Treatment options and pregnancy outcome in women with idiopathic recurrent miscarriage: a randomized placebo-controlled study

OBJECTIVE: To compare the use of enoxaparin alone with combination therapy of prednisone, aspirin and progesterone in the treatment of women with idiopathic recurrent miscarriage (IRM) in terms of live births and pregnancy outcome. METHODS: A prospective, randomized, single-blinded, placebo-controlled trial was conducted at a tertiary referral obstetric hospital. The participants were 170 women with a diagnosis of IRM. Women were recruited after full investigative screening. Women with > or =3 fetal losses and after exclusion of all known causes of recurrent miscarriage were randomly allocated to receive either enoxaparin alone, combination treatment consisting of prednisone, aspirin, and progesterone or placebo. Rates of live births, antenatal complications, delivery and neonatal outcomes were recorded prospectively. Data were statistically analyzed as appropriate. RESULTS: Ten patients were dropped out after random assignment. Eighty-one percent of the enoxaparin (46/57) group and 85% of the combination-treated group (45/53) were delivered of live infants compared to 48% (24/50) of the placebo (P < 0.05). Women who were treated with combination therapy had a 4.2% higher live birth rate than enoxaparin group. This difference was not significant. Miscarriage rates were significantly lower in the treated groups compared with placebo (P < 0.05). There were no significant differences in late obstetric complications or neonatal mortality between groups. CONCLUSIONS: A combination treatment consisting of high-dose, low-duration prednisone, progesterone and aspirin might be an effective treatment as enoxaparin alone. Both regimens were associated with a good pregnancy outcome.     

利伐沙班,伊诺肝素和低相对分子质量肝素钙治疗脊柱融合术后下肢肌间静脉血栓的效果

目的探讨利伐沙班,伊诺肝素和低相对分子质量肝素钙(LMWHca)对脊柱融合术后下肢肌间静脉血栓的治疗效果。方法回顾性分析我院2011年1月-2015年1月收治的100例脊柱融合术后发生下肢肌间静脉血栓的患者的临床资料,共160例肢体,分别采用利伐沙班(54例),伊诺肝素(52)和LMWHca(54例)治疗,疗程均为1~3个月,采用彩超观察血栓的消失情况,治疗过程中观察不良反应的发生情况。结果利伐沙班组和LMWHca组总有效率均高于伊诺肝素组(χ~2=13.2,12.8;P=0.01);而利伐沙班组和LMWHca组之间差异无统计学意义(χ~2=0.27,P0.05)。利伐沙班组和LMWHca组治疗后血小板功能相关参数均低于伊诺肝素组(F=5.22,5.23,5.19;P=0.01);而利伐沙班组和LMWHca组之间差异无统计学意义(t=0.24,P0.05)。利伐沙班组和LMWHca组治疗后内皮细胞功能相关参数均低于伊诺肝素组(F=5.08,5.12,5.12;P=0.01,0.01,0.010.05);而利伐沙班组和LMWHca组之间差异无统计学意义(t=0.23,P0.05)。利伐沙班组和素钙组不良反应发生率低于伊诺肝素组(χ2=13.4,13.6;P=0.01,0.010.05);而利伐沙班组和低分子肝素钙组之间差异无统计学意义(χ~2=0.00,P0.05)。结论 LMWHca和利伐沙班片治疗脊柱融合术后急性肌间静脉血栓疗效强大,安全性较高,但服药方式不同,可根据患者需要灵活使用。     

High-risk Acute Coronary Syndrome Patients with Non-ST-Elevation Myocardial Infarction: Definition and Treatment

Introduction  Early risk stratification of patients with acute coronary syndromes (ACS), unstable angina, or non-ST-elevation myocardial infarction ensures patients receive appropriate care. Materials and methods  Many risk-stratification models have been developed to identify high-risk ACS patients who would benefit most from an early invasive strategy and to determine patients at greater risk for bleeding complications. Although high-risk patients seem to benefit most from a combination of aggressive antithrombotic and early invasive therapies, stratification for risk of bleeding also helps in the choice and dosing of appropriate medical therapy. Results  The effective use of glycoprotein IIb/IIIa inhibitors, in particular, is dependent on accurate risk assessment, whereas the risk-to-benefit ratio of direct thrombin inhibitors in high-risk versus low-risk patients as part of an initial therapy plan requires clarification. Nevertheless, use of the same anticoagulant throughout the care pathway may reduce the rates of death or recurrent myocardial infarction, and bleeding complications.     

