Anticoagulation Strategies in Patients With Cancer: JACC Review Topic of the Week

Patients with active cancer are at an increased risk of arterial and venous thromboembolism (VTE) and bleeding events. Historically, in patients with cancer, low molecular weight heparins have been preferred for treatment of VTE, whereas warfarin has been the standard anticoagulant for stroke prevention in patients with atrial fibrillation (AF). More recently, direct oral anticoagulants (DOACs) have been demonstrated to reduce the risk of venous and arterial thromboembolism in large randomized clinical trials of patients with VTE and AF, respectively, thus providing an attractive oral dosing option that does not require routine laboratory monitoring. In this review, we summarize available clinical trial data and guideline recommendations, and outline a practical approach to anticoagulation management of VTE and AF in cancer.     

低分子肝素经大鼠胃肠道吸收的研究

目的考察低分子肝素(LMWH)溶液及乳剂在麻醉大鼠胃肠道的吸收情况以及磷脂对LMWH的促吸收作用.方法在体大鼠胃中给药、小肠及小肠各肠段循环液给药,一定时间后测定血液凝固时间的变化及循环液中药量的变化,以反映药物的吸收情况.结果LMWH在体小肠和十二指肠循环溶液及乳剂循环一定时间后,药量显著减少,血液凝固时间明显延长.结论LMWH在胃中无明显吸收,部分被破坏;在小肠中吸收,十二指肠吸收最好.磷脂乳剂对LMWH有一定的保护和促吸收作用.     

低分子肝素治疗急性脑梗死的临床观察

目的 观察低分子肝素治疗急性脑梗死的临床疗效及对出凝血时间、凝血酶原时间、血小板的影响。方法 ６０例急性脑梗死患者,分为治疗组、对照组各３０例。治疗组采用低分子肝素静滴,对照组用低分子右旋糖酐治疗。结果 治疗组总有效率９３．３％,显效率６３．３％,明显优于对照组（７３．３％,４６．６％）。有显著性差异（Ｐ〈０．０１）;对出凝血时间、凝血酶原时间、血小板无显著性差异（Ｐ〉０．０５）,无１例继发出血。结论 低分子肝素治疗急性脑梗死是安全有效的。     

电导率法研究低分子量肝素pH降低的原因

目的:研究低分子量肝素在较高温度下pH降低及颜色变黄的原因.方法:通过测定溶液电导率来确定低分子量肝素硫酸根与羧酸根比值,并与同类药物作比较.结果:高温下低分子量肝素末端醛基转化为了羧基可能是其pH降低的原因.结论:低分子量肝素类制剂须在30℃以下的室温,避光、避热保存,以保证其质量.     

低分子肝素生物活性测定方法的比较研究

目的:对低分子肝素(low molecular weight heparin,LMWH)生物活性即抗活化10因子(抗-FXa)和抗活化2因子(抗-FⅡa)测定的不同方法进行比较与研究,建立国家标准。方法:(1)比较量反应平行线与标准曲线2种分析方法在发色底物的分光光度法即利用发色底物对 FXa 或 FⅡa 特异的405 nm 显色反应测定抗-FXa 或抗-FⅡa 效价的差异。(2)比较发色底物的分光光度法与血液凝固法(观察兔全血或兔血浆的凝结时间)测定 LMWH 的抗凝血酶(抗-FⅡa)效价的异同。结果:量反应平行线法比标准曲线法测定结果可靠、准确、精确;发色底物分光光度法与血液凝固法的实验结果相似,其差异无统计学意义(P>0.05),并且具有良好相关性(r=0.997 P<0.01和 r=0.976 P<0.01)。结论:对 LMWH 的抗-FXa 和抗-FⅡa 效价测定采用发色底物的分光光度法;并以量反应平行线法进行分析。     

中西医结合治疗脑梗塞的临床观察

目的:观察地黄饮子联合低分子肝素治疗脑梗塞的疗效.方法:将68例脑梗塞病人随机分为治疗组和对照组各34例,对照组在常规治疗基础上加低分子肝素,治疗组在常规治疗基础上加低分子肝素联合中药地黄饮子.结果:治疗组基本治愈率为70.59%,总有效率为88.24%,对照组基本治愈率为52.94%,总有效率为64.71%,两组总有效率的比较具有显著差异.结论:地黄饮子加低分子肝素治疗脑梗塞具有很好的疗效,优于单独应用低分子肝素组.     

低分子量肝素治疗进展型脑梗死及对血流变影响

目的:探讨低分子量肝素对进展型脑梗死的疗效及血流变影响.方法:将80例进展型脑梗死患者,随机分为治疗组40例,对照组40例.两组在治疗前后均行神经功能缺损评分和临床疗效评定,并观察其疗效及有关实验室指标,追踪随访1年.结果:治疗组的有效率明显高于对照组,不良反应轻微,PLT、APTT无明显变化,但血流变指标明显下降,1年内复发率明显小于对照组.结论:低分子肝素治疗进展型脑梗死疗效肯定,对于减少复发亦有一定作用,并可改善血流变.     

