Disseminated Intravascular Coagulation Caused by the Carpet Viper (Echis carinatus): Trial of Heparin

Heparin has been advocated for the treatment of poisoning by Echis carinatus, a snake whose venom causes disseminated intravascular coagulation. Fourteen patients with proven E. carinatus bite who had incoagulable blood were treated with specific Echis antivenom. Seven of them were also given low-dose heparin, initially 50 units/kg body weight by i.v. injection, followed by 10 units/kg/h by i.v. infusion for 22 h. Response to treatment was assessed clinically and by repeated tests of blood coagulation. All patients showed a rapid return to normal blood coagulability after treatment and the heparinized group were not significantly different in any respect from the group given antivenom alone. Heparin did not reduce the local effects of envenoming. There appears to be no place for heparin in the treatment of E. carinatus poisoning provided that potent antivenom is available. The in vivo results were supported by in vitro studies in which it was found that Echis-induced thrombin was less sensitive to the inhibitory effect of heparin than physiological thrombin.     

不稳定性心绞痛尿激酶溶栓治疗的临床疗效——多中心随机对照研究

目的　对比尿激酶 (UK)与肝素在治疗不稳定性心绞痛 (UA)中的疗效。方法　采用单盲 ,有对照的完全随机化方法。UK溶栓组中按UK使用剂量分为高剂量组和低剂量组 ,后者在溶栓前增加静脉推注 3 0 0 0U肝素。研究以 3 0天病死率和急性心肌梗塞 (AMI)发生率为终点指标。结果　总共入选UA患者 5 3 4例 ,高剂量UK组 14 8例 ,低剂量UK组 113例 ,相应肝素作为对照组各为 15 5和 118例。在心脏事件 (死亡 AMI例数 )的发生率上 ,高剂量UK组高于肝素对照组 ( 10 1%与5 2 % ,P >0 0 5 ) ;而低剂量UK组低于肝素对照组 ( 3 5 %与 5 1% ,P >0 0 5 ) ,但均未达到统计学差异 ,而溶栓组间比较 ,低剂量UK组的心脏事件发生率明显低于高剂量UK组 ( 3 5 %与 10 1% ,P <0 0 5 ) ,并达到统计学显著性差异。在心脏事件的发生时间上 ,高剂量UK组心脏事件大多发生在溶栓治疗首日 ,其中发生在UK治疗的头 2个小时内占 4 6 7% ,而对照组大多数发生在入选治疗的 2 4小时后 ( 80 %与 12 5 % ,P <0 0 0 5 )。结论　高剂量UK组溶栓首日AMI发生率明显增加 ,提示该溶栓治疗方案不适于不稳定性心绞痛的治疗 ,降低UK剂量 ,溶栓前加强抗凝血酶治疗 ,虽可明显减少AMI的发生率 ,但是否优于对照组仍需进一步探讨。     

小剂量尿激酶延迟溶栓与阿斯匹林加肝素钠治疗急性心肌梗死的疗效比较

为探讨使用小剂量尿激酶延迟溶栓法治疗急性心肌梗死的临床疗效是否优于阿斯匹林加肝素钠 ,根据WHO的诊断标准 ,将 66例距发病时间 1 2～ 2 4h的急性心肌梗死患者随机分为两组 :尿激酶组 30例 ,阿斯匹林加肝素钠组 36例。以一周内心绞痛发生率、4周内病死率 ,心肌梗死并发症作为评定标准。结果发现 ,减少频发心绞痛发生率尿激酶组优于阿斯匹林加肝素钠组 (第一周 2 6 .7%比 36 .1 % ,P <0 .0 5) ,减少心衰竭并发症小剂量尿激酶组亦优于阿斯匹林加肝素钠组 (1 3 .3 %与 33 .3 % ,P <0 .0 5) ,4周病死率 ,两组间无显著差异 (3 .3 %与 2 .8% ,P >0 .0 5)。休克、严重心律失常、出血并发症两组间均无显著差异。此结果提示 ,小剂量尿激酶延迟溶栓治疗发病 1 2～2 4h内急性心肌梗死患者可降低频发心绞痛发生率及心肌梗死后心衰竭发生率。     

