磁治疗带预防髋膝关节术后下肢深静脉血栓形成

目的：评价磁治疗带预防髋膝关节术后下肢深静脉血栓形成（DVT）的疗效。方法：48例接受髋膝周围手术的患者随机分为2组，预防组术后应用磁治疗带治疗，对照组不采用任何预防措施，术后4－7d行患侧静脉造影，了解深静脉血栓的发生情况。结果：对照组中8例发生DVT占33．3％，预防组中1例占4．2％。2组比较差异有显著性（P＜0．05）。结论：磁治疗带能安全，有效地预防髋膝关节及其周围手术后下肢深静脉血栓形成。     

Deep-vein thrombosis rates after major orthopedic surgery in Asia. An epidemiological study based on postoperative screening with centrally adjudicated bilateral venography

BACKGROUND: The incidence of postsurgical venous thromboembolism is thought to be low in Asian ethnic populations. OBJECTIVE: We studied the incidence of deep-vein thrombosis (DVT) in Asian patients undergoing major orthopedic surgery of the lower limbs. PATIENTS/METHODS: We performed a prospective epidemiological study in 19 centers across Asia (China, Indonesia, South Korea, Malaysia, Philippines, Taiwan, and Thailand) in patients undergoing elective total hip replacement (THR), total knee replacement (TKR) or hip fracture surgery (HFS) without pharmacological thromboprophylaxis. The primary endpoint was the rate of DVT of the lower limbs documented objectively with bilateral ascending venography performed 6-10 days after surgery using a standardized technique and evaluated by a central adjudication committee unaware of local interpretation. RESULTS: Overall, of 837 Asian patients screened for this survey, 407 (48.6%, aged 20-99 years) undergoing THR (n = 175), TKR (n = 136) or HFS (n = 96) were recruited in 19 centers. DVT was diagnosed in 121 of 295 evaluable patients [41.0%, (95% confidence interval (CI): 35.4-46.7)]. Proximal DVT was found in 30 patients [10.2% (7.0-14.2)]. Total DVT and proximal DVT rates were highest in TKR patients (58.1% and 17.1%, respectively), followed by HFS patients (42.0% and 7.2%, respectively), then THR patients (25.6% and 5.8%, respectively). DVT was more frequent in female patients aged at least 65 years. Pulmonary embolism was clinically suspected in 10 of 407 patients (2.5%) and objectively confirmed in two (0.5%). CONCLUSIONS: The rate of venographic thrombosis in the absence of thromboprophylaxis after major joint surgery in Asian patients is similar to that previously reported in patients in Western countries.     

Fondaparinux for prevention of venous thromboembolism in major orthopedic surgery

OBJECTIVE: To review clinical information related to fondaparinux, a synthetic pentasaccharide recently approved for the prevention of deep-vein thrombosis (DVT) in patients undergoing major orthopedic surgeries and for extended DVT prophylaxis after hip fracture surgery. DATA SOURCES: Primary and review articles were identified by MEDLINE (1983-June 2003) using the key words pentasaccharide, Org31540, SR90107A, DVT prophylaxis, and fondaparinux. Additional sources were found listed in articles, abstracts, and unpublished data on file from the manufacturer. Articles selected were based on their coverage of the pharmacology, pharmacokinetics, safety, and efficacy of fondaparinux. STUDY SELECTION AND DATA EXTRACTION: All of the articles identified were evaluated and all information deemed relevant was included. DATA SYNTHESIS: Fondaparinux is a selective antithrombin-dependent, indirect inhibitor of activated factor Xa. It has a favorable and predictable pharmacokinetic profile when administered subcutaneously, and has a long half-life, allowing once-daily dosing. Fondaparinux lacks in vitro cross-reactivity with heparin-induced antibodies. Major Phase III studies have demonstrated that subcutaneous fondaparinux sodium 2.5 mg given at least 6 hours postoperatively resulted in a 55% reduction in the risk of venous thromboembolism (VTE) in patients undergoing hip fracture surgery, total hip replacement surgery, or knee replacement surgery compared with standard enoxaparin therapy. It has a safety profile similar to that of enoxaparin with respect to clinically relevant major bleeding, including fatal bleeding, nonfatal bleeding, and bleeding requiring repeat surgery. The use of fondaparinux for prolonged prophylaxis after hip fracture has demonstrated further reduction in VTE events without increasing the risk of bleeding.CONCLUSIONS: Fondaparinux is the first of a new class of synthetic factor Xa inhibitors that demonstrated greater efficacy compared with enoxaparin for the prevention of VTE in major orthopedic surgery without an increase in clinically relevant bleeding. Given the favorable cost-effectiveness analysis and improved efficacy profile, fondaparinux should be considered for formulary addition for DVT prophylaxis in patients undergoing hip and knee replacement surgery. In patients undergoing hip fracture surgery, fondaparinux should be considered the DVT prophylaxis of choice. Extended thromboprophylaxis up to 28 days resulted in additional reduction in VTE (both symptomatic and venography-proven DVT) in patients with hip fracture surgery.     

