【专题文献】之循证医学---全关节置换中的深静脉血栓预防
发布于 2010-09-18 · 浏览 4354 · IP 江苏江苏
这个帖子发布于 14 年零 262 天前，其中的信息可能已发生改变或有所发展。
DVT Prophylaxis in Total Joint Reconstruction
全关节置换中的深静脉血栓预防
KEYWORDS _ Prophylaxis _ Deep venous thrombosis _ Venous thromboembolism _ Total joint arthroplasty
关键词：预防 深静脉血栓 深静脉血栓栓塞 全关节置换
Deep venous thrombosis (DVT) is the end result of a complex interaction of events including the activation of the clotting cascade in conjunction with platelet aggregation. It has been clearly demonstrated that patients undergoing major lower extremity orthopedic surgery, especially total joint arthroplasty (TJA), are at high risk for developing a postoperative DVT or a subsequent pulmonary embolus (PE). In the arena of TJA, orthopedic surgeons are particularly concerned with proximal DVT and symptomatic or fatal PE.
深静脉血栓是包括凝血级链反应激活和血小板聚集在内的一系列繁杂事件的最终结果。骨科下肢大手术患者，特别是全关节置换（TJA），出现术后DVT或者由此产生的肺栓塞（PE）的风险较高。在TJA领域，骨科医生特别关心近端DVT和有症状的或者致死性DVT。Patients undergoing primary total hip arthroplasty (THA) or total knee arthroplasty (TKA) have exhibited rates of symptomatic PE as high as 20% and 8%, respectively when no prophylaxis has been administered.1 As a result, the use of venous thromboembolic (DVT and PE) prophylaxis, most commonly pharmacologic prophylaxis, has become the standard of care for patients undergoing elective TJA. The risk of fatal PE following primary hip or knee replacement has been consistently reported to be between 0.1% and 0.2%, regardless of the chemoprophylactic agent employed for prophylaxis.2–9
进行初次全髋置换（THA）或者全膝置换（TKA）的患者在不采取预防措施时有症状的PE发生率分别为20%和8%。结果，使用预防DVT的措施已经成为择期TJA患者的标准治疗模式，而最常用的就是药物预防。据目前报道，初次全髋或全膝置换术后，无论使用何种药物预防，致死性PE在0.1%-0.2%之间。
Based on the necessity of postoperative venous thromboembolic (VTE) prophylaxis following TJA, the National Quality Forum endorsed a voluntary consensus standard for inpatient hospital care in the earlier part of this decade. The surgical care improvement project (SCIP) guidelines, a result of the consensus, require documentation of initiation of DVT prophylaxis in the time period extending from 24 hours before surgery to 24 hours following surgery.10 The rationale for the SCIP guidelines stemmed from the government’s emphasis on pay-for-performance (P4P) whereby physicians receive increased compensation as a function of meeting certain ‘‘standards of care.’’11
由于TJA术后预防静脉血栓栓塞（VTE）的必要性，在本世纪第一个10年的初期，国家质量论坛（NQF）支持在住院病人医院内治疗标准方面达成共识。外科治疗改善工程（SCIP）指南作为该共识的结果，要求在术前24小时至术后24小时内，记录预防DVT开始的时间。推出SCIP指南是因为政府强调 “根据表现付费”（P4P），根据此政策，医生只要符合这些“治疗标准”即可获得更多的补偿。
Despite several years of evaluating this question, the best prophylaxis for thromboembolic disease remains controversial.12 The use of pharmacologic prophylaxis has been adopted as the standard of care for treatment of these patients by many orthopedic surgeons at most centers across North America.13 However, the controversy between the efficacy of VTE prophylaxis and the increased risk for bleeding in the postoperative period continues to exist. In recent years, this debate has brought about the development of clinical guidelines to improve patient care, address key questions, define evidence-based recommendations, and promote future research. Clinical guidelines are not meant to represent a predefined protocol or absolute rules for treatment, and should never substitute for clinical judgment.
尽管评估此问题已有数年，预防栓塞性疾病的最好方法仍有争议。药物预防已成为北美绝大多数中心骨科医生治疗的标准方法。然而，关于VTE预防的效果及增加术后出血风险之间的争论仍然存在。近年来，这种争论导致了临床指南的推出，指南提高了治疗，解决了关键问题，规定了循证医学推荐的治疗方法，并且促进了更进一步的研究。临床指南并不意味着是治疗的绝对标准而永远不需根据临床情况调整。
Dependent on the clinical guideline followed, from the American College of Chest Physicians (ACCP) or the American Academy of Orthopaedic Surgeons (AAOS), there are several recommended regimens available for treatment. Included in the options are low molecular weight heparins (LMWHs), synthetic pentasaccharides, adjusted-dose warfarin, aspirin, and mechanical prophylaxis. Several studies have evaluated the various modalities for DVT prophylaxis, and comparison studies have stratified the risks and benefits for each option.
根据临床指南，美国胸科医生协会（ACCP）或美国骨科医生协会（AAOS）都有几种推荐治疗方案。包括低分子肝素（LMWHs）,合成的戊多糖，调整剂量的华法林，阿斯匹林以及物理预防措施。已经有研究对各种不同DVT预防方案作了评估，并有对比研究将每种方法的收益与风险作了分层分析。
The following review addresses the controversy underlying VTE prophylaxis by outlining 2 guidelines and demonstrating the pros and cons of different DVT prophylaxis regimens based on the available evidence-based literature.
下文通过概述2个指南重点说明在预防VTE方面所存在的争论，并根据目前可以得到的循证医学文献说明不同预防DVT方案的利弊。
AMERICAN COLLEGE OF CHEST PHYSICIANS GUIDELINES
美国胸科医生协会指南
The ACCP was founded in 1935, and the first set of guidelines for venous thromboembolic prophylaxis (VTE) was published in 1986. The goal of these guidelines is to focus on the prevention of the overall rate of VTE. These guidelines are based on a review of prospective, randomized studies only. The guidelines have subsequently gone through several iterations with the most recent update in 2008.13 Inherent to these guidelines is that all primary THA and TKA patients are considered ‘‘high risk’’ regardless of patient age, activity level, and comorbidities.
ACCP成立于1935年，第一版预防VTE指南发表于1986年。这些指南的目的是强调预防VTE。这些指南仅仅是根据前瞻性，随机研究的文献回顾作出的。此指南随后已经更新了数次，最近一次更新是2008年。这些指南里不管患者的年龄、活动水平和伴发疾病，始终将所有的THA和TKA患者作为高危人群。
These guidelines have become commonplace in the evaluation of health care systems on behalf of hospitals, insurance companies, and attorneys. The recommendations were classified as Grade I (strong recommendation, with benefits outweighing risk, burden, and cost) or Grade II (recommendation with less certainty). Each class of recommendation was further substratified: (A) randomized controlled trials with consistent results and a low level of bias, (B) randomized controlled trials with inconsistent results or a major methodological design flaw, and (C) observational studies.13 The use of LMWH, fondaparinux (pentasaccharide), and warfarin (with an adjusted international normalized ratio [INR] between 2.0 and 3.0) all received a Grade IA recommendation for preventative treatment of total hip and knee arthroplasty; aspirin or low-dose unfractionated heparin received a Grade IA rating against their use for prophylaxis in patients following TJA. The use of intermittent pneumatic compression devices received a Grade IB rating for prevention in patients undergoing TKA.
这些指南在健康保健系统的评估中已非常普通。推荐分为Ⅰ级（强烈推荐，好处大于风险、负担和代价）或Ⅱ级（谨慎推荐）。每一级都进一步分层：（A）结果一致，偏倚水平低的随机对照研究（B）结果不一致，设计方法有缺陷的随机对照研究和（C）观察研究。LMWH，磺达肝素（戊多糖）和华法林（调整的INR在2.0和3.0之间）都获得了ⅠA级推荐，用于THA和TKA患者中预防性治疗；阿斯匹林或小剂量未分馏肝素获得了ⅠA级评级，不可用于TJA术后预防血栓。间断充气加压装置获得了ⅠB级评级，可用于TKA患者（DVT）的预防。
These guidelines also address the duration of prophylaxis. During the first iteration, the ACCP guidelines from 1998 and 2001 recommended 7 to 10 days of prophylaxis that coincided with the length of hospital stay (Grade IA recommendation). 14 In 2004, the guidelines were revised to recommend out of hospital prophylaxis for 28 to 35 days (Grade IA) but excluded patients undergoing TKA.15 With additional revisions, the 2008 guidelines currently recommend duration of prophylaxis with LMWH, fondaparinux, and warfarin for up to 10 days following THA and TKA (Grade IA), and up to 35 days following THA (Grade IA) or TKA (Grade IIB).13
这些指南也强调预防的疗程。在第一次更新中， 1998年的ACCP指南和2001年的指南推荐7－10天的预防治疗，巧合的是这与住院时间相等（ⅠA级推荐）。2004年，指南修改为推荐院外预防28-35天（ⅠA级），但TKA病人除外。2008年指南又作了修改，推荐LMWH，磺达肝素和华法林预防疗，THA和TKA 术后可用至10天（ⅠA级），THA或TKA术后可用至35天（ⅡB级）。
As with any guidelines being used to guide physicians in medical decision making, the risk versus benefit must be assessed. Implementation of the current ACCP guidelines has been associated with certain disadvantages, as reported in the orthopedic literature. Burnett and colleagues16 reported a 4.7% readmission rate, 3.4% irrigation and debridement rate, and 5.1% rate of prolonged hospitalization following 10 days of LMWH after TJA. Parvizi and colleagues17 have shown that patients with a wound hematoma or persistent wound drainage are at higher risk for a postoperative deep joint infection. As a direct consequence of the concerns for postoperative bleeding risk and potential for infection, orthopedic surgeons may prefer a more risk-averse method by which to prevent thromboembolic phenomena following TJA, especially because the rate of PE is similar regardless of the chemoprophylaxis agent used.