纳豆激酶对正常大鼠凝血系统的影响

目的通过检测正常大鼠的凝血酶原时间(PT)、活化部分凝血活酶时间(APTT)及凝血酶时间(TT),观察纳豆激酶(NK)冻干粉(NK-1)肌肉注射和固体发酶纳豆粉(NK-2)给药方式的NK抗凝血作用。方法将80只SD大鼠随机分为空白对照组、肝素对照1组、肝素对照2组、阿司匹林对照组、NK-1注射低剂量组、NK-1注射中剂量组、、NK-1注射高剂量组[注射剂量依次为1.6万～25.9万U/(kg·d)],NK-2口服低剂量组、NK-2口服中剂量组、NK-2口服高剂量组[口服剂量依次为0.5万～7.5万U/(kg·d)],每组8只。给药后观察各组大鼠血浆APTT、TT和PT指标变化。结果与空白对照组比较,NK-1注射高剂量组、NK-2口服高剂量组和阿司匹林对照组PT明显延长(P<0.05,P<0.01);肝素对照1、2组、NK-1注射低、中、高剂量组、NK-2口服高、中剂量组和阿司匹林对照组APTT明显延长(P<0.05,P<0.01);肝素对照2组、NK-1注射高剂量组TT明显延长(P<0.01)。结论 NK-1在1.6万～25.9万U/(kg·d)剂量范围内注射给药,与NK-2在0.5万～7.5万U/(kg·d)剂量范围内口服给药,对正常大鼠均具有一定的抗凝血作用,且抗凝血作用随剂量的升高而增强。     

High dose heparin as pretreatment for primary angioplasty in acute myocardial infarction: the Heparin in Early Patency (HEAP) randomized trial

OBJECTIVES: In the Heparin in Early Patency (HEAP) pilot study a beneficial effect of high-dose heparin on early patency in acute myocardial infarction (MI) was observed in a matched-control study. BACKGROUND: High dose bolus intravenous injection of heparin may achieve lysis of coronary thrombi and could enhance early patency of the infarct related vessel in patients with MI scheduled for primary angioplasty. METHODS: Before primary angioplasty, 584 patients with MI entered an open randomized trial of high dose (300 IU/kg) or low dose (0 or 5,000 IU) heparin. Of the 584 patients, 299 were randomized to high dose and 285 patients to low dose heparin. RESULTS: Thrombolysis In Myocardial Infarction (TIMI) flow grade 2 or 3 was observed before primary angioplasty in 65 patients (22%) in the high dose group and 60 patients (21%) in the low dose heparin group (p > 0.1), whereas TIMI flow grade 3 was observed in 38 (13%) and 24 patients (9%), respectively (p = 0.11). There were no differences in the clinical end points between the two groups. There were no hemorrhagic strokes, while 10% of the patients in the high dose group required blood transfusion versus 6% in the low dose/no heparin group (p = 0.07). No subsets of patients showed beneficial effects of high dose heparin, such as patients with longer delay between heparin administration and diagnostic angiogram or patients with short delay between symptom onset and admission. CONCLUSIONS: There is no benefit of high dose bolus heparin on early patency compared with no or low dose heparin.     

Subcutaneous unfractionated heparin for the treatment of venous thromboembolism

PURPOSE OF REVIEW: When unfractionated heparin is used to treat acute venous thromboembolism, it is usually given by intravenous infusion with dose adjustment in response to activated partial thromboplastin time measurements. These two requirements are a barrier to treatment of venous thromboembolism with unfractionated heparin, and it is uncertain if they are necessary. RECENT FINDINGS: Two recent studies compared subcutaneous unfractionated heparin and subcutaneous low-molecular-weight heparin, each given twice-daily, for the acute treatment of venous thromboembolism. The Galilei study used an initial dose of unfractionated heparin that was partially weight-adjusted, with subsequent dosing based on activated partial thromboplastin time results. The FIDO study treated patients with a first dose of unfractionated heparin of 333 IU/kg, followed by 250 IU/kg twice-daily without dose adjustment in response to the activated partial thromboplastin time or other coagulation tests. There was no difference in either study between the unfractionated heparin and low-molecular-weight heparin groups at the end of 3 months, for recurrent venous thromboembolism (Galilei: 4.2 vs. 3.9%; relative risk (RR) 1.1, 95% confidence interval (CI) 0.5 to 2.2. FIDO: 3.8 vs. 3.4%; RR 1.1, 95% CI 0.5 to 2.3) or major bleeding (Galilei: 1.4 vs. 1.9%; RR 0.7, 95% CI 0.2 to 2.2. FIDO: 1.7 vs. 3.4%; RR 0.5, 95% CI 0.2 to 1.3). SUMMARY: Recent studies suggest that twice-daily subcutaneous unfractionated heparin is as effective and safe as low-molecular-weight heparin for the acute treatment of venous thromboembolism, and that adjustment of unfractionated heparin dose in response to activated partial thromboplastin time measurements is not necessary with a weight-adjusted dose of unfractionated heparin.     

