全膝关节置换术后多次静脉应用氨甲环酸对纤溶活性及炎症反应的影响

The effects of multiple intravenous tranexamic acid administrations after total knee arthroplasty on fibrinolytic activity and inflammatory response

目的探讨全膝关节置换术后多次静脉应用氨甲环酸对纤溶活性及炎症反应的影响。方法回顾性分析2016年1月至2017年4月因膝关节重度骨关节炎行初次单侧全膝关节置换术的141例患者，根据术后静脉应用氨甲环酸的剂量分为三组：氨甲环酸≤3g组40例，氨甲环酸4g组50例，氨甲环酸95g组51例。比较三组患者总失血量、隐性失血量、输血率、最大血红蛋白下降值、血栓事件（下肢肌间静脉血栓、深静脉血栓及肺栓塞）发生率、围手术期纤溶指标（纤维蛋白及纤维蛋白原降解产物、D-二聚体）、炎性指标（C-反应蛋白、白细胞介素．6）水平，分析氨甲环酸应用剂量与纤溶及炎性指标的相关性。结果≤3g、4g及95g组围手术期总失血量分别为（748．22±394．34）ml、（537．16±270．43）ml、（541．31±290．00）ml，隐性失血量分别为（636．47±388．14）ml、（431．36±271．99）ml、（439．94±290．71）ml，最大血红蛋白下降值分别为（25．88±11．77）g／L、（19．68±10．68）g／L、（20．24±8148）g/L。相较≤3g组，4g及95g组总失血量（P=0．012，P=0．013）、隐性失血量（P=0．011，P=0．015）及最大血红蛋白下降值（P=0．005，P=0．010）更低。三组均无接受输血患者。术后2周下肢肌间静脉血栓发生率的组问差异无统计学意义（p〉0．05），均无深静脉血栓形成及肺栓塞发生。术后静脉应用氨甲环酸剂量与术后第1、3天纤维蛋白及纤维蛋白原降解产物（r=0．191，P=0．025；r=0．291，P=0．001）及术后第3天D-二聚体水平（r=-0．176，P=0．048）呈负相关；与术后第1天C-反应蛋白（r=0．184，P=0．036）和白细胞介素．6水平（r=0．269，P=0．002）呈负相关。结论全膝关节置换术后多次大量静脉应用氨甲环酸（≥4g）可进一步减少总失血量、隐性失血量和血红蛋白下降值，且不增加血栓事件的风险。随着氨甲环酸用量增加，其抗纤溶作用增强，可能具有潜在的抗炎作用。

Objective To explore the effects of multiple intravenous tranexamic acid （IV-TXA） administrations after total knee arthroplasty （TKA） on fibrinolytic activity and inflammatory response in an enhanced recovery after surgery （ERAS） program and to assess the efficacy and safety of IV-TXA. Methods One hundred and forty-one severe knee osteoarthritis patients following primary unilateral TKA from January 2016 to April 2017 were investigated retrospectively. The patients were divided into following three groups based on the dosage of IV-TXA after surgery： 40 patients received ≤3 g IV-TXA after surgery （group T1）, 50 patients received 4 g （group T2） and the other 51 patients received≥5 g IV-TXA （group T3）. The total blood loss （TBL）, hidden blood loss （HBL）, transfusion rate, maximum hemoglobin （Hb） drop, the incidence of intramuscular venous thrombosis, deep vein thrombosis （DVT） and pulmonary embolism （PE）, fibrinolysis parameters [fibrin（-ogen） degradation products （FDP）, D-dimer], and inflammation markers [C-reactive protein （CRP）, interleukin-6 （IL-6）] during perioperative period were evaluated. In addition, correlation analyses between the dosage of IV-TXA and fibrinolysis parameters and inflammation markers were conducted. Results The mean TBL, HBL and maximum Hb drop in group T2 （537.16±270.43 ml, 431.36±271.99 ml, 19.68± 10.68 g/L） and T3 （541.31±290.00 ml, 439.94±290.71 ml, 20.24±8.48 g/L） were lower than those in group T1 （748.22±394.34 ml, P=0.012, 0.013; 636.47±388.14 ml, P=0.011, 0.015; 25.88± 11.77 g/L, P=0.005, 0.010, respectively）. No patient needed transfusion in all groups. There was no statistically difference in the incidence of intramuscular venous thrombosis of lower limbs among three groups （P〉 0.05）. No episode of DVT or PE occurred in any group in two weeks after surgery. There were negative correlation between the dosage of IV-TXA and FDP at postoperative day 1 and day 3 （r=-0.191, P=0.025; r=-0.291, P=0.001） and D-dimer on postoperative day 3 （r=-0.176, P=0.048）. Moreover, the CRP （r=-0.184, P=0.036） and IL-6 （r=-0.269, P=0.002） level in serum on postoperative day 1 also showed a negative relationship with the dosage of IV-TXA after surgery. Conclusion The multiple IV-TXA （≥4 g） after surgery can further reduce the TBL, HBL and maximum Hb drop following primary TKA in ERAS program without increasing the risk of thrombotic events. Most importantly, the effect of anti-fibrinolysis will be enhanced and may have an anti-inflammatory effect with the dosage of IV-TXA increased.