和任何用于指导医生作决定的指南一样，必须评估风险与收益。目前的ACCP指南在实施中也有一些缺陷，这在骨科文献中已有报道。Burnett等报道再入院率4.7%，冲洗和清创率为3.4%，TJA术后LMWH治疗10天后延长住院时间率为5.1%.Parvizi等人认为有伤口血肿或持续伤口引流的患者是术后关节深部感染的高危人群。出于对术后出血和潜在感染风险的担心，骨科医生可能更喜欢在TJA术后使用风险更小的方法以预防血栓栓塞性肺炎，特别是无论使用何种药物预防时PE的发病率都相似。
AMERICAN ACADEMY OF ORTHOPEDIC SURGEONS GUIDELINES
美国骨科医生协会
A work group from the AAOSin conjunction with the Center for Clinical Evidence Synthesis (Tufts New England Medical Center) proposed a new set of guidelines for the prevention of symptomatic and fatal PE in patients undergoing elective TJA. The AAOS guidelines are a synthesis of an expert consensus as well as an analysis of 42 articles published since 1996, and focus on the prevention of symptomatic PE. The clinical outcomes of choice for evaluation included symptomatic and fatal PE, death, and major bleeding episodes following TJA.18 Consensus recommendations included the use of regional anesthesia, mechanical prophylaxis for all patients, rapid postoperative mobilization, and adequate patient education. Each patient required a preoperative evaluation for a determination of ‘‘standard’’ and ‘‘high’’ risk potential. The choice of a specific chemoprophylaxis agent was based on the individual risk-benefit profile for PE and bleeding complication.
AAOS的一个工作组与临床证据汇总中心（Tufts新英格兰医疗中心）联合推出一套新的预防择期TJA患者有症状的和致死性PE的指南。AAOS指南分析了1996年以来的42篇文章，是专家共识的汇总，重点是预防致死性PE。选择作为临床结果评估的内容包括有症状的和致死性的PE，死亡以及TJA术后大出血。共识推荐包括使用区域阻滞麻醉，所有患者使用物理预防，术后早期活动和对患者进行适当的教育。每个患者要求术前评估以确定是属于“标准”风险还是“高”风险。根据个人PE和出血并发症的风险－收益关系选择某种具体的药物。
Each recommendation was graded using the following system: (A) good evidence (level I studies with consistent findings) for recommending intervention, (B) fair evidence (level II or III studies with consistent findings) for recommending intervention, and (C) poor-quality evidence (level IV or V) for recommending intervention18 (Table 1). Of the total number of recommendations from this set of guidelines, only 4 of them were derived from a systematic review of the literature. Additional general consensus recommendations are listed in Table 2.18
每种推荐都是按以下体系分级：（A）支持推荐的证据确凿（结果一致的Ⅰ级研究），（B）支持推荐的证据较多（结果一致的Ⅱ级或Ⅲ级研究）（C）支持推荐证据不足（Ⅳ级或Ⅴ级研究）（表1）。在这个指南的所有推荐中，只有4项是源于文献的系统性回顾。其他的共识推荐见表2。
For patients at standard risk for both PE and major bleeding complications, the recommendation is as follows: aspirin, LMWH, pentasaccharide, or warfarin (INR goal of ≤2.0). This recommendation is based on level III evidence and was given a grade of B or C..
对于PE和大出血并发症风险标准的患者，推荐如下：阿斯匹林，LMWH，戊多糖或者华法林（INR≤2.0）。这种推荐是基于Ⅲ级证据，评级为B或C。
For patients at elevated risk for PE and standard risk for major bleeding complications, the recommendation is as follows: LMWH, pentasaccharide, or warfarin (INR goal of %2.0). This recommendation is based on level III evidence and was given a grade of B or C.
对于PE风险升高而大出血风险标准的患者，推荐如下：LMWH，戊多糖或者华法林（INR≤2.0）。这是基于Ⅲ级证据，评级为B或C。
For patients with standard risk of PE and elevated risk of major bleeding complications, the recommendation is as follows: aspirin, warfarin (INR goal of %2.0), or none. This recommendation is based on level III evidence and was given a grade of C.
对于PE风险标准而大出血风险升高的患者，推荐如下：阿斯匹林，华法林（INR≤2.0），或者什么都不用。这是基于Ⅲ级证据，评级C。
For patients with elevated risk of both PE and major bleeding complications, the recommendation is as follows: aspirin, warfarin (INR goal of %2.0), or none. This recommendation is based on level III evidence and was given a grade of C.
对于PE和大出血风险都升高的患者，推荐如下：阿斯匹林，华法林（INR≤2.0），或者什么都不用。这是基于Ⅲ级证据，评级C。
The most important concept that is fundamental to the AAOS guidelines for thromboembolic prophylaxis is that the risk versus benefit for each individual patient must be assessed in the preoperative period. The general recommendations presented in Table 2 are a result of the work group’s consensus, and address a majority of the perioperative issues with prophylaxis. For patients with elevated risks for PE, major bleeding complication, or both, these guidelines provide an effective manner by which to treat these patients in the postoperative period following TJA. However, a weakness inherent to the AAOS guidelines is the inability to accurately assess the preoperative risk for DVT/PE. In reality, based on the nature of TJA, arthroplasty patients may not truly be considered low risk. In addition, there are studies to demonstrate rates of VTE as high as 72% following the administration of aspirin,19 thus raising the question of whether the use of aspirin is adequate as a thromboprophylaxis agent.
AAOS血栓栓塞预防指南最重要的概念是在每一个患者术前必须评估风险和收益。表2中的总体推荐是工作组达成的共识，提到了围手术期预防血栓的绝大多数问题。对于PE风险升高，大出血并发症风险升高或者两者都升高的患者，这些推荐提供了TJA术后有效的治疗方法。然而，AAOS指南的不足是无法准确评估术前DVT/PE的风险。实际工作中，由于TJA的性质，可能不会真正认为关节置换患者是低风险的。另外，有研究表明使用阿斯匹林后VTE率高达72%,因而就引起一个疑问，使用阿斯匹林作为一种血栓预防药是否恰当。LOW MOLECULAR WEIGHT HEPARINS
低分子肝素
The use of LMWH has gained enthusiasm within the orthopedic community due to its well-documented bioavailability and the absence of monitoring for clotting indices (ie, INR). The efficacy of LMWH is well documented. In multiple randomized trials, including THA and TKA patients, LMWH has been more effective than warfarin in limiting overall DVT rates. However, LMWH is associated with higher bleeding rates. Because the selection of a prophylaxis agent is a balance between efficacy and safety, some surgeons choose other modes of prophylaxis due to concerns related to bleeding and its impact on overall outcomes. An additional consideration with any medication choice is the cost; the cost of LMWH remains relatively high as compared with aspirin and warfarin.
LMWH由于良好的生物利用度和不需要监测凝血指数（如INR）而在骨科医生中大受欢迎。LMWH的效果文献已有明确报道。包括THA和TKA患者的多中心随机试验显示LMWH比华法林能更有效地减少总体DVT发生率。然而，LMWH的出血率较高。因为选择预防血栓药物要求在安全性和有效性之间找到平衡，考虑到出血及出血对整个治疗疗效的影响，有些医生选用其他预防血栓的方法。另一个选用任何一种药物都要考虑的问题是花费;LMWH治疗的花费与阿斯匹林和华法林相比仍然比较高昂。
As with any postoperative chemoprophylaxis regimen, duration of treatment is always of concern. The ACCP guidelines have changed their recommendations since the initial guidelines introduced in 1998. The most recent recommendation from the ACCP in 2008 states that patients undergoing THA or TKA should receive chemoprophylaxis withLMWHfor 7 to 10 days (Grade IA recommendation), and this may be extended to up to 35 days following THA. Administration of LMWH for 35 days following TKA received a Grade 2B recommendation. 13 As stated previously, the choice of agent as well as the duration of prophylaxis is based on a risk versus benefit analysis which should be individualized for each arthroplasty patient.