The role of prednisolone in reducing limb oedema in children bitten by green pit vipers: a randomized, controlled trial

When green pit vipers (GPV), which are common venomous snakes in Thailand, bite humans they cause coagulopathy as well as local tissue oedema. The use of steroids to reduce such oedema is controversial. The role of low, oral doses of prednisolone in the treatment of GPV bites in children has therefore now been assessed, in a randomized, double-blinded, placebo-controlled, clinical trial in Bangkok. Overall, 43 children aged 3-15 years, each with a recent GPV bite to one limb, were randomly assigned to receive oral prednisolone (1 mg/kg.day) or placebo for 3 days, without antivenom or prophylactic antibiotics. The degree of limb oedema was assessed, immediately before the first dose and then daily, by measuring the limb circumference around the fang marks. By 72 h post-bite, both treatment groups showed significant decreases in the level of their limb oedema. Since, at each time-point, the patients in the two groups showed similar levels of limb oedema (and of reduction in such oedema), there appeared to be no benefit from the use of the prednisolone.     

Recombinant nematode anticoagulant protein c2, an inhibitor of the tissue factor/factor VIIa complex,in patients undergoing elective coronary angioplasty

OBJECTIVES: We investigated the safety and pharmacodynamics of escalating doses of recombinant nematode anticoagulant protein c2 (rNAPc2) in patients undergoing elective coronary angioplasty. BACKGROUND: Recombinant NAPc2 is a potent inhibitor of the tissue factor/factor VIIa complex, which has the potential to reduce the risk of thrombotic complications in coronary artery disease. METHODS: In a randomized, double-blinded, dose-escalation, multicenter trial, 154 patients received placebo or rNAPc2 at doses of 3.5, 5.0, 7.5, and 10.0 microg/kg body weight as a single subcutaneous administration 2 to 6 h before angioplasty. All patients received aspirin, unfractionated heparin during angioplasty, and clopidogrel in case of stent implantation. RESULTS: Minor bleeding rates for the doses 3.5 to 7.5 microg/kg were comparable to that with placebo (6.7%), whereas an incidence of 26.9% was observed at the 10.0 microg/kg dose level (p < 0.01). Major bleedings occurred in the 5.0 microg/kg (n = 3) and 7.5 microg/kg (n = 1) dose groups. The three patients in the 5.0 microg/kg dose group also received a glycoprotein IIb/IIIa receptor inhibitor at the moment of major bleeding. Systemic thrombin generation, as measured by prothrombin fragment 1+2 (F(1+2)), was suppressed in all rNAPc2 dose groups to levels below pretreatment values for at least 36 h. In the placebo group, a distinct increase of F(1+2) levels was observed following cessation of heparin. CONCLUSIONS: Inhibition of the tissue factor/factor VIIa complex with rNAPc2, at doses up to 7.5 microg/kg, in combination with aspirin, clopidogrel, and unfractionated heparin appears to be a safe and effective strategy to prevent thrombin generation during coronary angioplasty.     

Arterial complications following cardiac catheterization in children less than 10 kg

We sought to determine if a higher dose of heparin would reduce arterial complications in patients weighing 10 kg or less undergoing cardiac catheterization to investigate congenital heart disease. Sixty patients were given either 100 (group A) or 150 (group B) IU x kg(-1) of heparin in a double-blinded randomized manner. Initial arterial access was established using a 4F cannula in all patients. Mean activated clotting time measured 20 minutes following heparin administration was significantly lower in group A than in group B (199 versus 251 seconds). Only 3 out of 60 patients (5%) required treatment for loss of femoral pulse. The age, weight, activated clotting time, length of catheterization procedure, time taken to establish arterial access, and the duration of arterial cannulation were comparable between the groups. Weight under 4 kg, age under 1 month, and cannula size larger than 4F were identified as independent risk factors for the development of arterial complications. Arterial access using a 4F cannula is a safe procedure in children weighing 10 kg or less. The incidence of significant arterial complications is low, and they do not appear to be preventable by a higher dose of heparin.     

