达肝素与普通肝素对血浆抗凝血因子Ⅹa活性及活化凝血时间影响的对比研究

目的探讨冠心病患者择期PCI及冠状动脉造影术中应用达肝素替代普通肝素的可行性和有效性。方法共入选拟行择期PCI的患者87例,分为普通肝素组（10 000 IU）、小剂量（5 000 IU）达肝素组和大剂量（10 000 IU）达肝素组,分别于用药前及全部剂量的药物注射后10 min、20 min、1 h、2 h及4 h采血,测定活化凝血时间（ACT）及血浆抗凝血因子Ⅹa活性。结果（1）普通肝素组、小剂量达肝素组和大剂量达肝素组ACT均在全部剂量的药物注射后10 min升高至峰值,分别为524.68±278.32 s、191.26±39.35 s、304.20±42.71 s（P〈0.05）;其后各组ACT开始逐渐回落,在4 h后降至最低。（2）三组抗凝血因子Ⅹa活性均在药物全部注射后20 min达到峰值,分别为0.80±0.11 IU/mL、0.72±0.10 IU/mL及0.72±0.09 IU/mL,但各组间差异无统计学意义（P〉0.05）。结论与普通肝素相比,达肝素用于PCI中可达到手术所需抗凝效果。     

经皮冠状动脉介入治疗中静脉注射那屈肝素的抗血栓疗效及安全性评价

目的比较经皮冠状动脉介入治疗(PCI)中静脉注射那屈肝素或普通肝素的抗血栓疗效及安全性.方法采用前瞻性、随机、单盲、多中心研究的设计,共入选98例因患冠心病需行PCI的患者,随机分为那屈肝素组(0.075 ml/10 kg,手术时间超过1 h补充半量)及普通肝素组(100 U/kg,手术时间超过1 h补充2000 U).PCI前静脉注射那屈肝素或普通肝素.那屈肝素组前22例患者分别在注射前、注射后8 min、1 h、2 h和4 h,用发色底物法测定血浆抗Ⅹa因子活性.出血程度的判断根据TIMI研究的标准进行.结果 (1) 性别、年龄、体重、血压、血红蛋白含量、红细胞压积、合并糖尿病的例数、冠心病类型、进行冠状动脉介入治疗的部位、介入治疗的手术方式及术前血浆cTNI>2 ng/ ml的例数在二组之间分布均衡,差异均无统计学意义;(2) 那屈肝素组前22例患者血浆抗Ⅹa因子活性测定显示,用药前、用药后8 min、1 h、2 h及4 h血浆抗Ⅹa因子活性分别为(0.10±0.00) IU/ ml、(1.89±0.24)IU/ ml、(0.96±0.24) IU/ ml、(0.47±0.13)IU/ ml和(0.30±0.12) IU/ ml.注射那屈肝素后8 min及1 h,所有患者血浆抗Ⅹa因子活性均在治疗水平(>0.5 IU/ ml),注射后2 h及4 h分别仅有45%及9%的患者血浆抗Ⅹa因子活性维持在治疗水平.(3)那屈肝素组术后血红蛋白数量、红细胞压积及出血指数分别为(129.5±13.6) g/L、(39.0±3.9)%和(1.16±5.80) g/L,与普通肝素组相似[分别为(125.5±14.9) g/L、(37.9±4.6)%和(0.90±6.5) g/L,P值分别为0.175,0.205和0.858);(4) 二组均无显微镜下血尿、无黑便或大便隐血阳性的患者;均无按TIMI试验标准所诊断的大出血或轻度出血的患者,无需要输血的患者;无穿刺部位的血肿;(5) PCI术后30 天内二组均无死亡、心绞痛复发及需行血管再通术等临床事件发生,那屈肝素组有1例患者PCI术后发生急性心肌梗死,普通肝素组无发生心肌梗死的病例,二组之间差异无统计学意义.结论 PCI术前注射那屈肝素能达到理想的抗血栓疗效; 与普通肝素相比,那屈肝素不增加出血事件和心血管病事件的发生率.     