和任何术后药物预防治疗方案一样，常常需要考虑治疗疗程。ACCP指南自其1998年首次推出治疗推荐以来已经对其推荐作了修改。2008年ACCP最新的推荐认为THA或TKA的患者应当接受LMWH为期7-10天的药物预防治疗（ⅠA级推荐），并可延长到THA术后35天。TKA术后注射35天则获得了2B级推荐。如前所述，药物及疗程的选择是风险和收益的分析为基础的，这对每个关节置换患者都是不同的。
FONDAPARINUX
Fondaparinux is a newer synthetic pentasaccharide that is a potent inhibitor of Factor Xa in the clotting cascade. The typical dosing is 2.5 mg/d administered subcutaneously with the first dose being given at 6 to 12 hours postoperatively. This drug is not recommended for patients that weigh less than 50 kg or those with renal insufficiency. As with LMWH, the concern associated with the use of fondaparinux is for bleeding complications in the postoperative period.20
磺达肝素
磺达肝素是一种新的合成的戊多糖，是凝血集链反应中Ⅹa因子有效的抑制因子。经典的剂量是2.5mg/d 皮下注射，术后6-12小时首次给药。对体重不足50Kg的患者或肾功能不全的患者不推荐使用这种药物。和使用LMWH一样，使用磺达肝素需要注意术后出血并发症。
The use of fondaparinux received a Grade 1A recommendation from the ACCP for use in patients undergoing primary elective TJA. Regarding duration of treatment, the most recent changes to the ACCP guidelines in 2008 support the use of the agent for 35 days after THA (Grade 1A) and after TKA (Grade 1B).13,21 There are concerns about using this drug in patients at an increased rate of bleeding as seen in the AAOS guidelines, but this is not an evidence-based recommendation.
在择期性TJA手术的患者中使用磺达肝素获得了ACCP的1A级推荐。关于疗程，2008年的ACCP指南中支持磺达肝素用至THA（1A级）和TKA（1B级）术后35天。正如AAOS指南那样，也有人想将这种药物用于出血机率增加的病人，但这并不是循证医学的推荐治疗。
WARFARIN
华法林
Warfarin is the oldest vitamin K antagonist used for chemoprophylaxis, with the longest track record of use in the postoperative period following primary hip or knee arthroplasty. The traditional nature of medicine has helped maintain warfarin as a popular agent, because it was the treatment of choice when most orthopedic surgeons trained during residency. Warfarin has demonstrated efficacy as an effective chemoprophylaxis agent against thromboembolic disease; however, it is not without its disadvantages. Immediately post administration, the patient is in a relatively hypercoagulable state due to diminished levels of protein C and protein S via actions of the drug. Each patient requires daily dosing and the blood is monitored daily for an INR level to determine the appropriate dose to administer. Warfarin is very sensitive to dietary changes and has interactions with several medications that may be concomitantly taken by a patient for other comorbid conditions (Table 3). As a result, the goal INR is difficult to achieve and maintain.
华法林是预防血栓的最古老的维生素K拮抗剂，在初次全髋或全膝置换术后的使用历史也最悠久。医学的传统本质使得华法林始终是个受欢迎的药物，因为它是绝大多数骨科医生住院医生培训时的治疗选择。华法林已经证明了它是一个有效的预防血栓栓塞的药物，但是，它也并不是没有缺点。在注射后，药物作用使得C蛋白和S蛋白水平降低，患者处于相对高凝状态。每名患者都需要每日给药，每日监测血液INR水平以确实给药的剂量。华法林对饮食改变很敏感，并且可以和几种药物相互作用，而这些药物可能是为了治疗某些伴发的疾病的（表3）。因此，目标INR很难达到并维持。
A meta-analysis of all randomized controlled clinical trials reported on the overall efficacy of warfarin as a prophylactic agent following THA. Patients treated with warfarin had the lowest rate of proximal DVT as well as symptomatic PE, with a rate of 6.3% and 0.16%, respectively. The risk of major postoperative bleeding in these patients was no higher than that in patients treated with a placebo.4
一项对所有的随机对照研究做的荟萃分析报告认为华法林作为THA术后预防性用药总体是有效的。华法林治疗的患者近端DVT和有症状的PE的发生率最低，分别为6.3%和0.16%。这些患者中术后大出血的风险并不高于安慰剂组。
The use of warfarin as an effective prophylactic agent following TKA has been thoroughly demonstrated over several decades.22–26 Additional randomized clinical trials have compared the efficacy of warfarin with that of LMWH.24,26–29 In every study, LMWH was more effective than warfarin as a prophylactic agent, but there was no significant difference in the rates of symptomatic proximal DVT or PE. The postoperative bleeding rates were typically higher in the LMWH group.24,26,29
TKA术后作用华法林预防血栓已有数十年。其他的随机对照研究已经比较了华法林与LMWH（预防血栓的作用）。每个研究都认为LMWH比华法林更有效，但在预防近端DVT或者PE方面没有显著性差异。LMWH组的术后出血率往往更高。
With regard to the goal INR, different clinical guidelines present differing recommendations. According to the ACCP clinical guideline, a goal INR of 2.0 to 3.0 received a Grade 1A recommendation. This recommendationwasmade based on randomized trials that used an INR range of 2.0 to 3.0 as the target for prophylaxis.13 For each scenario depicted by the AAOS where the use of warfarin iswarranted, the goal INR is 2.0 or less. The difference in the goal INR is based on risk versus benefit between prophylaxis against thromboembolic disease and bleeding risk.TheAAOSguidelinesconsistentlymake recommendations that are more conservative and attempt to minimize the postoperative bleeding risk and hematoma formation.
而对于目标INR，不同的临床指南有不同的推荐。ACCP指南，目标INR为2.0-3.0并受到了1A级推荐。这种推荐是基于一个INR目标值为2.0-3.0的随机试验。而AAOS的所有允许使用华法林的要求都是INR等于或小于2.0。INR目标值不同是由预防血栓栓塞性疾病和出血风险的风险与收益决定的。AAOS指南推荐的治疗总是更保守些，试图将术后出血风险和血肿形成机率降到最小。
As with the use of LMWH, the ACCP guidelines have changed their recommendations regarding the duration of warfarin use following primary hip or knee replacement. The 2008 ACCP guidelines recommend up to 35 days of warfarin use (goal INR 2.0–3.0) with a Grade 1B recommendation for THA and a Grade 1C recommendation for TKA patients. The AAOS recommendation, for patients of standard risk for PE and bleeding, is 2 to 6 weeks of treatment with low-dose warfarin (goal INR %2.0). Even in patients with an elevated PE and bleeding risk, low-dose warfarin is recommended for 2 to 6 weeks.
正如LMWH的使用一样，ACCP指南已经修改了初次髋关节或膝关节置换术后华法林的使用疗程。2008年ACCP指南推荐华法林最多可用至术后中35天（目标INR2.0-3.0）,在THA和TKA分别获得了1B级和1C级推荐。对于PE和出血风险标准的患者，AAOS推荐使用低剂量的华法林治疗2至6周（目标INR≤2.0）。即使是在PE和出血风险升高的患者，仍然推荐使用低剂量的华法林治疗2至6周。
ASPIRIN
阿斯匹林
Acetylsalicylic acid (aspirin) has gained in popularity as an agent for DVT prophylaxis following total joint replacement because it is safe, inexpensive, does not require monitoring, is easy to administer, and lends itself to high patient compliance. The recommended dosing in the postoperative period is 325 mg twice daily for the duration of treatment.18 The use of aspirin is based on the premise that chemoprophylaxis should be administered to reduce the risk of PE and subsequent death, not DVT; inherent to this argument is that DVT should not be used as a surrogate for PE because all patients with a DVT do not inevitably get a PE.
乙酰基水杨酸（阿斯匹林）安全，不贵，不需监测，给药容易，因此成为全关节置换术后预防DVT的常用药，也因此导致了许多并发症。推荐的术后剂量为治疗期间325mg bid。使用阿斯匹林是有一个前提，即预防用药可减少PE及由此导致的死亡，而不是减少DVT。此种观点还认为DVT也不应当成为PE的同义词，因为DVT的患者并一定最终发展成PE。
Aspirin does not interfere with anesthetic administration because it does not increase the risk of neuraxial bleeding. The use of an epidural catheter for pain control requires that postoperative chemoprophylaxis be timed appropriately to minimize the risk of epidural hematoma formation.30 Aspirin functions by way of inhibiting platelet aggregation, and if given immediately preoperatively, can function in this manner intraoperatively and in the immediate postoperative period; other chemoprophylaxis agents exhibit a postoperative delay before the onset of the desired prophylaxis effect. The major benefit associated with aspirin use is its low prevalence of wound-healing problems, hematoma formation, and other serious bleeding complications that are readily associated with more potent anticoagulant agents.31
阿斯匹林不影响麻醉药品使用，因为它不增加轴索出血风险。硬膜外置管镇痛要求在术后恰当的时间给药，从而使硬膜外血肿形成的风险降到最小。阿斯匹林通过抑制血小板聚集发挥作用，如果术前立即给药，术后和术后即能发挥这种作用。其他的药物在达到所需的预防效果之前有术后延迟。使用阿斯匹林的一大好处是伤口愈合问题、血肿形成和其他严重的出血性并发症少，这些常与一些更强的抗凝药物有关。
In the arena of TKA, aspirin has been equally as effective as other anticoagulant agents when fatal PEis used as an end point.32 Lotke and colleagues33 reported on 2800 consecutive primary TKAs in patients treated with aspirin and mechanical prophylaxis, demonstrating a low rate of bleeding complication and a fatal PE risk of 0.1%. However, aspirin is not as effective in decreasing the risk of symptomatic DVT in the setting of THA. The Pulmonary Embolism Prevention trial was a randomized clinical trial designed to evaluate the efficacy of aspirin in preventing symptomatic VTE disease following THA. More than 4000 patients were randomized to receive aspirin (n 5 2047) or a placebo (n 5 2041) for 35 days following surgery. There was no statistical difference in the rate of symptomatic DVT between the 2 groups (P>.5).