Ultrasound screening for asymptomatic deep vein thrombosis after major orthopaedic surgery: the VENUS study

Summary.  Background:  Venography is currently used to assess the incidence of deep vein thrombosis (DVT) in dose-finding and confirmatory trials of new antithrombotic agents. Centrally adjudicated, complete compression ultrasound (CCUS) could be a non-invasive alternative to venography. Objectives:  A substudy of two, similarly designed, phase IIb trials of a novel, oral anticoagulant for the prevention of venous thromboembolism after elective hip or knee arthroplasty was undertaken to validate CCUS against venography. Patients/Methods:  Patients received study drugs until mandatory, bilateral venography was performed 7 ± 2 days after surgery. CCUS was performed within 24 h after venography by sonographers blinded to the venography result. Sonographers were trained and certified for the standardized examination and documentation procedure. Venograms and sonograms were adjudicated centrally at different sites by two independent readers; discrepancies between readers were resolved by consensus. Results:  A total of 1104 matching pairs of evaluable venograms and sonograms were obtained from the participants of the two trials ( n  = 1435): 19% of venograms and 20% of sonograms were not evaluable. The observed frequency of any DVT was 18.9% with venography and 11.5% with CCUS. Sensitivity of CCUS compared with venography was 31.1% for any DVT (95% confidence interval 23.4, 38.9), 21.0% (2.7, 39.4) for proximal DVT, and 30.8% (23.1, 38.6) for distal DVT. The figures for specificity were 93.0% (91.0, 95.1), 98.7% (98.0, 99.5), and 93.3% (91.5, 95.3), respectively. Conclusions:  Based on these results, centrally adjudicated CCUS will be unable to replace venography for DVT screening early after major orthopaedic surgery in studies evaluating anticoagulant drugs.     

人工髋关节置换后深静脉血栓形成影响因素的回顾分析

背景:目前尚缺少严格遵照<中国骨科大手术静脉血栓栓塞症预防指南>进行血栓预防的大宗人工髋关节置换后深静脉血栓栓塞症发生情况的报道.目的:调查人工髋关节置换患者在进行规范预防性抗凝治疗后下肢深静脉血栓的发生情况.方法:纳入2005-01/2010-07于北京协和医院骨科接受人工髋关节置换的患者,对置换后出现下肢深静脉血栓形成者进行回顾性分析,包括高危因素、预防措施、症状特点、治疗方案及转归.结果与结论:共纳入670例人工髋关节置换患者,其中16例发生下肢深静脉血栓,11例为人工股骨头置换患者,5例为单侧全髋关节置换患者.诊断分布为股骨颈骨折14例,股骨头无菌性坏死1例,血友病性关节炎1例.其合并症1~4个,包括高血压、糖尿病、类风湿性关节炎、慢性肾功能不全等.围手术期皆应用规范物理、药物疗法预防下肢深静脉血栓形成.14例表现为下肢肿胀、疼痛;2例以肺栓塞为首发症状.多数预后良好;1例死于与下肢深静脉血栓形成无关的肺部感染,1例抗凝治疗后并发脑出血导致植物生存状态.提示进行规范预防治疗可以降低下肢深静脉血栓形成发生率,但仍不能完全杜绝其发生.髋部骨折、长期卧床、高龄、代谢性内科疾病仍是下肢深静脉血栓形成的高危因素.     