急性冠状动脉综合征高危患者围介入期应用依诺肝素和那屈肝素有效性和安全性的比较

目的比较急性冠状动脉综合征(ACS)高危患者在接受冠状动脉介入术(PCI)治疗的围手术期使用依诺肝素和那屈肝素的有效性和安全性。方法84例ACS高危患者随机分为依诺肝素组(44例)和那屈肝素组(40例),负荷剂量阿司匹林(300mg)和氯吡格雷(300mg)口服后继以口服维持量(阿司匹林300mg/d,氯吡格雷75mg/d),皮下注射依诺肝素1mg/kg或那屈肝素0.01ml/kg,q12h,共7d,每日及术前术后测定抗Xa因子活性。使用低分子肝素(LMWH)后48h行PCI,最后一次注射LMWH后8h内进入导管室,术中不追加LMWH或普通肝素。结果第3次给药后4h,两组87.5%患者抗Χa因子活性>0.5IU/ml,48h后95.5%患者抗Χa因子活性>0.5IU/ml,基本达到较稳定水平。30d内随访中,依诺肝素组和那屈肝素组临床主要心脏事件差异无统计学意义(P>0.05),两组之间出血发生率的差异也无统计学意义(P>0.05);两组每日测定的抗Χa因子活性差异亦无统计学意义(P>0.05)。结论两种LMWH在高危ACS患者围手术期使用均安全有效。     

冠状动脉介入治疗中不同肝素的抗凝效果比较

目的通过监测抗-Xa因子活性及活化凝血酶原时间(APTT)值评价低分子肝素(LMWH)联合普通肝素(UH)在冠状动脉介入(PCI)治疗中的安全性和有效性,探讨适合人群的PCI抗凝策略。方法入选50例急性冠脉综合征(ACS)病人,均给予1mg/kg的达肝素(法安明)每隔12h皮下注射1次,至少48h后行PCI,术前连续使用LMWH,末次给药距离造影不超过8h。对照组术中不加用UH,术后取血测定抗-Xa活性及APTT值,试验组行PCI前追加UH,术后测定抗-Xa活性及APTT值。结果对照组仅有69.5%病人的抗-Xa活性>0.5U/L,APTT值为(38.6±13.9)s,试验组80.2%的病人抗-Xa活性>1.2U/L,20%抗-Xa活性>1.5U/L,APTT值为(160.3±87.2)s。结论皮下注射达肝素48h后PCI术中追加普通肝素对ACS病人安全、有效,但应门诊随访。     

经皮冠状动脉介入治疗中静脉注射不同剂量那屈肝素的抗血栓疗效比较

目的比较冠状动脉介入治疗术(PCI)中静脉注射2种不同剂量那屈肝素的抗血栓疗效,明确取得理想抗血栓疗效的最佳剂量.方法采用前瞻性、随机、双盲的设计,共入选42例因患冠心病需行PCI术的患者,随机分为小剂量那屈肝素组(0.075 ml/10 kg)及大剂量组(0.1 ml/10 kg).PCI术前静脉注射那屈肝素,分别在注射前、注射后8 min、1 h、2 h和4 h,用发色底物法测定血浆抗Ⅹa因子活性.同时还观察了出血指数(定义为PCI治疗术后24 h内血红蛋白的下降值)及30 d内出血事件.结果 (1)小剂量组注射那屈肝素前、注射后8 min及1 h血浆抗Ⅹa因子活性分别为(0.10±0.00) IU/ml、(1.89±0.24) IU/ml、(0.96±0.24) IU/ml,均与大剂量组相应时间点的血浆抗Ⅹa因子活性[分别为(0.10±0.00) IU/ml,(1.89±0.30) IU/ml,(0.93±0.14) IU/ml]相似(P值分别为0.162、0.962和0.702).那屈肝素注射后2 h及4 h,小剂量组抗Ⅹa因子活性[分别为(0.47±0.13) IU/ml和(0.30±0.12) IU/ml]低于大剂量组[分别为(0.75±0.14) IU/ml和(0.45±0.08) IU/ml,P值均小于0.001]. (2)小剂量组的出血指数(3.3±3.8)g/L与大剂量组(0.2±6.4)g/L相似(P=0.061).(3)二组30 d内均未发现根据TIMI试验标准确定的大出血或轻度出血,均未发生死亡、心绞痛复发、心肌梗死及需行血管再通术等临床事件.结论 PCI术前注射二种剂量的那屈肝素均能达到理想的抗血栓效果,其中小剂量组能维持其有效的抗血栓疗效1 h,大剂量组能维持长达2 h的抗血栓效果.     

