应用Sonoclot体外监测低分子肝素及磺达肝癸钠的抗凝作用

目的:探讨Sonoclot凝血仪在分析监测凝血与血小板功能的临床价值。方法:在gb试剂杯加入不同浓度的低分子肝素钠(0～1.6 IU/mL抗Xa因子)、低分子肝素钙(0～1.64 IU/mL抗Xa因子)、磺达肝癸钠(0～1.52μg/mL),抽取10例健康志愿者血样,并加入有药物的试剂杯中,用Sonoclot凝血仪进行检测,检测指标分别包括激活凝血时间(ACT)、凝血速率(CR)和血小板功能(PF)。结果:(1)3种抗凝药物随着浓度的增加,其ACT值逐渐增加,CR值逐渐下降,PF值逐渐下降。(2)对于同一治疗量的3种抗凝药物,低分子肝素钠(1.2 IU/mL抗Xa因子)与低分子肝素钙(1.23 IU/mL抗Xa因子),其ACT、CR、PF 3个参数的比较,P>0.05,无统计学差异。磺达肝癸钠(0.77μg/mL)与低分子肝素钠(1.2 IU/mL抗Xa因子)和低分子肝素钙(1.23 IU/mL抗Xa因子)相比,其ACT、CR、PF 3个参数均有差异性,均P<0.01。结论:Sonoclot凝血仪可以快速检测低分子肝素及磺达肝癸钠的抗凝效果以及对于血小板功能的影响,可以对临床给药剂量和个体化治疗做出指导。     

导管室中应用达肝素时抗凝活性的监测

目的:本研究旨在探讨激活凝血时间(ACT)是否可作为达肝素在导管室中应用时有效的抗凝监测手段.方法:共入选108例患者,冠状动脉造影(CAG)术前5min一次静脉注射达肝素60IU/kg,术中不再追加抗凝药物.所有患者均在静脉注射达肝素后5min取血测量ACT.其中30例患者作为抗凝活性检测组分别在达肝素注射前和注射后6个时间点取血检测抗凝参数ACT、aPTT、抗Xa因子和抗Ⅱa因子活性,观察静脉注射达肝素后的时间-抗凝效应关系.结果:静脉注射达肝素后5minACT值由基线121s升高到193s,10min时达峰值208s,并持续120min无明显下降(P＜0.001).aPTT、血浆抗Xa和抗Ⅱa因子活性也呈类似趋势.结论:ACT和aPTT对静脉注射达肝素敏感.ACT可以用来监测PCI期间静脉注射达肝素的抗凝活性.     

PTCA和支架置入术的ACT监测

目的探讨监测活化凝血时间（ACT）对冠状动脉造影＋经皮腔内冠状动脉成形术（PTCA）＋支架置入的术中和术后肝素剂量的评价：方法应用ACT机监测行PTCA及支架置入术的175例患者,根据ACT值及时调整肝素剂量。结果175例中29例联合应用欣维宁（盐酸替罗菲班氯化钠注射液）的患者术后ACT值均达到靶目标值,146例未联合应用欣维宁者中有18例术后ACT值未达标,需追加肝素,发生率最高的是55～65岁组患者,占该组患者的20％。结论在VFCA和支架置入术中和术后监测ACT有助于手术安全有效的进行.     

国产与进口低分子肝素在血液透析中抗凝作用的比较

目的比较国产与进口低分子肝素在血液透析中的抗凝效果和安全性。方法60例血液透析病人随机分为2组,透析过程中分别注射单剂量国产和进口低分子肝素。透析时取血检测部分凝血活酶时间(aPTT)、凝血酶原时间(PT)、凝血酶时间(TT)及因子Xa活性;透析结束后观察透析器及管道凝血情况、动脉穿刺点压迫止血时间。结果两组病人体外循环凝血发生率低且无显著差异,患者均无出血倾向。两组患者在动脉穿刺点压迫止血时间、血浆因子Xa水平及aPTT、TT、PT的变化等方面均无显著差异(P>0.05)。结论国产与进口低分子肝素在血液透析中的抗凝效果及安全性基本相同,国产低分子肝素可替代进口低分子肝素。     

