利伐沙班用于急性肺栓塞的抗凝效果及对血清Hcy、BNP、TnI与D-D水平的影响

目的:探讨利伐沙班用于急性肺栓塞的抗凝效果及对血清脑钠肽(Brain natriuretic peptide,BNP)、肌钙蛋白I (Troponin I,TnI)、D-二聚体(D-Dimer,D-D)、同型半胱氨酸(homocysteine,Hcy)水平的影响。方法:选择2014年2月至2017年12月在我院进行治疗的(高)中危组急性肺栓塞患者106例,并将其随机分为观察组和对照组。对照组皮下注射低分子肝素钙搭配华法林治疗,观察组予以利伐沙班治疗,观察和比较两组患者的临床疗效、治疗前后血清BNP、TnI、D-D、Hcy水平的变化及不良反应的发生情况。结果:治疗后,观察组患者总有效率为94.37%,显著高于对照组(42.10%,P0.05);观察组患者血清BNP、TnI、D-D、Hcy及肺动脉收缩压水平均显著低于对照组(P0.05),而动脉收缩压、动脉血氧分压水平较对照组水平显著升高(P0.05)。结论:利伐沙班应用于治疗急性肺栓塞的抗凝效果显著优于低分子肝素钙搭配华法林治疗,其可有效降低患者血清BNP、TnI、D-D、Hcy水平以及肺动脉收缩压。     

血栓通注射液联合利伐沙班预防下肢骨折术后下肢深静脉血栓形成疗效及对患者血液流变学的影响

目的:探讨血栓通注射液联合利伐沙班预防下肢骨折术后下肢深静脉血栓(DVT)形成的疗效及对患者血液流变学的影响。方法:选取2012年4月到2015年7月西安医学院第一附属医院收治的125例下肢骨折术后患者,随机分为对照组63例和观察组62例,对照组患者给予血栓通治疗,观察组患者在对照组的基础上给予利伐沙班治疗。观察两组治疗前后DVT发生率、血清D-二聚体(DD)、同型半胱氨酸(Hcy)以及高敏C-反应蛋白(hs-CRP)、血液流变学指标包括红细胞压积(HTC)、全血黏度(WBV)和纤维蛋白原的变化以及用药安全性。结果:术后3周,观察组DVT的总发生率为9.7%(6例),显著低于对照组的44.4%(28例),差异具有统计学意义(P0.05)。治疗后,两组患者的血清DD、Hcy、hs-CRP、HTC、WBV以及纤维蛋白原水平均较治疗前明显降低(P0.05),且观察组该6个指标显著低于对照组,差异均具有统计学意义(P0.05)。此外,观察组的不良反应发生率为9.68%,对照组为7.94%,两组间比较无明显差异(P0.05)。结论:血栓通注射液联合利伐沙班可有效减少DVT的发生并改善患者的血液高凝状态,是一种预防下肢骨折术后DVT形成的有效方案。     

利伐沙班与低分子肝素对老年AECOPD患者症状缓解、血气分析指标及凝血功能的影响

目的:探讨利伐沙班与低分子肝素对老年慢性阻塞性肺疾病急性加重期(AECOPD)患者症状缓解、血气分析指标及凝血功能的影响。方法:选取2016年8月~2019年11月期间我院收治的老年AECOPD患者72例,按照抽签法分为对照组(n=36,低分子肝素治疗)和研究组(n=36,利伐沙班治疗),对比两组疗效、症状缓解、血气分析指标及凝血功能,记录治疗期间不良反应情况。结果:研究组治疗10d后总有效率较对照组高(P<0.05)。两组咳嗽、咳痰、发热、呼吸困难症状缓解时间对比差异无统计学意义(P>0.05)。治疗10d后两组氧分压(PaO₂)、氧饱和度(SaO₂)升高,二氧化碳分压(PaCO₂)降低(P<0.05),研究组治疗10d后PaO₂、SaO₂较对照组高,PaCO₂低于对照组(P<0.05)。治疗10d后两组纤维蛋白原(Fib)升高,D-二聚体(D-D)、活化部分凝血活酶时间(APTT)、血浆凝血酶原时间(PT)、凝血酶时间(TT)均降低(P<0.05),治疗10d后研究组D-D低于对照组(P<0.05),治疗10d后两组Fib、APTT、TT、PT组间比较无差异(P>0.05)。两组不良反应发生率比较无差异(P>0.05)。结论:老年AECOPD患者采用利伐沙班与低分子肝素治疗,均可改善患者临床症状且安全性较好,但采用利伐沙班治疗者疗效更好,血气分析指标及凝血功能改善更佳。     