达肝素与普通肝素对血浆抗凝血因子Xa活性及活化凝血时间影响的对比研究

目的 探讨冠心病患者择期PCI及冠状动脉造影术中应用达肝素替代普通肝素的可行性和有效性.方法 共人选拟行择期PCI的患者87例,分为普通肝素组(10 000 IU)、小剂量(5 000 IU)达肝素组和大剂量(10000 IU)达肝素组,分别于用药前及全部剂量的药物注射后10 min、20 min、1 h、2 h及4 h采血,测定活化凝血时间(ACT)及血浆抗凝血因子Xa活性.结果 (1)普通肝素组、小剂量达肝素组和大剂量达肝素组ACT均在全部剂量的药物注射后10 min升高至峰值,分别为524.68±278.32 s、191.26±39.35 s、304.20±42.71 s(P＜0.05);其后各组ACT开始逐渐回落,在4 h后降至最低.(2)三组抗凝血因子Xa活性均在药物全部注射后20 min达到峰值,分别为0.80±0.11 IU/mL、0.72±0.10 IU/mL及0.72±0.09 IU/mL,但各组问差异无统计学意义(P＞0.05).结论 与普通肝素相比,达肝素用于PCI中可达到手术所需抗凝效果.     

三种低分子量肝素在急性冠脉综合征介入治疗中安全性和有效性的比较研究

目的 比较三种低分子量肝素(依诺肝素、那屈肝素和达肝素)在急性冠脉综合症(ACS)介入治疗中的安全性和有效性.方法 本研究采用前瞻性、随机、单盲、单中心设计,76例入选的ACS患者随机分为依诺肝素组(1mg/kg)、那屈肝素组(0.01ml/kg)和达肝素组(120IU/kg),每12h皮下注射一次,至少使用48h后行冠状动脉造影或经皮冠状动脉介入术(PCI),所有手术在末次注射低分子量肝素(LMWH)后8h以内完成,术中不追加LMwH或普通肝素(UFH),监测三组手术前和手术结束时的部分活化凝血酶原激酶时间(APTT)和抗Xa因子活性,同时观察30d终点事件包括死亡、急性心肌梗死、急性左心衰和靶血管再次重建和严重出血事件,结果三组病例手术前和手术结束时平均APTT差异无统计学意义,术前和手术结束时APTT≥45s的病例数在依诺肝素组、那屈肝素组和达肝素组分别为24例(96.0%)、23例(95.8%)和26例(96.3%),差异无统计学意义.三组手术前和手术结束时抗Xa因子差异无统计学意义,但达到抗Xa因子≥0.5IU/L的比例不同,在依诺肝素组、那屈肝素组和达肝素组分别为:术前23例(92.0%)、21例(87.5%)和17例(63.O%)(P=0.018),手术结束时22例(88.0%)、19例(79.2%)和15例(55.6%)(P=0.022).30d随访三组终点事件的发生率差异无统计学意义,未发生严重出血事件发生.依诺肝素组发生1例因急性左心衰导致死亡,1例术后血小板＜10×1012/L,另有1例输血200mJ;那屈肝素组发生1例靶电管再次重建;达肝素组1例术中支架后急性血栓形成,导致急性前间壁心肌梗死,结论依诺肝索、那屈肝素和达肝索在ACS患者心导管室应用中均安全有效,术前皮下注射LMWH 4次且手术在末次注射的8h内完成,不需在冠状动脉造影和介人手术中静脉追加LMWH或UFH.     

