骨科大手术中的静脉血栓的预防:口服抗凝药的系统回顾和间接比较

目的:基于有效的循证证据,以低分子肝素为对照组,分析达比加群、阿哌沙班和利伐沙班在骨科大手术后预防静脉血栓的有效性与安全性。方法:在Pub Med和Embase中系统地检索随机对照试验以及参考文献中关键的文章,这些文章评价了以低分子肝素为对照组,达比加群、阿哌沙班和利伐沙班在进行了骨科大手术的病人中的作用。结果:评价的结果包括总静脉血栓(total VTE)、深静脉血栓(DVT)、肺栓塞(PE)、死亡和主要出血事件(major bleeding)。笔者独立地评价了每1篇文章的方法质量同时独立地提取了文献数据。在总静脉血栓预防方面,利伐沙班和阿哌沙班优于达比加群,分别为[RR=0.37,95%CI(0.23,0.60)]和[RR=0.58,95%CI(0.35,0.96)]。利伐沙班和阿哌沙班之间没有区别[RR=0.64,95%CI(0.33,1.25)]。利伐沙班与阿哌沙班相比增加了出血风险[RR=1.57,95%CI(1.20,2.07)],利伐沙班与达比加群相比增加了出血风险[RR=1.25,95%CI(0.93,1.70)]。阿哌沙班和达比加群在出血方面没有差别[RR=0.78,95%CI(0.58,1.07)]。结论:在接受骨科大手术病人之中,利伐沙班和阿哌沙班2种药物与达比加群相比,预防静脉血栓的效果更好,出血风险相似。利伐沙班与阿哌沙班相比,预防静脉血栓的效果相似,但是增加了出血的风险。     

利伐沙班与低分子肝素对髋关节置换术后并发症的影响

目的 比较利伐沙班和低分子肝素在预防全髋关节置换术术后对患者深静脉血栓(DVT)形成的影响及疗效。方法 126例行全髋关节置换术的患者随机分为利伐沙班组和低分子肝素组。低分子肝素组(n=70)术前12 h或术后24 h给予低分子肝素注射液,皮下注射,40 mg,1 次·d^-1,连续给药14 d。利伐沙班组(n=56)术后6~8 h给予利伐沙班口服,10 mg,1次·d^-1,连续给药35 d。观察2组术中出血量和术后引流量,比较2组的安全性指标以及术后DVT的发生率。结果 2组术中出血量、术后引流量、术后下肢DVT发生率比较差异无统计学意义(P>0.05)。利伐沙班组增加了患者术后出血、切口感染、切口不愈合或延期愈合等不良事件的风险,与低分子肝素组比较差异有统计学意义(P<0.05)。结论 在全髋关节置换术后预防DVT方面,利伐沙班和低分子肝素的疗效相似,但术后伤口并发症发生率明显高于低分子肝素,使用利伐沙班的安全性需要进一步验证。     

低分子肝素及利伐沙班预防全髋关节置换术后失血的观察

探讨人工全髋关节置换患者术后应用低分子肝素或利伐沙班对术后出血量的影响。回顾性分析2012年2月至2014年2月共240例行人工全髋关节置换患者,按术后是否应用低分子肝素或利伐沙班分为空白对照组、低分子肝素组及利伐沙班组。统计比较各组术后血红蛋白、血小板的变化及术后总失血量、显性失血量及隐性失血量。 低分子肝素组总失血量明显高于对照组（P＜0.01）,利伐沙班组总失血量明显高于对照组（P＜0.01）。低分子肝素组及利伐沙班组的显性失血量及隐性失血量也明显高于对照组。低分子肝素组与利伐沙班组出血量无明显差异。3组患者中隐性失血量占总失血量的比例无明显差异。髋骨关节置换术后应用低分子肝素及利伐沙班可增加失血量,包括隐性失血量的增加,2种抗凝药物的疗效相当,应密切关注血红蛋白及血小板的变化,充分认识隐性失血,对患者有效血容量的丢失作出正确评估。     

利伐沙班预防髋关节置换术后深静脉血栓形成60例

目的 研究利伐沙班在髋关节置换术后预防深静脉血栓形成的临床疗效.方法 选择医院2009年1月至2011年1月行髋关节置换术的患者120例,随机分成两组(利伐沙班组和低分子肝素组),各60例.利伐沙班组在术后6 h口服10mg利伐沙班,低分子肝素组在术后24 h内皮下注射40mg低分子肝素,均每日1次,持续用药14 d.术后14 d对两组患者行下肢静脉彩色多普勒超声检查,比较两组深静脉血栓形成情况以及术后深静脉血栓发生率.结果 低分子肝素组发生深静脉血栓9例,发生率为15.00%;利伐沙班组发生深静脉血栓2例,发生率为3.33%.两组比较差异有统计学意义(P<0.05).利伐沙班组无不良反应发生.结论 利伐沙班能有效预防髋关节置换术后深静脉血栓形成,且具有良好的安全性,值得,临床推广.     