国产与进口低分子肝素在血液透析中抗凝作用的比较

OBJECTIVE: To compare the anticoagulation efficacy and clinical safety of domestically manufactured and imported low-molecular-weight-heparin during hemodialysis. METHODS: Sixty patients on hemodialysis were randomly divided into 2 groups, who received intravascular injections of domestically manufactured or imported low-molecular-weight heparin to prevent coagulation. Active partial thromboplastin time (aPTT), prothrombin time (PT), thrombin time (TT) and factor Xa activity were determined during dialysis. RESULTS: No incidence of major bleeding was encountered in all of these patients. Similarly low incidences of clotting in extracorporeal circuit were found in either group. No significant differences in aPTT, PT, TT and plasma levels of factor Xa were observed between the two groups. CONCLUSION: Low-molecular-weight heparin domestically manufactured is safe and efficient for anticoagulation during hemodialysis as compared with the imported heparin.     

不同抗凝技术在危重症患者实施连续性肾脏替代治疗中的应用比较

目的：探讨局部体外肝素、枸橼酸及低分子肝素抗凝在危重症患者实施连续性肾脏替代治疗（CRRT）中的有效性和安全性.方法：选择行CRRT治疗患者60例,除外活动性出血及严重凝血功能障碍者,分为3组,局部体外肝素组14例,行CRRT 30例次;枸橼酸组25例,行CRRT 81例次;低分子肝素组21例,行CRRT 53例次.监测治疗前后血肌酐、电解质、酸碱指标、活化部分凝血酶原时间（APTr）及血小板计数（PLT）变化.记录治疗中患者生命体征、血滤器凝血情况及临床出血事件.结果：3组患者治疗后血肌酐均显著下降,组间无显著性差异（P＞0.05）,电解质酸碱指标均趋于稳定.低分子肝素组滤器凝血程度较另外2组重（P＜0.05）.局部体外肝素组治疗后PLT显著下降（P＜0.05）.低分子肝素组治疗后APTT延长、PLT下降（P＜0.05）.局部体外肝素组及低分子肝素组均有出血事件发生.结论：局部体外肝素、枸橼酸及低分子肝素抗凝均能有效应用于危重症患者CRRT治疗,加强监测可减少并发症的发生.     

Low molecular weight heparins and heparinoids

Several low molecular weight (LMW) heparin preparations, including dalteparin, enoxaparin and nadroparin, as well as the heparinoid danaparoid sodium, are approved for use in Australia. LMW heparins are replacing unfractionated heparin for the prevention and treatment of venous thromboembolism and the treatment of non-ST-segment-elevation acute coronary syndromes. The advantages of LMW heparins over unfractionated heparin include a longer half-life (allowing once-daily or twice-daily subcutaneous dosing), high bioavailability and predictable anticoagulant response (avoiding the need for dose adjustment or laboratory monitoring in most patients), and a low risk of heparin-induced thrombocytopenia and osteoporosis. Laboratory monitoring of LMW heparin therapy should be considered in newborns and children, patients with renal impairment, those who are pregnant, and those at the extremes of bodyweight (eg, < 40 kg or > 100 kg). LMW heparins should: be avoided or used with caution in patients undergoing neuraxial anaesthesia, owing to the potential for epidural haematoma formation; not be used (ie, are contraindicated) in patients with immune heparin-induced thrombocytopenia, as they may cross-react with anti-heparin antibodies. Conventional unfractionated heparin retains a role in the management of patients at high risk of bleeding, undergoing invasive procedures, and patients with renal failure owing to its shorter half-life, reversibility with protamine sulfate, and extrarenal metabolism. The heparinoid danaparoid sodium is effective for the treatment of heparin-induced thrombocytopenia.     