在TKA领域，当把致死性PE作为终点时，阿斯匹林与其他抗凝药物同样有效。Lotke等报告了2800连续的以阿斯匹林和机械预防治疗的初次TKA病例，结果显示出血性并发症发生率低，致死性PE风险为0.1%.然而，阿斯匹林在THA病人中并不能有效减少有症状的DVT风险。肺栓塞预防试验是一个用来评估阿斯匹林在预防THA术后有症状的VTE疾病方面有效性的随机试验。超过4000名患者术后随机接受阿斯匹林（n=2047）或安慰剂（n=2041）治疗35天。2组间有症状的DVT没有显著性差异（P＞0.5）。
In general, venous thromboembolic events following primary hip and knee arthroplasty has decreased significantly over the past decade, mainly due to a multidisciplinary approach. Rapid postoperative mobilization, optimization of surgical technique, and improved perioperative pain management, including the use of regional anesthesia, have all contributed to decreasing the DVT risk. The ACCP guidelines do not support the use of aspirin for prophylaxis following TJA, because this drug has not been extensively evaluated in multicenter randomized trials. The AAOS guidelines support the use of aspirin for 6 weeks except in patients that are at high risk for PE and have standard bleeding complication risk; these patients are not candidates for aspirin use because of the identified preoperative elevated risk for PE.
总体而言，初次髋和膝关节置换术后静脉血栓栓塞事件在过去10年间已经显著减少，这主要是多学科共同作用的结果。术后早期活动，优化手术技术，改善围手术期疼痛控制，包括使用区域阻滞麻醉，都对降低DVT风险起到了作用。ACCP指南不支持在TJA术后使用阿斯匹林预防血栓性疾病，因为该药还没有在多中心随机试验中得到进一步评估。AAOS指南支持使用6周阿斯匹林，除非患者的PE风险升高，而出血并发症风险是标准的;由于证实了术前PE风险升高，这些患者不适宜使用阿斯匹林。
Because the selection of a prophylaxis agent is a balance between safety and efficacy, aspirin combined with mechanical devices is an attractive regimen for some orthopedic surgeons for their routine TJA patients. Although aspirin is less potent than other chemoprophylactic agents, it is also associated with less bleeding. Aspirin needs to be evaluated in large randomized trials that assess symptomatic events to determine its true efficacy.
由于选择预防用药需在安全性与有效性之间找到平衡，在常规TJA患者中将阿斯匹林和机械装置联合使用对于一些骨科医生来说是一个具有吸引力的方案。虽然阿斯匹林比其他的药物要弱一些，但它引起的出血也少。还需要大的随机试验来评估阿斯匹林的有症状事件以确定其真正的有效性。
MECHANICAL PROPHYLAXIS (PNEUMATIC COMPRESSION BOOTS AND INTERMITTENT PLANTAR COMPRESSION DEVICES)
物理防预防（气动加压靴和间歇性足底加压泵）
The use of mechanical prophylaxis is predicated on the premise that decreasing lower extremity venous stasis in conjunction with increasing venous blood flow will decrease the likelihood of clot formation.34,35 Pneumatic compression boots affect local fibrinolysis, but do not affect systemic fibrinolytic activity.36 Intermittent plantar compression devices were designed to replicate the hemodynamic effects of normal walking by rapid emptying of the plantar arch during the compression phase of the device.12 The advantages of mechanical prophylaxis are evident and include an absence of monitoring and no risk of bleeding. In addition, intermittent plantar compression devices are thought to be less cumbersome than pneumatic boots, which extend the length of the entire lower leg. However, the major disadvantages are that prophylaxis ceases on patient discharge from the hospital, and patient compliance is critical to either device being effective.
物理预防的原理是可以减少下肢静脉淤滞，促进静脉回流，从而减少血栓形成。气动加压靴对局部纤溶有影响，但不影响全身的纤溶。间歇性足底加压泵按摩时可以模仿正常步行时的血流动力学效果。物理预防的优点是显而易见的，包括不需监测，无出血风险，另外，间歇性足底加压泵比气动靴小巧，气动靴可包括整个下肢。而它主要的缺点是患者出院后就无法继续治疗，而且患者的依从性会影响治疗效果。
Several randomized clinical trials have demonstrated that pneumatic compression boots can limit distal thrombus formation.23,37–41 As a result, there has been concern regarding the efficacy of mechanical compression in reducing the rates of proximal clot formation in the setting of THA. Small randomized trials have compared pneumatic compression boots and warfarin in patients undergoing THA and have demonstrated that mechanical prophylaxis is less effective than chemoprophylaxis in the prevention of proximal clot formation.39–41 Regarding intermittent plantar compression devices, low-powered studies have shown a decrease in overall thrombosis rates following THA.42–44 However, given the risk of PE from a proximal clot source, further investigation is required before mechanical prophylaxis can be recommended as a sole means of prophylaxis in patients undergoing THA.
几个随机试验显示气动加压靴可以减少远端血栓形成。因此，有人考虑物理预防能否减少THA患者近端血栓的形成。有人做了几个小型随机试验在THA患者中比较气动加压靴和华法林的作用，结果显示在预防近端血栓形成方面，物理预防不如药物预防更有效。一些低级别的研究显示间歇性足底加压泵能降低THA术后总体血栓率。但是，考虑到由近端血栓形成PE的风险，还需进一步研究以确定 物理预防能否作为THA患者唯一的预防血栓的方法。
The use of mechanical prophylaxis in the setting of TKA, both pneumatic compression and intermittent plantar compression, has been studied in several small studies.19,23,44–49 Although these studies were low powered, a significant reduction in thrombus formation following TKA was demonstrated. On basis of these reports, both pneumatic compression and intermittent plantar compression devices are effective in reducing clot formation following primary TKA. However, larger, multicenter randomized trials comparing mechanical and chemoprophylaxis regimens are necessary to determine the true efficacy of these devices.
已有几个关于气动加压靴和间歇性足底加压泵等物理预防方法在TKA患者中应用的小型研究。虽然这些研究级别比较低，但结果显示TKA术后血栓形成明显减少。根据这些研究报告，气动加压靴和间歇性足底加压泵能有效减少TKA术后血栓的形成。然而，还需做更大型的多中心随机试验来比较物理预防与药物预防的效果，从而确定这些物理预防方法真正的效果。
AUTHORS’ COMMENTARY ON CURRENT GUIDELINES
作者对目前指南的评价
The basic difference between the ACCP and the AAOS guidelines is that the chest physicians believe that asymptomatic clots are clinically relevant. Therefore, the ACCP guidelines were developed from the data obtained from randomized trials, which used venogram data as a surrogate outcome measure. In contrast, the AAOS guidelines reflect the concerns of orthopedic surgeons with a focus on symptomatic clots, PE, and bleeding risk. Furthermore, the AAOS guidelines highlight the importance of developing prophylaxis regimens for each individual patient based on PE and bleeding risk. This is an important concept, which moves us toward risk stratification. Unfortunately, it is difficult to risk stratify most patients based on available data but it is a goal to strive for in the future.
ACCP与AAOS指南根本不同是胸科医生认为无症状的血栓临床上更重要。因此ACCP指南是从随机试验的数据发展而来的，在这些随机试验中使用静脉造影发现静脉血栓。而AAOS则反映了骨科医生对有症状的血栓，PE和出血风险的关注。而且，AAOS指南强调根据PE和出血风险制定出个性化的预防方案。这是一个重要的概念，要求我们进行风险分层。不幸的是，根据掌握的绝大多数患者的数据，风险分层都有困难，但这是我们将来努力的目标。Surgeons need to be aware that the SCIP guidelines recommend LMWH, fondaparinux, and/or warfarin for THA and TKA patients. Pneumatic compression devices are also acceptable for patients undergoing TKA procedures. Therefore, aspirin and pneumatic compression devices are acceptable for TKA patients. A surgeon may choose to use another regimen because of concerns about bleeding, but this must be documented in the medical record.
