Pipilis Athanasios, Makrygiannis Stamatis, Anagnostou Georgios, Kaliampakos Sotirios, Tsakonas Georgios, Sourlas Nikolaos, Mallios Panagiotis, Kostelidou Theodora
1st Cardiac Department, Diagnostic and Therapeutic Centre of Athens "Hygeia", 4, Erythrou Stavrou Str, Maroussi, 151 23, Athens, Greece.
Haematology Anticoagulation Department, Diagnostic and Therapeutic Centre of Athens "Hygeia", 4, Erythrou Stavrou Str, Maroussi, 151 23, Athens, Greece.
J Thromb Thrombolysis. 2017 Jul;44(1):9-13. doi: 10.1007/s11239-017-1503-3.
According to current recommendations, patients on dabigatran should stop the drug 24-96 h before scheduled surgery. This may seem too long for non-elective cases. The aim of our study was to assess the number of patients on dabigatran who could theoretically undergo surgery 12 h post last drug dosing. We measured dabigatran plasma trough concentration by Hemoclot assay in 75 consecutive patients receiving dabigatran. Coagulation was assessed by aPTT and thromboelastography (TEG). Plasma levels ≤30 ng/ml were considered low. TEG parameters measured were clot reaction time (R), clot growth index (k), angle (α), maximal amplitude (MA) and the percentage of clot lysed after 30 min (LY30). Twelve patients (16%) had low plasma dabigatran levels 11.6 ± 0.9 h post last dosing. These patients compared to those with higher levels had significantly different aPTT (37.7 ± 4.4 vs. 49.6 ± 9.2 s; p < 0.001) and TEG R (6.7 ± 1.3 vs. 8.4 ± 2.6 min; p = 0.002). Only three of the patients with low levels had an aPTT >40 s. Within those with levels >30 ng/ml, four patients (6.4%) had plasma dabigatran levels ≥200 ng/ml, all with aPTT >65 s and TEG R >11 min. When the analysis was restricted to patients with creatinine clearance >80 ml/min, six (27.3%) had low plasma dabigatran levels. In this theoretical study, with a low risk population, it is suggested that one-sixth of patients receiving dabigatran have low drug concentrations at 12 h. Further studies are needed to confirm that such patients with low trough levels can actually undergo safely early surgery if necessary.
根据目前的建议，服用达比加群的患者应在预定手术前24 - 96小时停药。对于非择期手术病例而言，这一时间可能显得过长。我们研究的目的是评估理论上在最后一次给药12小时后能够接受手术的服用达比加群的患者数量。我们通过Hemoclot检测法对75例连续服用达比加群的患者测定了达比加群血浆谷浓度。通过活化部分凝血活酶时间（aPTT）和血栓弹力图（TEG）评估凝血情况。血浆水平≤30 ng/ml被视为低水平。测定的TEG参数包括凝血反应时间（R）、凝血形成指数（k）、角度（α）、最大振幅（MA）以及30分钟后凝血溶解百分比（LY30）。12例患者（16%）在最后一次给药11.6±0.9小时后血浆达比加群水平较低。与血浆水平较高的患者相比，这些患者的aPTT（37.7±4.4秒对49.6±9.2秒；p<0.001）和TEG R（6.7±1.3分钟对8.4±2.6分钟；p = 0.002）有显著差异。血浆水平低的患者中只有3例aPTT>40秒。在血浆水平>30 ng/ml的患者中，4例患者（6.4%）血浆达比加群水平≥200 ng/ml，所有患者aPTT>65秒且TEG R>11分钟。当分析仅限于肌酐清除率>80 ml/min的患者时，6例（27.3%）患者血浆达比加群水平较低。在这项针对低风险人群的理论研究中，提示六分之一服用达比加群的患者在12小时时药物浓度较低。需要进一步研究以确认这些谷浓度低的患者在必要时是否真的能够安全地尽早接受手术。
