低分子肝素与普通肝素治疗不稳定型心绞痛的对比分析

目的 比较低分子肝素（LMWH）与普通肝素（UFH）治疗不稳定型心绞痛（UA）的有效性及安全性：方法 65例UA病人，随机分为LMWH组（33例）和UFH组（32例），对比观察风组病人心绞痛改善程度、心电图变化情况及不良反应：结果 LMWH组和UFH组心绞痛改善程度比较，两组总有效率比较有统计学意义（93．9％和75．0％，P〈0．05），心电图变化情况总有效率比较无统计学意义（66．7％和62．5％，P〉0．05），不良反应发生率比较有统计学意义（9．1％和15．6％，P〈0、05）。结论 LMWH治疗UA较UFH治疗可显著减少心绞痛的发作，且不良反应少。     

Thrombotic Reactant Markers in Non-ST Segment Elevation Acute Coronary Syndromes Treated with Either Enoxaparin (Low Molecular Weight Heparin) or Unfractionated Heparin

Background: This study was designed to analyze the impact of treatment with either unfractionated heparin or enoxaparin (low molecular weight heparin) on plasma markers of thrombotic and endogenous thrombolytic activity in patients with non-ST segment elevation acute coronary syndromes.Methods: A subset of 174 patients derived from the 3,171 patients of the ESSENCE study was evaluated. Eighty-seven patients were assigned to intravenous unfractionated heparin (target aPTT: 55–85 sec) (group UH), and 87 assigned to subcutaneous enoxaparin (1 mg/kg/q12hr) (group ENOX) for a minimum of 48 hours of treatment (average duration of treatment 88±45 hours). The thrombin time, and plasma levels of anti-factor Xa activity, prothrombin fragment F 1+2, thrombin-antithrombin complex (TAT), and D-dimer, were assayed at baseline, and at or close to peak activity 24–36 hrs, and at 72–90 hrs for those remaining on treatment with antithrombotic therapy. Major ischemic and hemorrhagic events were assessed throughout hospitalization. The levels of the thrombotic markers measured at or close to peak activity at 36 hours are presented below, and compared to clinical outcome at 30 days.Results: In UH patients, the thrombin time increased 7 fold while the mean value for anti-Xa activity was 0.27 IU/ml; in ENOX patients the thrombin time increased 2.3 fold, and the mean value for anti-Xa activity was 0.83 IU/ml. In UH pts, basal levels of F 1+2, TAT, and D-dimer declined by (paired) –0.8, –3.3, and –66, respectively. In ENOX pts, basal levels of F 1+2, TAT, and D-dimer declined by (paired) –0.3, –4.7, and –23, respectively. No significant differences were observed between the paired differences in thrombotic markers (UH vs ENOX), nor in the rate of recurrent ischemic events or major hemorrhage.Conclusions: In this subset of patients enrolled in the ESSENCE study, enoxaparin 1 mg/kg ql2hr significantly increased anti-Xa activity above that seen with unfractionated heparin, and reduced thrombin production without prolonging the thrombin time. The high anti-Xa activity achieved with enoxaparin was not associated with a loss of safety.     

Enoxaparin,a Low Molecular Weight Heparin,Inhibits Platelet-Dependent Prothrombinase Assembly and Activity by Factor-Xa Neutralization

Background: The available evidence suggests strongly that intravascular thrombosis is mediated predominantly by tissue-factor and its activation of factor X, which in the presence of factor Va, calcium, and phospholipid (prothrombinase complex) effectively converts prothrombin to thrombin. In vitro experiments have shown that low molecular weight heparins (LMWHs) have greater anti-Xa activity than unfractionated heparin; however, it remains unclear as to whether their antithrombotic effects in vivo are determined by a similar mechanism. We determined the ability of plasma obtained from patients with either unstable angina or non-ST segment elevation myocardial infarction (MI) receiving the LMWH enoxaparin (anti Xa:IIa ratio 3:1) to inhibit tissue factor-mediated thrombin generation and to inactivate platelet prothrombinase.Methods: Platelet rich plasma was prepared by suspending washed donor platelets in the plasma of 7 patients participating in the TIMI 11A study. Samples were obtained before, 1 hour after a 30-mg IV bolus of enoxaparin and 6 hours after the third subcutaneous injection (1.0–1.25 mg/kg given subcutaneously every 12 hrs). Tissue factor (0.1 ng/ml) and 10 mM CaCl₂ were added to initiate extrinsic coagulation. At timed intervals prothrombin activation fragment 1.2 (F1.2) levels (thrombin generation) were measured using an ELISA technique. Inactivation of reformed platelet prothrombinase by samples obtained at the same time points was also determined.Results: Patient plasma obtained 1 hr after treatment initiation and 6 hours after the third subcutaneous injection inhibited tissue factor mediated prothrombinase assembly by 31% and 11%, respectively and platelet prothrombinase activity by 27% and 22%, respectively.Conclusion: We conclude that enoxaparin in plasma concentrations achieved routinely in clinical practice is able to: (1) inhibit tissue factor mediated extrinsic coagulation by preventing platelet surface prothrombinase assembly, and (2) inactivate platelet prothrombinase activity and resulting thrombin generation. These observations suggest that a LMWH's anti-Xa activity (and anti-Xa:IIa profile) is important in determining its overall antithrombotic potential. Clinical trials comparing agents with differing anti-Xa:IIa properties will be required, however, to provide proof of concept.     