氨甲环酸联合利伐沙班对单侧全膝关节置换术后患者出血量、凝血功能以及膝关节功能的影响

目的:探讨氨甲环酸联合利伐沙班对单侧全膝关节置换术后患者出血量、凝血功能及膝关节功能的影响。方法:选取2015年1月-2016年1月在解放军425医院骨科初次行单侧全膝关节置换术的患者66例为研究对象,按照随机数字表法分为治疗组与对照组,每组各33例。治疗组患者在止血带释放前向关节腔内注射氨甲环酸,对照组患者则给予氯化钠注射液进行静脉滴注,在术后6-12h内两组患者均口服利伐沙班。记录并对比两组患者总失血量、隐性出血量、输血率、输血量,对比两组患者手术前后凝血功能指标、膝关节功能评分、膝关节活动度、疼痛视觉模拟评分(VAS),并观察两组患者并发症发生情况。结果:与对照组对比,治疗组患者的总失血量、隐性出血量、输血量及输血率均明显降低(P0.05);治疗组与对照组患者术前与术后3 d的活化部分凝血酶时间(APTT)、凝血酶原时间(PT)、纤维蛋白原(FG)水平比较均无显著差异(P0.05);术前两组患者的美国膝关节协会评分(AKSS)及膝关节活动度比较无显著差异(P0.05),术后7 d,治疗组与对照组患者的AKSS评分及膝关节活动度均较术前升高(P0.05),且治疗组患者的AKSS评分及膝关节活动度高于同时期对照组(P0.05);术前两组VAS评分比较无显著差异(P0.05),术后1 d,两组患者的VAS评分比较及与同组术前比较均无显著差异(P0.05),术后7 d,两组患者的VAS评分明显较术前及术后1 d降低(P0.05),但两组之间比较无显著差异(P0.05)。两组患者并发症总发生率对比无显著差异(P0.05)。结论:氨甲环酸联合利伐沙班可有效降低行单侧全膝关节置换术患者的出血量,加快关节功能的恢复,且不影响患者的凝血功能,值得临床推广。     

利伐沙班和达比加群酯在高龄非瓣膜性房颤患者中的有效性及安全性观察

目的:探讨利伐沙班及达比加群酯在高龄老年非瓣膜性AF患者中应用的有效性及安全性。方法:回顾性分析2016年9月至2018年3月于我院心血管内科住院治疗的高龄非瓣膜性房颤患者202例(利伐沙班组116例,达比加群酯组86例),平均随访9个月,比较两组患者基本临床资料、栓塞事件和临床相关出血事件。结果:利伐沙班组和达比加群酯组各有4例患者达到有效性终点,两组药物有效性无显著性差异(P0.05)。其中,缺血性脑卒中是最常见的栓塞事件(4/8)。利伐沙班组共有15例患者发生出血事件,达比加群酯组共有10例患者发生出血事件,两组药物安全性亦无显著性差异(P0.05)。胃肠道出血是最常见的出血事件(7/25)。结论:利伐沙班及达比加群酯在高龄老年非瓣膜性AF患者中应用的有效性及安全性均无明显差异。     

不同剂量利伐沙班对老年髋关节置换术患者凝血功能及下肢深静脉血栓的影响

目的:探讨不同剂量利伐沙班对老年髋关节置换术患者凝血功能及下肢深静脉血栓(DVT)的影响。方法:选择2013年6月~2016年6月期间我院收治的200例老年髋关节置换术患者,按随机数字表法分为两组各100例,术后分别予利伐沙班5 mg、10mg口服以预防DVT。术前及术后1d、7d检测纤维蛋白原(Fbg)、凝血酶原时间(PT)、凝血酶时间(TT)、活化部分凝血酶原时间(APTT)及D-二聚体(D-D),同时行下肢彩色多普勒超声检查判断DVT发生情况,观察临床出血事件。结果:术后1d两组Fbg水平明显降低,PT明显延长(均P0.05);术后7d两组Fbg水平与术后1d相比明显回升,PT明显缩短(均P0.05)。两组各时期的Fbg与PT均无明显差异(P0.05)。术后1d两组D-D水平均明显升高(P0.05),且利伐沙班5 mg组明显高于利伐沙班10 mg组(P0.05);术后7d两组D-D水平均较术后1d明显降低(P0.05),且利伐沙班10 mg组明显低于利伐沙班5 mg组(P0.05)。利伐沙班10 mg组术后早期DVT发生率明显低于利伐沙班5 mg组(P0.05)。两组预防性抗凝后临床出血事件的发生率比较无统计学差异(P0.05)。结论:老年髋关节置换术后口服大剂量(10 mg)利伐沙班,可有效改善血液高凝状态,降低DVT发生率,且不会明显增加临床出血事件,值得推广。     

Rivaroxaban modulates electrical and mechanical characteristics of left atrium

Background

Rivaroxaban reduces stroke in patients with atrial fibrillation (AF). Left atrium (LA) plays a critical role in the pathophysiology of AF. However, the electromechanical effects of rivaroxaban on LA are not clear.