使用依诺肝素48 h行冠脉造影的安全性和有效性

目的 低分子量肝素(LMWH)可以有效取代普通肝素(UH)应用于急性冠脉综合征(ACS)的治疗.然而,这些患者行冠脉造影(CAG)的最佳抗凝策略尚不明了.国外有关LMWH在冠脉造影中的应用研究表明,皮下应用低分子肝素至少48h(≥4次)冠脉造影,术中不追加抗凝剂是安全有效的,但此方案不一定适合我国.我科室曾沿用此法人选176例ACS患者,结果显示CAG前肝素抗-X a因子活性(0.808±0.265)IU/ml,93.2%的患者抗-X a活性＞0.5 IU/ml.本研究扩大样本量,试图进一步评价LMWH在心导管室应用的安全性和有效性,探索适合国人的心导管检查抗凝策略.方法 与结果人选278例ACS患者.所有患者按照1 mg(100 IU)/kg每隔12 h(7 am～7 pm)皮下注射依诺肝素(克赛),在接受至少48 h(≥4次)的LMWH后进行导管检查.末次注射(7 am)距离冠脉造影不超过8 h(3 pm之前).穿刺前(≈末次注射的3～5 h内)取血测定抗-X a活性.如病情需要,可行经皮冠脉介入术(PCI),术中追加普通肝素5000 IU.结果 显示冠脉造影前肝素抗-X a活性为(0.745±0.304)IU/ml,79.7%的患者抗-X a活性＞0.5 IU/ml,5.4%抗-X a活性＞1.2 IU/ml.1例在造影过程中,另3例在PCI中出现血栓,无严重出血事件.结论 皮下注射依诺肝素至少48h行冠脉造影抗凝强度偏低,可能需要寻找新的抗凝方案.     

抗Xa因子活性测定评价依诺肝素在心导管室中应用的安全性和有效性

目的　低分子量肝素可以有效的取代普通肝素应用于急性冠状动脉综合征 (ACS)的治疗。然而 ,ACS患者在行心导管检查时最佳的抗凝策略尚不明了。本研究旨在用抗Xa因子活性检测评价低分子量肝素在心导管室中应用的安全性和有效性 ,探索适合国人的心导管检查及经皮冠状动脉介入治疗 (PCI)的抗凝策略。方法　共入选ACS患者 1 76例。在每 1 2h(7:0 0 1 9:0 0 )皮下注射依诺肝素 1mg kg至少 48h后 ,不追加普通肝素或低分子量肝素于心导管室行冠状动脉造影 ,不进行凝血系统监测。 60例 (34 1 % )患者继之行PCI。结果　在心导管检查前的肝素抗Xa因子活性是 (0 81±0 2 7)IU ml,93 2 %的患者抗Xa因子活性 >0 50IU ml,且抗Xa因子活性与从注射到开始导管检查的时间无关 (P =0 0 97)。PCI组术后 30d无死亡、急性冠状动脉再闭塞或急诊血管重建事件。 3例(5 0 % )PCI患者术中出现血栓和 (或 )栓塞事件。单纯冠状动脉造影组有 1例因三支血管病变在术后1 7d等待冠状动脉旁路移植术时发生急性心肌梗死而行急诊PCI;另 1例患者在冠状动脉造影后 2 1d死于十二指肠穿孔。 1 76例入选患者无一例出现严重出血事件 ;PCI组有 3例 (5 0 % )患者出现轻度穿刺部位出血 ,单纯冠状动脉造影组为 5例 (4 3 % )。结论　本研究初步表明     

瓣膜性房颤桥接期抗Xa因子对白细胞介素、超敏C反应蛋白的影响

目的探讨瓣膜性房颤桥接期观察抗Ⅹa因子不同活性期对白细胞介素(IL)-1、IL-6、IL-8及超敏C反应蛋白(hs-CRP)的影响。方法选取2016年9月至2017年1月该院治疗的瓣膜性房颤患者80例,其中男52例,女28例,年龄35~75岁,随机分为观察组40例,对照组40例。观察组基础治疗联合低分子肝素钙,低分子肝素钙注射液每次100 IU/kg,2次/d,隔12 h皮下注射给药。对照组基础治疗联合普通肝素钙治疗。肝素钙(规格:2 ml,1.25万U)5 000 IU静脉滴注,2次/12 h。注射后3、12、24 h抽血检测。抗Ⅹa因子活性测定采用微量生色底物法测定,hs-CRP水平测定采用胶乳增强免疫透射比浊法,IL-1、IL-6、IL-8测定应用酶联免疫吸附(ELISA)法进行测定。结果两组治疗后3、12、24 h的抗Ⅹa因子活性均具有显著差异(P<0.01),且抗Ⅹa因子活性规律为3 h>12 h>24 h;观察组的抗感染作用较对照组更强(P<0.05);不同抗Ⅹa因子活性情况下,炎症因子CRP、IL-1、IL-6、IL-8的表达水平具有显著差异(P<0.01),总体抗感染趋势为3 h>12 h>24 h。结论低分子肝素钙和普通肝素钙在瓣膜性房颤桥接期的治疗,前者抗Xa活性更佳,并且抗炎症因子CRP、IL-1、IL-6、IL-8作用与抗Xa活性呈正相关。     