新型促凝试剂检测低分子肝素抗凝活性体外研究

目的 探讨活化凝血时间(ACT)新型促凝试剂检测低分子肝素(LMWH)的灵敏性.方法 2009年10月至2010年1月招募30例健康志愿者,抽取血标本依次加入不同剂量LMWH(达肝素钠),最终血标本达肝素钠浓度范围为0.1~1.8 U/ml,分别应用新型促凝剂磁棒与传统促凝剂高岭土测定ACT、纤维蛋白凝结速率(CR)值,对不同达肝素钠浓度与相应的ACT、CR值进行相关性分析并求得回归方程.结果 随达肝素钠浓度增加,用2种促凝剂分别测得的ACT值均逐渐延长而CR值逐渐减小,2种促凝剂的ACT值均与达肝素钠浓度成直线相关关系(P<0.01),CR值均与达肝素钠浓度呈指数相关关系(P<0.01).分析ACT值与达肝素钠浓度的直线回归方程发现,磁棒的直线斜率明显高于高岭土(1097.6 s/U比59.3 s/U,P<0.01).结论新型促凝试剂磁棒对达肝素钠抗凝活性灵敏性较高,有可能用于临床LMWH抗凝活性的床旁检测.

Abstract：

Objective To explore the sensitivity of new activated clotting time (ACT) reagent for laboratory monitoring of low molecular weight heparin (LMWH).Methods Blood samples were collected from 30 healthy volunteers and different doses of LMWH (dalteparin) added. The dalteparin concentration of final blood samples was 0.1-1.8 U/ml. ACT and clot rate (CR) were measured with traditional reagent kaolin and new reagent magbar. Linear regression analysis was performed and a regression equation established between different dalteparin concentrations and their corresponding ACT and CR values.ResultsWith rising dalteparin concentrations, the ACT values became gradually extended and the CR values were gradually reduced by both kaolin and magbar. Analysis of dose-response curves was obtained in vitro. And an excellent linear relationship was observed between the ACT and dalteparin concentrations for two reagents (P<0.01). An exponential relationship was observed between the CR and dalteparin concentrations (P<0.01). Differences in slope of regression curves of ACT were observed with the tested reagents (magbar 1097.6 s/U vs kaolin 59.3 s/U, P<0.01).Conclusion This in vitro study has shown that the sensitivity of new ACT test reagent (magbar) is good for laboratory monitoring of dalteparin. The new reagent magbar may be used for bedside monitoring of anticoagulant activity of LMWH.     

体外循环中紫绀型患者肝素用量的初步探讨

本文采用全血活化凝固时间(ACT)法测定了16例紫绀型先心病患者的2组肝素用量。旨在探讨紫绀型先心病患者术中适宜的肝素用量。结果首次肝素化量2mg/kg适用于大多数紫绀型先心病患者,此剂量既能保证体外循环的安全运行,又可避免抗凝过分所带来的危害。     

体外循环采用高岭土激活全血凝固时间监测43例临床报告

目的:心脏手术体外循环,采用高岭土作为试剂激活全血凝固时间监测,以下简称ACT监测,极大的提高了体外循环转流的安全性。方法:本组对43例病人使用高岭土做为试剂,对体外循环转流前ACT基础值(即生理值),体外循环转流中和体外循环转流后病员ACT值进行监测。结果:对心脏手术体外循环前和转流中肝素用量,以及停机后中和肝素的鱼精蛋白用量提供了可靠的参考依据,保证与减少了体外循环手术中的凝血及手术后创面的出血与渗血。结论:心脏手术体外循环中用高岭土进行ACT监测,此方法经济、简单、便于操作、确保了心脏手术体外循环的安全进行。     

Low-molecular-weight heparin and prevention of postoperative deep vein thrombosis

The efficacy of low-molecular-weight heparin as a prophylactic agent was assessed in 150 consecutive patients over the age of 40 undergoing major abdominal surgery. Fifty of these patients received 1250 activated partial thromboplastin time (APTT) units of low-molecular-weight heparin every 12 hours: three developed isotopic deep vein thrombosis, which was confirmed by phlebography in two cases. The other 100 patients received a single injection of 1850 APTT units of low-molecular-weight heparin. Three of them developed isotopic deep vein thrombosis; phlebography failed to confirm the presence of thrombi in each case. None of the 150 patients studied died from fatal or contributory pulmonary emboli. Low-molecular-weight heparin was not associated with any increase in preoperative or postoperative bleeding. The effect of equal amounts of postoperative bleeding. The effect of equal amounts of low-molecular-weight heparin and unfractionated heparin on the coagulation mechanism during surgery was investigated in another 30 patients. The clotting assays and results of in-vivo platelet function tests indicated that both preparations produced similar effect. Intragroup comparisons, however, showed significant differences in the anti-factor Xa activity, lipoprotein lipase release, and plasma prekallikrein concentrations. A single injection of low-molecular-weight heparin daily is a convenient way of preventing deep vein thrombosis in high-risk patients undergoing major abdominal surgery.     

