Safety and Effectiveness of Reduced Dose Versus Standard Dose Enoxaparin Venous Thromboembolism Prophylaxis in Underweight Medically Ill Patients

Background: Enoxaparin is commonly used for venous thromboembolism (VTE) prophylaxis in hospitalized patients. Published literature exists for dose adjustment in higher body weights and renal dysfunction, but sparse literature on optimal dosing of prophylactic enoxaparin in underweight patients exists. Objective: To determine if there is a difference in adverse outcomes or effectiveness if enoxaparin VTE prophylaxis dosing is reduced to 30 mg subcutaneously once daily from standard dosing in underweight medically ill patients. Methods: This study was a retrospective chart review of a total of 171 patients, with 190 individual courses of enoxaparin included. Patients were ≥18 years of age, weighed ≤50 kg, and were given at least 2 days of consecutive therapy. Patients were excluded if they were taking anticoagulation upon admission, had a creatinine clearance <30 mL/min, were admitted to the ICU or a trauma or surgical service, or presented with bleeding or thrombosis. The Padua score and a modified score from the IMPROVE trial were used to evaluate baseline thrombotic risk and bleeding risk, respectively. Bleeding events were classified using the Bleeding Academic Research Consortium criteria. Results: No difference was seen in baseline risk of bleeding or thrombosis when comparing the reduced and standard dosing groups. No differences were observed with rates of bleeding, thrombotic events, mortality, or 30-day readmission. Conclusion: Both reduced and standard dosing strategies appeared effective for VTE prophylaxis, but neither showed superiority in reducing bleeding events. Additional larger studies are needed to evaluate safety and effectiveness of reduced dose of enoxaparin in this patient population.     

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.     

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。     

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.     

Cost-Effectiveness of Enoxaparin versus Low-Dose Heparin for Prophylaxis Against Venous Thrombosis after Major Trauma

We attempted to determine health and economic outcomes from the perspective of an integrated health system of administering enoxaparin 30 mg twice/day versus heparin 5000 U twice/day for prophylaxis against venous thrombosis after major trauma. A decision-analytic model was developed from best literature evidence, institutional data, and expert opinion. We assumed that 40% of proximal deep vein thromboses (DVTs) and 5% of distal DVTs are diagnosed and confirmed with initial or repeat duplex scanning; 50% of undiagnosed proximal DVTs result in pulmonary embolism; 2% and 1% of undiagnosed proximal DVTs will lead to readmission for DVT and pulmonary embolism, respectively, and pulmonary embolism-related mortality rates range from 8–30%. Length of hospital stay data and 1996 institutional drug use and acquisition cost data were used to estimate the cost of enoxaparin and heparin therapy. Diagnosis and treatment costs for DVT and pulmonary embolism were derived from institutional charge data using costxharge ratios. A second analysis of patients with lower extremity fractures was completed. One-way and multiway sensitivity analyses were performed. For 1000 mixed trauma patients receiving enoxaparin versus heparin, our model showed that 62.2 (95% CI −113 to −12) DVTs or pulmonary emboli would be avoided, resulting in 67.6 (8 to 130) life-years saved at a net cost increase of $104,764 (−$329,300 to $159,600). Enoxaparin versus heparin resulted in a cost of $1684 (−$3600 to $9800) for each DVT or pulmonary embolus avoided and a discounted cost/life-year saved of $2303 (−$8100 to $19,000). For 1000 patients with lower extremity fractures, enoxaparin versus heparin resulted in a cost of $751 (−$4200 to $3300) for each DVT or pulmonary embolus avoided and a discounted cost/life-year saved of $1017 (−$10,200 to $6300). Although enoxaparin increases overall health care costs, it is associated with a cost/additional life-year saved of only $2300, which is generally lower than the commonly used hurdle rate of $30,000/life-year saved. The cost-effectiveness ratio is more favorable in patients with lower extremity fractures than in the general mixed trauma population.     

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.     

利伐沙班与依诺肝素用于恶性肿瘤合并静脉血栓栓塞症疗效与安全性比较的Meta分析

目的:比较利伐沙班与依诺肝素用于恶性肿瘤合并静脉血栓栓塞症的疗效与安全性,为临床用药提供循证参考.方法:计算机检索PubMed、Embase、Cochrane图书馆、Clinical Trials、中国期刊全文数据库、中国生物医学文献数据库、维普网等数据库,收集利伐沙班对比依诺肝素的临床试验或观察性研究,检索时限均为各...     

Pharmacological Prevention of Venous Thromboembolism in Medical Patients at Risk

Acutely ill general medical patients are at moderate-to-high risk of venous thromboembolism (VTE); approximately 10-30% may develop deep vein thrombosis or pulmonary embolism, the latter being a leading contributor to deaths in hospital. Medical conditions associated with a high risk of VTE include cardiac disease, cancer, respiratory disease, inflammatory bowel disease, and infectious disease. Predisposing risk factors for VTE in medical patients include history of VTE, history of malignancy, complicating infections, increasing age, thrombophilia, prolonged immobility, and obesity. Unfractionated heparin (UFH), low-molecular weight heparin (LMWH), and fondaparinux sodium have been shown to be effective agents in the prevention of VTE in medical patients. In this setting, UFH has a higher rate of bleeding complications than LMWH. There is no evidence supporting the use of aspirin, warfarin, or mechanical methods to prevent VTE in medical patients. We recommend either LMWH or fondaparinux sodium as well tolerated and effective thromboprophylactic agents in medical patients.     

