Efficacy and safety of fondaparinux versus enoxaparin in patients undergoing percutaneous coronary intervention treated with the glycoprotein IIb/IIIa inhibitor tirofiban

Background: In worldwide, the mortality rate of acute myocardial infarction(AMI) raises year by year. Although the applications of percutaneous coronary intervention(PCI) and anticoagulants effectively reduce the mortality of patients with acute coronary syndrome(ACS), but also increase the incidence of bleeding. Therefore, drugs with stable anticoagulant effects are urgently required.Methods: We enrolled 894 patients with acute coronary syndrome who underwent percutaneous coronary intervention in Shenyang Northern Hospital from February 2010 to May 2012; 430 patients were included in the fondaparinux group(2.5mg/d), and 464 were included in the enoxaparin group(1mg/kg twice daily). Fondaparinux and enoxaparin were applied for 3–7 days. All patients were treated with tirofiban [10μg/kg for 3min initially and 0.15μg/(kg·min) for 1 to 3 days thereafter]. The primary efficacy endpoint was the incidence of a major adverse cerebrovascular or cardiovascular event. The primary safety endpoint was bleeding within 30 days and 1 year after percutaneous coronary intervention.Results: One-year data were available for 422 patients in the fondaparinux group and for 453 in the enoxaparin group. The incidence of a major adverse cerebrovascular or cardiovascular event(10.9% vs 12.6%, P=0.433) and cardiac mortality(0.5% vs 1.5%, P=0.116) were generally lower in the fondaparinux group than in the enoxaparin group, although the differences were not significant. Compared with the enoxaparin group, the fondaparinux group had a significantly decreased rate of bleeding at 30 days(0.9% vs 2.9%, P=0.040) and 1 year(2.4% vs 5.5%, P=0.018). In addition, the rate of major bleeding events was lower in the fondaparinux group, but this difference was not significant(0.2% vs 0.9%, 0.2% vs 1.1%).Conclusion: In tirofiban-treated patients with acute coronary syndrome undergoing percutaneous coronary intervention, fondaparinux presented similar efficacy for ischemia events as enoxaparin. However, fondaparinux significantly decreased the incidence of bleeding, thus providing safer anticoagulation therapy.

Effects of aspirin and enoxaparin in a rat model of liver fibrosis

AIM To examine the effects of aspirin and enoxaparin on liver function, coagulation index and histopathology in a rat model of liver fibrosis.METHODS Forty-five male Sprague-Dawley rats were randomly divided into the control group(n = 5) and model group(n = 40). Thioacetamide(TAA) was used to induce liver fibrosis in the model group. TAA-induced fibrotic rats received TAA continuously(n = 9), TAA + low-dose aspirin(n = 9), TAA + high-dose aspirin(n = 9) or TAA + enoxaparin(n = 9) for 4 wk. All rats were euthanized after 4 wk, and both hematoxylin-eosin and Masson staining were performed to observe pathological changes in liver tissue. RESULTS Liver fibrosis was assessed according to the METAVIR score. Compared with untreated cirrhotic controls, a significant improvement in fibrosis grade was observed in the low-dose aspirin, high-dose aspirin and enoxaparin treated groups, especially in the high-dose aspirin treated group. Alanine aminotransferase and total bilirubin were higher, albumin was lower and both prothrombin time and international normalized ratio were prolonged in the four treatment groups compared to controls. No significant differences among the four groups were observed.CONCLUSION Aspirin and enoxaparin can alleviate liver fibrosis in this rat model.

Effect of low molecular weight heparin (enoxaparin) on congenital cataract surgery