按体重给药与小剂量rt-PA治疗国人急性心肌梗死的随机对照研究

目的探讨国人应用重组组织型纤溶酶原激活剂（rt-PA）溶栓治疗急性心肌梗死（AMI）的合适剂量.方法所有入选患者随机分入按体重给药和小剂量rt-PA两个治疗组,按体重给药组（W组）93例,AMI患者在应用阿司匹林和肝素治疗基础上,首先给予8 mg的rt-PA静脉推注,继之按1 mg/kg算出需静脉点滴维持的总量给予静脉滴注（最低不少于42 mg,最高不多于92 mg）,90 min滴注完毕.小剂量组（L组）91例AMI患者,在应用阿司匹林和肝素治疗基础上,先给予8 mg的rt-PA静脉推注,继之42 mg在90 min内滴注完毕.观察终点：包括两组梗死相关动脉开通率（根据临床标准判断）、左室射血分数、发病30天主要心血管事件发生率.结果 W组93例患者中据临床标准判定再通者74例（79.6%）,L组91例患者中据临床标准判定再通者59例（64.8%）,两组比较有统计学意义（P=0.026）,W组左室射血分数略好于L组（P=0.259）和发病30天主要心血管事件发生率低于L组（P＜0.05）.结论按体重给药应用rt-PA治疗急性心肌梗死疗效和安全性优于国内常用的小剂量rt-PA治疗.     

持续小剂量肝素治疗脓毒症患者急性肺损伤/急性呼吸窘迫综合症的临床研究

目的探讨持续小剂量肝素对脓毒症患者急性肺损伤/急性呼吸窘迫综合症的治疗作用。方法 119例脓毒症患者随机分为对照治疗组（61例）和肝素治疗组（58例）,对照组采用抗感染、呼吸支持等综合治疗,肝素组在对照治疗基础上加用持续小剂量肝素输注,比较两组患者治疗3天后氧合指数,APACHEⅡ积分,SOFA积分以及PLT、PT、APTT、FIB变化以及出血倾向。结果肝素组治疗后氧合指数明显好转,APACHEⅡ积分,SOFA积分明显低于对照组（P〈0.05）,PLT、PT、APTT、FIB两组治疗前后均无差异。结论持续小剂量肝素治疗严重脓毒症患者急性肺损伤/急性呼吸窘迫综合症可有效提高氧合指数,减轻患者炎症反应,且具有良好的安全性。     

Low molecular weight (LMW) heparin derivatives in experimental extra-corporeal circulation (ECC)

Low molecular weight (LMW) heparin has been shown to prevent experimental venous thrombosis. In order to investigate its biological action and its potential use in open heart surgery, we have conducted an experimental study using extracorporeal circulation (ECC) in sheep as an experimental model. 18 sheep were randomly selected to receive either LMW heparin (2 mg/kg), high dose heparin (HD; 160 U/kg), or low dose heparin (LD; 60 U/kg). The HD heparin yielded the same circulating anti-activated factor X (anti-Xa) activities as the LMW heparin and the LD heparin yielded the same anti-thrombin activity. LMW heparin and HD heparin were both effective in preventing blood clotting in the ECC circuit, demonstrating the antithrombotic activity of the LMW heparin. Clotting in the circuit was observed following LD heparin administration showing that the efficacy of LMW heparin does not only rely upon its weak anti-activated partial thromboplastin time (APTT) and anti-thrombin activity. Fibrinogen, fibrinogen degradation products (FDP), factor V (FV), platelet count, antithrombin III (AT III), fast acting antiplasmin (AP) were evaluated during and after ECC. The defects in hemostasis were similar in the three groups. Conclusions were: (1) heparin chain depolymerization diminishes the anti-APTT activity without altering the anti-thrombotic property; (2) LMW heparin is an effective alternative to heparin in cardiac surgery; (3) the absence of postoperative circulating anti-APTT activity might be associated with a reduced incidence of hemorrhagic complication, but we were not able to demonstrate it.     