人工髋关节置换后深静脉血栓形成影响因素的回顾分析

背景：目前尚缺少严格遵照《中国骨科大手术静脉血栓栓塞症预防指南》进行血栓预防的大宗人工髋关节置换后深静脉血栓栓塞症发生情况的报道。目的：调查人工髋关节置换患者在进行规范预防性抗凝治疗后下肢深静脉血栓的发生情况。方法：纳入2005-01/2010-07于北京协和医院骨科接受人工髋关节置换的患者,对置换后出现下肢深静脉血栓形成者进行回顾性分析,包括高危因素、预防措施、症状特点、治疗方案及转归。结果与结论：共纳入670例人工髋关节置换患者,其中16例发生下肢深静脉血栓,11例为人工股骨头置换患者,5例为单侧全髋关节置换患者。诊断分布为股骨颈骨折14例,股骨头无菌性坏死1例,血友病性关节炎1例。其合并症1~4个,包括高血压、糖尿病、类风湿性关节炎、慢性肾功能不全等。围手术期皆应用规范物理、药物疗法预防下肢深静脉血栓形成。14例表现为下肢肿胀、疼痛;2例以肺栓塞为首发症状。多数预后良好;1例死于与下肢深静脉血栓形成无关的肺部感染,1例抗凝治疗后并发脑出血导致植物生存状态。提示进行规范预防治疗可以降低下肢深静脉血栓形成发生率,但仍不能完全杜绝其发生。髋部骨折、长期卧床、高龄、代谢性内科疾病仍是下肢深静脉血栓形成的高危因素。     

Epidemiology of venous thromboembolism in Asian patients undergoing major orthopedic surgery without thromboprophylaxis. The SMART Study

Summary.  Background:  In Asian patients undergoing surgery, the incidence of venous thromboembolism (VTE) is thought to be low relative to Western patients, and the routine use of thromboprophylaxis is controversial. Objectives:  The aim of this work was to study the epidemiology of VTE in Asian patients undergoing orthopedic surgery without thromboprophylaxis. Patients and methods:  We performed a prospective observational study of a cohort of consecutive Asian patients hospitalized for total hip or knee replacement or hip fracture surgery without thromboprophylaxis. The primary study outcome was the incidence of the composite of symptomatic VTE or sudden death at hospital discharge. This outcome was also assessed at 1 month's follow-up. Results:  Between April 2001 and July 2002, 2420 patients were enrolled. Median age was 68 years and the median duration of hospital stay was 13 days. The rate of symptomatic VTE or sudden death as notified by investigators was 2.3%[55 patients, 99% confidence interval (CI) 1.6, 3.2] and 1.2% (28 patients, 99% CI 0.7, 1.8) after adjudication by an independent committee. Chronic heart failure, varicose veins and a history of VTE were independent risk factors ( P <  0.05) for the occurrence of the primary endpoint. At 1 month's follow-up, the incidence of adjudicated symptomatic VTE or sudden death was 1.5% (35/2264 patients). Conclusion:  In Asian patients, the incidence of symptomatic VTE after major orthopedic surgery is not low, consistent with the rates observed in Western countries. The use of thromboprophylaxis should be considered in Asian patients undergoing such high-risk surgical procedures.     

Association between asymptomatic deep vein thrombosis detected by venography and symptomatic venous thromboembolism in patients undergoing elective hip or knee surgery

BACKGROUND: Venography is commonly used to compare the efficacy of different thromboprophylaxis strategies for preventing deep vein thrombosis (DVT) in patients undergoing total hip replacement (THR) or total knee replacement (TKR). METHODS: We explored the relation between asymptomatic DVT and symptomatic venous thromboembolism (VTE) in patients undergoing THR or TKR treated with standard doses of enoxaparin (30 mg b.i.d. or 40 mg o.d.) by comparing the incidence of asymptomatic DVT in venographic studies with the incidence of symptomatic VTE in studies where venography was not performed. RESULTS: In 10 venographic studies involving 5796 patients, the incidence of asymptomatic DVT after THR was 13.2% [95% CI, 12.2-14.2%] and after TKR was 38.1% (95% CI, 35.5-40.8%). In two studies involving 3500 patients who did not undergo venography, the 90-day incidence of symptomatic VTE after THR was 2.7% (95% CI, 2.1-3.4%) and after TKR was 1.8% (95% CI, 0.9-2.7%). For every symptomatic VTE in THR studies where venography was not performed there were five asymptomatic DVTs in the venographic studies; for TKR, the ratio was 1:21. The incidence of asymptomatic DVT and the symptomatic VTE/asymptomatic DVT ratio was influenced by the venogram reading committee (Gothenburg vs. Hamilton: total DVT after THR, 19.5% vs. 8.7%, P < 0.0001; for TKR, 42.7% vs. 27.2%, P < 0.0001). CONCLUSIONS: Comparisons across trials show a consistent relation between asymptomatic venographic DVT in patients undergoing elective THR or TKR surgery and symptomatic VTE in patients not undergoing venography. Differences exist in the strength of the relation depending on the type of surgery and the venogram reading committee.     