Low Molecular Weight Heparin and Unfractionated Heparin in the Early Pharmacologic Management of Acute Coronary Syndromes: A Meta-analysis of Randomized Clinical Trials

Background: The standard of care in Acute Coronary Syndromes (ACS) includes a full complement of antischemic and antithrombotic therapy. Although aspirin is used widely and concomitant anticoagulation is recommended, the comparative benefits of low molecular weight heparin (LMWH) and unfractionated heparin (UFH) have not been defined. Methods/Results: A meta-analysis including all randomized clinical trials comparing LMWH and UFH for the treatment of non-ST segment elevation acute coronary syndromes was performed. Risk ratios (RR), using the DerSimonian-Laird Model, were calculated from a total of 13,320 patients. Death (RR 0.98, 95% CI 0.73–1.31), death and myocardial infarction (MI) (RR 0.86, 95% CI 0.74–1.01), death, MI, recurrent angina or revascularization (RR 0.89, 95% CI 0.74–1.07) and major hemorrhage (RR 1.01, 95% CI 0.81–1.25) occurred with similar frequencies for the anticoagulant-based strategies. Conclusions: Fixed dose LMWH therapy given subcutaneously compares favorably with UFH titrated to a target level of anticoagulation and should be considered a safe, effective, and clinically acceptable alternative in the early management of patients with non-ST segment elevation ACS. The superiority of LMWH preparations characterized by high in vitro factor Xa to thrombin inhibitory capacity is supported by clinic trial data but requires further investigation.     

低分子肝素在不稳定型心绞痛的应用

本文旨在观察低分子肝素治疗不稳定型心绞痛的疗效并讨论其作用.25例常规治疗欠佳的病人加用低分子肝素0.4ml,腹壁皮下注射2次/日,疗程10～14天,观察临床疗效、心电图ST段及血液流变指标治疗前后改变.结果显示,显效14例,占56%.有效8例,占32%,总有效率88%.心电图ST段总均数由治疗前的0.113±0.071降为0.068±0.039,P相似文献   

Low Molecular Weight Heparin in Atrial Fibrillation Management: Facts, Fiction, Future

Background: Atrial fibrillation (AF) is the most common sustained arrhythmia and various AF disease management strategies can be utilized. Methods: A prospective, randomized pilot study of two AF disease management strategies was conducted at a single university hospital in patients newly diagnosed with AF. The impact of low molecular weight heparin (LMWH) on AF management strategies is discussed with respect to the current guidelines for AF management, existing data on LMWH for AF, and recent investigations pertaining to AF. Results: 18 patients were enrolled. The accelerated emergency department based strategy utilizing LMWH resulted in a significant reduction in length of stay (2.1 ± 2.3 versus <1 day) and a trend toward lower costs ($1,706 ± 1,512 versus $879 ± 394; p = 0.15) when compared to the more traditional strategy of hospital admission. Measured clinical outcomes were similar for both treatment strategies. Conclusions: The investigation showed that an outpatient, emergency department based disease management strategy for new, uncomplicated AF could result in clinically acceptable, cost-effective innovations in AF treatment strategies. LMWH is an example of an agent allowing innovations in disease management strategies.     

