The assessment of anticoagulant activity to predict bleeding outcome in atrial fibrillation patients receiving dabigatran etexilate
The assessment of anticoagulant activity to predict bleeding outcome in atrial fibrillation patients receiving dabigatran etexilate
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DOI：
10.1097/mbc.0000000000000558
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发表时间：
2016-06
影响因子：
1.1
通讯作者：
Yaoting Chang;Yu-Feng Hu;J. Liao;C. Chern;Yenn-Jiang Lin;S. Chang;Cheng-hsueh Wu;S. Sung;Kang-Ling Wang;T. Lu;T. Chao;L. Lo;L. Hsu;Chih‐Ping Chung;P. Chang;W. Hsu;C. Chiou;Shih‐Ann Chen
中科院分区：
文献类型：
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作者：
Yaoting Chang;Yu-Feng Hu;J. Liao;C. Chern;Yenn-Jiang Lin;S. Chang;Cheng-hsueh Wu;S. Sung;Kang-Ling Wang;T. Lu;T. Chao;L. Lo;L. Hsu;Chih‐Ping Chung;P. Chang;W. Hsu;C. Chiou;Shih‐Ann Chen
特殊情况下可能需要测定达比加群酯的抗凝作用。目前尚无数据表明，在接受达比加群酯治疗房颤的患者中，任何凝血试验与出血结局有关。非瓣膜性房颤患者接受110 mg （DE110）或150 mg （DE150）的达比加群酯治疗。在前瞻性随访期间，血块凝血酶抑制剂（HTI）测定、凝血酶原时间和活化的部分凝血活酶时间（APTT）测量与出血事件相关。208例患者（74.7±10.3岁，67.9%男性，中位随访364天）中有17例出血事件（8.2%），而15例出血事件患者使用DE110。与DE110相比，接受DE150的患者年龄更小，且多为男性，且HAS-BLED和CHA2DS2VASc评分更低，肾功能更好。患者HTI水平变化很大（DE110, 10 - 90百分位数：20.5-223.9 ng/ml）。根据受体-操作者特征曲线，HTI水平的中位数临界值为117.7 ng/ml，可用于预测出血事件（C-statistics: 0.65; P = 0.036），但凝血酶原时间或APTT的临界值无法确定。Kaplan-Meier分析显示，达比加群酯水平大于117.7 ng/ml与较高的出血率相关（15.4% vs. 4.9%, P = 0.01）。经多因素Cox回归分析，HTI水平、卒中史和男性是出血事件的独立危险因素。在接受常规临床护理的患者中，达比加群酯- hti水平与出血独立相关。由于达比加群酯- hti水平变化很大，可能需要在多个时间点采血以提高可靠性。
Special circumstances may require the measurement of the anticoagulant effect of dabigatran etexilate. No data currently link any given coagulation test to bleeding outcomes in patients receiving dabigatran etexilate for atrial fibrillation. Nonvalvular atrial fibrillation patients receiving dabigatran etexilate of 110 mg (DE110) or 150 mg (DE150) were consecutively enrolled. The hemoclot thrombin inhibitor (HTI) assay, prothrombin time, and activated partial thromboplastin time (APTT) measurements were correlated with bleeding events during a prospective follow-up. There were 17 bleeding events (8.2%) in 208 patients (74.7 ± 10.3 years old, 67.9% male, median follow-up: 364 days), whereas 15 patients with bleeding events used DE110. Compared with DE110, the patients receiving DE150 were younger and more often male and had lower HAS-BLED and CHA2DS2VASc scores and better renal function. Patients’ HTI levels were very variable (DE110, 10–90th percentile: 20.5–223.9 ng/ml). A receiver-operator characteristic curve gave a median cutoff HTI level of 117.7 ng/ml to predict bleeding events (C-statistics: 0.65; P = 0.036), but no cutoff could be determined for prothrombin time or APTT. Based on the Kaplan–Meier analysis, a dabigatran etexilate level greater than 117.7 ng/ml was associated with a higher bleeding rate (15.4% vs. 4.9%, P = 0.01). After multivariate Cox regression analysis, HTI levels, history of stroke, and male sex were independent risk factors for bleeding events. Dabigatran etexilate-HTI levels were independently associated with bleeding in patients receiving routine clinical care. Blood sampling at multiple time points might be needed to increase reliability because of high variation of dabigatran etexilate-HTI levels.