Prevention of venous thromboembolism with an oral factor Xa inhibitor,YM150, after total hip arthroplasty. A dose finding study (ONYX‐2)

Background: Anticoagulant prophylaxis substantially reduces the risk of venous thromboembolism (VTE) after major orthopedic surgery. The direct factor Xa inhibitor YM150 is currently under investigation for the prevention of VTE, stroke and ischemic vascular events in patients after orthopedic surgery, with atrial fibrillation and with acute coronary syndrome, respectively. Objectives: To investigate the efficacy and safety of YM150 for the prevention of VTE following elective total hip arthroplasty. Patients/methods: Patients were randomized to postoperative, once‐daily, oral YM150 (5, 10, 30, 60 or 120 mg) (double‐blind) or preoperative subcutaneous (open label) enoxaparin (40 mg) for 5 weeks. The primary efficacy endpoint comprised VTE diagnosed by mandatory bilateral venography or verified symptomatic deep vein thrombosis (DVT) plus all deaths up to 9 days after surgery. The primary safety outcome was major bleeding up to 9 days after surgery. Results: Primary efficacy endpoint: of 1017 patients randomized, 960 patients were evaluable for safety and 729 patients for efficacy. A dose‐related decrease in VTE incidence from YM150 5 to 60 mg (P = 0.0005) and from 5 to120 mg (P = 0.0002) was found. The VTE incidence was 27.4%, 31.7%, 19.3%, 13.3% and 14.5% for 5, 10, 30, 60 and 120 mg YM150, respectively, and 18.9% for enoxaparin. Primary safety endpoint: there was one major bleed with YM150 (60 mg) and one with enoxaparin. Conclusions: The oral direct FXa inhibitor YM150 demonstrated a significant dose response regarding efficacy. Doses from 30 to 120 mg had comparable efficacy to enoxaparin, without compromising safety regarding major bleeding events.     

Semuloparin for prevention of venous thromboembolism after major orthopedic surgery: results from three randomized clinical trials,SAVE‐HIP1, SAVE‐HIP2 and SAVE‐KNEE

Background:  Semuloparin is a novel ultra‐low‐molecular‐weight heparin under development for venous thromboembolism (VTE) prevention in patients at increased risk, such as surgical and cancer patients. Objectives:  Three Phase III studies compared semuloparin and enoxaparin after major orthopedic surgery: elective knee replacement (SAVE‐KNEE), elective hip replacement (SAVE‐HIP1) and hip fracture surgery (SAVE‐HIP2). Patients/Methods:  All studies were multinational, randomized and double‐blind. Semuloparin and enoxaparin were administered for 7–10 days after surgery. Mandatory bilateral venography was to be performed between days 7 and 11. The primary efficacy endpoint was a composite of any deep vein thrombosis, non‐fatal pulmonary embolism or all‐cause death. Safety outcomes included major bleeding, clinically relevant non‐major (CRNM) bleeding, and any clinically relevant bleeding (major bleeding plus CRNM). Results:  In total, 1150, 2326 and 1003 patients were randomized in SAVE‐KNEE, SAVE‐HIP1 and SAVE‐HIP2, respectively. In all studies, the incidences of the primary efficacy endpoint were numerically lower in the semuloparin group vs. the enoxaparin group, but the difference was statistically significant only in SAVE‐HIP1. In SAVE‐HIP1, clinically relevant bleeding and major bleeding were significantly lower in the semuloparin vs. the enoxaparin group. In SAVE‐KNEE and SAVE‐HIP2, clinically relevant bleeding tended to be higher in the semuloparin group, but rates of major bleeding were similar in the two groups. Other safety parameters were generally similar between treatment groups. Conclusions:  Semuloparin was superior to enoxaparin for VTE prevention after hip replacement surgery, but failed to demonstrate superiority after knee replacement surgery and hip fracture surgery. Semuloparin and enoxaparin exhibited generally similar safety profiles.     

