Pharmacological Prevention of Thromboembolism in Patients with Left Ventricular Dysfunction

Chronic left ventricular systolic dysfunction is a well recognized problem with an increasingly significant impact on healthcare in the form of congestive heart failure (CHF). Advances in medicine have led to improved survival after myocardial infarction (MI) and as a result, an increased prevalence of left ventricular systolic dysfunction. An increased incidence of thromboembolism, especially stroke, in patients with left ventricular systolic dysfunction is also well recognized. Pharmacological strategies to prevent stroke have been proposed in numerous studies. For example, anticoagulation in patients with atrial fibrillation and heart failure has been shown to reduce mortality rates and the incidence of stroke; however, its role in patients with left ventricular dysfunction and normal sinus rhythm is unclear and utilization of anticoagulation in these patients varies widely. The role of aspirin to prevent thromboembolism in patients with CHF is controversial. The relatively new pharmacological agent ximelagatran, which has an advantage of unmonitored oral administration has the potential to change the anticoagulation strategy in patients with heart failure. Important trials to define optimal therapy for reducing the risk of thromboembolism and death in patients with left ventricular systolic dysfunction and sinus rhythm include the recently reported WATCH (Warfarin and Antiplatelet Therapy in Chronic Heart failure) trial and the WARCEF (Warfarin versus Aspirin in Reduced Cardiac Ejection Fraction) trial, which is currently underway. The WATCH trial failed to outline significant differences between aspirin (acetylsalicylic acid), warfarin, and clopidogrel in the primary composite endpoint of all-cause mortality, nonfatal MI, and nonfatal stroke. Combined data from WATCH and WARCEF may provide sufficient statistical power to clarify outcomes such as stroke and death in patients with reduced cardiac ejection fraction. The pooled data may also help define optimal preventative measures for thromboembolism in patients with left ventricular systolic dysfunction and sinus rhythm.     

静脉血栓栓塞在骨科中的防治探析

目的探讨合理的防治骨科静脉血栓栓塞的方法。方法选择2012年12月至2013年12月在我院接受骨科手术的患者142例,随机分成研究组和对照组每组71例,对照组采用术前常规护理及治疗,研究组在常规护理的同时,进行预防性宣教并给予综合护理,统计两组患者静脉血栓栓塞的发生率。结果研究组患者深静脉血栓形成发生率为8.45%,肺动脉血栓栓塞症发生率为1.41%;对照组深静脉血栓形成发生率为50.70%,肺动脉血栓栓塞症发生率为11.27%,研究组静脉血栓栓塞的发生率显著低于对照组,有统计学意义(P<0.05)。结论在骨科手术中提前对患者进行有效的预防能显著降低静脉血栓栓塞的发生率,术后进行综合性治疗患者的临床治愈率较高。     

Venous Thromboembolism in Multiple Trauma Patients

Thromboembolic complications are frequent in patients with multiple trauma. The efficacy of unfractionated heparin for venous thrombosis prophylaxis has not been established. Based on limited prospective data, low-molecular-weight heparin appears to be more effective than unfractionated heparin and at least as effective as compression devices for preventing thromboembolic complications in these patients. Vena cava filters should be considered in high-risk patients who cannot receive anticoagulant therapy, but long-term filter use without concomitant anticoagulant therapy is associated with a substantial risk of recurrent thromboembolism.     