Direct Oral Anticoagulants: New Drugs and New Concepts

Direct oral anticoagulants (DOACs) are approved for multiple thromboembolic disorders and provide advantages over existing agents. As with all anticoagulants, management protocols for the eventuality of bleeding are important. Randomized phase III studies generally show that DOACs have a similar risk of clinically relevant bleeding compared with standard anticoagulants, with reductions in major bleeding in some cases. This may be particularly important in patients with atrial fibrillation, for whom the rate of intracranial hemorrhage was approximately halved with DOACs compared with warfarin. Conversely, the risk of gastrointestinal bleeding may be increased. Specific patient characteristics, such as renal impairment, comedications, and particular aspects of each drug, including the proportion eliminated by the kidneys, must be taken into account when assessing the risk of bleeding. Although routine coagulation monitoring of DOACs is not required, it may be useful under some circumstances. Of the traditional clotting assays, a sensitive and calibrated prothrombin time may be useful for detecting the presence or absence of clinically relevant factor Xa inhibitor concentrations (rivaroxaban or apixaban), but specific anti–factor Xa assays can measure drug levels quantitatively. For dabigatran, the results of an activated partial thromboplastin time test may exclude a clinically relevant pharmacodynamic effect, but a calibrated dilute thrombin time assay can be used for quantification of drug levels. In the event of mild or moderate bleeding, normal hemostatic support measures are recommended. For life-threatening bleeding, use of nonspecific prohemostatic agents may be considered, although clinical evidence is scarce. Specific antidotes are in development.     

Lower dosage of recombinant tissue-type plasminogen activator (rt-PA) in the treatment of acute pulmonary embolism: A systematic review and meta-analysis

Background and Objective

According to US Food and Drugs Administration (FDA), 2 hour recombinant tissue plasminogen activator (rt-PA) 100 mg infusion is recommended for eligible patients with acute pulmonary embolism (PE). However,there exists evidence implying that a lower dosage of rt-PA can be equally effective but potentially safer compared with rt-PA 100 mg regimen. The aim of this systematic review and meta-analysis is to assess the efficacy and safety of low dose rt-PA in the treatment of acute PE.

Material and Method

We searched Pubmed, EMBASE, the Cochrane library and CBM Literature Database for randomized controlled trials (RCT) focusing on low dose rt-PA for acute PE. Outcomes were described in terms of changes of image tests and echocardiography, major bleeding events, all-cause death, and recurrence of PE.

Results

Five studies (440 patients) were included, three of which compared low dose rt-PA (0.6 mg/kg, maximum 50 mg or 50 mg infusion 2 h) with standard dose (100 mg infusion 2 h). There were more major bleeding events in standard dose rt-PA group than in low dose group (OR 0.33, 95%CI 0.12-0.91;P = 0.94,I² = 0%), while there were no statistical differences in recurrent PE or all cause mortality between these two groups. Two studies compared low dose (0.6 mg/kg, maximum 50 mg/2 min bolus or 10 mg bolus, ≤ 40 mg/2 h) with heparin. There was no significant difference in major bleeding events (OR 0.73, 95% CI 0.14-3.98;P = 0.72), recurrent PE or all cause mortality. No dose-related heterogeneity was found for all the included studies.

Conclusions

The results of this meta-analysis were hypothesis-generating. Based on the limited data, our systematic review suggested that low dose rt-PA had similar efficacy but was safer than standard dose of rt-PA. In addition, compared with heparin, low dose rt-PA didn’t increase the risk of major bleeding for eligible PE patients.     

Thromboprophylaxis use and concordance with guidelines among medical and surgical patients in Morocco

Introduction

No data are available on thromboprophylaxis use in Morocco. Our aim was to characterize patients at risk of venous thromboembolism and assess the rate of appropriate thromboprophylaxis.

Materials and Methods

This was a national, observational, multicentre survey of venous thromboembolism risk and thromboprophylaxis use in hospitalized patients. Data were collected on a predefined date in three university hospitals in Morocco using a standardized pre-printed form. Thromboembolic risk was assessed according to the American College of Chest Physicians (ACCP) 2008 guidelines. Patients were classified as “thromboprophylaxis indicated” or “thromboprophylaxis not indicated”.

Results

784 patients were analysed: 307 (39.2%) medical and 477 (60.8%) surgical. 421 (53.7%) were female. Medical patients were older than surgical patients (57.6 ± 11.5 vs. 46.2 ± 16.9 years, p < 0.0001) and were more likely to have risk factors for thromboembolism (50.5% vs. 45.7% of patients, p = NS). 57% of patients without contraindications or bleeding risk were at risk of thromboembolism according to ACCP guidelines and thromboprophylaxis was prescribed to 42.8% of these patients. In contrast, 7.4% of patients with no thromboembolic risk also received thromboprophylaxis (proportion agreement: 61.0%; Kappa = 0.296). Over half (54.5%) of medical patients at risk of thromboembolism did not receive thromboprophylaxis whereas 6.3% of those with no risk did receive it (proportion agreement: 76.4%; Kappa = 0.433). These figures were 57.9% and 9.2%, respectively, for surgical patients (proportion agreement: 52.7%; Kappa = 0.191). Thromboprophylaxis was given to 19.2% of patients with contraindications or a bleeding risk.

Conclusions

Educational initiatives are imperative to inform doctors about appropriate thromboprophylaxis.