AVE5026, a new hemisynthetic ultra-low-molecular-weight heparin for the prevention of venous thromboembolism in patients after total knee replacement surgery – TREK: a dose-ranging study

Summary.  Background: AVE5026 is a new hemisynthetic ultra-low-molecular-weight heparin, with a novel anti-thrombotic profile resulting from high anti-factor (F)Xa activity and residual anti-FIIa activity. AVE5026 is in clinical development for venous thromboembolism (VTE) prevention, a frequent complication after total knee replacement (TKR) surgery. Objectives: This study evaluated the dose-response of AVE5026 for the prevention of VTE in patients undergoing TKR surgery. Patients/methods: In this parallel-group, double-blind, double-dummy study, 690 patients were randomized, and 678 treated with once-daily doses of AVE5026 (5, 10, 20, 40, or 60 mg) or enoxaparin 40 mg in the calibrator arm. The primary efficacy end point was VTE until post-operative day 11, defined as deep vein thrombosis (DVT) detected by bilateral venography, symptomatic DVT, non-fatal pulmonary embolism (PE) and VTE-related death. The primary safety outcome was the incidence of major bleeding. Results: The primary efficacy outcome was assessed in 464 patients. There was a significant dose-response across the five AVE5026 groups for VTE prevention ( P  <   0.0001), with the incidence of VTE ranging from 5.3% to 44.1% compared with 35.8% in the enoxaparin group and for proximal DVT ( P  =   0.0002). Also, a significant dose-response for AVE5026 was seen for major bleeding ( P  =   0.0231) and any bleeding ( P  =   0.0003). Six patients in the AVE5026 groups, four in the 60 mg group, experienced major bleeding; none did in the enoxaparin group. Conclusions: The safety and efficacy results of this study suggest that a AVE5026 dose of between 20 and 40 mg presents an adequate benefit-to-risk ratio.     

Prolonged prophylaxis with dalteparin to prevent late thromboembolic complications in patients undergoing major abdominal surgery: a multicenter randomized open-label study

BACKGROUND: Patients undergoing major abdominal surgery carry a high risk of venous thromboembolism (VTE), but the optimal duration of postoperative thromboprophylaxis is unknown. OBJECTIVES: To evaluate the efficacy and safety of thromboprophylaxis with the low molecular weight heparin (dalteparin), administered for 28 days after major abdominal surgery compared to 7 days' treatment. PATIENTS/METHODS: A multicenter, prospective, assessor-blinded, open-label, randomized trial was performed in order to evaluate prolonged thromboprophylaxis after major abdominal surgery. In total, 590 patients were recruited, of whom 427 were randomized and received at least 1 day of study medication, and 343 reached an evaluable endpoint. The primary efficacy endpoint was objectively verified VTE occurring between 7 and 28 days after surgery. All patients underwent bilateral venography at day 28. RESULTS: The cumulative incidence of VTE was reduced from 16.3% with short-term thromboprophylaxis (29/178 patients) to 7.3% after prolonged thromboprophylaxis (12/165) (relative risk reduction 55%; 95% confidence interval 15-76; P=0.012). The number that needed to be treated to prevent one case of VTE was 12 (95% confidence interval 7-44). Bleeding events were not increased with prolonged compared with short-term thromboprophylaxis. CONCLUSIONS: Four-week administration of dalteparin, 5000 IU once daily, after major abdominal surgery significantly reduces the rate of VTE, without increasing the risk of bleeding, compared with 1 week of thromboprophylaxis.     

The direct thrombin inhibitor melagatran followed by oral ximelagatran compared with enoxaparin for the prevention of venous thromboembolism after total hip or knee replacement: the EXPRESS study