Safety and efficacy of dalteparin in percutaneous coronary intervention in Chinese patients with non-ST-elevation acute coronary artery syndromes: comparison with unfractionated heparin

Objective To prospectively evaluate the safety and therapeutic efficacy ofdalteparin in patients with high risk non-ST- elevation acute coronary syndromes （ACS） during percutaneous coronary intervention （PCI）. Methods A total of 175 patients with high risk non-ST-elevation ACS were randomly assigned to 2 groups [dalteparin group and unfractionated heparin （UFH） group]. The patients in dalteparin group were given dalteparin at a dose of 5,000U subcutaneously soon after diagnosis and then an additional 60U/ kg intravenous bolus ofdalteparin before emergent PCI. Vascular access sheaths were removed immediately after PCI or coronary artery angiography; the patients in UFH group were given UFH intravenously at a dose of 25mg just before PCI and an additional 65mg bolus was administered if angiographic findings showed that the patients were suitable for percutaneous transluminal coronary angioplasty （PTCA）. Sheaths were removed at 4-6 hours after PCI; Results Eighty-three patients in dalteparin group underwent PCI while 82 patients in UFH group underwent PCI; anti-Xa activities of 52 patients in daltepafin group were measured. The average anti-Xa activity was （0. 83± 0.26） U/ml at 15 minutes after intravenous injection of dalteparin and anti-Xa〉0.SU/ml was obtained in 96.1% of the patients; hematomas at puncture sites were significantly fewer in dalteparin group as compared with UFH group （2.3% vs 9.2%, P 〈 0.05）; none of the patients in 2 groups suffered major bleeding events. No death, acute arterial reocclusion or emergent revascularization events occurred at 30 days after PCI. Conclusions Our study demonstrated that early subcutaneous injection ofdalteparin at a dose 5,000U after diagnosis and an additional 60U/kg intravenous bolus ofdalteparin before PCI is safe and efficacious for patients with high risk non-ST-elevation ACS undergoing emergent PCI.     

The activated clotting time can be used to monitor the low molecular weight heparin dalteparin after intravenous administration

OBJECTIVES: This study was designed to compare the dose response of dalteparin versus unfractionated heparin (UFH) on the activated clotting time (ACT), and to determine whether the ACT can be used to monitor intravenous (IV) dalteparin during percutaneous coronary intervention (PCI). BACKGROUND: The use of low molecular weight heparin (LMWH) during PCI has been limited by the presumed inability to monitor its anticoagulant effect using bedside assays. METHODS: This study was performed in three phases. In vitro, ACTs were measured on volunteer (n = 10) blood samples spiked with increasing concentrations of dalteparin or UFH. To extend these observations in vivo, ACTs were then measured in patients (n = 15) who were sequentially treated with IV dalteparin and then UFH. Finally, a larger monitoring study was undertaken involving patients (n = 110) who received dalteparin 60 or 80 international U (IU)/kg alone or followed by abciximab. We measured ACT (Hemochron), activated partial thromboplastin time (aPTT), plasma anti-Xa and anti-IIa levels, tissue factor pathway inhibitor (TFPI) concentration, and plasma dalteparin concentration. RESULTS: Dalteparin induced a significant rise in the ACT with a smaller degree of variance as compared to UFH. Five min after administration of IV dalteparin 80 IU/kg the ACT increased from 125 s (122 s, 129 s) to 184 s (176 s, 191 s) (p < 0.001). The aPTT, anti-Xa and anti-IIa activities, and TFPI concentration also demonstrated significant increases following IV dalteparin. CONCLUSIONS: The ACT and aPTT are sensitive to IV dalteparin at clinically relevant doses. These data suggest that the ACT may be useful in monitoring the anticoagulant effect of intravenously administered dalteparin during PCI.     