AIM: To assess the efficacy of intracameral enoxaparin (a low-molecular-weight heparin) infusion, in variable doses on postoperative inflammatory response in congenital cataract surgery.METHODS: It is a prospective, randomized controlled trial. Eighty eyes of 53 children with congenital cataract were enrolled in this study. Every eye had primary posterior capsulorrhexis and intraocular lens (IOL) implantation after lens aspiration. The eyes were divided into 4 equal groups. In group 1 balanced salt solution (BSS) without enoxaparin was used as an irrigation solution. Whereas in group 2, 3 and 4, 40mg, 20mg and 10mg enoxaparin in 500mL BSS was used respectively. The inflammatory response in the anterior chamber was compared among the groups with slit-lamp biomicroscopy.RESULTS: The mean follow-up period was (17.75±3.95) months in group 1, (18.00±5.15) months in group 2, (19.20±5.47) months in group 3 and (18.65±5.16) months in group 4. Mean number of inflammatory cells in the anterior chamber in group 1 was significantly higher than that of group 2, 3, 4 (P<0.001). There was fibrin formation in the anterior chambers of 3 eyes in group 1 and one eye in group 4. There was synechiae formation in 3 eyes of group 1 and one eye of group 4. There was no significant difference among the groups by means of fibrin or synechiae formation (P>0.05). There were IOL precipitates in 4 eyes of group 1 and 2 eyes of group 4. IOL precipitate formation was significantly higher in group 1 than that of group 2 and 3 in which there was no IOL precipitate (P=0.048). There was IOL subluxation in only one eye of group 1, 3 and 4 while no subluxation was observed in group 2 (P>0.05). There was no statistically significant difference detected about IOL subluxation occurance in all 4 groups (P>0.05). CONCLUSION: Complications of cataract surgery in congenital cataract patients associated with postoperative inflammatory response found to be decreased with the use of enoxaparin in intraocular infusion solutions. Furthermore according to our results the anti-inflammatory effect of enoxaparin was dose dependant.

Dose-dependent neuroprotective effect of enoxaparin on cold-induced traumatic brain injury

Recent evidence exists that enoxaparin can reduce brain injury because of its anticoagulant activity. To investigate the potential therapeutic effect of enoxaparin on cold-induced traumatic brain injury, at 20 minutes after modeling, male BALB/c mouse models of cold-induced traumatic brain injury were intraperitoneally administered 3 and 10 mg/kg enoxaparin or isotonic saline solution. Twenty-four hours later, enoxaparin at 10 mg/kg greatly reduced infarct volume, decreased cell apoptosis in the cortex and obviously increased serum level of total antioxidant status. By contrast, administration of enoxaparin at 3 mg/kg did not lead to these changes. These findings suggest that enoxaparin exhibits neuroprotective effect on cold-induced traumatic brain injury in a dose-dependent manner.

Enoxaparin dosing errors in the emergency department

BACKGROUND:The study aimed to determine the frequency of enoxaparin dosing errors for patients who had a measured emergency department(ED)weight compared to those who did not have a measured ED weight,and to determine if demographic variables(e.g.,weight,height,age,Englishspeaking,race)impact the likelihood of receiving an inappropriate dose.METHODS:This is a retrospective,electronic chart review of patients who received a dose of enoxaparin in the ED between January 1,2008 and July 1,2013.We identified all patients>18 years who received a dose of enoxaparin while in the ED,were admitted,and had at least one inpatient weight within the first four days of hospitalization.Patients were excluded if they received enoxaparin for prophylaxis or a dose of more than 1.25mg/kg.RESULTS:A total of 1,944 patients were included.Patients were more likely to experience an error if they did not have a measured ED weight.Over-doses of>10mg were more likely to occur in patients without a measured ED weight.Patients with no documented ED weight or with a staffestimated ED weight were more likely to experience a dosing error than those with a patient-stated weight.Patients were more likely to experience an error if their first inpatient weight was more than 96kg,they were more than 175-cm tall,or were English speaking.CONCLUSION:Dosing errors are more likely to occur when patients are not weighed in the ED.Modifications to current workflows to incorporate weighing those patients who receive weightdosed medications may be warranted.

Enoxaparin sensitizes human non-small-cell lung carcinomasto gefitinib by inhibiting DOCK1 expression,vimentin phosphorylation,and Akt activation