外科医生应该知道SCIP指南推荐在THA和TKA患者中使用LMWH，磺达肝素，和/或华法林。气动加压靴也可用于TKA患者。因此，阿斯匹林和气动加压靴可用于TKA患者。医生可能会因为考虑到出血而选用其他治疗方案，但这一定要记录在病历中。
全关节置换中的深静脉血栓预防
KEYWORDS _ Prophylaxis _ Deep venous thrombosis _ Venous thromboembolism _ Total joint arthroplasty
关键词：预防 深静脉血栓 深静脉血栓栓塞 全关节置换
Deep venous thrombosis (DVT) is the end result of a complex interaction of events including the activation of the clotting cascade in conjunction with platelet aggregation. It has been clearly demonstrated that patients undergoing major lower extremity orthopedic surgery, especially total joint arthroplasty (TJA), are at high risk for developing a postoperative DVT or a subsequent pulmonary embolus (PE). In the arena of TJA, orthopedic surgeons are particularly concerned with proximal DVT and symptomatic or fatal PE.
深静脉血栓是包括凝血级链反应激活和血小板聚集在内的一系列繁杂事件的最终结果。骨科下肢大手术患者，特别是全关节置换（TJA），出现术后DVT或者由此产生的肺栓塞（PE）的风险较高。在TJA领域，骨科医生特别关心近端DVT和有症状的或者致死性DVT。Patients undergoing primary total hip arthroplasty (THA) or total knee arthroplasty (TKA) have exhibited rates of symptomatic PE as high as 20% and 8%, respectively when no prophylaxis has been administered.1 As a result, the use of venous thromboembolic (DVT and PE) prophylaxis, most commonly pharmacologic prophylaxis, has become the standard of care for patients undergoing elective TJA. The risk of fatal PE following primary hip or knee replacement has been consistently reported to be between 0.1% and 0.2%, regardless of the chemoprophylactic agent employed for prophylaxis.2–9
进行初次全髋置换（THA）或者全膝置换（TKA）的患者在不采取预防措施时有症状的PE发生率分别为20%和8%。结果，使用预防DVT的措施已经成为择期TJA患者的标准治疗模式，而最常用的就是药物预防。据目前报道，初次全髋或全膝置换术后，无论使用何种药物预防，致死性PE在0.1%-0.2%之间。
Based on the necessity of postoperative venous thromboembolic (VTE) prophylaxis following TJA, the National Quality Forum endorsed a voluntary consensus standard for inpatient hospital care in the earlier part of this decade. The surgical care improvement project (SCIP) guidelines, a result of the consensus, require documentation of initiation of DVT prophylaxis in the time period extending from 24 hours before surgery to 24 hours following surgery.10 The rationale for the SCIP guidelines stemmed from the government’s emphasis on pay-for-performance (P4P) whereby physicians receive increased compensation as a function of meeting certain ‘‘standards of care.’’11
由于TJA术后预防静脉血栓栓塞（VTE）的必要性，在本世纪第一个10年的初期，国家质量论坛（NQF）支持在住院病人医院内治疗标准方面达成共识。外科治疗改善工程（SCIP）指南作为该共识的结果，要求在术前24小时至术后24小时内，记录预防DVT开始的时间。推出SCIP指南是因为政府强调 “根据表现付费”（P4P），根据此政策，医生只要符合这些“治疗标准”即可获得更多的补偿。
Despite several years of evaluating this question, the best prophylaxis for thromboembolic disease remains controversial.12 The use of pharmacologic prophylaxis has been adopted as the standard of care for treatment of these patients by many orthopedic surgeons at most centers across North America.13 However, the controversy between the efficacy of VTE prophylaxis and the increased risk for bleeding in the postoperative period continues to exist. In recent years, this debate has brought about the development of clinical guidelines to improve patient care, address key questions, define evidence-based recommendations, and promote future research. Clinical guidelines are not meant to represent a predefined protocol or absolute rules for treatment, and should never substitute for clinical judgment.
尽管评估此问题已有数年，预防栓塞性疾病的最好方法仍有争议。药物预防已成为北美绝大多数中心骨科医生治疗的标准方法。然而，关于VTE预防的效果及增加术后出血风险之间的争论仍然存在。近年来，这种争论导致了临床指南的推出，指南提高了治疗，解决了关键问题，规定了循证医学推荐的治疗方法，并且促进了更进一步的研究。临床指南并不意味着是治疗的绝对标准而永远不需根据临床情况调整。
Dependent on the clinical guideline followed, from the American College of Chest Physicians (ACCP) or the American Academy of Orthopaedic Surgeons (AAOS), there are several recommended regimens available for treatment. Included in the options are low molecular weight heparins (LMWHs), synthetic pentasaccharides, adjusted-dose warfarin, aspirin, and mechanical prophylaxis. Several studies have evaluated the various modalities for DVT prophylaxis, and comparison studies have stratified the risks and benefits for each option.
根据临床指南，美国胸科医生协会（ACCP）或美国骨科医生协会（AAOS）都有几种推荐治疗方案。包括低分子肝素（LMWHs）,合成的戊多糖，调整剂量的华法林，阿斯匹林以及物理预防措施。已经有研究对各种不同DVT预防方案作了评估，并有对比研究将每种方法的收益与风险作了分层分析。
The following review addresses the controversy underlying VTE prophylaxis by outlining 2 guidelines and demonstrating the pros and cons of different DVT prophylaxis regimens based on the available evidence-based literature.
下文通过概述2个指南重点说明在预防VTE方面所存在的争论，并根据目前可以得到的循证医学文献说明不同预防DVT方案的利弊。
AMERICAN COLLEGE OF CHEST PHYSICIANS GUIDELINES
美国胸科医生协会指南
The ACCP was founded in 1935, and the first set of guidelines for venous thromboembolic prophylaxis (VTE) was published in 1986. The goal of these guidelines is to focus on the prevention of the overall rate of VTE. These guidelines are based on a review of prospective, randomized studies only. The guidelines have subsequently gone through several iterations with the most recent update in 2008.13 Inherent to these guidelines is that all primary THA and TKA patients are considered ‘‘high risk’’ regardless of patient age, activity level, and comorbidities.
ACCP成立于1935年，第一版预防VTE指南发表于1986年。这些指南的目的是强调预防VTE。这些指南仅仅是根据前瞻性，随机研究的文献回顾作出的。此指南随后已经更新了数次，最近一次更新是2008年。这些指南里不管患者的年龄、活动水平和伴发疾病，始终将所有的THA和TKA患者作为高危人群。
These guidelines have become commonplace in the evaluation of health care systems on behalf of hospitals, insurance companies, and attorneys. The recommendations were classified as Grade I (strong recommendation, with benefits outweighing risk, burden, and cost) or Grade II (recommendation with less certainty). Each class of recommendation was further substratified: (A) randomized controlled trials with consistent results and a low level of bias, (B) randomized controlled trials with inconsistent results or a major methodological design flaw, and (C) observational studies.13 The use of LMWH, fondaparinux (pentasaccharide), and warfarin (with an adjusted international normalized ratio [INR] between 2.0 and 3.0) all received a Grade IA recommendation for preventative treatment of total hip and knee arthroplasty; aspirin or low-dose unfractionated heparin received a Grade IA rating against their use for prophylaxis in patients following TJA. The use of intermittent pneumatic compression devices received a Grade IB rating for prevention in patients undergoing TKA.
这些指南在健康保健系统的评估中已非常普通。推荐分为Ⅰ级（强烈推荐，好处大于风险、负担和代价）或Ⅱ级（谨慎推荐）。每一级都进一步分层：（A）结果一致，偏倚水平低的随机对照研究（B）结果不一致，设计方法有缺陷的随机对照研究和（C）观察研究。LMWH，磺达肝素（戊多糖）和华法林（调整的INR在2.0和3.0之间）都获得了ⅠA级推荐，用于THA和TKA患者中预防性治疗；阿斯匹林或小剂量未分馏肝素获得了ⅠA级评级，不可用于TJA术后预防血栓。间断充气加压装置获得了ⅠB级评级，可用于TKA患者（DVT）的预防。
These guidelines also address the duration of prophylaxis. During the first iteration, the ACCP guidelines from 1998 and 2001 recommended 7 to 10 days of prophylaxis that coincided with the length of hospital stay (Grade IA recommendation). 14 In 2004, the guidelines were revised to recommend out of hospital prophylaxis for 28 to 35 days (Grade IA) but excluded patients undergoing TKA.15 With additional revisions, the 2008 guidelines currently recommend duration of prophylaxis with LMWH, fondaparinux, and warfarin for up to 10 days following THA and TKA (Grade IA), and up to 35 days following THA (Grade IA) or TKA (Grade IIB).13
这些指南也强调预防的疗程。在第一次更新中， 1998年的ACCP指南和2001年的指南推荐7－10天的预防治疗，巧合的是这与住院时间相等（ⅠA级推荐）。2004年，指南修改为推荐院外预防28-35天（ⅠA级），但TKA病人除外。2008年指南又作了修改，推荐LMWH，磺达肝素和华法林预防疗，THA和TKA 术后可用至10天（ⅠA级），THA或TKA术后可用至35天（ⅡB级）。
As with any guidelines being used to guide physicians in medical decision making, the risk versus benefit must be assessed. Implementation of the current ACCP guidelines has been associated with certain disadvantages, as reported in the orthopedic literature. Burnett and colleagues16 reported a 4.7% readmission rate, 3.4% irrigation and debridement rate, and 5.1% rate of prolonged hospitalization following 10 days of LMWH after TJA. Parvizi and colleagues17 have shown that patients with a wound hematoma or persistent wound drainage are at higher risk for a postoperative deep joint infection. As a direct consequence of the concerns for postoperative bleeding risk and potential for infection, orthopedic surgeons may prefer a more risk-averse method by which to prevent thromboembolic phenomena following TJA, especially because the rate of PE is similar regardless of the chemoprophylaxis agent used.