Summary.  Background : Ximelagatran and its subcutaneous (s.c.) form melagatran are novel direct thrombin inhibitors for the prevention and treatment of thromboembolic disease. Methods : In a double-blind study, 2835 consecutive patients undergoing total hip or knee replacement were randomized to either melagatran/ximelagatran or enoxaparin. Melagatran 2 mg was started immediately before surgery; 3 mg was then administered postoperatively, followed by 24 mg of oral ximelagatran b.i.d. beginning the next day. Enoxaparin 40 mg, administered subcutaneously o.d., was started 12 h before surgery. Both treatments were continued for 8–11 days. The main efficacy outcome measures were major venous thromboembolism (VTE); [proximal deep vein thrombosis (DVT), non-fatal and/or fatal pulmonary embolism (PE), death where PE could not be ruled out], and total VTE (proximal and distal DVT; PE; death from all causes). DVT was detected by mandatory bilateral ascending venography at the end of the treatment period or earlier if clinically suspected. The main safety outcome was bleeding. Results : The rates of major and total VTE were significantly lower in the melagatran/ximelagatran group compared with the enoxaparin group (2.3% vs. 6.3%, P  = 0.0000018; and 20.3% vs. 26.6%, P  < 0.0004, respectively). Fatal bleeding, critical site bleeding and bleeding requiring reoperation did not differ between the two groups. 'Excessive bleeding as judged by the investigator' was more frequent with melagatran/ximelagatran than with enoxaparin. Conclusions : In patients undergoing total hip or knee replacement, preoperatively initiated s.c. melagatran followed by oral ximelagatran was significantly more effective in preventing VTE than preoperatively initiated s.c. enoxaparin.     

Does venous microemboli detection add to the interpretation of D-dimer values following orthopedic surgery?

The identification of risk factors for deep venous thrombosis (DVT) following orthopedic surgery remains unclear. We have investigated the relationship between plasma levels of D-dimer (DD), the presence or absence of microemboli 1 day after surgery, and the occurrence of DVT 7 days after total hip or knee replacement. The prevalence of DVT was 25 (13.3%) among 188 patients and was lower in 112 patients with DD < 2808 ng mL(-1) than in the 56 patients with higher DD levels: respectively, 8.0% vs. 21.4% (p < 0.05). D-dimer is not suitable for individual estimation of DVT risk. Microemboli were found in 112 (60%) of 186 subjects. The presence/absence or the frequency of the microemboli showed no relationship with the occurrence of DVT. Last, when evaluating the risk of DVT in orthopedic surgery, microemboli detection does not add to the interpretation of DD concentration.     

A phase II study of the oral factor Xa inhibitor LY517717 for the prevention of venous thromboembolism after hip or knee replacement

BACKGROUND: LY517717 is an oral direct inhibitor of activated factor X that is currently under clinical development. OBJECTIVES: The aims of this proof-of-concept study in patients undergoing total knee replacement (TKR) or total hip replacement (THR) were to determine whether LY517717 can safely reduce the risk of venous thromboembolism (VTE) and to identify at least one dose of LY517717 that is non-inferior to enoxaparin. METHODS: In a double-blind, parallel-arm, dose-ranging study, patients undergoing TKR or THR were randomly allocated to receive once-daily oral LY517717 (25, 50, 75, 100, 125 or 150 mg), started 6-8 h after wound closure, or s.c. enoxaparin, 40 mg, started in the evening before surgery. The primary efficacy endpoint was the composite of deep venous thrombosis (DVT), detected by mandatory bilateral venography performed at the end of the study treatment (between days 5 and 9), and objectively confirmed symptomatic DVT and/or pulmonary embolism (PE), occurring during the treatment period. The combination of major and minor bleeding was the primary safety endpoint. RESULTS: Five hundred and seven patients received at least one dose of LY517717 or enoxaparin (safety population). Three hundred and ninety-one patients had evaluable bilateral venography or experienced a clinical DVT and/or PE (primary efficacy population). LY517717 treatment resulted in a dose-dependent decrease in the incidence of thromboembolic events (P = 0.0001). The incidences of VTE with 100, 125, and 150 mg of LY517717 were 19%, 19% and 16%, respectively, compared to 21% with enoxaparin. The efficacies of 100-mg, 125-mg and 150-mg doses of LY517717 were non-inferior to that of enoxaparin according to prespecified criteria. Bleeding events were uncommon in both LY517717 and enoxaparin patients. CONCLUSIONS: Doses of 100, 125 and 150 mg of LY517717 are non-inferior to enoxaparin for the prevention of VTE after TKR or THR, and are associated with similar low rates of bleeding.     

Prevention of venous thromboembolism in orthopedic surgery with vitamin K antagonists: a meta-analysis.