Low Molecular Weight Heparin Therapy for Percutaneous Coronary Intervention: A Practice in Evolution

Unfractionated heparin (UFH) remains the principal antithrombotic agent during percutaneous coronary intervention (PCI) but is associated with significant limitations including an unpredictable anticoagulation dose response, the requirement for frequent monitoring, and transient rebound hypercoagulability. Low molecular weight heparin (LMWH) represents an attractive alternative due to its predictable dose response relationship, superior antithrombotic efficacy and potential for improved clinical safety, and has been used increasingly in patients with acute coronary syndromes prior to coronary angiography. The rationale and existing data regarding the use of LMWH in PCI is summarized and reviewed. Preliminary clinical guidelines for the use of LMWH in the transition from medical stabilization of patients with acute coronary syndromes to invasive management in the catheterization laboratory are presented.     

血栓通注射液与低分子肝素钙联合治疗不稳定型心绞痛的临床观察

目的观察血栓通注射液联合低分子肝素钙治疗不稳定型心绞痛的临床疗效。方法将100例病人随机分为两组,对照组在常规治疗的基础上加用低分子肝素钙治疗,治疗组在上述治疗的基础上,加用血栓通治疗。观察治疗前后心绞痛发作次数、心绞痛持续时间、发作间隔时间、24h Holter缺血总时间等变化。结果治疗组总有效率为94%,优于对照组的86%（P〈0.05）,且治疗组在心绞痛发作次数、持续时间、发作间隔时间及24h Holter缺血总时间改善方面优于对照组（P〈0.05）。结论血栓通联合低分子肝素钙治疗不稳定型心绞痛疗效确切。     

Treatment of Deep Vein Thrombosis with Low Molecular Weight Heparin at Patient's Home

We have applied the low molecular weight heparin dalteparin as once-daily subcutaneous injections to the treatment of deep vein thrombosis (DVT) on an outpatient basis since 1994. Until today, 377 consecutive patients with DVT below the inguinal ligament have been treated at home with dalteparin. The patients administered the injections themselves or with the help of either a relative or a primary nurse. Here we report the outcome of the 212 patients treated during 1994–1995, which has been followed for 2 years after the start of treatment. At the 2-year follow-up only 13 patients (6.6%) had suffered a recurrent DVT and of these none were on continuous dicumarol treatment. No cases of major bleedings were seen. This new therapeutic approach for the treatment of DVT is safe, most of the patients are able to treat themselves, and the patients are satisfied with the home treatment model.     

低分子肝素钙治疗不稳定型心绞痛疗效观察

目的 :观察低分子肝素钙治疗不稳定型心绞痛的疗效。方法 :选择不稳定型心绞痛住院病人 3 5例 ,随机分成两组 ,A组 15例给予常规抗心绞痛治疗 ;B组 2 0例给予常规抗心绞痛治疗同时加低分子肝素钙 5 0 0 0AXaIU ,皮下注射 ,每 12h 1次 ,7d为一疗程。观察治疗前后临床症状、心电图变化 ,并于用药前后测定凝血时间(TT)、凝血酶原时间 (PT)、部分凝血酶时间 (APTT )。结果 :A、B两组病人的临床疗效分别为 5 3 %和 90 %(P <0 .0 1) ,B组TT、PT、APTT较治疗前延长 (P <0 .0 5 ) ,无明显出血的不良反应。结论 :低分子肝素钙对控制不稳定型心绞痛效果显著 ,而且使用安全方便。     

低分子肝素佐治充血性心力衰竭的临床研究

目的探讨低分子肝素对充血性心力衰竭患者心功能、凝血功能的影响。方法将62例慢性心力衰竭患者随机分为两组,对照组31例给予强心、利尿、扩血管、p受体阻滞剂、血管紧张素转换酶抑制剂、醛固酮受体拮抗剂等常规治疗;治疗组31例在此基础上加用低分子肝素5000U／次皮下注射,2次／d,共15d,2周后检查心脏超声。评估心功能、测定血浆D一二聚体,血浆纤维蚤白原水平。结果两组治疗后左室舒张末径（LVEDd）水平明显降低,左室射血分数（LVEF）水平明显升高,与治疗前比较差异有统计学意义（P〈0．05）;并且治疗组治疗后LVEDd、LVEF水平改善明显优于对照组,两组比较差异有统计学意义（P〈0．05）;治疗组血浆D-二聚体、血浆纤维蛋白原（FPG）水平明显降低（P〈0．05）。结论低分予肝素既能降低血浆D—dimer、FPG水平,又可改善充血性心力衰竭心脏功能,有益于充血性心力衰竭的治疗。     

低分子肝素钠在重度及极重度AECOPD疗效观察

目的 探讨重度及以上AECOPD应用抗凝治疗的临床意义.方法 选取60例入住病房的重度及以上AECOPD患者,随机分为实验组(抗凝)30例,对照组30例,均给予常规氧疗、抗感染、解痉平喘、化痰等治疗,实验组同时给予低分子肝素治疗1周.治疗前后分别检查动脉血气分析中PaO2、PaCO2,同时取静脉血测C-反应蛋白浓度(C-RP).结果抗凝治疗结束后,实验组中动脉血气分析中PaO2、PaCO2较对照组有明显改善,实验组的CRP浓度较对照组下降.两组比较差异均有统计学意义.结论 抗凝治疗可以改善重度及以上AECOPD患者的动脉血气分析中PaCO2、PaCO2,同时减轻患者体内炎症反应.     