和任何用于指导医生作决定的指南一样，必须评估风险与收益。目前的ACCP指南在实施中也有一些缺陷，这在骨科文献中已有报道。Burnett等报道再入院率4.7%，冲洗和清创率为3.4%，TJA术后LMWH治疗10天后延长住院时间率为5.1%.Parvizi等人认为有伤口血肿或持续伤口引流的患者是术后关节深部感染的高危人群。出于对术后出血和潜在感染风险的担心，骨科医生可能更喜欢在TJA术后使用风险更小的方法以预防血栓栓塞性肺炎，特别是无论使用何种药物预防时PE的发病率都相似。
AMERICAN ACADEMY OF ORTHOPEDIC SURGEONS GUIDELINES
美国骨科医生协会
A work group from the AAOSin conjunction with the Center for Clinical Evidence Synthesis (Tufts New England Medical Center) proposed a new set of guidelines for the prevention of symptomatic and fatal PE in patients undergoing elective TJA. The AAOS guidelines are a synthesis of an expert consensus as well as an analysis of 42 articles published since 1996, and focus on the prevention of symptomatic PE. The clinical outcomes of choice for evaluation included symptomatic and fatal PE, death, and major bleeding episodes following TJA.18 Consensus recommendations included the use of regional anesthesia, mechanical prophylaxis for all patients, rapid postoperative mobilization, and adequate patient education. Each patient required a preoperative evaluation for a determination of ‘‘standard’’ and ‘‘high’’ risk potential. The choice of a specific chemoprophylaxis agent was based on the individual risk-benefit profile for PE and bleeding complication.
AAOS的一个工作组与临床证据汇总中心（Tufts新英格兰医疗中心）联合推出一套新的预防择期TJA患者有症状的和致死性PE的指南。AAOS指南分析了1996年以来的42篇文章，是专家共识的汇总，重点是预防致死性PE。选择作为临床结果评估的内容包括有症状的和致死性的PE，死亡以及TJA术后大出血。共识推荐包括使用区域阻滞麻醉，所有患者使用物理预防，术后早期活动和对患者进行适当的教育。每个患者要求术前评估以确定是属于“标准”风险还是“高”风险。根据个人PE和出血并发症的风险－收益关系选择某种具体的药物。
Each recommendation was graded using the following system: (A) good evidence (level I studies with consistent findings) for recommending intervention, (B) fair evidence (level II or III studies with consistent findings) for recommending intervention, and (C) poor-quality evidence (level IV or V) for recommending intervention18 (Table 1). Of the total number of recommendations from this set of guidelines, only 4 of them were derived from a systematic review of the literature. Additional general consensus recommendations are listed in Table 2.18
每种推荐都是按以下体系分级：（A）支持推荐的证据确凿（结果一致的Ⅰ级研究），（B）支持推荐的证据较多（结果一致的Ⅱ级或Ⅲ级研究）（C）支持推荐证据不足（Ⅳ级或Ⅴ级研究）（表1）。在这个指南的所有推荐中，只有4项是源于文献的系统性回顾。其他的共识推荐见表2。
For patients at standard risk for both PE and major bleeding complications, the recommendation is as follows: aspirin, LMWH, pentasaccharide, or warfarin (INR goal of ≤2.0). This recommendation is based on level III evidence and was given a grade of B or C..
对于PE和大出血并发症风险标准的患者，推荐如下：阿斯匹林，LMWH，戊多糖或者华法林（INR≤2.0）。这种推荐是基于Ⅲ级证据，评级为B或C。
For patients at elevated risk for PE and standard risk for major bleeding complications, the recommendation is as follows: LMWH, pentasaccharide, or warfarin (INR goal of %2.0). This recommendation is based on level III evidence and was given a grade of B or C.
对于PE风险升高而大出血风险标准的患者，推荐如下：LMWH，戊多糖或者华法林（INR≤2.0）。这是基于Ⅲ级证据，评级为B或C。
For patients with standard risk of PE and elevated risk of major bleeding complications, the recommendation is as follows: aspirin, warfarin (INR goal of %2.0), or none. This recommendation is based on level III evidence and was given a grade of C.
对于PE风险标准而大出血风险升高的患者，推荐如下：阿斯匹林，华法林（INR≤2.0），或者什么都不用。这是基于Ⅲ级证据，评级C。
For patients with elevated risk of both PE and major bleeding complications, the recommendation is as follows: aspirin, warfarin (INR goal of %2.0), or none. This recommendation is based on level III evidence and was given a grade of C.
对于PE和大出血风险都升高的患者，推荐如下：阿斯匹林，华法林（INR≤2.0），或者什么都不用。这是基于Ⅲ级证据，评级C。
The most important concept that is fundamental to the AAOS guidelines for thromboembolic prophylaxis is that the risk versus benefit for each individual patient must be assessed in the preoperative period. The general recommendations presented in Table 2 are a result of the work group’s consensus, and address a majority of the perioperative issues with prophylaxis. For patients with elevated risks for PE, major bleeding complication, or both, these guidelines provide an effective manner by which to treat these patients in the postoperative period following TJA. However, a weakness inherent to the AAOS guidelines is the inability to accurately assess the preoperative risk for DVT/PE. In reality, based on the nature of TJA, arthroplasty patients may not truly be considered low risk. In addition, there are studies to demonstrate rates of VTE as high as 72% following the administration of aspirin,19 thus raising the question of whether the use of aspirin is adequate as a thromboprophylaxis agent.
AAOS血栓栓塞预防指南最重要的概念是在每一个患者术前必须评估风险和收益。表2中的总体推荐是工作组达成的共识，提到了围手术期预防血栓的绝大多数问题。对于PE风险升高，大出血并发症风险升高或者两者都升高的患者，这些推荐提供了TJA术后有效的治疗方法。然而，AAOS指南的不足是无法准确评估术前DVT/PE的风险。实际工作中，由于TJA的性质，可能不会真正认为关节置换患者是低风险的。另外，有研究表明使用阿斯匹林后VTE率高达72%,因而就引起一个疑问，使用阿斯匹林作为一种血栓预防药是否恰当。LOW MOLECULAR WEIGHT HEPARINS
低分子肝素
The use of LMWH has gained enthusiasm within the orthopedic community due to its well-documented bioavailability and the absence of monitoring for clotting indices (ie, INR). The efficacy of LMWH is well documented. In multiple randomized trials, including THA and TKA patients, LMWH has been more effective than warfarin in limiting overall DVT rates. However, LMWH is associated with higher bleeding rates. Because the selection of a prophylaxis agent is a balance between efficacy and safety, some surgeons choose other modes of prophylaxis due to concerns related to bleeding and its impact on overall outcomes. An additional consideration with any medication choice is the cost; the cost of LMWH remains relatively high as compared with aspirin and warfarin.
LMWH由于良好的生物利用度和不需要监测凝血指数（如INR）而在骨科医生中大受欢迎。LMWH的效果文献已有明确报道。包括THA和TKA患者的多中心随机试验显示LMWH比华法林能更有效地减少总体DVT发生率。然而，LMWH的出血率较高。因为选择预防血栓药物要求在安全性和有效性之间找到平衡，考虑到出血及出血对整个治疗疗效的影响，有些医生选用其他预防血栓的方法。另一个选用任何一种药物都要考虑的问题是花费;LMWH治疗的花费与阿斯匹林和华法林相比仍然比较高昂。
As with any postoperative chemoprophylaxis regimen, duration of treatment is always of concern. The ACCP guidelines have changed their recommendations since the initial guidelines introduced in 1998. The most recent recommendation from the ACCP in 2008 states that patients undergoing THA or TKA should receive chemoprophylaxis withLMWHfor 7 to 10 days (Grade IA recommendation), and this may be extended to up to 35 days following THA. Administration of LMWH for 35 days following TKA received a Grade 2B recommendation. 13 As stated previously, the choice of agent as well as the duration of prophylaxis is based on a risk versus benefit analysis which should be individualized for each arthroplasty patient.