下肢关节手术后静脉血栓风险因素及评估体系分析

目的：在规范化治疗的前提下：（1）分析关节术后静脉血栓发生的影响因素;（2）评估各量表对血栓发生的指示作用,并试图给出新的识别高危人群的临界分值,为进一步个体化给药方案的制定奠定基础。方法：对2015年1月至3月骨科收治的下肢关节病、需行手术的87例患者术后静脉血栓发生情况进行分析。考察因素：性别、年龄、BMI、手术、骨折、活动能力、下肢水肿、静脉曲张、恶性肿瘤、肺疾病、脑梗史、脑梗家族史及输血。患者术后1、3、7天及出院后6周行双下肢静脉彩超检查静脉血栓。单因素分析采用卡方检验,多因素分析采用logistic回归分析。采用ROC曲线分析,以Caprini、Autar和Wells量表指征血栓发生的敏感性和特异性。结果：87名患者术后血栓发生例数为7例,发生在下肢远端静脉,发生率约为8%。卡方检验及logistic回归分析结果显示,手术、股骨颈骨折、活动能力、静脉曲张、恶性肿瘤是显著影响规范化治疗后血栓发生的因素,其中活动能力与股骨颈骨折为重要因素。血栓风险的Caprini、Autar 和Wells评分ROC曲线下面积分别为0.84（Caprini）、0.78（Autar）和0.56（Wells）,Caprini评分的最佳临界值点为8.5,对应的敏感性和特异性分别为0.86和0.74。结论：活动能力与股骨颈骨折是规范化下肢关节手术治疗后血栓发生的重要影响因素。 Caprini评分对静脉血栓高危人群有一定的识别能力,当临界分值定为8.5时,对血栓发生的识别有最好的敏感性和特异性。该结果提示,在目前规范化治疗体系下,Caprini评分高于8.5的下肢关节手术患者可能需要进一步的个体化治疗。如考察患者对抗凝药物的敏感性,以调整用法用量,并定时监测效应指标等。     

Extended Venous Thromboembolism Prophylaxis in Medically Ill Patients

Prophylaxis for venous thromboembolism (VTE) in hospitalized acutely ill medical patients is a well‐established practice. Despite the increased use of inpatient prophylaxis, the duration of hospitalization is typically shorter than the duration of VTE prophylaxis provided in clinical trials. In addition, VTE events after hospitalization are not unusual, with most events occurring within 30 days of hospital discharge. Therefore, the 30‐day time period postdischarge has been identified as a stage in which patients are still at high risk of developing VTE. Attempts to provide extended prophylaxis with enoxaparin, rivaroxaban, or apixaban in patients with acute medical illness have been met with mixed results. Although some of these agents have reduced the incidence of VTE with extended prophylaxis, all of these agents have also demonstrated a significant increase in major bleeding that seems to offset any potential benefit. A recent trial of a new direct factor Xa inhibitor, betrixaban, demonstrated a reduction in VTE events with extended prophylaxis without significantly increasing the risk of major bleeding. Understanding appropriate patient selection, dosing, and outcomes associated with betrixaban will be important to potentially reducing the continued risk of VTE in patients with acute medical illness.     

利伐沙班预防全膝关节置换术后静脉血栓栓塞症的成本-效果研究

目的:评估利伐沙班预防人工全膝关节置换术后静脉血栓栓塞症的成本与效果。方法:应用决策树(急性期)和Markov模型(长期)分析与比较利伐沙班与依诺肝素预防人工全膝关节置换术后静脉血栓栓塞症的成本与效果。结果:基础病例分析结果显示利伐沙班明显占优。模型预测利伐沙班治疗组病人比依诺肝素组病人5年内可额外增加0.0019质量调整生命年(QALY),且节省242元。此外,治疗与静脉血栓栓塞症相关并发症的费用利伐沙班组为581元,依诺肝素组则为1059元。概率敏感性分析结果显示当支付意愿阈值为20000元/QALY时,约90%以上患者认为利伐沙班较依诺肝素更具成本-效果。结论:实施人工全膝关节置换术病人若术后服用利伐沙班,其预防静脉血栓栓塞症的效果优于依诺肝素。     

抗凝药物防治癌症患者静脉血栓栓塞症的药物经济学系统评价

目的:系统评价抗凝药物预防或治疗癌症患者静脉血栓栓塞症(VTE)的药物经济性.方法:计算机检索PubMed、Embase、Cochrane图书馆、中国知网、万方数据、维普网、中国生物医学文献服务系统以及The NHS Economic Evaluation Database、The Healthy Technology...     