Once-Daily Enoxaparin in The Outpatient Setting Versus Unfractionated Heparin in Hospital for the Treatment of Symptomatic Deep-Vein Thrombosis

Background: Once- and twice-daily low-molecular-weight heparin administered in hospital have been shown to be effective and safe for treating deep-vein thrombosis. The aim of this study was to compare the efficacy and safety of deep-vein thrombosis treatment using once-daily subcutaneous enoxaparin in the outpatient setting with intravenous unfractionated heparin in hospital.Methods: This randomized, parallel-group, open-label study was conducted in 18 centers in 4 countries. In total, 298 patients with symptomatic deep-vein thrombosis who were eligible for home treatment were randomized to treatment with enoxaparin in the outpatient setting (1.5 mg/kg subcutaneously once-daily) or unfractionated heparin in hospital (5000 IU bolus and 1250 IU/hour intravenous infusion) for ≥5 days. Clinical endpoints were assessed during a 6-month follow-up period.Results: Among all patients treated with enoxaparin, there was a trend towards fewer recurrent deep-vein thromboses (1.3% vs. 5.4%; p = 0.060) and pulmonary emboli (1.3% vs. 4.1%; p = 0.17) compared with patients treated with unfractionated heparin. When considering a post-hoc combined endpoint of deep-vein thrombosis and pulmonary embolism, significantly fewer events occurred in the enoxaparin group than in the unfractionated-heparin group (2.7% vs. 8.8%; p = 0.026). The incidences of bleeding events and adverse events in the enoxaparin and unfractionated-heparin groups were similar.Conclusions: Once-daily subcutaneous enoxaparin in the outpatient setting is at least as effective and as well tolerated as in-hospital intravenous unfractionated heparin for treatment of deep-vein thrombosis.     

Adjunctive Pharmacologic Treatment: Focus on the Development of Low Molecular Weight Heparins

Journal of Thrombosis and Thrombolysis -     

Enoxaparin is superior to unfractionated heparin for preventing clinical events at 1-year follow-up of TIMI 11B and ESSENCE.

BACKGROUND: Enoxaparin treatment is associated with a 20% reduction in clinical events during the acute phase of management of patients with unstable angina/non ST elevation myocardial infarction. Interest in the use of enoxaparin would be enhanced further if evidence of a durable treatment benefit over the long term could be provided. METHODS: Event rates at 1 year for the composite end-point of death/non-fatal myocardial infarction/urgent revascularization and its individual components were ascertained from the TIMI 11B and ESSENCE databases. RESULTS: There was no evidence of heterogeneity between TIMI 11B and ESSENCE in tests for interactions between treatment and trial. A significant treatment benefit of enoxaparin on the rate of death/non-fatal myocardial infarction/urgent revascularization was observed at 1 year (hazard ratio 0.88;P=0.008). The event rate was 25.8% in the unfractionated heparin group and 23.3% in the enoxaparin group, an absolute difference of 2.5%. A progressively greater treatment benefit of enoxaparin was observed as the level of patient risk at baseline increased. Treatment effects for the individual end-point elements ranged from 9-14%, favouring enoxaparin. CONCLUSIONS: The stable absolute difference in event rates of 2.5% seen at 8 days and again at 1 year favouring enoxaparin may be due to more effective control of the thrombotic process surrounding the index event. Once the pharmacological effect of enoxaparin had dissipated there was no rebound increase in events. Thus, those patients who had received enoxaparin acutely were protected from experiencing a deterioration of the original therapeutic benefit. These findings regarding enoxaparin add to the data to be considered by clinicians when selecting an antithrombin for the acute phase of management of unstable angina/non-ST elevation myocardial infarction.     