Effects of therapeutic doses of heparin on thrombolysis with tissue-type plasminogen activator in rabbits

The objective of the study was to evaluate the ability of heparin to enhance the thrombolytic effect of recombinant tissue type plasminogen activator (rt-PA) and to prevent thrombus growth during and after thrombolysis with rt-PA. In the thrombolysis studies, three groups of rabbits were infused with rt-PA at a dose of 0.5 mg, 1 mg, or 2.5 mg over 3 hours, respectively. Rabbits in each group were randomized to receive, in addition to rt-PA, heparin, 20 or 60 antifactor Xa U/kg/h, or saline over 6 hours. The three doses of rt-PA produced the same extent of thrombolysis both in the two groups treated with heparin (34% +/- 6%, 52% +/- 7%, and 79% +/- 8% in the lower dose group; 39% +/- 6%, 49% +/- 4%, and 81% +/- 6% in the higher dose group) and in the group treated with saline (37% +/- 4%, 47% +/- 5%, and 84% +/- 7%). In the thrombus growth inhibition studies 0.5 mg of rt-PA was infused over 3 hours in each rabbit. In addition, the rt-PA-treated rabbits were randomized to receive heparin, 20 or 60 antifactor Xa U/kg/h over 6 hours, or saline. At the end of infusion, no statistically significant differences in thrombus growth were found in three groups of rabbits (54.8 +/- 7.4 micrograms and 52.4 +/- 12.1 micrograms in the low and high dose of heparin groups, respectively, and 59.4 +/- 10.4 micrograms in the saline group). In different experiments rabbits were randomized to receive heparin, 60 antifactor Xa U/kg/h, or saline at the end of the rt-PA infusion. In these experiments heparin inhibited thrombus growth more efficiently than saline (41.1 +/- 6.5 micrograms and 58.7 +/- 12.9 micrograms, respectively, P less than .05). In vitro experiments confirmed that heparin is unable to prevent fibrin accretion on the clots during lysis with rt-PA while both D-Phe-Pro-Arg-CH2-Cl (PPACK) and hirudin are able to prevent the accretion of fibrin. We conclude that the data obtained in these animal models do not support the concomitant use of heparin and rt-PA. However, heparin could be used successfully after rt-PA to inhibit thrombus growth.     

Usefulness of subcutaneous low molecular weight heparin (ardeparin) for reduction of restenosis after percutaneous transluminal coronary angioplasty.

In addition to its anticoagulant effects, heparin is known to have antiproliferative effects on vascular smooth muscle cells. Ardeparin is a partially depolymerized (low molecular weight) heparin that has a longer half-life than unfractionated heparin. Following successful coronary balloon angioplasty, 565 patients were randomized to treatment with twice-daily subcutaneous ardeparin 50 anti-Xa U/kg (low dose) or 100 anti Xa U/kg body weight (high dose), or placebo for 3 months. Follow-up angiography was performed in 415 patients at 4 months, or earlier if clinically indicated. Additionally, patients underwent treadmill exercise electrocardiography at 2 weeks and 4 months. This study was designed to test the hypothesis that 3 months of subcutaneous dosing of ardeparin would reduce angiographic restenosis after coronary balloon angioplasty. Ardeparin had no effect on the incidence of angiographic restenosis (prespecified definition: > or = 50% luminal diameter narrowing plus a loss of 50% of initial gain or absolute decrease of 20% of luminal diameter). Neither the mean luminal diameters nor mean percent diameter stenoses were different among the treatment groups before, after, or 4 months after balloon angioplasty. On exercise electrocardiography at 2 weeks and 4 months, patients in all treatment groups had similar exercise tolerance, incidence of angina, and frequency of ST depression. Thus, ardeparin treatment given subcutaneously for 3 months after successful balloon angioplasty does not reduce either angiographic or clinical measures of restenosis.     