Key Articles and Guidelines for the Prevention of Venous Thromboembolism

Venous thromboembolism (VTE) is an important medical problem that affects millions of patients each year. With appropriate prophylaxis, many of these thromboembolic events can be prevented. Although strong evidence supporting VTE prophylaxis spans several decades, several large American and global registries have documented very poor use of appropriate prophylaxis. Because of increasing regulatory requirements, hospitals nationwide are in the process of developing documentation of appropriate VTE prophylaxis programs for both surgical and medical patients. A wide range of clinicians must understand what constitutes appropriate VTE prophylaxis in various patient populations. With the existence of numerous pharmacologic agents, abundance of data from major clinical trials, and several nationally recognized clinical guidelines, compiling the needed reference material to make evidence-based decisions on appropriate VTE prophylaxis can be difficult for clinicians. Therefore, we provide a bibliography of key articles and guidelines related to the prevention of VTE in various patient groups. We hope this compilation will serve as a resource for pharmacists, physicians, nurses, residents, and students responsible for the care of patients who may be at risk for VTE.     

Coagulopathy,Venous Thromboembolism,and Anticoagulation in Patients with COVID-19

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to a worldwide pandemic, and patients with the infection are referred to as having COVID-19. Although COVID-19 is commonly considered a respiratory disease, there is clearly a thrombotic potential that was not expected. The pathophysiology of the disease and subsequent coagulopathy produce an inflammatory, hypercoagulable, and hypofibrinolytic state. Several observational studies have demonstrated surprisingly high rates of venous thromboembolism (VTE) in both general ward and intensive care patients with COVID-19. Many of these observational studies demonstrate high rates of VTE despite patients being on standard, or even higher intensity, pharmacologic VTE prophylaxis. Fibrinolytic therapy has also been used in patients with acute respiratory distress syndrome. Unfortunately, high quality randomized controlled trials are lacking. A literature search was performed to provide the most up-to-date information on the pathophysiology, coagulopathy, risk of VTE, and prevention and treatment of VTE in patients with COVID-19. These topics are reviewed in detail, along with practical issues of anticoagulant selection and duration. Although many international organizations have produced guidelines or consensus statements, they do not all cover the same issues regarding anticoagulant therapy for patients with COVID-19, and they do not all agree. These statements and the most recent literature are combined into a list of clinical considerations that clinicians can use for the prevention and treatment of VTE in patients with COVID-19.     

Appropriate Enoxaparin Dose for Venous Thromboembolism Prophylaxis in Patients with Extreme Obesity

Objective:

To evaluate the appropriate dose of enoxaparin for venous thromboembolism (VTE) prophylaxis in patients with extreme obesity.

Methods:

A literature search was performed using MEDLINE (1950-April 2013) to analyze all English-language articles that evaluated incidence of VTE and/or anti-Xa levels with enoxaparin for thromboprophylaxis in patients with extreme obesity.

Results:

Eight studies were included in the analysis. Six of the studies were done in patients undergoing bariatric surgery. Mean body mass index ranged from 44.9 to 63.4 kg/m² within studies. Studies done with bariatric surgery patients utilized doses of enoxaparin that ranged from the standard dose of 30 mg subcutaneous (SQ) every 12 hours to 60 mg SQ every 12 hours. Other studies evaluated doses ranging from 40 mg SQ every 24 hours to 0.5 mg/kg/day. Only 3 studies evaluated the incidence of VTE as the primary endpoint; the other studies evaluated anti-Xa levels. The studies showed that appropriate anti-Xa levels were achieved more often with higher than standard doses of enoxaparin. One study showed that enoxaparin 40 mg SQ every 12 hours decreased the incidence of VTE in patients undergoing bariatric surgery compared to standard doses. Overall risk of bleeding was similar between study groups.

Conclusions:

Higher than standard doses of enoxaparin may be needed for patients with extreme obesity. Patients undergoing bariatric surgery may benefit from enoxaparin 40 mg SQ every 12 hours. Additional large randomized, controlled trials are needed to determine the efficacy and safety of higher than standard doses of enoxaparin for VTE prophylaxis in patients with extreme obesity.Key Words: enoxaparin, extreme obesity, prophylaxis venous thromboembolismProphylaxis of venous thromboembolism (VTE), including deep vein thrombosis (DVT) and its extension pulmonary embolism (PE), is a mainstay of modern hospital care for many patients. In the United States, VTE is estimated to occur in up to 1 million people and accounts for over 200,000 deaths annually; more than half of VTE cases occur in the hospital setting.¹When enoxaparin, one of the most commonly used low-molecular-weight heparins (LMWH), is chosen over viable alternatives for VTE prophylaxis, it is most often dosed at 40 mg subcutaneous (SQ) every 24 hours or 30 mg SQ every 12 hours.² For most patients, this has been proven to be a safe and effective dose.² However, these fixed doses do not take into consideration that the distribution of LMWH is weight based, and the efficacy of standard doses in obese and extreme obese patients may be decreased, putting these patients at a higher risk of thromboembolism.^3–5The Centers for Disease Control and Prevention (CDC) defines extreme obesity as a body mass index (BMI) of greater than or equal to 40.0 kg/m². With the CDC citing obesity and extreme obesity rates of 35.7% and 6.3% in the United States, an appropriate dosing strategy for enoxaparin thromboprophylaxis in these patients is needed.⁶The most common laboratory test for monitoring the anticoagulation effect of enoxaparin is plasma anti-Xa level. This is an expensive test that is rarely performed due to the predictable pharmacodynamic profile of enoxaparin. Some patients may benefit from measuring anti-Xa levels. These include obese patients, patients with renal dysfunction, pediatric patients, and pregnant women. However, this recommendation is limited to patients receiving treatment doses of enoxaparin.² Measuring anti-Xa levels in patients receiving exonaparin for thromboprophylaxis is not a proven predictor of outcomes, and there is no consensus about an appropriate therapeutic range. Sanofi-aventis reports that mean peak anti-factor Xa activity was found to be 0.16 IU/mL and 0.38 IU/mL after the 20 mg and 40 mg SQ doses, respectively, were clinically tested.⁷ It has been suggested in the literature that peak anti-Xa levels between 0.2 and 0.5 U/mL obtained 3 to 5 hours following SQ injections of enoxaparin will be appropriate for thromboprophylaxis.^8,9Some studies have found a strong negative correlation between body weight and anti-Xa activity after a 40 mg SQ injection of enoxaparin.^4,10 In addition, other studies have shown that obese and extremely obese patients may not achieve suggested anti-Xa levels when standard doses of enoxaparin are used for VTE prophylaxis.^3,5,11The 2012 American College of Chest Physicians guidelines recommend the use of a LMWH such as enoxaparin or low-dose unfractionated heparin (LDUH) in 3 distinct categories of patient for VTE prophylaxis.² These include acutely ill patients with an increased risk of thrombosis and a low risk of bleeding, critically ill patients with a low risk of bleeding, and postsurgical patients with a moderate to high risk of VTE and a low risk of bleeding. The guidelines state, “It may be prudent to consult with a pharmacist regarding dosing in bariatric surgery patients and other patients who are obese who may require higher doses of LDUH or LMWH.”^2(pp270-271)Some institutions, including Temple University Hospital, are currently using higher than standard doses of enoxaparin for thromboprophylaxis in hospitalized patients with extreme obesity. Given the rise in the prevalence of extreme obesity, the purpose of this article is to provide an overview of the literature to better inform clinicians on the appropriate thromboprophylactic dose of enoxaparin in patients with extreme obesity.     

依度沙班预防骨科大手术后静脉血栓栓塞的meta分析

目的 比较依度沙班与低分子肝素预防骨科大手术后静脉血栓栓塞（venous thromboembolism,VTE）的有效性和安全性。方法 检索Cochrane Library、PubMed、EMBASE、中国知网、万方和维普科技期刊等数据库。收集依度沙班与低分子肝素预防骨科大手术后VTE随机对照试验。应用RevMan 5.3.5软件进行分析。结果 最终纳入5项研究,涉及2 585例患者。依度沙班组总VTE发生率[RR=0.47,95% CI（0.38,0.56）,P<0.000 01]、无症状性深静脉血栓发生率[RR=0.47,95% CI（0.31,0.71）,P=0.000 4]均低于低分子肝素组。依度沙班组总出血事件发生率高于低分子肝素组[RR=1.22,95% CI（1.01,1.49）,P=0.04]。亚组分析发现依度沙班不同剂量组总VTE发生率均低于低分子肝素组,15 mg组、30 mg组与低分子肝素组总出血事件发生率差异均无统计学意义。结论 依度沙班预防骨科大手术后VTE优于低分子肝素,但增加了总出血事件发生率。15,30 mg依度沙班可能为较安全剂量。     