The activated clotting time (ACT) can be used to monitor enoxaparin and dalteparin after intravenous administration

BACKGROUND: The use of low-molecular weight heparin (LMWH) during percutaneous coronary intervention (PCI) has been limited by the presumed inability to monitor its anticoagulant effect using bedside assays. OBJECTIVES: This study was designed to compare the dose-response of enoxaparin, dalteparin and unfractionated heparin (UFH) on the activated clotting time (ACT), and to determine whether the ACT or aPTT can be used to monitor intravenous (IV) low molecular weight heparin (LMWH). METHODS: A total of 130 patients undergoing cardiac catheterization were assigned to intravenous enoxaparin 0.5 mg/kg, dalteparin 50 international units/kg or UFH 50 units/kg. Of the 130 patients, 46 (35%) underwent PCI, all of whom received a glycoprotein (GP) IIb/IIIa inhibitor. We measured ACT, activated partial thromboplastin time (aPTT) and plasma anti-Xa levels after serial sampling. RESULTS: Both enoxaparin and dalteparin induced a significant rise in the ACT and aPTT, with an ACT dose-response approximately one-half the magnitude of that obtained using UFH. The time course of changes in the ACT and aPTT after administration of enoxaparin and dalteparin was virtually identical, with a return to baseline at approximately 2 hours. The enoxaparin and dalteparin-treated patients successfully underwent PCI with no major hemorrhagic complications. CONCLUSIONS: The ACT is equally sensitive to IV enoxaparin and dalteparin. These data support an ACT-guided strategy for intravenously administered LMWH during PCI. Additional studies with larger patient populations may be indicated to determine the ideal target ACT for LMWH in PCI.     

依诺肝素0.75 mg/kg动脉推注在冠状动脉造影和介入术中的应用

目的在中国人群中评价冠状动脉（冠脉）造影和经皮经腔冠脉介入术（PCI）中应用依诺肝素0．75mg／kg经动脉鞘管注射抗凝的安全性及有效性。方法160例择期PCI术患者随机分为两组,依诺肝素组给予依诺肝素0．75mg／kg,手术时间超过90min者再给0．3mg／kg;普通肝素组给予普通肝素100U／kg。结果注射依诺肝素后2h内,患者血浆抗Xa因子水平在0．5IU／ml以上。补充依诺肝素后可使所有患者血浆抗Xa因子水平4h内维持于0．5IU／ml以上。依诺肝素组鞘管内血栓发生率明显高于普通肝素组（26．6％比10．0％,P〈0．001）。两组30d内不良临床事件和出血事件发生率相似。结论择期PGI术中应用依诺肝素0．75mg／kg经动脉鞘管弹丸式注射进行抗凝是安全和有效的,有效抗凝强度至少可维持2h,手术时间超过2h的患者应补充依诺肝素。     

Dalteparin in combination with abciximab during percutaneous coronary intervention

BACKGROUND: Despite proved efficacy for either dalteparin or platelet glycoprotein IIb/IIIa blockade in improving clinical outcomes of patients with non-ST-segment elevation acute coronary syndromes, algorithms guiding concomitant therapy with these agents have not been devised. The purpose of this study was to assess anticoagulant effect and clinical safety for several dose regimens of dalteparin administered in combination with abciximab during percutaneous coronary intervention (PCI). METHODS AND RESULTS: Patients undergoing PCI with standard dose abciximab received dalteparin as follows: 120 IU/kg subcutaneously (SQ) to a maximum of 10,000 U if < or =8 hours before PCI (n = 3); for PCI 8-12 hours after the SQ dose, an additional 40 IU/kg intravenously (IV) was administered (n = 1); for PCI >12 hours after SQ dalteparin or with no prior dalteparin therapy, random allocation to 40 (n = 27) or 60 (n = 28) IU/kg IV during PCI was performed. Those patients who received 60 IU/kg of dalteparin IV had a lower incidence of procedural thrombosis (0% vs 11.1%, P <.01), more consistent antithrombotic effect (anti-factor Xa activity) and a similar incidence of major bleeding (3.7% vs 2.6%) compared with patients who received 40 IU/kg of intravenous dalteparin. CONCLUSIONS: Dalteparin 60 IU/kg IV appears to be safe and effective when administered in conjunction with abciximab for percutaneous coronary intervention.     