Results

Conventional microelectrodes and a whole-cell patch-clamp were used to record the action potentials (APs) and ionic currents in rabbit LA preparations and isolated single LA cardiomyocytes before and after the administration of rivaroxaban. Rivaroxaban (10, 30, 100, and 300 nM) concentration-dependently reduced LA (n = 7) AP durations at 90% repolarization (APD₉₀) from 76 ± 2 to 79 ± 3, 67 ± 4 (P < 0.05, vs. control), 59 ± 5, (P < 0.01, vs. control), and 56 ± 4 ms (P < 0.005, vs. control), respectively. Rivaroxaban (10, 30, 100, and 300 nM) concentration-dependently increased the LA (n = 7) diastolic tension by 351 ± 69 (P < 0.05, vs. control), 563 ± 136 (P < 0.05, vs. control), 582 ± 119 (P < 0.05, vs. control), and 603 ± 108 mg (P < 0.005, vs. control), respectively, but did not change LA contractility. In the presence of L-NAME (100 μM) and indomethacin (10 μM), additional rivaroxaban (300 nM) treatment did not significantly further increase the LA (n = 7) diastolic tension, but shortened the APD₉₀ from 73 ± 2 to 60 ± 6 ms (P < 0.05, vs. control). Rivaroxaban (100 nM) increased the L-type calcium current and ultra-rapid delayed rectifier potassium current, but did not change the transient outward potassium current in isolated LA cardiomyocytes.

Conclusions

Rivaroxaban modulates LA electrical and mechanical characteristics with direct ionic current effects.     

The new oral anticoagulants in atrial fibrillation: an update

In patients with nonvalvular atrial fibrillation, oral anticoagulation with the vitamin K antagonists acenocoumarol, phenprocoumon and warfarin reduces the risk of stroke by more than 60 %, whereas single or double antiplatelet therapy is much less effective and sometimes associated with a similar bleeding risk as vitamin K antagonists. Besides bleeding, and intracranial haemorrhage in particular, INR monitoring remains the largest drawback of vitamin K antagonists. In the last decade oral agents have been developed that directly block the activity of thrombin (factor IIa), as well as drugs that directly inhibit activated factor X (Xa), which is the first compound in the final common pathway to the activation of thrombin. These agents have been approved for stroke prevention in atrial fibrillation and are now reimbursed under a national guideline for their safe use. They have advantages in that they do not need monitoring and have a fast onset and offset of action, but lack an established specific antidote. This survey addresses the role of modern anticoagulation for stroke prevention in atrial fibrillation.     

Design of a liquid nano-sized drug delivery system with enhanced solubility of rivaroxaban for venous thromboembolism management in paediatric patients and emergency cases

Abstract

The increasing incidence of venous thromboembolism (VTE) in paediatric population has stimulated the development of liquid anticoagulant formulations. Thus our goal is to formulate a liquid formulation of poorly-water soluble anticoagulant, rivaroxaban (RIVA), for paediatric use and to assess the possibility of its intravenous administration in emergencies. Self-nanoemulsifying drug delivery systems (SNEDDSs) were developed and characterized. SNEDDS constituents were estimated from the saturated solubility study followed by plotting the corresponding ternary phase diagrams to determine the best self-emulsified systems. Thermodynamic stability, emulsification, dispersibility, robustness to dilution tests, in vitro dissolution, particle size, and zeta potential were executed to optimize the formulations. The optimized formulation, that composed of Capryol 90:Tween 20:PEG 300 (5:45:50), increased RIVA solubility (285.7-fold than water), it formed nanoemulsion with a particle size of 16.15?nm, PDI of 0.25 and zeta potential of ?21.8. It released 100.83?±?2.78% of RIVA after 5?min. SNEDDS was robust to dilution with oral and parenteral fluids and showed safety to human RBCs. SNEDDS showed enhanced bioavailability after oral and intravenous administration than the oral drug suspension (by 1.25 and 1.26-fold, respectively). Moreover, it exhibited enhanced anticoagulant efficacy in the prevention and treatment of carrageenan-induced thrombosis rat model.     

利伐沙班联合血塞通在预防老年髋部术后深静脉血栓形成中的疗效及对 血液高凝状态的影响

目的:探究利伐沙班联合血塞通在预防老年髋部术后深静脉血栓(DVT)形成中的疗效及对血液高凝状态的影响。方法:收集2012年9月-2015年10月期间我院下肢骨折行手术治疗患者118例为研究对象,采用随机数字法将其分为观察组(60例)和对照组(58例),对照组患者给予血塞通治疗,观察组患者在对照组基础上给予利伐沙班联合治疗,观察并比较两组患者治疗前后血液炎性指标、流变学指标及DVT的发生率。结果:观察组患者术后DVT发生率为11.67%,显著低于对照组的44.83%,差异具有统计学意义(P0.05);治疗后两组患者C反应蛋白(CRP)、同型半胱氨酸及二聚体(D-D)水平较治疗前均出现显著下降(P0.05),且观察组CRP、同型半胱氨酸及D-D水平均低于对照组,差异均有统计学意义(P0.05);治疗后两组患者全血黏度、红细胞压积、纤维蛋白原水平较治疗前均出现显著下降(P0.05),且观察组全血黏度、红细胞压积、纤维蛋白原水平均低于对照组,差异均有统计学意义(P0.05)。结论:利伐沙班联合血塞通在预防老年髋部术后DVT形成中疗效显著,可显著降低术后患者DVT的发生率,改善血液高凝状态,具有十分重要的临床价值。