for ALI in two Dutch hospitals between January 2004 and April 2021 were analysed retrospectively. Patients were treated with two dosing regimens (low dose: 50 000 IU/hour; high dose: 100 000 IU/hour) of urokinase and, after 2018, with a single low dose regimen of alteplase (rtPA) due to urokinase manufacturing problems. The incidence of major bleeding and associated APTT and fibrinogen levels were reviewed from patient charts.
Of the 443 included cases, 277 underwent CDT with urokinase and 166 with rtPA. The incidence of major bleeding in the whole cohort was 7%. Patients with a fibrinogen levels < 1.0 g/L developed more major bleeding than those in whom the fibrinogen level did not drop below 1.0 g/L (15% vs. 6%; p = .041). Systemic heparinisation during CDT or high (> 80 seconds) APTT were not significantly associated with major bleeding. Angiographic success (47% vs. 72%; p = .003) and 30 day amputation free survival (53% vs. 82%; p < .001) were lower for cases with major bleeding. Older age (odds ratio [OR] 1.06, 95% confidence interval [CI] 1.02 - 1.11), cardiac history (OR 3.35, 95% CI 1.39 - 8.06), high dose regimens (≥ 75 000 IU/hour urokinase; OR 2.67, 95% CI 1.18 - 6.04), and fibrinogen values < 1.0 g/L (OR 5.59, 95% CI 1.98 - 15.77) were independent predictors for major bleeding during CDT.
High dose thrombolytic regimens and fibrinogen levels of ≤ 1.0 g/L are associated with more major bleeding during thrombolytic therapy. Major bleeding significantly worsened the clinical outcome. A prospective comparative study is needed to assess the benefit of monitoring fibrinogen levels.
All consecutive patients treated with CDT for ALI in two Dutch hospitals between January 2004 and April 2021 were analysed retrospectively. Patients were treated with two dosing regimens (low dose: 50 000 IU/hour; high dose: 100 000 IU/hour) of urokinase and, after 2018, with a single low dose regimen of alteplase (rtPA) due to urokinase manufacturing problems. The incidence of major bleeding and associated APTT and fibrinogen levels were reviewed from patient charts.
Of the 443 included cases, 277 underwent CDT with urokinase and 166 with rtPA. The incidence of major bleeding in the whole cohort was 7%. Patients with a fibrinogen levels < 1.0 g/L developed more major bleeding than those in whom the fibrinogen level did not drop below 1.0 g/L (15% vs. 6%; p = .041). Systemic heparinisation during CDT or high (> 80 seconds) APTT were not significantly associated with major bleeding. Angiographic success (47% vs. 72%; p = .003) and 30 day amputation free survival (53% vs. 82%; p < .001) were lower for cases with major bleeding. Older age (odds ratio [OR] 1.06, 95% confidence interval [CI] 1.02 - 1.11), cardiac history (OR 3.35, 95% CI 1.39 - 8.06), high dose regimens (≥ 75 000 IU/hour urokinase; OR 2.67, 95% CI 1.18 - 6.04), and fibrinogen values < 1.0 g/L (OR 5.59, 95% CI 1.98 - 15.77) were independent predictors for major bleeding during CDT.
High dose thrombolytic regimens and fibrinogen levels of ≤ 1.0 g/L are associated with more major bleeding during thrombolytic therapy. Major bleeding significantly worsened the clinical outcome. A prospective comparative study is needed to assess the benefit of monitoring fibrinogen levels.
摘要：
目的：根据不一致的文献，最近在急性肢体缺血（ALI）的导管定向溶栓（CDT）中定期测量纤维蛋白原作为剂量指导已从欧洲指南中删除。这项研究旨在确定低纤维蛋白原水平和高活化部分凝血活酶时间（APTT）是否与CDT期间大出血风险增加有关。
方法：回顾性分析2004年1月至2021年4月在两家荷兰医院接受CDT治疗ALI的所有连续患者。患者接受两种给药方案（低剂量：50000IU/小时;高剂量：100000IU/小时）的尿激酶和，2018年后，由于尿激酶制造问题，使用阿替普酶（rtPA）的单一低剂量方案。从患者图表中回顾了大出血的发生率以及相关的APTT和纤维蛋白原水平。
结果：在443个病例中，277用尿激酶进行CDT,166用rtPA进行CDT。整个队列中大出血的发生率为7%。纤维蛋白原水平<1.0g/L的患者比纤维蛋白原水平未低于1.0g/L的患者发生更严重的出血（15％vs.6%；p=.041）。CDT或高（>80秒）APTT期间的全身肝素化与大出血没有显着相关。血管造影成功率（47%vs.72%；p=.003）和30天无截肢生存率（53%vs.82%；p<.001）对于大出血病例较低。年龄较大(赔率比[OR]1.06，95%置信区间[CI]1.02-1.11)，心脏病史（OR3.35，95%CI1.39-8.06），高剂量方案（≥75000IU/小时尿激酶；OR2.67，95％CI1.18-6.04），纤维蛋白原值<1.0g/L（OR5.59，95％CI1.98-15.77）是CDT期间大出血的独立预测因子。
结论：大剂量溶栓方案和纤维蛋白原水平≤1.0g/L与溶栓治疗期间更严重的出血有关。大出血显著恶化临床结果。需要进行前瞻性比较研究来评估监测纤维蛋白原水平的益处。
方法：回顾性分析2004年1月至2021年4月在两家荷兰医院接受CDT治疗ALI的所有连续患者。患者接受两种给药方案（低剂量：50000IU/小时;高剂量：100000IU/小时）的尿激酶和，2018年后，由于尿激酶制造问题，使用阿替普酶（rtPA）的单一低剂量方案。从患者图表中回顾了大出血的发生率以及相关的APTT和纤维蛋白原水平。
结果：在443个病例中，277用尿激酶进行CDT,166用rtPA进行CDT。整个队列中大出血的发生率为7%。纤维蛋白原水平<1.0g/L的患者比纤维蛋白原水平未低于1.0g/L的患者发生更严重的出血（15％vs.6%；p=.041）。CDT或高（>80秒）APTT期间的全身肝素化与大出血没有显着相关。血管造影成功率（47%vs.72%；p=.003）和30天无截肢生存率（53%vs.82%；p<.001）对于大出血病例较低。年龄较大(赔率比[OR]1.06，95%置信区间[CI]1.02-1.11)，心脏病史（OR3.35，95%CI1.39-8.06），高剂量方案（≥75000IU/小时尿激酶；OR2.67，95％CI1.18-6.04），纤维蛋白原值<1.0g/L（OR5.59，95％CI1.98-15.77）是CDT期间大出血的独立预测因子。
结论：大剂量溶栓方案和纤维蛋白原水平≤1.0g/L与溶栓治疗期间更严重的出血有关。大出血显著恶化临床结果。需要进行前瞻性比较研究来评估监测纤维蛋白原水平的益处。