妇科肿瘤161例围手术期预防静脉血栓栓塞症的分析

目的：对妇科恶性肿瘤手术患者静脉血栓栓塞症（venous thromboembolism,VTE）的预防现状进行分析。方法：对2017年12月~2018年8月南京鼓楼医院收治的161例妇科恶性肿瘤手术患者的基本资料、VTE预防措施、抗凝药物使用情况等进行回顾性分析。结果：161例妇科恶性肿瘤手术患者的深静脉血栓发生率为1.9%;接受机械联合药物预防的患者有32例（19.9%）,接受机械预防的患者有129例（80.1%）。结论：静脉血栓栓塞症是妇产科围手术期严重的并发症,而合并恶性肿瘤者尤甚。围手术期对患者进行VTE风险评估、分级,采取措施预防是非常必要的,但是如何评估患者风险、如何采取预防措施仍待权威“指南”提供统一方案,以便参照落实。     

肿瘤相关性血栓栓塞症的研究进展

恶性肿瘤是静脉血栓栓塞症（VTE）的高危因素之一。随着肿瘤患者的数量增加,静脉血栓栓塞的发病率也呈上升趋势。因为血栓形成的病理生理是多因素的,迄今为止没有一种适合所有预防和治疗的药物。大多数的临床指南推荐低分子量肝素（LMWHs）用于癌症患者住院期间VTE的预防和治疗,不推荐对门诊癌症患者进行常规血栓预防。在安全性和有效性得到充分的证实之前,不推荐对恶性肿瘤静脉血栓的患者使用新型口服抗凝药。这篇综述系统阐述了肿瘤合并VTE的流行病学、风险评估、预防和治疗以及新型抗凝药的研究状况。     

利伐沙班对比低分子肝素预防髋骨骨折患者发生静脉血栓的有效性和安全性的Meta分析

目的:系统评价利伐沙班对比低分子肝素预防髋骨骨折患者发生静脉血栓栓塞(VTE)的有效性和安全性,为临床应用提供循证参考。方法:计算机检索自建库起至2018年6月收录于Cochrane图书馆、PubMed、Embase、中国期刊全文数据库、维普网、万方数据的文献,收集利伐沙班(试验组)对比低分子肝素(对照组)预防髋骨骨折患者发生VTE的随机对照试验(RCT),对符合标准的文献进行资料提取,并采用Cochrane系统评价员手册5.1.0进行质量评价后,采用Rev Man 5.3统计软件对深静脉血栓形成(DVT)发生率、术后引流量、活化部分凝血活酶时间(APTT)水平、凝血酶原时间(PT)及药品不良反应(ADR)发生率进行Meta分析。结果:共纳入8项RCT,合计949例患者。Meta分析结果显示,与低分子肝素相比,利伐沙班能显著降低患者的DVT发生率[RR=0.55,95%CI(0.36,0.83),P=0.004];两组患者的术后引流量[MD=-0.24,95%CI(-5.27,4.8),P=0.93]、APTT[MD=0.56,95%CI(-0.75,1.86),P=0.40]、PT[MD=0.04,95%CI(-0.03,0.11),P=0.25]及ADR发生率[RR=1.73,95%CI(0.15,20.48),P=0.66]比较,差异均无统计学意义。结论:利伐沙班对髋骨骨折患者发生VTE的预防效果优于低分子肝素,且安全性相当。     

PAI-1与F5基因多态性与重症医学科患者静脉血栓风险发生的相关性研究

目的 探索PAI-1与F5基因多态性检测在重症医学科(ICU)患者静脉血栓风险评估中的应用价值.方法 选取我院ICU2019年6月～2020年2月行静脉血栓风险基因检测并经彩色多普勒超声血流成像确诊有不同程度下肢深静脉血栓形成的患者90例,作为VTE组.同期选取排除静脉血栓高风险及经彩色多普勒超声血流成像诊断下肢静脉血...     

基于分级管理的静脉血栓栓塞症患者全程化抗凝管理模式的建立与评价

目的:建立基于分级管理的静脉血栓栓塞症患者全程化抗凝管理模式(Integrated and hierarchical anticoagulation management mode for patients with venous thromboembolism,VTE-IHAM),并评价实践效果.方法:以文献计量学的...