阿加曲班预防危重症患者深静脉血栓形成的有效性与安全性

Efficiency and safety of argatroban for preventing critical patients from developing deep vein thrombosis

目的探讨阿加曲班对危重症患者抗凝治疗的有效性与安全性。方法采用前瞻性随机对照研究,将预期住ICU时间>7 d且具有血栓形成高危因素的62例患者纳入本研究,按随机数字表法分组:阿加曲班组(n=32),每日给予阿加曲班注射剂20 mg,静脉滴注,2次/d,共7 d;依诺肝素组(n=30),每日给予依诺肝素钠注射剂4 000 IU(0.4 m L),皮下注射,1次/d,共7 d。两组其余药物及脏器支持治疗相同。两组均于治疗前、治疗24和72 h以及第7日晨抽取静脉血,检测凝血指标和肝肾功能,彩色超声检查有无深静脉血栓(DVT)形成,临床观察患者有无DVT形成的临床症状、全身出血情况、ICU住院时间以及住院28 d病死率。结果两组患者血浆凝血酶原时间(PT)、国际标准比值(INR)和部分活化凝血酶时间(a PTT)较治疗前均有明显升高,血小板计数(PLT)、纤维蛋白原(Fib)和D-二聚体(D-D)处于较低的正常水平,阿加曲班组在24 h可达到抗凝治疗目标,依诺肝素组在72 h才达到抗凝治疗要求,但在7 d后均能达到治疗目标,组间比较在24和72 h差异有统计学意义(P<0.05),在7 d后差异无统计学意义(P>0.05)。阿加曲班组有1例DVT形成、1例出血事件、无过敏反应和肝功能损伤发生;依诺肝素组有6例DVT形成、4例出血事件、1例过敏反应和1例肝功能损伤。与依诺肝素组比较,阿加曲班组机械通气时间(h)、ICU住院时间(d)明显缩短(160.50±30.36对183.60±29.85,11.41±3.51对15.83±4.95,均P<0.05),但28 d病死率不下降(15.6%对13.3%,P>0.05)。结论阿加曲班能够快速达到抗凝治疗目标,对预防DVT形成有很好的作用,且不良事件发生率低,可缩短ICU住院时间和机械通气时间,但不改变28 d病死率。

Objective To investigate the efficiency and safety of argatroban for anticoagulation therapy of critical ill patients.Methods Prospective randomized controlled study was adopted.A total of 62 patients with high risk of thrombosis who were expected to stay in ICU for more than 7 d were selected and randomly divided into the argatroban group（n=32） and enoxaparin group（n=30）.Patients of the argatroban group were intravenously injected with 20 mg of argatroban twice a day for 7 d and patients of the enoxaparin group were injected with 4 000 IU（0.4 mL） of enoxaparin once a day for 7 d.Other drugs and organ support therapy of two groups were the same.Venous blood of two groups was drawn before treatment and at 24 h,72 h,and in the morning of 7 d after treatment.Coagulation indexes and liver and kidney functions were detected.Color ultrasound examination was conducted to detect whether deep vein thrombosis（DVT） has developed.Clinical symptoms of DVT bleeding,ICU stay time,and mortality of hospitalization time of 28 d of patients were observed.Results Prothrombin time,international normalized ratio,and activated partial thromboplastin time of two groups after treatment were significantly higher than those of before treatment.Platelet count,fibrinogen,and D-dime were at low end of normal range.The argatroban group and enoxaparin group met the goal of anticoagulation therapy 24 h and 72 h after treatment,respectively.Both groups met the goal of therapy7 d after treatment.The differences between two groups at 24 h and 72 h were statistically significant（P〈0.05）,while the differences between two groups on 7 d were not statistically significant（P〉0.05）.For the argatroban group,1 patient developed DVT,1 patient developed bleeding,and no allergic reactions and liver dysfunction occurred.For the enoxaparin group,6 patients developed DVT,4 patients developed bleeding,1 patient developed allergic reactions,and 1 patient developed liver damage.Compared with the enoxaparin group,the mechanical ventilation time（h） and ICU stay time（d） of the argatroban group were significantly shorter（160.50±30.36 vs 183.60±29.85,11.41 ±3.51 vs 15.83 ±4.95,P〈0.05）.However,the mortality of hospitalization time of 28 d remained the same.Conclusion Argatroban can quickly meet the goal of anticoagulation therapy,satisfactorily prevent the development of DVT,and shorten the ICU stay time and mechanical ventilation time with low incidence of adverse events,but does not change the mortality of hospitalization time of 28 d.