Degree of Anticoagulation after One Subcutaneous and One Subsequent Intravenous Booster Dose of Enoxaparin: Implications for Patients with Acute Coronary Syndromes Undergoing Early Percutaneous Coronary Intervention

BACKGROUND: Many cardiologists continue to be reluctant to utilize low-molecular-weight heparin in the treatment of patients with non-ST-segment-elevation acute coronary syndrome because they are concerned about how to manage such patients if they have received only one dose of subcutaneous enoxaparin and are then taken within hours of such treatment to the cardiac catheterization laboratory for percutaneous coronary intervention (PCI). Although we and others have recommended that such patients who have received only one subcutaneous enoxaparin dose receive an intravenous 0.3 mg/kg enoxaparin "booster" dose immediately prior to PCI, there are little actual data to support this recommendation. METHODS: 20 middle-aged subjects were treated with 1 mg/kg subcutaneously-administered enoxaparin and then 6 hours later with a "booster" dose of 0.3 mg/kg intravenously-administered enoxaparin. Anti-Xa levels, as well as ENOX Times, were assessed at baseline, at 2, 4 and 6 hours after the initial SC dose, and at 5 min, 1 and 2 hours after the IV booster dose. RESULTS: At 2 and 6 hours after the initial subcutaneous enoxaparin dose, thirty-five percent of patients had anti-Xa levels below 0.6 IU/mL; twenty percent and ten percent had anti-Xa levels below 0.5 IU/mL at 2 and 6 hours after the initial subcutaneous dose, respectively. After the IV booster dose, all patients had anti-Xa levels in the therapeutic range during the 5 minutes to 2 hours during which blood samples were obtained. There was no significant "overshoot" with this booster dose above what is considered to be the upper therapeutic range. ENOX times showed an overall moderate correlation with anti-Xa levels. CONCLUSIONS: A strategy of administering a 0.3 mg/kg IV booster dose to patients who have received only one subcutaneous dose of enoxaparin and then undergo PCI within the first 2-6 hours of such treatment reliably leads to anti-Xa levels in the therapeutic range.     

急性心肌梗死经皮冠状动脉介入治疗患者心肌胶原与左心室重构的关系

目的探讨急性心肌梗死经皮冠状动脉介入(percutaneous coronary intervention,PCI)治疗患者心肌胶原变化与左心室重构关系。方法选择2011年12月至2012年9月入住宝安区人民医院的急性心肌梗死患者共70例为研究对象。按照入院后患者是否行直接PCI治疗分为直接PCI治疗组(n=30)和择期PCI治疗组(n=30),其中10例(其中直接PCI治疗组5例,择期PCI治疗组5例)患者出院后不愿意随访。所有入选患者术前、术后3 d及术后30 d均分别以酶联免疫吸附法测定血清Ⅰ型C端胶原前肽(carboxy-terminal propeptide of type I procollagen,PICP)、Ⅲ型N端胶原前肽(amino-terminal propeptide of type III procollagen,PⅢNP)和Ⅰ型C端胶原末肽(carboxy-terminal telopeptide of collagen type I,CITP)浓度;术后3 d、术后30 d均行心脏超声检查;术后30 d行单光子发射计算机断层显像测量心肌梗死面积。结果术后30 d直接PCI治疗组血清PICP、PⅢNP、CITP浓度较择期PCI治疗组明显降低,差异有统计学意义[PICP:(7.76±1.47)ng/mL vs.(10.73±1.67)ng/mL,P﹤0.05;PⅢNP:(11.17±4.72)ng/mL vs.(37.80±6.83)ng/mL,P﹤0.05;CITP:(31.18±6.78)ng/mL vs.(45.10±9.70)ng/mL,P﹤0.05]。术后30 d直接PCI治疗的左心室舒张末期内径、左心室收缩末期内径、心肌梗死面积明显低于择期PCI治疗组[(46.57±6.10)mm vs.(52.63±6.50)mm,P﹤0.05;(34.25±4.86)mm vs.(37.33±3.56)mm,P﹤0.05;22.8%±3.4%vs.28.2%±6.8%,P﹤0.05]。结论直接PCI治疗可有效地挽救濒死的心肌,减轻心室重构,保护心功能,改善患者远期预后。检测血清心肌胶原浓度能作为预测心室重构的指标。     