Gefitinib is widely used for the treatment of lung cancer in patients with sensitizing epidermal growth factor receptor mutations,but patients tend to develop resistance after an average of 10 months.Low molecular weight heparins,such as enoxaparin,potently inhibit experimental metastasis.This study aimed to determine the potential of combined enoxaparin and gefitinib(enoxaparin+gefitinib)treatment to inhibit tumor resistance to gefitinib both in vitro and in vivo.A549 and H1975 cell migration was analyzed in wound closure and Transwell assays.Akt and extracellular signal related kinase 1/2(Erk1/2)signaling pathways were identified,and a proteomics analysis was conducted using SDSPAGE/liquid chromatography-tandem mass spectrometry analysis.Molecular interaction networks were visualized using the cytoscape bioinformatics platform.Protein expression of dedicator of cytokinesis1(DOCK1)and cytoskeleton intermediate filament vimentin were identified using an enzyme-linked immunosorbent assay,Western blotting,and small interfering RNA transfection of A549 cells.In xenograft A549-luc-C8 tumors in nude mice,enoxaparin+gefitinib inhibited tumor growth and reduced lung colony formation compared with gefitinib alone.Furthermore,the combination had stronger inhibitory effects on cell migration than either agent used individually.Additional enoxaparin administration resulted in better effective inhibition of Akt activity compared with gefitinib alone.Proteomics and network analysis implicated DOCK1 as the key node molecule.Western blot verified the effective inhibition of the expression of DOCK1 and vimentin phosphorylation by enoxaparin+gefitinib comparedwith gefitinib alone.DOCK1 knockdown confirmed its role in cell migration,Akt expression,and vimentin phosphorylation.Our data indicate that enoxaparin sensitizes gefitinib antitumor and antimigration activity in lung cancer by suppressing DOCK1 expression,Akt activity,and vimentin phosphorylation.

1例剖宫产术后静脉血栓栓塞症患者的抗凝实践

1例33岁女性患者,因剖宫产术后发生左下肢深静脉血栓和肺栓塞,给予依诺肝素(5000 IU,q 12 h,ih)抗凝治疗。用药前患者PLT 381×10^(9)·L^(-1),使用依诺肝素后PLT进行性升高,用药后第11天PLT升至744×10^(9)·L^(-1),经过对药品不良反应相关性分析,高度怀疑是依诺肝素引起的血小板增多症。建议停用依诺肝素,并根据INR不断调整华法林剂量口服抗凝治疗直至INR达标,静脉血栓栓塞好转。停用依诺肝素后,患者的PLT进行性下降,停药后第21天PLT降至355×10^(9)·L^(-1),停药后第41天随访PLT(241×10^(9)·L^(-1))降至正常。

基于属性层次分析模型和加权TOPSIS法的低分子肝素注射液药物利用评价标准建立与应用

目的进一步提高低分子肝素(LMWH)注射液的临床合理用药水平。方法以药品说明书(含达肝素、那屈肝素钙、依诺肝素钠)为基础,参考相关指南和文献,通过德尔菲法建立LMWH注射液的药物利用评价(DUE)标准。提取2023年1月至7月某三级医院使用LMWH注射液的住院患者病历(300份,使用前述3种LMWH各100份),采用逼近理想解排序(TOPSIS)法评价该药的使用合理性。结果病历中评价指标与最优方案的相对接近程度,≥80%(合理)的占16.00%,70%~<80%(基本合理)的占44.00%,60%~<70%(基本合理)的占39.00%,<60%(不合理)的占1.00%。其中,达肝素、那屈肝素钙、依诺肝素钠的平均Ci分别为(79.19±0.12)%、(72.62±0.10)%、(76.22±0.10)%,组间比较,差异有统计学意义(F=9.016,P<0.001);用药不合理病历数分别为1份、2份、0份,不合理问题主要为适应证不适宜,给药时机与给药剂量不适宜,实验室检查未完善及不良反应未进行监测和上报。结论该研究中建立的标准与方法可用于评价LMWH临床使用的合理性。