血液透析患者肝素和低分子量肝素的合理剂量

目的 探讨血液透析(HD)患者应用普通肝素(UFH)和低分子量肝素(LMWH)的合理剂量.方法 选取38例HD患者,随机分为4个治疗组,给予6种抗凝方法.小剂量UFH组(10例):uFH首剂35 U/kg,追加10U·kg~(-1)·h~(-1);小剂量UFH+预冲组:病例和UFH剂量同小剂量UFH组,并HD前给予40 mg/L肝素生理盐水预冲;大剂量UFH组(10例):UFH首剂55 U/kg,追加16 U·kg~(-1).h~(-1);小剂量LMWH组(10例):透析前30 min法安明60 U/kg(3500 U)静脉注射;小剂量LMWH+预冲组:病例和LMWH剂量同小剂量LMWH组,并HD前给40 mg/L肝素生理盐水预冲;大剂量LMWH组(8例):透析前30 min法安明80 U/kg(5000 U)静脉注射.分别在透析前管路动脉端、透析2 h管路动脉端和静脉端、透析结束管路动脉端采血,利用Sconoclot血凝分析仪测试玻璃珠活化凝血时间(gbACT)值、凝结速率(CR)值和血小板功能(PF)值.结果 (1)小剂量UFH组和小剂量UFH+预冲组:与HD前比较,HD 2 h的动脉端和静脉端的gbACT值均明显延长、CR值明显减少,HD结束后gbACT值和CR值无明显变化;但2组间各个时点的各种检测指标无明显差别.(2)小剂量LMWH组:各个时点的gbACT值无明显差别;与HD前比较,CR值在HD 2 h的动脉端和静脉端均明显减少,但HD结束后无明显变化.(3)小剂量LMWH+预冲组:与HD前比较,gbACT值HD 2 h动脉端明显延长,但HD 2 h静脉端和HD结束无明显变化;CR值HD 2 h的动脉端和静脉端均较小剂量LMWH组进一步减少,但HD结束后恢复至透析前水平.(4)大剂量UFH组和大剂量LMWH组:与HD前比较,在HD 2 h的动脉端和静脉端以及HD结束,gbACT值均明显延长,CR值明显减少.结论 小剂量UFH抗凝效果充分、且不增加出血风险;小剂量LMWH可达到一定的抗凝效果;大剂量UFH和LMWH可引起出血风险;40 mg/L肝素生理盐水预冲增加小剂量LMWH抗凝效果,但也增加HD过程中的出血风险.     

低相对分子质量肝素抗凝时高岭土-血栓弹力图R时间目标值研究

目的 探讨低相对分子质量肝素（low molecular weight heparin,LMWH）抗凝时,高岭土-血栓弹力图R时间目标值.方法 测定不同浓度LMWH抗凝时血液aPTT和R时间,检测94例（131例次）LMWH抗凝患者的高岭土-血栓弹力图R时间和肝素酶-血栓弹力图△R％,比较R时间和△R％判断抗凝效果是否一致.结果 aPTT和R时间均与LMWH浓度（在0～2.0抗Xa u/ml范围）呈正直线相关（P＜0.01）.aPTT为正常值2倍时,LMWH浓度为0.55 ～1.32抗Xa u/ml.抗Xa活性在此范围内的R时间为10.2～16.8 min.131例次LMWH抗凝患者R时间为8.14±5.97min,肝素酶-血栓弹力图△R％为9.06 ±25.26％;R时间和肝素酶△R％判断LMWH抗凝效果符合率为87.8％,两种方法判断效果基本一致（Kappa=0.61,P＜0.001）.结论 LMWH治疗血栓性疾病时,高岭土-血栓弹力图R时间目标值为10.2～ 16.8 min（正常值5～ 10 min）.     