Comparative pharmacokinetics of LMWHs

A variety of pharmaceutical preparations of low-molecular-weight heparins (LMWHs) are available. They belong to the same family of compounds-ie, heparin derivatives with a narrow distribution of mean molecular weights (MWs). LMWHs have different methods of preparation, which result in variations in mean MW, distribution of MW, and pharmacokinetic (PK) and pharmacodynamic (PD) profiles. The mean MW of these compounds ranges from 3,600 to 6,500 daltons. The ratio of anti-Xa (aXa) and anti-IIa (aIIa) activities of the different LMWHs ranges from 1.5 to >10. After subcutaneous (SC) injection of a prophylactic or therapeutic dose, the peak values for plasma aXa or aIIa activity may vary twofold to threefold because of differences in bioavailability, plasma clearance (Clplasma), and half-life (t1/2). The injection of equivalent amounts of product, based on aXa and aIIa international units (IU), may result in different areas under the curve for the respective activities. Although tinzaparin has a high aIIa specific activity per milligram (and consequently, a low aXa/aIIa ratio), SC injection of 40 mg of enoxaparin (4,000 aXa IU) results in a higher aXa peak value in patients with total hip replacement than 4,500 aXa IU of tinzaparin. Differences in aIIa and aXa peak activities are more striking when high doses of LMWHs are used. The activated partial thromboplastin time (aPTT) can be significantly prolonged, an effect that is related to aIIa and aXa activity. The volume of distribution of LMWHs is of the same order of magnitude as that of the plasma volume. The mean retention time of aXa activity varies from 5.2 (dalteparin) to approximately 7 h (enoxaparin, nadroparin). Bioavailability of prophylactic doses of LMWHs ranges from 86% (dalteparin) to 98% (enoxaparin, nadroparin). PK parameters appear to be minimally affected by a patient's age. The Clplasma is different for each LMWH: 16 mL/min enoxaparin, 21 mL/min nadroparin, 33 mL/min dalteparin, 19 mL/min reviparin, and 22 mL/min tinzaparin. Accumulation of product has been observed for almost all LMWHs in patients with renal insufficiency. LMWHs are effective and safe for treatment or prophylaxis of venous thromboembolism during pregnancy, because they do not cross the placenta. No data are available regarding the passage of LMWHs into the milk in lactating women. Although LMWHs are also effective in prevention and treatment of thromboembolic disease in children, optimal use of these agents in pediatric patients has not been determined. In summary, the PD and PK of LMWHs have been well documented and have demonstrated that LMWHs have a more predictable response, a greater bioavailability, and a longer aXa t1/2 than unfractionated heparin. However, their distribution of MW affects their physicochemical and biological properties, as well as PK characteristics. The concept of aXa/aIIa ratio (determined in vitro) does not account for the differing PK of aXa and aIIIa activity in circulating blood.     

Monitoring unfractionated heparin in pediatric patients with congenital heart disease having cardiac catheterization or cardiac surgery

Determine the effect of age and congenital heart disease (CHD) on whole blood tests for monitoring unfractionated heparin (UFH) in children. Determine correlation with anti-Xa levels in children undergoing cardiac catheterization or cardiac surgery. A prospective cross-sectional study of 211 healthy children about to have minor surgery (median age 3.5 years) and 110 CHD patients (median age 2.1 years) undergoing cardiac catheterization or cardiac surgery. Commonly used whole blood tests (two activated clotting times and an activated partial thromboplastin time; ACT+, ACT-LR, and APTT, respectively) were obtained before procedures and after UFH in CHD patients. Data were analyzed for effect of age and CHD and correlation with anti-Xa levels. In healthy subjects the ACT+ was lower in younger (<3 years) patients while the ACT-LR and APTT were unaffected. CHD patients exhibited an opposite trend with higher values in the younger patients. After bolus heparin the ACT+ exhibited the strongest correlation (r = 0.89) with anti-Xa levels in both locations (the APTT was too sensitive at post-bolus levels). When anti-Xa levels were below 1.0 IU/ml (range of thromboembolism therapy 0.35–0.7 IU/ml), the APTT correlation coefficient was 0.72. Some whole blood coagulation tests are affected by age in healthy children similar to laboratory tests and are variably influenced by the presence of CHD. ACT+ is the most reliable predictor of anti-Xa levels in both catheterization and surgery for pediatric patients. The APTT exhibited stronger correlation with antiXa than previous reports of laboratory APTT and warrants further evaluation for monitoring heparin thromboembolism therapy.