和任何术后药物预防治疗方案一样，常常需要考虑治疗疗程。ACCP指南自其1998年首次推出治疗推荐以来已经对其推荐作了修改。2008年ACCP最新的推荐认为THA或TKA的患者应当接受LMWH为期7-10天的药物预防治疗（ⅠA级推荐），并可延长到THA术后35天。TKA术后注射35天则获得了2B级推荐。如前所述，药物及疗程的选择是风险和收益的分析为基础的，这对每个关节置换患者都是不同的。
FONDAPARINUX
Fondaparinux is a newer synthetic pentasaccharide that is a potent inhibitor of Factor Xa in the clotting cascade. The typical dosing is 2.5 mg/d administered subcutaneously with the first dose being given at 6 to 12 hours postoperatively. This drug is not recommended for patients that weigh less than 50 kg or those with renal insufficiency. As with LMWH, the concern associated with the use of fondaparinux is for bleeding complications in the postoperative period.20
磺达肝素
磺达肝素是一种新的合成的戊多糖，是凝血集链反应中Ⅹa因子有效的抑制因子。经典的剂量是2.5mg/d 皮下注射，术后6-12小时首次给药。对体重不足50Kg的患者或肾功能不全的患者不推荐使用这种药物。和使用LMWH一样，使用磺达肝素需要注意术后出血并发症。
The use of fondaparinux received a Grade 1A recommendation from the ACCP for use in patients undergoing primary elective TJA. Regarding duration of treatment, the most recent changes to the ACCP guidelines in 2008 support the use of the agent for 35 days after THA (Grade 1A) and after TKA (Grade 1B).13,21 There are concerns about using this drug in patients at an increased rate of bleeding as seen in the AAOS guidelines, but this is not an evidence-based recommendation.
在择期性TJA手术的患者中使用磺达肝素获得了ACCP的1A级推荐。关于疗程，2008年的ACCP指南中支持磺达肝素用至THA（1A级）和TKA（1B级）术后35天。正如AAOS指南那样，也有人想将这种药物用于出血机率增加的病人，但这并不是循证医学的推荐治疗。
WARFARIN
华法林
Warfarin is the oldest vitamin K antagonist used for chemoprophylaxis, with the longest track record of use in the postoperative period following primary hip or knee arthroplasty. The traditional nature of medicine has helped maintain warfarin as a popular agent, because it was the treatment of choice when most orthopedic surgeons trained during residency. Warfarin has demonstrated efficacy as an effective chemoprophylaxis agent against thromboembolic disease; however, it is not without its disadvantages. Immediately post administration, the patient is in a relatively hypercoagulable state due to diminished levels of protein C and protein S via actions of the drug. Each patient requires daily dosing and the blood is monitored daily for an INR level to determine the appropriate dose to administer. Warfarin is very sensitive to dietary changes and has interactions with several medications that may be concomitantly taken by a patient for other comorbid conditions (Table 3). As a result, the goal INR is difficult to achieve and maintain.
华法林是预防血栓的最古老的维生素K拮抗剂，在初次全髋或全膝置换术后的使用历史也最悠久。医学的传统本质使得华法林始终是个受欢迎的药物，因为它是绝大多数骨科医生住院医生培训时的治疗选择。华法林已经证明了它是一个有效的预防血栓栓塞的药物，但是，它也并不是没有缺点。在注射后，药物作用使得C蛋白和S蛋白水平降低，患者处于相对高凝状态。每名患者都需要每日给药，每日监测血液INR水平以确实给药的剂量。华法林对饮食改变很敏感，并且可以和几种药物相互作用，而这些药物可能是为了治疗某些伴发的疾病的（表3）。因此，目标INR很难达到并维持。
A meta-analysis of all randomized controlled clinical trials reported on the overall efficacy of warfarin as a prophylactic agent following THA. Patients treated with warfarin had the lowest rate of proximal DVT as well as symptomatic PE, with a rate of 6.3% and 0.16%, respectively. The risk of major postoperative bleeding in these patients was no higher than that in patients treated with a placebo.4
一项对所有的随机对照研究做的荟萃分析报告认为华法林作为THA术后预防性用药总体是有效的。华法林治疗的患者近端DVT和有症状的PE的发生率最低，分别为6.3%和0.16%。这些患者中术后大出血的风险并不高于安慰剂组。
The use of warfarin as an effective prophylactic agent following TKA has been thoroughly demonstrated over several decades.22–26 Additional randomized clinical trials have compared the efficacy of warfarin with that of LMWH.24,26–29 In every study, LMWH was more effective than warfarin as a prophylactic agent, but there was no significant difference in the rates of symptomatic proximal DVT or PE. The postoperative bleeding rates were typically higher in the LMWH group.24,26,29
TKA术后作用华法林预防血栓已有数十年。其他的随机对照研究已经比较了华法林与LMWH（预防血栓的作用）。每个研究都认为LMWH比华法林更有效，但在预防近端DVT或者PE方面没有显著性差异。LMWH组的术后出血率往往更高。
With regard to the goal INR, different clinical guidelines present differing recommendations. According to the ACCP clinical guideline, a goal INR of 2.0 to 3.0 received a Grade 1A recommendation. This recommendationwasmade based on randomized trials that used an INR range of 2.0 to 3.0 as the target for prophylaxis.13 For each scenario depicted by the AAOS where the use of warfarin iswarranted, the goal INR is 2.0 or less. The difference in the goal INR is based on risk versus benefit between prophylaxis against thromboembolic disease and bleeding risk.TheAAOSguidelinesconsistentlymake recommendations that are more conservative and attempt to minimize the postoperative bleeding risk and hematoma formation.
而对于目标INR，不同的临床指南有不同的推荐。ACCP指南，目标INR为2.0-3.0并受到了1A级推荐。这种推荐是基于一个INR目标值为2.0-3.0的随机试验。而AAOS的所有允许使用华法林的要求都是INR等于或小于2.0。INR目标值不同是由预防血栓栓塞性疾病和出血风险的风险与收益决定的。AAOS指南推荐的治疗总是更保守些，试图将术后出血风险和血肿形成机率降到最小。
As with the use of LMWH, the ACCP guidelines have changed their recommendations regarding the duration of warfarin use following primary hip or knee replacement. The 2008 ACCP guidelines recommend up to 35 days of warfarin use (goal INR 2.0–3.0) with a Grade 1B recommendation for THA and a Grade 1C recommendation for TKA patients. The AAOS recommendation, for patients of standard risk for PE and bleeding, is 2 to 6 weeks of treatment with low-dose warfarin (goal INR %2.0). Even in patients with an elevated PE and bleeding risk, low-dose warfarin is recommended for 2 to 6 weeks.
正如LMWH的使用一样，ACCP指南已经修改了初次髋关节或膝关节置换术后华法林的使用疗程。2008年ACCP指南推荐华法林最多可用至术后中35天（目标INR2.0-3.0）,在THA和TKA分别获得了1B级和1C级推荐。对于PE和出血风险标准的患者，AAOS推荐使用低剂量的华法林治疗2至6周（目标INR≤2.0）。即使是在PE和出血风险升高的患者，仍然推荐使用低剂量的华法林治疗2至6周。
ASPIRIN
阿斯匹林
Acetylsalicylic acid (aspirin) has gained in popularity as an agent for DVT prophylaxis following total joint replacement because it is safe, inexpensive, does not require monitoring, is easy to administer, and lends itself to high patient compliance. The recommended dosing in the postoperative period is 325 mg twice daily for the duration of treatment.18 The use of aspirin is based on the premise that chemoprophylaxis should be administered to reduce the risk of PE and subsequent death, not DVT; inherent to this argument is that DVT should not be used as a surrogate for PE because all patients with a DVT do not inevitably get a PE.
乙酰基水杨酸（阿斯匹林）安全，不贵，不需监测，给药容易，因此成为全关节置换术后预防DVT的常用药，也因此导致了许多并发症。推荐的术后剂量为治疗期间325mg bid。使用阿斯匹林是有一个前提，即预防用药可减少PE及由此导致的死亡，而不是减少DVT。此种观点还认为DVT也不应当成为PE的同义词，因为DVT的患者并一定最终发展成PE。
Aspirin does not interfere with anesthetic administration because it does not increase the risk of neuraxial bleeding. The use of an epidural catheter for pain control requires that postoperative chemoprophylaxis be timed appropriately to minimize the risk of epidural hematoma formation.30 Aspirin functions by way of inhibiting platelet aggregation, and if given immediately preoperatively, can function in this manner intraoperatively and in the immediate postoperative period; other chemoprophylaxis agents exhibit a postoperative delay before the onset of the desired prophylaxis effect. The major benefit associated with aspirin use is its low prevalence of wound-healing problems, hematoma formation, and other serious bleeding complications that are readily associated with more potent anticoagulant agents.31
阿斯匹林不影响麻醉药品使用，因为它不增加轴索出血风险。硬膜外置管镇痛要求在术后恰当的时间给药，从而使硬膜外血肿形成的风险降到最小。阿斯匹林通过抑制血小板聚集发挥作用，如果术前立即给药，术后和术后即能发挥这种作用。其他的药物在达到所需的预防效果之前有术后延迟。使用阿斯匹林的一大好处是伤口愈合问题、血肿形成和其他严重的出血性并发症少，这些常与一些更强的抗凝药物有关。
In the arena of TKA, aspirin has been equally as effective as other anticoagulant agents when fatal PEis used as an end point.32 Lotke and colleagues33 reported on 2800 consecutive primary TKAs in patients treated with aspirin and mechanical prophylaxis, demonstrating a low rate of bleeding complication and a fatal PE risk of 0.1%. However, aspirin is not as effective in decreasing the risk of symptomatic DVT in the setting of THA. The Pulmonary Embolism Prevention trial was a randomized clinical trial designed to evaluate the efficacy of aspirin in preventing symptomatic VTE disease following THA. More than 4000 patients were randomized to receive aspirin (n 5 2047) or a placebo (n 5 2041) for 35 days following surgery. There was no statistical difference in the rate of symptomatic DVT between the 2 groups (P>.5).