BACKGROUND: The benefit-to-risk ratio of vitamin K antagonists (VKA), relative to active comparators, especially low-molecular-weight heparins (LMWH), for preventing venous thromboembolism in patients undergoing major orthopedic surgery is debated. OBJECTIVES: We performed a meta-analysis of all randomized trials in orthopedic surgery comparing adjusted doses of VKA to control treatments. PATIENTS AND METHODS: An exhaustive literature search, both manual and computer-assisted, was performed. Studies were selected on the basis of randomization procedure (VKA vs. a control group). At least one of the following outcome measures was to be evaluated: deep vein thrombosis (DVT), pulmonary embolism (PE), death, major hemorrhage or wound hematoma. Four reviewers assessed each article to determine eligibility for inclusion and outcome measures. RESULTS: VKAs were more effective than placebo or no treatment in reducing DVT [567 patients, relative risk (RR) = 0.56, 95% confidence interval (CI) 0.37, 0.84, P < 0.01] and clinical PE (651 patients, RR = 0.23, 95% CI 0.09, 0.59, P < 0.01). These results were obtained at the cost of a higher rate of wound hematoma (162 patients, RR = 2.91, 95% CI 1.09, 7.75, P = 0.03). VKAs were also more effective than intermittent pneumatic compression (534 patients, RR = 0.46, 95% CI 0.25, 0.82, P = 0.009) in preventing proximal DVT. In contrast, VKAs were less effective than LMWH in preventing total DVT and proximal DVT (9822 patients, RR = 1.51, 95% CI 1.27, 1.79, P < 0.001; and 6131 patients, RR = 1.51, 95% CI 1.04, 2.17, P = 0.028, respectively). The differences between VKA and LMWH in major hemorrhage and wound hematoma were not significant. CONCLUSIONS: In patients undergoing major orthopedic surgery, VKAs are less effective than LMWH, without any significant difference in the bleeding risk.     

A randomized study comparing the efficacy and safety of nadroparin 2850 IU (0.3 mL) vs. enoxaparin 4000 IU (40 mg) in the prevention of venous thromboembolism after colorectal surgery for cancer

BACKGROUND: The optimal thromboprophylactic dosage regimen of low-molecular-weight heparins in high-risk general surgery remains debatable. OBJECTIVES: We performed a randomized, double-blind study to compare the efficacy and safety of nadroparin 2850 IU (0.3 mL) and enoxaparin 4000 IU (40 mg) in the prevention of venous thromboembolism (VTE) after colorectal surgery for cancer. Patients and methods: Patients undergoing resection of colorectal adenocarcinoma were randomized to receive once daily either 2850 IU nadroparin or 4000 IU enoxaparin s.c. for 9 +/- 2 days. The primary efficacy outcome was the composite of deep vein thrombosis (DVT) detected by bilateral venography or documented symptomatic DVT or pulmonary embolism up to day 12. The main safety outcome was major bleeding. A blinded independent committee adjudicated all outcomes. RESULTS: Out of 1288 patients analyzed, efficacy was evaluable in 950 (73.8%) patients. The VTE rate was 15.9% (74/464) in nadroparin-treated patients and 12.6% (61/486) in enoxaparin-treated patients, a relative risk of 1.27 (95% confidence interval; CI: 0.93-1.74) that did not met the criterion for non-inferiority of nadroparin. The rate of proximal DVT was comparable in the two groups (3.2% vs. 2.9%, respectively), but that of symptomatic VTE was lower in nadroparin-treated patients (0.2% vs. 1.4%). There was significantly (P = 0.012) less major bleeding in nadroparin- than in enoxaparin-treated patients (7.3% vs. 11.5%, respectively). CONCLUSION: Compared with those receiving enoxaparin 4000 IU, patients treated with nadroparin 2850 IU showed a higher incidence of asymptomatic distal DVT, but a lower incidence of symptomatic VTE. Nadroparin treatment was safer in terms of bleeding risk.     

Incidence of venous thromboembolism following major abdominal surgery: a multi-center, prospective epidemiological study in Japan