依诺肝素钠诱导血小板减少症

1例63岁男性患者行二尖瓣和主动脉瓣置换术,术后第1天开始给予依诺肝素钠抗凝治疗（4000 U,2次/d皮下注射）。术前及术后第1天血小板计数均正常。术后第2天血小板计数为41×10^9/L,给予重组人白细胞介素11皮下注射（1.5 mg/次,1次/d）。术后第3天血小板计数为22×10^9/L,遂停用依诺肝素钠。术后第4、5天血小板计数分别为45×109/L、59×10^9/L。第6天复查,血小板计数为128×10^9/L。     

MTT法测定低分子量肝素对兔结膜成纤维细胞增殖的抑制作用

观察低分子量肝素（ｌｏｗｍｏｅｃｕｌａｒｗｅｉｇｈｔｈｅｐａｒｉｎ,ＬＭＷＨ）对兔结膜成纤维细胞增殖的抑制作用,探讨其与地塞米松联合应用的价值,并与肝素的抑制作用相比较。方法应用ＭＴＴ法测定不同浓度的ＬＭＷＨ对结膜成纤维细胞增殖的抑制作用,同时比较单独应用ＬＭＷＨ、地塞米松、同一抗凝单位的肝素及ＬＭＷＨ联合地塞米松对成纤维细胞增殖的抑制作用。结果ＬＭＷＨ对兔结膜民纤维细胞增殖的抑制作用与浓度成正相     

利伐沙班和依诺肝素钠在行经皮冠状动脉介入治疗后预防深静脉血栓形成的效果比较

目的 研究利伐沙班与依诺肝素钠对预防经股动脉行经皮冠状动脉介入治疗（PCI）后卧床患者血栓形成的临床疗效,了解两种药物的用药原则.方法 2011年2月至2012年5月诊断为冠心病并经股动脉行PCI治疗患者398例,随机分为利伐沙班组（n=198）和依诺肝素钠组（n=200）.利伐沙班组术后4～6h后开始口服利伐沙班5mg,bid,疗程7d.依诺肝素钠组术后4～6h皮下注射依诺肝素钠4000 IU,qd,疗程7d.监测术前及术后7d两组血小板计数（Plt）、活化部分凝血活酶时间（APTT）、D-二聚体,并观察治疗期间出血情况,术后7d比较两组深静脉血栓形成（DVT）发生情况,同时随访12个月内的DVT发生情况,采用“生存分析”观察不同药物治疗患者的累积血栓风险概率.结果 （1）术后7dDVT发生率比较：利伐沙班组有4例发生DVT,发生率为2.02％,依诺肝素钠组出现12例,发生率为6.00％,两组比较差异有统计学意义（P＜0.05）.采用“生存分析”观察不同药物治疗患者的12个月累积血栓风险概率,依诺肝素钠组（10.69％）高于利伐沙班组（5.58％）,差异仍有统计学意义（P＜0.05）.（2）两组患者Plt、APPT及D-二聚体含量,手术前及术后7d比较差异无统计学意义（P均＞0.05）.两组术后及治疗期间均未出现严重出血及大伤口血肿,伤口渗血量及止血时间差异无统计学意义（P均＞0.05）.结论 利伐沙班在经股动脉行PCI治疗后预防DVT的近远期预防效果优于依诺肝素钠,而其安全性与依诺肝素钠相当.     

利伐沙班与伊诺肝素比较预防骨科大手术后深静脉血栓的Meta分析

目的系统评价利伐沙班与伊诺肝素预防骨科大手术后深静脉血栓的疗效。方法计算机检索MEDLINE、EMbase、Cochrane图书馆临床对照试验资料库(2009年第3期)、Current Controlled Trials、The National Reseach Register、中国生物医学文献数据库、中国期刊全文数据库,并手工检索相关领域杂志。检索不受语种限制,时间均从建库至2009年12月。纳入利伐沙班与伊诺肝素(低分子肝素)比较预防骨科大手术后深静脉血栓的随机对照试验(RCT),进行资料提取和质量评价后,采用RevMan5.0.25软件进行Meta分析。结果共纳入7个RCT,包括15458例患者。Meta分析结果显示:利伐沙班与伊诺肝素比较,能减少主要疗效终点风险达60%[RR=0.40,95%C(I0.28,0.57),P<0.00001],能减少主要的次要疗效终点风险达71%[RR=0.29,95%C(I0.15,0.56),P<0.00001],能减少其他疗效终点风险达56%[RR=0.44,95%CI(0.29,0.66),P<0.00001];治疗期间严重出血事件的发生率两者相似[RR=1.16,95%CI(0.68,1.999),P=0.59],次要安全性终点发生率两者也相似。结论利伐沙班预防骨科大手术后深静脉血栓的疗效肯定,能显著降低术后发生深静脉血栓风险。     