依诺肝素钠联合间苯三酚治疗先兆流产患者的效果及对E_(2)、P、β-HCG水平的影响

目的分析依诺肝素钠联合间苯三酚治疗先兆流产患者的临床效果。方法选取2020年3月至2023年2月于本院诊治的76例先兆流产患者为研究对象,依据入院时间顺序编号的奇偶性将其分为对照组(奇数)与观察组(偶数),各38例。对照组肌肉注射间苯三酚注射液治疗,观察组在对照组的基础上皮下注射依诺肝素钠注射液治疗。比较两组的治疗效果。结果观察组的腹痛缓解时间、阴道止血时间、腰酸缓解时间短于对照组(P<0.05)。治疗后5 d,两组的雌二醇(E_(2))、孕酮(P)、β-人绒毛膜促性腺激素(β-HCG)水平高于治疗前,且观察组高于对照组(P<0.05)。治疗后5 d,观察组的活化部分凝血酶时间(APTT)、凝血酶原时间(PT)、凝血酶时间(TT)、组织型纤溶酶原激活物(T-PA)水平高于对照组,纤溶酶原激活物抑制剂-1(PAI-1)水平低于对照组(P<0.05)。观察组的不良妊娠结局总发生率低于对照组(P<0.05)。结论依诺肝素钠联合间苯三酚可促进先兆流产患者的临床症状消退,调节内分泌指标,改善凝血功能,在一定程度上可降低先兆流产及其他并发症发生风险,有助于提升患者的妊娠安全性,具有重要应用价值。

寿胎丸合四君子汤联合依诺肝素治疗抗心磷脂抗体阳性复发性流产患者的效果

目的:观察寿胎丸合四君子汤联合依诺肝素治疗抗心磷脂抗体(ACA)阳性复发性流产(RSA)患者的效果。方法:选取2020年10月至2022年10月该院收治的86例ACA阳性RSA患者进行前瞻性研究,按照随机数字表法分为观察组与对照组各43例。对照组采用依诺肝素钠注射液治疗,观察组在对照组基础上加用寿胎丸合四君子汤治疗,比较两组临床疗效、中医证候积分、D-二聚体水平、纤维蛋白原水平、白细胞介素(IL)-10水平和妊娠成功率。结果:观察组治疗总有效率为88.37%,明显高于对照组的69.77%,差异有统计学意义(P<0.05);治疗后,观察组头晕耳鸣、腰酸膝软、神疲肢倦等中医证候积分和D-二聚体、纤维蛋白原水平低于对照组,IL-10水平高于对照组,差异均有统计学意义(P<0.05);随访1年,观察组妊娠成功率为83.72%,明显高于对照组的62.79%,差异有统计学意义(P<0.05)。结论:寿胎丸合四君子汤联合依诺肝素治疗ACA阳性RSA患者可提高治疗总有效率、妊娠成功率和IL-10水平,降低中医证候积分、D-二聚体水平和纤维蛋白原水平,效果优于单纯依诺肝素治疗。

A randomized comparative study of using enoxaparin instead of unfractionated heparin in the intervention treatment of coronary heart disease

Background Low molecular weight heparin (LMWH) was more effective than unfractionated heparin (UFH) in treating acute coronary syndrome (ACS). However, it remains uncertain whether LMWH can be used in patients undergoing percutaneous coronary intervention (PCI) instead of UFH. This study aimed to evaluate the efficacy and safety of using enoxaparin instead of UFH in the intervention treatment of patients with coronary heart disease (CHD) Methods From October 2003 to Febuary 2005, 966 patients with CHD were enrolled into this study. Among 966 patients, 455 patients received the PCI, including 283 patients with Non-ST segment elevation ACS (NSTEACS), 511 patients did not received PCI due to mild, moderate lesions or were suitable for coronary artery bypass graft (CABG). The 966 patients were randomized to enoxaparin group (484 patients) and UFH group (482 patients). Patients in the enoxaparin group were given enoxaparin at least twice subcutaneously (1 mg/kg,q12 h) before catheterization. Plasma anti-Xa activity was determined 1-8 hours after the last dose of enoxaparin was determined. The catheterization was performed within 8 hours after the last dose of enoxaparin. The sheath was removed immediately after the procedure. Patients in the UFH group were given UFH 25 mg intravenously before coronary angiography. Additional 65 mg was given intravenously if PCI was to be performed. The sheath was removed 4 hours after the procedure. Results A total of 227 patients in the enoxaparin group and 228 patients in the UFH group received PCI. In the enoxaparin group,one patient developed acute thrombosis during PCI and resulted in acute myocardial infarction (AMI), no acute or subacute thrombosis was found during hospitalization. In the UFH group, no acute or subacute thrombosis occurred during PCI procedure and hospitalization. Therefore, the incidence of major adverse cardiovascular events (MACEs) during the hospitalization was 0.44% in the enoxaparin group and 0 in the UFH group. In the enoxaparin group, the sheath was removed immediately after the procedure and 8 patients had hematoma on the puncture site. In the UFH group, the sheath was removed 4 hours after the procedure and 20 cases had hematoma on the puncture site. The incidence of hematoma on the puncture site was significantly higher in the UFH group than that in the enoxaparin group (P<0.05). Anti-Xa activity was determined in 174 patients in LMWH group. The mean anti-Xa activity was (0.87±0.23) U/ml, and 94.8% of them had anti-Xa activity >0.5 U/ml and 6.9% of the patient >1.2 U/ml. There was no death and AMI occurred in enoxaparin group, but one patient had AMI caused by subacute thrombosis in UFH group during 30-day follow-up. MACE rate at 30-day follow-up was 0 in enoxaparin group and 0.43% in UFH group. Conclusions The results of the study suggest that it is safe and efficient to give enoxaparin at least twice beforethe PCI procedure, and the sheath can be removed immediately after PCI. For NSTEACS patient who has received enoxaparin more than twice during the hospitalization can undergo PCI directly and no UFH is necessary before or during PCI.