枸橼酸体外抗凝在连续性血液净化治疗中的综合效果观察

目的探讨枸橼酸体外抗凝在连续性血液净化治疗中的综合效果。方法选取2009年12月～2011年5月于本院进行连续性血液净化治疗的46例患者为研究对象,将其随机分为对照组（肝素组）23例和观察组（枸橼酸钠组）23例,后将两组的滤器使用时间、滤器及静脉壶凝血程度、滤器前后2、4、6、8h全血活化凝血时间、治疗前后血尿素氮、肌酐、Ca2＋、pH、碱剩余、HCO3-、K＋进行统计及比较。结果观察组的滤器使用时间长于对照组,滤器及静脉壶凝血程度优于对照组,滤器后2、4、6、8h全血活化凝血时间长于对照组,血尿素氮、肌酐低于对照组,P均〈0.05,均有显著性差异,而治疗后两组的Ca2＋、pH、碱剩余、HCO3-、K＋均无显著性差异,P均〉0.05。结论枸橼酸体外抗凝在连续性血液净化治疗中的综合效果较受肯定,安全性较高,综合优势优于肝素。     

枸橼酸钠抗凝在连续性血液灌流中的应用

目的：评价枸橼酸钠抗凝在连续性血液灌流中的抗凝效果。方法：将35例实施连续性血液灌流的重度有机磷中毒患者根据抗凝方案分为低分子肝素组和枸橼酸钠组。比较2组治疗过程中跨膜压的变化,同时比较治疗后血小板、部分凝血活酶时间、HCO3-、游离钙、Na＋和24h内出血情况。结果：低分子肝素组治疗2h和治疗4h的跨膜压均较枸橼酸钠组明显增高（P〈0．01）;治疗后低分子肝素组部分凝血活酶时间较枸橼酸钠组明显延长（P〈0．01）;2组治疗后血小板、HCO3-、游离钙和Na＋差异均无统计学意义（P〉0．05）。结论：在连续性血液灌流过程中应用枸橼酸钠抗凝具有可行性和安全性。     

Guidelines to control heparin treatment

With new guidelines for the control of heparin infusion rates the proportion of kaolin cephalin clotting time ratios was significantly improved compared with ratios achieved without their use. Further improvement might result from careful preparation and delivery of the infusion.     

预冲式枸橼酸钠抗凝技术在连续性血液净化高危出血患者中的应用

目的观察局部枸橼酸抗凝在连续性血液净化中的应用效果，探讨高危出血倾向患者进行连续性血液净化时的安全性和有效性。方法选择67例高危出血倾向的患者随机分为2组：局部枸橼酸抗凝组（RCA组）43例，行血液净化106例次；对照组24例，行无肝素血液净化87例次。监测全血ACT（活化凝血时间）、观察体外循环凝血情况；监测血清游离钙、枸橼酸、血钠、碳酸氢根浓度；监测血尿素氮、肌酐、治疗时间、实际超滤量等。结果RCA组：置换液输入前WBACT与治疗前差异不显著，输入置换液后两组滤器后WBACT（s）较滤器前在2、4、6h各时间点的延长均有显著性差异（P〈0．01）；治疗后患者碱剩余（BE）及PH值无大幅度上升，无碱中毒出现；体内ACT较治疗前无明显延长。两组滤器凝血、静脉壶凝血情况、治疗前后血肌酐、尿素氮以及治疗时间和实际超滤量比较，差异有显著性意义（P〈0．05，P〈0．01）；观察组治疗前后血清游离钙、钠、碳酸氢根浓度及体外活化凝血时间（ACT）比较，差异无显著性意义（均P〉0．05）；未发生高钠血症和代谢性碱中毒并发症。结论连续性血液净化治疗时，局部预冲式枸橼酸抗凝体外抗凝效果确切，对体内凝血功能无明显影响；并发症少，可以在临床推广应用。     