几种抗凝药物预防损伤后小动脉血栓形成的实验研究

目的观察利伐沙班、氯吡格雷、依诺肝素钠等几种抗凝药物预防损伤后小动脉血栓形成的效果。方法损伤大鼠股动脉制作血栓模型,将大鼠分5组：a组：术前至术后1周,每日1次依诺肝素钠注射;b组：术前至术后1周,每日1次利伐沙班灌胃;c组：术前至术后1周,每日1次氯吡格雷灌胃;d组（肝素对照组）：术前至术后1周,每日2次注射肝素;e组（空白对照组）：术前至术后1周,每日1次注射等容量生理盐水。术后2h及1周检查吻合口通畅情况,术后1周测定大鼠血浆活化的部分凝血活酶时间（APTT）和凝血酶原时间（PT）。结果a、b、c、d组各时间点的吻合12I通畅率比e组均有非常显著性的提高,但其中c组较低,差异均有统计学意义,a、b、d组基本相同,差异无统计学意义;a组切口皮下出现张力性血肿1处,d组切口皮下出现张力性血肿4处,其他组未出现血肿;d组术后1周A阿T、PT较其它4组延长,与空白对照组及c组相比差异性有显著性意义（P〈0．05）,a、b、c三组问及其与对照组相比APlT、PT差异无统计学意义（P〉0．05）。结论利伐沙班、氯吡格雷、依诺肝素钠等抗凝药物在不增加出血倾向的前提下能预防损伤小动脉吻合口的血栓形成,氯毗格雷相对利伐沙班、依诺肝素抗凝效果较差,其中利伐沙班仅须每日1次口服给药,使用方便,依从性、耐受性更好,可作为显微外科抗凝用药的理想选择。     

Fluctuations of anti-Xa concentrations during maintenance enoxaparin therapy for neonatal thrombosis

Aim: To evaluate fluctuations in anti‐Xa concentrations in infants treated with enoxaparin for thrombosis and describe clinical outcomes. Methods: A retrospective chart review was performed on infants treated with enoxaparin in the Neonatal Intensive Care Unit, and data on enoxaparin doses, anti‐Xa concentrations, clinical characteristics and outcomes were abstracted. Results: Our cohort (n = 26) had a median gestation of 36 (range, 23–41) weeks, birthweight of 2522 (510–3912) grams and 5‐min Apgar score of 8(4–9). Fifteen (57.7%) infants were males. Thromboses was diagnosed at a median age of 22 (range, 1–97) days; enoxaparin was initiated at 27.5 (range, 4–98) days at a mean (SD) dose of 1.4 (0.3) mg/kg every 12 h. Therapeutic anti‐Xa concentrations (0.5–1 U/mL) were achieved at a mean (SD) dose of 2.1 (0.6) mg/kg at 12.5 (12.2) days of treatment. Of the 143 anti‐Xa concentrations, 39 (27%) were within the therapeutic range. During maintenance therapy following initial therapeutic anti‐Xa concentration, 40% concentrations were therapeutic. Minor bleeding was noted in four infants and intracranial bleed in one infant; four infants died. During treatment, thrombocytopenia, renal and hepatic impairment during treatment were noted in 7, 2 and 4 infants, respectively. Clot resolution was observed in 21 (81%) infants. Conclusions: Anti‐Xa concentrations fluctuate during maintenance enoxaparin therapy, with therapeutic levels being achieved only sporadically in young infants. Despite this, enoxaparin appears efficacious in thrombosis resolution. Further studies on the impact of stringent control of concentrations on outcomes in this population are warranted.     

Catheter thrombosis during primary percutaneous coronary intervention for acute ST elevation myocardial infarction despite subcutaneous low-molecular-weight heparin, acetylsalicylic acid, clopidogrel and abciximab pretreatment

BACKGROUND: Subcutaneous enoxaparin is increasingly employed as the antithrombin of choice in non-ST elevation myocardial infarction and in conjunction with various fibrinolytic regimens in acute ST elevation myocardial infarction (STEMI). Few data exist describing the use of subcutaneous or intravenous enoxaparin as an anticoagulant in the highly thrombotic setting of primary percutaneous coronary intervention (PCI) for STEMI. METHODS: The Which Early ST Elevation Therapy (WEST) study compared fibrinolysis (with and without early cardiac catheterization) with primary PCI in a setting that expedited both strategies on first medical contact. Patients assigned primary PCI are administered acetylsalicylic acid 325 mg, clopidogrel 300 mg and subcutaneous enoxaparin 1 mg/kg before transport to a PCI centre. Of 36 initial patients treated with primary PCI, three patients had procedures that were complicated by extensive thrombosis within coronary catheters and on PCI equipment. RESULTS: Index cases were men aged 43 to 68 years who presented with confirmed STEMI and angiographically proven acute total or subtotal occlusion of a major epicardial coronary segment. During PCI, performed 76 min to 102 min following enoxaparin administration, a clot developed within the guide catheter or on the coronary guidewires and balloon catheter shafts, thus necessitating the replacement of all PCI equipment. In one case, there was evidence of continued intracoronary clot propagation and embolization. CONCLUSION: A single, conventional, weight-adjusted dose of subcutaneous enoxaparin before expedited primary PCI for STEMI may not provide a reliable antithrombotic effect. Supplementary intravenous enoxaparin is now strongly recommended within the WEST study, and a substudy evaluating pre- and postprocedural antifactor Xa activity has been initiated.