Unfractionated Heparin with Sequential Enoxaparin in Patients with Complex Coronary Artery Lesions during Percutaneous Coronary Intervention

背景: 尽管有它的限制， Unfractionated 肝磷脂(UFH ) 在经皮的冠的干预(一种总线标准) 期间被用作主要抗凝剂选择。一些研究显示静脉内的 enoxaparin 能是一种有效、安全的选择。我们的队同时根据指南(班 IIA ) 独自使用了 enoxaparin 并且在一种总线标准期间发现一点导管血栓。我们与 UFH 在联合用 enoxaparin 推荐新 anticoagulation 策略。Enoxaparin 没有反复在一种总线标准期间监视 anticoagulation 的需要有更可预言的抗凝剂回答。这回顾的研究试图评估与复杂冠的动脉 disease.Methods 在一种总线标准病人与 UFH 在联合使用 enoxaparin 的功效和安全:在2015年1月和2017年4月之间，在 0.75 mg/kg (观察组)的剂量在 3000 U 正静脉内的 enoxaparin 的起始的剂量收到了静脉内的 UFH 的 600 个一种总线标准病人和在 100 U/kg (控制组)的剂量收到了 UFH 的 600 个一种总线标准病人连续地在这回顾的研究被包括。端点是在流血的心肌的梗塞( TIMI )和输送和30天、1年的主要不利cardio脑血管的事件( MACCE ) .Results 的手术后的 48-h thrombolysis :基线临床， angiographic ，和程序的特征在组之间是类似的，除了每在观察组的病人有更少的 stent 培植( 2.13 对 2.25 在控制组织， P = 0.002 )。流血的 TIMI (3.3% 对 4.7%) 没显示出观察组和控制组之间的重要差别。在 30 天的后续期间， MACCE 的率在观察组是 0.9% ， 1.5% 在控制组织。处于 MACCE 的率没有重要差别，死亡，心肌的梗塞，目标容器 revascularization ，脑血管的事件，并且在在在组之间以及在 transfemoral approach.Conclusions 的亚群分析的一种总线标准以后的 30 天和 1 年以内的咽峡炎:有顺序的 enoxaparin 的 UFH 在复杂冠的动脉疾病的一种总线标准作为 UFH 有类似的抗凝剂效果和安全。

依诺肝素钠导致肝功能异常的表现及其危险因素的Logistic回归分析

目的:探讨依诺肝素钠导致肝功能异常的表现及影响因素。方法:通过医院信息系统,收集2021—2022年中日友好医院呼吸病区住院期间使用依诺肝素钠的患者病历资料,根据Roussel Uclaf因果关系评估法2015版,筛选出评价结果为“高度可能”“可能性大”和“可能”的患者,并进行分析。结果:入组患者506例,其中男性292例,女性214例;依诺肝素钠高剂量(100 AXaIU/kg,每12 h给药1次)217例,低剂量(2000/4000 AXaIU,1日1次)289例。其中38例患者(占7.5%)发生依诺肝素钠相关性肝功能指标异常(因果关系评价结果均为“可能性大”以及以上),主要表现为氨基转移酶升高,胆红素水平正常。二元Logistic回归分析显示,高剂量组患者(31例)的肝功能异常发生率高于低剂量组(7例),差异有统计学意义(P<0.001);男性患者(29例)的肝功能异常发生率高于女性(9例),差异有统计学意义(P=0.023);年龄、吸烟史、饮酒史、用药时长各组间的差异均无统计学意义(P>0.05)。停用、更换非肝素类抗凝血药可以获得良好的转归。结论:依诺肝素钠导致的肝功能异常是一类可逆、初始症状缓和的不良反应,主要表现为氨基转移酶升高,更换非肝素类药物后能转归。高剂量依诺肝素钠及男性患者是发生肝功能异常的高危因素,临床使用依诺肝素钠过程中需加强对该类患者的用药监护。