层层自组装壳聚糖/肝素复合涂层膜对支架血栓形成的影响

目的:观察层层自组装壳聚糖/肝素复合涂层膜对支架血栓形成的影响.方法:通过逐层自组装的方式将壳聚糖和肝素逐层结合在316L不锈钢槽内,制成不同层数的涂层膜,以凝固法测定健康人血液在聚合物膜和不锈钢上作用2 h后的部分凝血活酶时间(APTT)、凝血酶原时间(PT)和凝血酶时间(TT),并检测其抗凝血功能的稳定性.制备壳聚糖/肝素复合涂层膜支架,研究复合涂层膜支架在猪动静脉分流血栓模型中对支架血栓形成的影响.结果:备组复合涂层膜APTT和TT均较316L不锈钢组极显著延长(P<0.01),并且APTT和TT延长和复合涂层膜层数增加相关.复合涂层膜在2周内上述凝血功能无显著差异(P>0.05).在猪动静脉分流血栓模型中,复合膜涂布的金属支架形成的血栓重量极显著低于316L裸支架(P<0.001).结论:层层自组装壳聚糖/肝素复合涂层膜具有极显著的抗支架血栓作用,而且具有良好的稳定性.     

肝素在分子吸附再循环治疗肝衰竭中的应用及对凝血指标的影响

目的:观察分子吸附再循环系统(molecular adsorbent recirculating system,MARS)治疗肝衰竭时无肝素和肝素循环对患者凝血指标的影响,评价2种抗凝技术的安全性.方法:对174例凝血酶原活动度(PTA)≤40％的肝衰竭患者按随机分组原则进行前瞻性实验性研究.根据抗凝方式不同分为无肝素...     

Low-molecular-weight heparin (LMWH) in the treatment of thrombosis

Thromboembolic complications are a common and costly medical problem, associated with significant morbidity and mortality, especially in postoperative patients. There have been reports of death due to thromboembolic complications even after short procedures, e.g. arthroscopy. Low-molecular-weight heparins (LMWHs) (e.g., certoparin, dalteparin, enoxaparin, nadroparin, reviparin, tinzaparin) have been tested for treatment of deep vein thrombosis in comparison to unfractionated heparin (UFH) in many patients being effective and safe alternative for treatment of deep vein thrombosis (DVT) and venous thromboembolism (VTE). Fixed-dose subcutaneous LMWH once daily is in most cases of equivalent efficacy and safety compared to conventional UFH therapy. There may be less risk for bleeding, less platelet activation together with a control of markers of haemostatic system activation, and either no progression or regression of thrombus size in patients treated with LMWH. The handling of LMWH is more comfortable for patients and less time consuming for nurses and laboratories compared to UFH. The cost-effectiveness analysis showed that LMWH are more cost effective than UFH. It has been calculated that outpatient treatment with LMWH may save 1641 dollars per patient in comparison to hospital treatment. This economic benefit of outpatient treatment of DVT seems to be realized in different health systems. Women with antiphospholipid antibodies and a history of either prior thrombotic events or pregnancy loss are at high risk during pregnancy for either another fetal death or thrombosis and may benefit from treatment with LMWH. In patients with malignant tumors secondary prophylaxis or long-term treatment with LMWH is successful. Patients with a contraindication for oral anticoagulants may benefit from treatment with LMWH as do patients on chronic anticoagulation treatment scheduled for an operative intervention. In most instances LMWH (dalteparin, enoxaparin, nadroparin) treatment for DVT may be given once daily at a fixed dose without any harm, based on a prolonged antithrombin activity. Effectiveness and safety of LMWH (dalteparin, enoxaparin, nadroparin, tinzaparin) in comparison to UFH treatment on outpatient basis has been demonstrated in several studies. In summary, LMWHs have an established role in the treatment of DVT and pulmonary embolism (PE), on an in- and outpatient basis and could realize substantial savings. Most studies were performed with dalteparin, enoxaparin and nadroparin. There is evidence that LMWHs may help to prolong survival in cancer patients and to avoid complications of the acute coronary syndrome.