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...     

保守治疗老年髋部骨折下肢深静脉血栓的预防

目的：观察保守治疗老年髋部骨折患者下肢深静脉血栓形成(DVT)的发生率及低分子肝素预防其形成的效果和安全性。方法：120例新鲜髋部骨折患者，随机抽取60例干预组给予依诺肝素治疗40mg／d，共14d，60例不用依诺肝素(对照组)。观察2组DVT的发生率，血浆部分凝血活酶时间(APTT)、凝血酶原时间(PT)、凝血酶凝固时间(TT)、活化凝血因子X(FXa)含量及活性、纤维蛋白原(Fib)含量及D-二聚体(D-D)含量的变化。结果：对照组DVT发生率为56．67％(34／60)，干预组为3．33％(2／60)，差别有统计学意义。2组APTT、PT及TT差别无统计学意义，而FXa含量及活性，Fib含量及D-D的含量在干预组较对照组下降(P＜0．05)。干预组未见明显的不良反应。结论：在老年髋部骨折保守治疗中应用低分子肝素进行干预，可降低DVT的发生率，且无明显的不良反应。     

有效运用血栓弹力图在腹部创伤患者术后并发深静脉血栓预防中的应用价值

目的探讨有效运用血栓弹力图在腹部创伤患者术后并发深静脉血栓预防中的应用价值。方法对2012年6月至2014年12月收治的100例腹部创伤患者的临床资料进行统计分析。结果高危组患者干预后3 d的R值显著低于干预前(P<0.05),1周、2周的R值均显著高于干预前(P<0.05);干预后3 d的MA值显著高于干预前(P<0.05),干预后1周、2周的MA值均显著低于干预前(P<0.05)。结论有效运用血栓弹力图在腹部创伤患者术后并发深静脉血栓预防中具有较高的应用价值。     

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。     

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。     

Extended Dalteparin Prophylaxis for Venous Thromboembolic Events

Background

Deep vein thrombosis (DVT) and pulmonary embolism (PE) are manifestations of venous thromboembolic events (VTEs). Patients undergoing major surgical procedures such as total hip replacement (THR), total knee replacement (TKR), and hip fracture surgery (HFS) are at an elevated risk for VTEs. The American College of Chest Physicians’ (ACCP) guidelines recommend that such patients receive thromboprophylaxis for at least 10 days. In patients undergoing THR or HFS, extended prophylaxis for up to 28–35 days is the recommended approach for those at high risk of thromboembolic events. The NAFT (North American Fragmin Trial) compared the prophylactic efficacy of dalteparin with that of warfarin during the in-hospital period, and with that of placebo during the period of hospital discharge until day 35 postsurgery, in patients who underwent total hip arthroplasty. During both the in-hospital and the post-discharge time periods, dalteparin significantly reduced the occurrence of DVT. Given the clinical relevance of these results, the low specificity of the ACCP recommendations regarding optimal prophylaxis duration, and the importance of optimizing the efficiency of DVT prophylaxis in the practice setting, a cost-utility analysis was conducted comparing dalteparin 10-day and 35-day (extended) with a warfarin 10-day protocol, in patients undergoing major orthopedic surgeries such as THR, TKR, or HFS.

Design and setting

A three-arm decision model was developed using the prevalence of symptomatic DVT from NAFT publications, epidemiologic studies, and published meta-analyses. Healthcare resource use was abstracted from a survey of clinicians and from the economic literature. Utility estimates were obtained by interviewing a sample of 24 people from the general public using the time trade-off technique. The clinical, economic and utility data were then used to estimate the cost per quality-adjusted life-year (QALY) gained with dalteparin for 10 or 35 days relative to 10 days of warfarin.

Study perspective

Canadian provincial healthcare system.

Main outcome measures and results

The cost per QALY gained with 10 days of dalteparin was below $Can1000 for all the surgeries evaluated (all costs are reported in 2007 Canadian dollars [$Can1 = $US1, as of December 2007]). In the case of extended prophylaxis, the incremental cost per QALY gained with 35 days of dalteparin over warfarin was $Can40 100, $Can46 500, and $Can31 200 for patients undergoing THR, TKR, and HFS, respectively. Reducing the duration of prophylaxis from 35 to 28 days generated ratios that were below $Can35 000 for all three surgeries evaluated.

Conclusions

Ten days of dalteparin following major orthopedic surgery is a clinically and economically attractive alternative to warfarin for DVT prophylaxis. In the case of the 35-day dalteparin protocol, the results also indicated acceptable economic value to a publicly funded healthcare system, particularly in the settings of HFS and THR. In addition, reducing the duration of prophylaxis to 28 days postsurgery would be associated with a more favorable return on public healthcare expenditures.     

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。     

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...