在TKA领域，当把致死性PE作为终点时，阿斯匹林与其他抗凝药物同样有效。Lotke等报告了2800连续的以阿斯匹林和机械预防治疗的初次TKA病例，结果显示出血性并发症发生率低，致死性PE风险为0.1%.然而，阿斯匹林在THA病人中并不能有效减少有症状的DVT风险。肺栓塞预防试验是一个用来评估阿斯匹林在预防THA术后有症状的VTE疾病方面有效性的随机试验。超过4000名患者术后随机接受阿斯匹林（n=2047）或安慰剂（n=2041）治疗35天。2组间有症状的DVT没有显著性差异（P＞0.5）。
In general, venous thromboembolic events following primary hip and knee arthroplasty has decreased significantly over the past decade, mainly due to a multidisciplinary approach. Rapid postoperative mobilization, optimization of surgical technique, and improved perioperative pain management, including the use of regional anesthesia, have all contributed to decreasing the DVT risk. The ACCP guidelines do not support the use of aspirin for prophylaxis following TJA, because this drug has not been extensively evaluated in multicenter randomized trials. The AAOS guidelines support the use of aspirin for 6 weeks except in patients that are at high risk for PE and have standard bleeding complication risk; these patients are not candidates for aspirin use because of the identified preoperative elevated risk for PE.
总体而言，初次髋和膝关节置换术后静脉血栓栓塞事件在过去10年间已经显著减少，这主要是多学科共同作用的结果。术后早期活动，优化手术技术，改善围手术期疼痛控制，包括使用区域阻滞麻醉，都对降低DVT风险起到了作用。ACCP指南不支持在TJA术后使用阿斯匹林预防血栓性疾病，因为该药还没有在多中心随机试验中得到进一步评估。AAOS指南支持使用6周阿斯匹林，除非患者的PE风险升高，而出血并发症风险是标准的;由于证实了术前PE风险升高，这些患者不适宜使用阿斯匹林。
Because the selection of a prophylaxis agent is a balance between safety and efficacy, aspirin combined with mechanical devices is an attractive regimen for some orthopedic surgeons for their routine TJA patients. Although aspirin is less potent than other chemoprophylactic agents, it is also associated with less bleeding. Aspirin needs to be evaluated in large randomized trials that assess symptomatic events to determine its true efficacy.
由于选择预防用药需在安全性与有效性之间找到平衡，在常规TJA患者中将阿斯匹林和机械装置联合使用对于一些骨科医生来说是一个具有吸引力的方案。虽然阿斯匹林比其他的药物要弱一些，但它引起的出血也少。还需要大的随机试验来评估阿斯匹林的有症状事件以确定其真正的有效性。
MECHANICAL PROPHYLAXIS (PNEUMATIC COMPRESSION BOOTS AND INTERMITTENT PLANTAR COMPRESSION DEVICES)
物理防预防（气动加压靴和间歇性足底加压泵）
The use of mechanical prophylaxis is predicated on the premise that decreasing lower extremity venous stasis in conjunction with increasing venous blood flow will decrease the likelihood of clot formation.34,35 Pneumatic compression boots affect local fibrinolysis, but do not affect systemic fibrinolytic activity.36 Intermittent plantar compression devices were designed to replicate the hemodynamic effects of normal walking by rapid emptying of the plantar arch during the compression phase of the device.12 The advantages of mechanical prophylaxis are evident and include an absence of monitoring and no risk of bleeding. In addition, intermittent plantar compression devices are thought to be less cumbersome than pneumatic boots, which extend the length of the entire lower leg. However, the major disadvantages are that prophylaxis ceases on patient discharge from the hospital, and patient compliance is critical to either device being effective.
物理预防的原理是可以减少下肢静脉淤滞，促进静脉回流，从而减少血栓形成。气动加压靴对局部纤溶有影响，但不影响全身的纤溶。间歇性足底加压泵按摩时可以模仿正常步行时的血流动力学效果。物理预防的优点是显而易见的，包括不需监测，无出血风险，另外，间歇性足底加压泵比气动靴小巧，气动靴可包括整个下肢。而它主要的缺点是患者出院后就无法继续治疗，而且患者的依从性会影响治疗效果。
Several randomized clinical trials have demonstrated that pneumatic compression boots can limit distal thrombus formation.23,37–41 As a result, there has been concern regarding the efficacy of mechanical compression in reducing the rates of proximal clot formation in the setting of THA. Small randomized trials have compared pneumatic compression boots and warfarin in patients undergoing THA and have demonstrated that mechanical prophylaxis is less effective than chemoprophylaxis in the prevention of proximal clot formation.39–41 Regarding intermittent plantar compression devices, low-powered studies have shown a decrease in overall thrombosis rates following THA.42–44 However, given the risk of PE from a proximal clot source, further investigation is required before mechanical prophylaxis can be recommended as a sole means of prophylaxis in patients undergoing THA.
几个随机试验显示气动加压靴可以减少远端血栓形成。因此，有人考虑物理预防能否减少THA患者近端血栓的形成。有人做了几个小型随机试验在THA患者中比较气动加压靴和华法林的作用，结果显示在预防近端血栓形成方面，物理预防不如药物预防更有效。一些低级别的研究显示间歇性足底加压泵能降低THA术后总体血栓率。但是，考虑到由近端血栓形成PE的风险，还需进一步研究以确定 物理预防能否作为THA患者唯一的预防血栓的方法。
The use of mechanical prophylaxis in the setting of TKA, both pneumatic compression and intermittent plantar compression, has been studied in several small studies.19,23,44–49 Although these studies were low powered, a significant reduction in thrombus formation following TKA was demonstrated. On basis of these reports, both pneumatic compression and intermittent plantar compression devices are effective in reducing clot formation following primary TKA. However, larger, multicenter randomized trials comparing mechanical and chemoprophylaxis regimens are necessary to determine the true efficacy of these devices.
已有几个关于气动加压靴和间歇性足底加压泵等物理预防方法在TKA患者中应用的小型研究。虽然这些研究级别比较低，但结果显示TKA术后血栓形成明显减少。根据这些研究报告，气动加压靴和间歇性足底加压泵能有效减少TKA术后血栓的形成。然而，还需做更大型的多中心随机试验来比较物理预防与药物预防的效果，从而确定这些物理预防方法真正的效果。
AUTHORS’ COMMENTARY ON CURRENT GUIDELINES
作者对目前指南的评价
The basic difference between the ACCP and the AAOS guidelines is that the chest physicians believe that asymptomatic clots are clinically relevant. Therefore, the ACCP guidelines were developed from the data obtained from randomized trials, which used venogram data as a surrogate outcome measure. In contrast, the AAOS guidelines reflect the concerns of orthopedic surgeons with a focus on symptomatic clots, PE, and bleeding risk. Furthermore, the AAOS guidelines highlight the importance of developing prophylaxis regimens for each individual patient based on PE and bleeding risk. This is an important concept, which moves us toward risk stratification. Unfortunately, it is difficult to risk stratify most patients based on available data but it is a goal to strive for in the future.
ACCP与AAOS指南根本不同是胸科医生认为无症状的血栓临床上更重要。因此ACCP指南是从随机试验的数据发展而来的，在这些随机试验中使用静脉造影发现静脉血栓。而AAOS则反映了骨科医生对有症状的血栓，PE和出血风险的关注。而且，AAOS指南强调根据PE和出血风险制定出个性化的预防方案。这是一个重要的概念，要求我们进行风险分层。不幸的是，根据掌握的绝大多数患者的数据，风险分层都有困难，但这是我们将来努力的目标。Surgeons need to be aware that the SCIP guidelines recommend LMWH, fondaparinux, and/or warfarin for THA and TKA patients. Pneumatic compression devices are also acceptable for patients undergoing TKA procedures. Therefore, aspirin and pneumatic compression devices are acceptable for TKA patients. A surgeon may choose to use another regimen because of concerns about bleeding, but this must be documented in the medical record.
外科医生应该知道SCIP指南推荐在THA和TKA患者中使用LMWH，磺达肝素，和/或华法林。气动加压靴也可用于TKA患者。因此，阿斯匹林和气动加压靴可用于TKA患者。医生可能会因为考虑到出血而选用其他治疗方案，但这一定要记录在病历中。
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