Rozen Laurence, Faraoni David, Sanchez Torres Cristel, Willems Ariane, Noubouossie Denis C F, Barglazan Dragos, Van der Linden Philippe, Demulder Anne
From the Laboratory of Haemostasis, Brugmann University Hospital, Université libre de Bruxelles ULB, Brussels, Belgium (LR, DCFN, AD), Department of Anesthesiology, Peri-operative and Pain Medicine, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, USA (DF), Department of Anaesthesiology, Queen Fabiola Children's University Hospital (CST, PVDL), Paediatric Intensive Care Unit, Queen Fabiola Children's Hospital (AW), and Chemistry Laboratory, Brugmann University Hospital, Université libre de Bruxelles ULB, Brussels, Belgium (DB).
Eur J Anaesthesiol. 2015 Dec;32(12):844-50. doi: 10.1097/EJA.0000000000000316.
Although recent studies have assessed tranexamic acid (TXA) pharmacokinetics in different subgroups, the effective concentration of TXA required to completely inhibit fibrinolysis remains to be determined.
An in-vitro determination of the effective TXA concentration needed for 95% inhibition (EC95) of tissue-type plasminogen activator (t-PA) activated fibrinolysis, using an experimental model designed for thromboelastometry (ROTEM).
A prospective interventional study.
Department of Anaesthesiology, Queen Fabiola Children's University Hospital and Laboratory of Haematology and Haemostasis, Brugmann University Hospital. Patients were enrolled between June 2013 and October 2014.
Twenty children, aged between 1 and 10 years, undergoing elective cardiac catheterisation were included (10 with cyanotic and 10 with noncyanotic diseases). Exclusion criteria were child requiring a procedure in a moribund state. Ten adult volunteers were also included as controls.
Citrated whole blood samples were obtained from children and volunteers.
The extrinsic coagulation pathway was activated by tissue factor using the EXTEM test on ROTEM. The degree of lysis measured 30 min (LI30) after the clotting time (CT), and clot amplitudes measured at different times were recorded at baseline, after addition of 1535 units t-PA ml(-1), and following the addition of increasing TXA concentrations in t-PA activated samples.
The concentration-effect analysis performed with lysis index after 30 min (LI30) allowed the determination of TXA efficacy concentration 50% (EC50), and calculation of the EC95, which was significantly lower in cardiac surgery children than in adults [8.6 μg ml(-1); 95% confidence interval (95% CI) 6.9 to 14.9 versus 11.3 μg ml(-1); 95% CI 10.6 to 12.9, P < 0.001].
In this in-vitro study, we observed that the EC95 TXA concentration that completely inhibited t-PA induced hyperfibrinolysis in children with congenital heart was significantly lower than the concentration required in healthy adult volunteers. Further studies are needed to confirm that this plasma concentration can effectively inhibit fibrinolysis activation in children undergoing cardiac surgery.
尽管最近的研究评估了不同亚组中氨甲环酸（TXA）的药代动力学，但完全抑制纤维蛋白溶解所需的TXA有效浓度仍有待确定。
使用专为血栓弹力图法（ROTEM）设计的实验模型，体外测定组织型纤溶酶原激活剂（t-PA）激活的纤维蛋白溶解95%抑制率（EC95）所需的TXA有效浓度。
一项前瞻性干预研究。
法比奥拉女王儿童医院麻醉科以及布鲁格曼大学医院血液学和止血实验室。患者于2013年6月至2014年10月入组。
纳入20名年龄在1至10岁之间接受择期心导管插入术的儿童（10名患有紫绀型疾病，10名患有非紫绀型疾病）。排除标准为处于濒死状态需要进行手术的儿童。还纳入10名成年志愿者作为对照。
从儿童和志愿者中采集枸橼酸化全血样本。
在ROTEM上使用EXTEM试验通过组织因子激活外源性凝血途径。在凝血时间（CT）后30分钟测量溶解程度（LI30），并记录在基线、加入1535单位t-PA/ml(-1)后以及在t-PA激活样本中加入递增浓度的TXA后不同时间测量的血凝块幅度。
用30分钟后的溶解指数（LI30）进行的浓度-效应分析可确定TXA的半数有效浓度（EC50），并计算出EC95，其在心脏手术儿童中显著低于成年人[8.6μg/ml；95%置信区间（95%CI）6.9至14.9，而成年人中为11.3μg/ml；95%CI 10.6至12.9，P<0.001]。
在这项体外研究中，我们观察到在先天性心脏病儿童中完全抑制t-PA诱导的高纤维蛋白溶解的TXA EC95浓度显著低于健康成年志愿者所需的浓度。需要进一步研究以证实该血浆浓度能有效抑制接受心脏手术儿童的纤维蛋白溶解激活。