低分子量肝素和降纤酶治疗急性脑梗死的疗效

目的比较低分子量肝素和降纤酶治疗急性脑梗死的疗效。方法将90例急性脑梗死患者随机分为降纤酶治疗组（A组,46例）,给予降纤酶10U、5U、5U,每日静滴;低分子量肝素组（B组,44例）,给予低分子量肝素钠0.5m l/次,皮下注射2次/d,连续9d。结果 A组基本痊愈率、显效率高于B组（P〈0.05）。实验室指标显示A组用药后纤维蛋白原降低,与用药前相比有明显差异（P〈0.05）。结论应用降纤酶治疗急性脑梗死疗效优于低分子量肝素钠。     

无肝素及低分子肝素在有出血倾向的血液透析患者的应用研究

目的研究无肝素及低分子肝素在有出血倾向的血液透析患者的应用安全性和有效性。方法选择伴有中、高危出血倾向的维持性血液透析(MHD)患者24例,随机分为A组12例(无肝素透析),B组12例(低分子肝素透析),观察临床出血情况,透析前后部分凝血酶活化时间、凝血酶原时间、血小板、管道及透析器凝血情况。结果透析后两组无一例出血加重,A组7例发生凝血,B组无体外凝血发生。结论无肝素与低分子两种透析抗凝方法,低分子肝素透析明显优于无肝素。     

前列地尔联用低分子量肝素治疗老年骨折非大面积肺栓塞疗效观察

目的：观察前列地尔联用低分子肝素治疗老年骨折后并发非大面积肺栓塞的疗效。方法：老年骨折后并发非大面积肺栓塞的患者62例,随机分成2组。对照组30例予低分子量肝素钠4100U皮下注射,每12h1次,疗程7～14d;治疗组在予低分子量肝素钠的同时予前列地尔脂微球载体制剂。两组患者同时接受动脉血气、血氧饱和度（SaO2）、超声心动图检查。结果：治疗组与对照组比较,治疗后PaO2、PaC02、SaO2、PASP、MPAP、RAP、PVR、RVEF水平变化有统计学差异（P〈0．05）。对照组总有效率为66．7％o,治疗组总有效率为90．6％,两组比较差异有统计学意义。结论：采用前列地尔联用低分子量肝素可以有效治疗老年骨折后并发非大面积肺栓塞的患者,且出血风险小。     

Comparison of two treatment durations (6 days and 14 days) of a low molecular weight heparin with a 6-day treatment of unfractionated heparin in the initial management of unstable angina or non-Q wave myocardial infarction: FRAX.I.S. (FRAxiparine in Ischaemic Syndrome)

Aim To assess the benefit of short-term low molecular weightheparin nadroparin compared with unfractionated heparin in unstableangina or non-Q wave myocardial infraction patients and to determinewhether a longer, 2-week low molecular weight heparin regimenwould offer additional clinical benefit. Patients, Methods and Results This was a multicentre, prospective,randomized, double-blind study in three parallel groups, involving3468 patients. Patients received one of three treatment regimens:the unfractionated heparin group received an intravenous bolusof unfractionated heparin 5000IU, followed by an activated partialthromboplastin time adjusted infusion of unfractionated heparinfor 6±2 days; the nadroparin 6 group received an intravenousbolus of nadroparin 86 anti-Xa IU.kg^–1, followed by twicedaily subcutaneous injections of nadroparin 86 anti-Xa IU.kg^–1for6±2 days, and the nadroparin 14 group received an intravenousbolus of nadroparin 86 anti-Xa IU.kg^–1, followed by twicedaily subcutaneous injections of nadroparin 86 anti-Xa IU.kg^–1for14 days. No statistically significant differences were observedbetween the three treatment regimens with respect to the primaryoutcome (cardiac death, myocardial infarction, refractory angina,or recurrence of unstable angina at day 14). The absolute differencesbetween the groups in the incidence of the primary outcome were:–0·3% (P=0·85) for the nadroparin 6 groupvs the unfractionated heparin group and +1·9% (P=0·24)for the nadroparin 14 group vs the unfractionated heparin group.Furthermore, there were no significant intergroup differencesregarding any of the secondary efficacy outcomes. However, therewas an increased risk of major haemorrhages in the nadroparin14 group compared with unfractionated heparin (3·5% vs1·6%;P=0·0035). Conclusions Treatment with nadroparin for 6±2 days providessimilar efficacy and safety to treatment with unfractionatedheparin, for the same period, in the therapeutic managementof acute unstable angina or non-Q wave myocardial infarction,and may be easier to administer. A prolonged regimen of nadroparin(14 days) does not provide any additional clinical benefit.