替罗非班对急性冠状动脉综合征患者肝剂量及血小板的影响

目的：探讨对急性冠状动脉综合征患者在常规治疗基础上联合替罗非班强化抗血小板治疗对肝素抗凝剂量及血小板数量和功能的影响。资料和方法：选择因急性冠状动脉综合征入院的患者共64例，分为双联抗血小板和肝素抗凝的常规治疗组(n=36)和在此基础上联合使用替罗非班组(n=28)，以达到肝素抗凝使激活的部分凝血时间延长2倍为标准，比较两组肝素使用剂量、ADP诱导的血小板聚集率及血小板数量变化情况。结果：替罗非班组肝素用量（500±120U/h）显著低于常规组(760±148U/h, P<0.01)，用药后两组的血小板聚集率均显著低于用药前(P<0.01)，但替罗非班组降低更显著(P<0.01)，替罗非班组用药后血小板降低(P<0.05)。结论：联合应用替罗非班可降低肝素抗凝剂量，显著抑制血小板聚集活性，并呈降低降低血小板数量的趋势。     

替罗非班对急性冠状动脉综合征肝素剂量及血小板的影响

目的探讨替罗非班对急性冠状动脉综合征患者肝素剂量及血小板计数和功能的影响。方法选择因急性冠状动脉综合征入院患者64例，分为常规治疗组36例和替罗非班组28例，常规治疗组使用抗血小板药和肝素抗凝；替罗非班组在上述基础上联合使用替罗非班，以达到肝素抗凝使激活的部分凝血时间延长2倍为标准，比较两组肝素用量、二磷腺苷（ADP）诱导的血小板聚集及血小板数。结果替罗非班组肝素用量（500±120）U／h显著低于常规组（760±148）U／h，差异有统计学意义（t=7.558，P〈0．01），用药后两组的血小板聚集率均显著低于用药前（P〈0．01），但替罗非班组降低更显著（P〈0．01），替罗非班组用药后血小板数降低（P〈0.05）。结论联合应用替罗非班可降低抗凝肝素剂量，显著抑制血小板聚集，并呈降低血小板数的趋势。     

Low dose heparin in the prevention of deepvein thromboses in patients with acute myocardial infarction

Patients with acute myocardial infarction of less than 48 hours duration were randomized into three groups. The “fully anticoagulated” group received heparin by intravenous infusion and warfarin sodium to maintain a whole blood clotting time of 30 to 90 minutes and a prothrombin index of 10% to 35%. The “low dose” heparin group received 500 units by intravenous infusion every 12 hours. The control group received no anticoagulants. The radioactive fibrinogen test was used to diagnose the presence of leg vein thromboses.The control group had an incidence of venous thrombosis of 29.7% compared with 13.9% in the low dose group and 11.3% in the fully anticoagulated group. Patients in the control group who had cardiac failure had a significantly higher incidence of venous thromboses (71.4%) when compared with patients not in failure (20.0%). In the two treatment groups no significant difference was observed in patients with and without cardiac failure.Patients with cardiac failure complicating an acute myocardial infarction have a high incidence of venous thromboses. Anticoagulants significantly reduce this incidence and low dose intravenous heparin is as efficacious as full anticoagulation.     

Hirudin, heparin, and placebo during deep arterial injury in the pig. The in vivo role of thrombin in platelet-mediated thrombosis

Three dosages (0.3, 0.7, and 1.0 mg/kg) of recombinant hirudin, a specific inhibitor of thrombin, were compared with heparin (50 units/kg) and placebo for reducing thrombus formation in the carotid arteries of 50 pigs after deep injury by balloon dilatation. Each drug was administered as a bolus followed immediately by a continuous infusion of the same dose per hour. Major end points were quantitative indium-111-labeled platelet and iodine-125-labeled fibrinogen deposition and the incidence of mural thrombosis. This study showed that heparin, at a dose that prolonged the activated partial thromboplastin time (APTT) to twice the control time, did not prevent mural thrombosis or significantly reduce platelet deposition compared with placebo but did reduce fibrinogen deposition. Recombinant hirudin markedly reduced platelet and fibrinogen deposition in a dose-related manner and totally eliminated mural thrombosis at an APTT of two to three times that of control. Platelet deposition (x 10(6)/cm2, mean +/- SEM) in areas of deep arterial injury for the placebo, heparin, and 0.3, 0.7, and 1.0 mg/kg hirudin groups was 54 +/- 21, 33 +/- 9, 22 +/- 6, 8 +/- 1, and 7 +/- 1, respectively; electron microscopy showed a single layer (or less) of platelets at the two highest hirudin dosages. The incidence of macroscopic mural thrombosis was 76% with placebo, 57% with heparin, 46% with 0.3 mg/kg hirudin; there were no thrombi with 0.7 or 1.0 mg/kg hirudin (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)     

Suppression of intimal hyperplasia with low molecular weight heparin in a sheep model.