1例碘美普尔肾损伤致依诺肝素严重肝损伤病例的药学实践

1例67岁的男性肺腺癌合并心力衰竭患者在使用碘美普尔后出现急性肾损伤(血清肌酐149μmol·L^(-1),尿素氮13.23 mmol·L^(-1),尿酸439μmol·L^(-1))和严重肝损伤(丙氨酸氨基转移酶592 U·L^(-1),天冬氨酸氨基转移酶782 U·L^(-1),γ-谷氨酰转移酶121 U·L^(-1))。通过用药分析,药师判断该患者使用碘美普尔对比剂后引发急性肾损伤,导致依诺肝素钠在体内蓄积,继发严重肝损伤。药师建议观察肾功能变化并停用依诺肝素钠、暂停甲磺酸阿美替尼,此后患者肝肾功能均恢复正常。该病例提示对于具有对比剂肾病高危因素的患者,使用对比剂后可能出现急性肾损伤,引起药物蓄积性不良反应。对这类患者药师应做好药学监护,发生不良反应后及时进行用药分析和充分的临床评估,协助医生调整治疗方案。

1例依诺肝素钠致肝损伤的药学监护实践

目的 探讨临床药师在药物性肝损伤(DILI)治疗中的药学监护作用。方法 1例系统性红斑狼疮(SLE)并肠系膜血管炎患者入院第6天,肝功能指标出现异常[其中丙氨酸氨基转移酶(ALT)> 1.5倍参考值上限(ULN),γ-谷氨酰转肽酶(GGT)> 3 ULN],临床药师经查阅文献和分析病例资料后判断DILI为依诺肝素钠所致可能性大,为混合型、急性,建议换服阿司匹林片(100 mg,口服,每天1次)预防血栓,加用异甘草酸镁(200 mg,静脉滴注,每天1次)+多烯磷脂酰胆碱(20 mL,口服,每天1次)+熊去氧胆酸(250 mg,口服,每天2次)护肝。入院第9天,将激素换为甲泼尼龙琥珀酸钠(120 mg,静脉滴注,每天1次);第12天,停用熊去氧胆酸;第14天,甲泼尼龙琥珀酸钠减量为80 mg,用法不变;第17天,停用异甘草酸镁。结果 医师采纳药师建议,入院第23天,患者肝功能指标逐渐恢复正常,予以出院。结论 临床药师参与DILI的用药治疗和药学监护,有助于判断其发生的可能性,还可优化治疗方案,促进合理、安全用药。

中西医结合治疗慢性肺源性心脏病合并心衰50例临床观察

目的:探讨慢性肺源性心脏病合并心衰的治疗中,辅助使用心脉隆合依诺肝素的临床效果。方法:选取符合条件的慢性肺源性心脏病合并心衰患者共100名,使用随机数字表法,分成各50例的两组,即对照组和观察组。对照组采用目前指南推荐使用的慢性肺源性心脏病合并心衰的常规治疗方式,观察组在对照组治疗药物基础上加用心脉隆及依诺肝素。对比两组临床疗效、LEVF、NT-proBNP、MPAP。结果:治疗后,观察组心肺功能相关辅助检查、NT-proBNP、MAPA均优于对照组,差异均具有统计学意义(P<0.05)。观察组治疗总有效率92%高于对照组的78%,差异具有统计学意义(P<0.05)。结论:应用心脉隆联合依诺肝素辅助治疗慢性肺源性心脏病合并心衰患者,疗效显著。