(定量)构效关系预测利伐沙班有机杂质遗传毒性

目的 通过对利伐沙班原料中有机杂质进行遗传毒性预测,并以杂质遗传毒性进行分类,为实际生产中质量保障体系的建立提供依据。方法 分析利伐沙班的合成工艺,结合实际生产中有可能采用的生产工艺,推测有机杂质,按照国际认可的指导原则,采用基于专家规则和基于统计学规则的2个互补的（定量）构效关系评估[（quantitative） structure-activity relationships, （Q）SAR]预测软件,对18个有机杂质进行遗传毒性预测分析,并依据预测结果按照其致突变性和致癌性进行分类。结果 在18个有机杂质中,需要按遗传毒性杂质控制的杂质有5个,可以按非遗传毒性杂质控制的杂质有13个。结论 采用（Q）SAR评估有关物质的遗传毒性,可实现快速确定杂质毒性特征的目的。预测结果提示利伐沙班应针对具有遗传毒性警示结构的5个杂质建立有效的质量控制体系。     

Rivaroxaban reversal with prothrombin complex concentrate or tranexamic acid in healthy volunteers

Essentials

• Specific reversal agents for managing severe factor Xa inhibitor‐associated bleeding are lacking.
• We assessed 4‐factor‐prothrombin complex concentrate (4F‐PCC) and tranexamic acid (TXA).
• 4F‐PCC, but not TXA, reduced the prothrombin time and increased endogenous thrombin potential.
• These agents may be viable options for reversal of therapeutic doses of rivaroxaban.

Summary

Background

Oral activated factor X inhibitors such as rivaroxaban are widely used, but specific reversal agents are lacking. Although four‐factor prothrombin complex concentrate (4F‐PCC) and tranexamic acid (TXA) are sometimes used to manage serious bleeding, their efficacy is unknown. Prior studies in healthy subjects taking rivaroxaban revealed that 4F‐PCC partially reverses the prolonged prothrombin time (PT), and fully restores the endogenous thrombin potential (ETP). The effect of TXA has not been evaluated.

Methods

In this double‐blind, parallel‐group study, 147 healthy volunteers given rivaroxaban 20 mg twice daily for 3 days were randomized after their morning dose on day 4 to receive intravenous 4F‐PCC (50 IU kg^?1), TXA (1.0 g), or saline. Standardized punch biopsies were performed at baseline and after 4F‐PCC, TXA or saline administration. Reversal was assessed by measuring bleeding duration and bleeding volume at biopsy sites, and by determining the PT and ETP.

Results

As compared with saline, 4F‐PCC partially reversed the PT and completely reversed the ETP, whereas TXA had no effect. Neither 4F‐PCC nor TXA reduced bleeding duration or volume. All treatments were well tolerated, with no recorded adverse events.

Conclusions

Although 4F‐PCC reduced the PT and increased the ETP in volunteers given supratherapeutic doses of rivaroxaban, neither 4F‐PCC nor TXA influenced punch biopsy bleeding.

     

Rivaroxaban for thromboprophylaxis among patients recently hospitalized for acute infectious diseases: a subgroup analysis of the MAGELLAN study

Essentials

• Net benefit of venous thromboprophylaxis (VTE) in patients hospitalized for infections is unknown.
• MAGELLAN trial subgroup analysis was performed for patients hospitalized for acute infectious diseases.
• At day 35, prolonged rivaroxaban prophylaxis reduced VTE compared to enoxaparin (4.2% vs. 6.6%).
• Rivaroxaban prophylaxis reduced VTE in patients hospitalized for active lung infections.

Summary

Background

Despite the well‐established association between infection and venous thromboembolism (VTE), there are few data specifically assessing the efficacy and safety of the VTE prophylaxis strategies for patients hospitalized for acute infectious diseases.

Objectives

To estimate the incidence of VTE and bleeding outcomes, comparing prolonged prophylaxis with rivaroxaban 10 mg daily for 35 days with enoxaparin 40 mg daily for 10 days.

Patients/Methods

A subgroup analysis of patients hospitalized for acute infectious diseases in the MAGELLAN trial was performed. The primary efficacy outcome was the composite of asymptomatic proximal or symptomatic VTE at days 10 and 35. The principal safety outcome was the composite of major or clinically relevant non‐major bleeding.

Results

Three thousand one hundred and seventy‐three patients with acute infectious diseases leading to hospitalization were randomized to either rivaroxaban (n = 1585) or enoxaparin/placebo (n = 1588), and received at least one dose of study medication. At day 10, primary composite efficacy outcomes did not differ between prophylaxis strategies (rivaroxaban, 2.7%; and enoxaparin, 3.7%). At day 35, there were fewer VTE events with rivaroxaban (4.2%) than with enoxaparin (6.6%) (relative risk [RR] 0.64; 95% confidence interval [CI] 0.45–0.92). Patients with pulmonary infections randomized to rivaroxaban had a lower incidence of VTE both at 10 days (RR 0.50, 95% CI 0.28–0.90) and at 35 days (RR 0.54, 95% CI 0.33–0.87). Primary safety outcome events were increased with rivaroxaban (RR 2.42, 95% CI 1.60–3.66).

Conclusions

Prolonged rivaroxaban prophylaxis reduced the incidence of VTE in patients hospitalized for acute infectious diseases, particularly those involving the lungs. Efficacy benefits were, in part, offset by bleeding outcomes. ClinicalTrials.gov Number: NCT 00571649.