BACKGROUND: Both unfractionated heparin (UH) and low molecular weight heparin (LMWH) in therapeutic anticoagulant doses have been shown to inhibit the development of intimal hyperplasia (IH) but with an increased risk of haemorrhage. In this study we investigated the effect of a "low dose" and "high dose" of UH and LMWH on the inhibition of IH together with their effect on plasma anti-Xa activity (AXa) and activated partial thromboplastin time (APTT) using a carotid artery sheep model. METHODS: A gelatin sealed Dacron patch graft was implanted into the common carotid artery of sheep which were randomly allocated to a control group (Group 1, n=10) or to one of four treatment groups receiving either low-dose LMWH enoxaparin 1 mg/kg/day (group 2, n=11), high-dose LMWH enoxaparin 2 mg/kg/day (Group 3, n=13), low-dose UH 125 u/kg/day (Group 4, n=10) or high-dose UH 250 u/kg/day (Group 5, n=10). The LMWH was administered subcutaneously once daily for four weeks and the UH in two divided doses per day for four weeks. During the treatment period, AXa and APTT were assayed from blood collected prior to and at 1 and 2 h after heparin administration on day 3, 7, 14, 21 and 28. On day 28, all animals were sacrificed and grafts were collected for analysis after taking blood samples prior to, then at 0.5, 1, 2, 3, 4, 6, 8, 12 and 24 h following the last injection. Measurements of intimal thickness were obtained under light microscopy from eight transverse sections of each grafted artery using an eyepiece graticule. RESULTS: IH measurements (Mean+/-SD) were: Group 1 (controls) 288+/-86 microm, Group 2 (low-dose LMWH) 222+/-50 mm (p<0.05 compared to Group 1), Group 3 (high-dose LMWH) 203+/-78 microm (p<0.01), Group 4 (low-dose UH) 275+/-61 microm, and Group 5 (high-dose UH) 206+/-71 microm (p<0.01). There was no significant difference between Groups 2, 3 and 5. Groups 2, 3 and 5 demonstrated significant AXa during the 28 days period of which Groups 2 and 5 showed a significant increase in AXa levels with time. In the 24 h study after the last dose of treatment both Groups 2 and 3 showed longer AXa than group 5 (12-24 h vs 8 h). When compared to the control group, significant elevation of APTT was demonstrated in Groups 3 and 5. Group 5 had significantly longer APTT than Group 3. In the 24 h study, APTT reflected the changes of AXa in all groups. CONCLUSIONS: In this study the LMWH enoxaparin was effective in reducing the formation of IH both at a standard anticoagulant therapeutic dose of 2 mg/kg/day and also at a lower dose of 1 mg/kg/day.     

老年不稳定型心绞痛患者介入治疗中比伐卢定的安全性及有效性

目的 探讨老年不稳定型心绞痛患者择期行经皮冠状动脉介入治疗（PCI）时应用比伐卢定的有效性与安全性。方法 2010年11月至2013年3月拟择期行PCI治疗的60～75岁老年不稳定型心绞痛患者90例。比伐卢定组（47例）PCI术前静脉注射比伐卢定0.75mg/kg作为负荷剂量,5min后检测活化凝血时间（ACT）,若ACT小于225s,再静脉注射比伐卢定0.3mg/kg,术中静脉滴注1.75mg/（kg·h）至手术结束。普通肝素组（43例）术前静脉注射普通肝素钠100U/kg,5min后检测ACT,若ACT小于225s,再静脉注射肝素钠3000U（若1h后手术仍未结束,再静脉注射肝素钠1000U）。主要安全性及有效性指标为两组患者PCI术后30d内出血事件发生率、主要心脏不良事件（MACE）发生率及术中使用的ACT达标情况监测。结果 比伐卢定组与普通肝素组比较,PCI术后30d内出血率与MACE发生率差异无统计学意义（P＞0.05）,有效性指标与普通肝素组一致。结论 比伐卢定在老年不稳定型心绞痛患者PCI术中的使用是安全有效的。