BACKGROUND: Venous thromboembolism (VTE) has been considered to be a rare surgical complication in Japan. AIM: To investigate the incidence and risk factors of VTE in Japanese patients undergoing major abdominal surgery. METHODS: A prospective, multi-center epidemiological study was conducted from December, 2001 to August 2002 in 39 medical institutes throughout Japan. A total of 173 patients with general (n = 128), gynecologic (n = 23), and urologic (n = 22) surgery were analyzed. For the diagnosis of deep vein thrombosis (DVT), bilateral venography was performed in all patients. Lung ventilation/perfusion scintigraphy was carried out in patients suspected of pulmonary thromboembolism (PTE). RESULTS: There were 36 patients with distal DVT (20.8%) and five patients with proximal DVT (2.9%). One patient was diagnosed as PTE. Overall, VTE was diagnosed in 42 patients (24.3%). By univariate analysis, only age (60 years or older) was identified as a significant risk factor in the whole study population. When analyzed by the stepwise multiple logistic regression model, female gender, operation site, age, and operation time were four risk factors found to be significant. The incidence of VTE was closely related to the number of risk factors that patients had. As many as 44% of patients with three or four risk factors developed VTE while those with one or two risk factors showed about a 17% incidence of VTE. Four patients lacking any risk factors did not develop VTE. CONCLUSIONS: Venous thromboembolism is common in Japanese patients undergoing major abdominal surgery. Pharmacologic thromboprophylaxis is considered essential, particularly in those patients with multiple, potential risk factors.     

Epidemiology of venous thromboembolism after lower limb arthroplasty: the FOTO study

BACKGROUND: In view of recent substantial changes in the management of orthopedic surgery patients, a study was performed in order to update data on the epidemiology of venous thromboembolism (VTE) in patients undergoing lower limb arthroplasty according to contemporary practise. METHODS: We performed a prospective observational study of a cohort of consecutive patients hospitalized for total hip or knee replacement in June 2003. The primary study outcome was the incidence of symptomatic VTE at 3 months. All events were adjudicated by an independent critical event committee. RESULTS: Data from 1080 patients (mean age 68.0 years) were available; 63.2% were undergoing total hip replacement and 36.8% total knee replacement. Pharmacological thromboprophylaxis was administered for a mean time of 36 days. Injectable antithrombotics were used in more than 99% of patients, irrespective of the type of surgery. The incidence of the primary study outcome was 1.8% (20 events; 95% CI: 1.0-2.6%). The incidences were 1.3% and 2.8% in hip and knee surgery patients, respectively. There were two pulmonary embolisms, both in knee surgery patients; neither was fatal. Thirty-five per cent of VTEs occurred after hospital discharge. An age of at least 75 years and the absence of ambulation before hospital discharge were the only significant (P < 0.05) predictors of VTE. The rate of clinically significant bleeding was 1.0% and the rate of death was 0.9%. CONCLUSIONS: The incidence of symptomatic VTE after lower limb arthroplasty is low, even if there is still a need to improve thromboprophylaxis, notably in patients undergoing knee arthroplasty.     

Extended prophylaxis with bemiparin for the prevention of venous thromboembolism after abdominal or pelvic surgery for cancer: the CANBESURE randomized study

Summary. Background: There is not enough clinical evidence to make a strong recommendation on the optimal duration of thromboprophylaxis using low‐molecular weight heparins (LMWH) in patients undergoing major cancer surgery. Patients and methods: CANBESURE is a randomized, double‐blind study which enrolled patients admitted for abdominal or pelvic surgery for cancer. They received 3500 IU of bemiparin subcutaneously once daily for 8 days and were then randomized to receive either bemiparin or placebo for 20 additional days. Bilateral venography was performed after 20 days and evaluated blinded. The primary efficacy outcome was the composite of deep vein thrombosis (DVT), non‐fatal pulmonary embolism (PE) and all‐cause mortality at the end of double‐blind period. Major venous thromboembolism (proximal deep‐vein thrombosis, non‐fatal pulmonary embolism and venous thromboembolism‐related deaths) was also evaluated. The primary safety outcome was major bleeding. Results: Six hundred and twenty‐five and 488 patients were included in the safety and main efficacy analyzes, respectively. The primary efficacy outcome occurred in 25 out of 248 patients (10.1%) in the bemiparin group and 32 out of 240 (13.3%) in the placebo group (relative risk reduction 24.4%; 95% CI: ?23.7–53.8%; P = 0.26). At the end of double‐blind period, major venous thromboembolism occurred in 2 (0.8%) and 11 (4.6%) patients, respectively (relative risk reduction 82.4%; 95% CI: 21.5–96.1%; P = 0.010). No significant difference was found in major bleedings. Conclusions: Four weeks compared with 1 week of prophylaxis with bemiparin after abdominal or pelvic cancer surgery did not significantly reduce the primary efficacy outcome, but decreased major venous thromboembolism (VTE) without increasing hemorrhagic complications.