Equivalence of DOACS and LMWH for thromboprophylaxis after hip fracture surgery: Systematic review and meta-analysis

BackgroundPatients with hip fractures (HF) have an increased risk of venous thromboembolism (VTE). In elective orthopedic surgery direct oral anticoagulants (DOACs) have proven to be similarly or more effective compared to low molecular weight heparin (LMWH), but DOACs are not yet approved for thromboprophylaxis in trauma patients with HF. The aim of this study was to systematically review the literature comparing the effectiveness of DOACs and LMWH for thromboprophylaxis in trauma patients with surgically treated HF.Materials and MethodsWe searched PubMed, the Cochrane Library, Web of Science, and Embase. The primary outcome was the incidence of VTE (symptomatic and asymptomatic combined). Secondary outcomes were symptomatic VTE; a symptomatic VTE, symptomatic deep venous thrombosis (DVT); symptomatic pulmonary embolism (PE); major, clinically relevant non-major (CRNM), and minor bleeding. Meta-analysis was performed to compare the odds of VTE and secondary outcomes between DOACs and LMWH.ResultsThe search resulted in 738 titles. Five studies matched inclusion criteria. In total, 4748 hip fracture patients were analyzed (DOACs: 2276 patients, LMWH: 2472 patients). The pooled odds ratio for the risk of VTE for DOAC use was 0.52 (95% confidence interval 0.25–1.11, p = 0.09) compared to LMWH. No statistically significant differences between DOAC and LMWH were found for asymptomatic VTE, symptomatic DVT, PE, major or CRNM bleeding, and minor bleeding.ConclusionsMeta-analysis of the literature suggests that DOACs are associated with equivalent effectiveness and safety compared to LMWH.     

Factor Xa Inhibitors and Direct Thrombin Inhibitors Versus Low-Molecular-Weight Heparin for Thromboprophylaxis After Total Hip or Total Knee Arthroplasty: A Systematic Review and Meta-Analysis

Background

The purpose of this study is to perform a meta-analysis to compare outcomes of venous thromboembolism (VTE) prophylaxis with low-molecular-weight heparin (LMWH) vs other anticoagulants in patients who received total knee (TKA) or total hip arthroplasty (THA).

Stratifying Venous Thromboembolism Risk in Arthroplasty: Do High-Risk Patients Exist?

BackgroundWhile there are many possible complications associated with total joint arthroplasty (TJA), venous thromboembolism (VTE) is both frequent and potentially severe. Despite this importance, there are inconsistent recommendations for prophylaxis based on patient risk factors.MethodsA predictive model was constructed to compare low-molecular-weight heparin(LMWH) and aspirin (ASA) for prevention of VTE-associated complications following TJA.The model used risks from prior prophylaxis studies to estimate the risk of developing a symptomatic deep vein thrombosis, pulmonary embolism, thrombocytopenia, and operative or nonoperative site bleeding. We also evaluated the progression to 4 possible final health states: postphlebitis syndrome, intracranial hemorrhage, death, or baseline health. Within published ranges, we selected assumptions that were favorable to LMWH such that these analyses represent a best case scenario for LMWH or an alternative more aggressive low-molecular-weight heparin alternative (LMWHA). Events and outcomes were assigned quality-adjusted life-year (QALY) losses according to prior studies to determine the effect on patients’ outcomes for ASA and LMWHA prophylaxis.ResultsAssessing VTE risk populations from 0.2% to 2% with life expectancies ranging from 5 to 40 years postoperatively, patients with a risk ratio less than 3.7 showed increased expected QALY with ASA compared to LMWHA. For patients with a baseline VTE risk of 1% and a 15 year life expectancy, a risk ratio of 13.4 was needed to identify patients that would benefit from LMWHA. With life expectancy increased to 30 years, the risk ratio needed to idetify these patients was 7.4.ConclusionPatients undergoing TJA should receive ASA chemoprophylaxis in nearly all situations, unless the patient has a significantly increased VTE risk compared to the baseline population and a long life expectancy.     

Insufficient Evidence for Routine Use of Thromboprophylaxis in Ambulatory Patients with an Isolated Lower Leg Injury Requiring Immobilization: Results of a Meta-Analysis

Abstract Background:   There are no generally accepted guidelines for the prevention of venous thromboembolism (VTE) in ambulatory patients requiring immobilization after an isolated lower leg injury. Our objective was to evaluate the effectiveness and safety of pharmacological interventions for preventing VTE in these patients. Study Design:   Meta-analysis of randomized controlled trials. Materials and Methods:   We searched PubMed/Medline, EMBASE and the Cochrane Central Register of Controlled Trials for trials with random allocation of thromboprophylaxis, notably low molecular weight heparin (LMWH) versus no prophylaxis or placebo, in ambulatory patients with below-knee or lower leg (including the knee joint) immobilization. Outcome was analyzed using MIX to calculate the pooled risk ratio/relative risk (RR) for each outcome, along with its 95% confidence interval (CI). Results:   The RR of asymptomatic deep vein thrombosis (DVT) was 0.66 (95% CI 0.44; 1.02) for below-knee immobilization and 0.51 (95% CI 0.37; 0.70) for lower leg immobilization. Low molecular weight heparin versus no prophylaxis or placebo was evaluated. The incidence of symptomatic DVT and PE was too low to show any statistically significant difference between thromboprophylaxis and controls in both groups. Although only one adverse bleeding event was considered to bemajor, the RR for any adverse bleeding event was 1.94 (95% CI 1.03; 3.67). Conclusion:   There is insufficient evidence to warrant routine use of thromboprophylaxis in ambulatory patients with below-knee or lower leg immobilization after an isolated lower leg injury. The incidence of symptomatic VTE is too low to show a relevant clinical benefit from thromboprophylaxis.     

Meta-analysis of trials comparing ximelagatran with low molecular weight heparin for prevention of venous thromboembolism after major orthopaedic surgery

BACKGROUND: Use of low molecular weight heparin (LMWH) is standard practice for preventing postoperative venous thromboembolism (VTE). Ximelagatran is a new direct thrombin inhibitor for this indication. METHODS: A systematic review was conducted to compare the efficacy and safety of LMWH with ximelagatran in orthopaedic surgery. RESULTS: Six eligible, well conducted clinical trials (10 051 patients) were identified. Overall, the risk of VTE (OR (odds ratio) 1.22 (95 per cent confidence interval (c.i.) 0.89 to 1.67)) and serious bleeding (OR 0.70 (95 per cent c.i. 0.42 to 1.18)) was not significantly different for LMWH compared with ximelagatran. Exploratory analyses to investigate statistical heterogeneity found that results varied by surgical subtype and treatment regimen. Compared with postoperative ximelagatran, LMWH had a significantly lower rate of VTE (OR 0.68 (95 per cent c.i. 0.56 to 0.82); P < 0.001), with no significant difference in bleeding rate (OR 1.09 (95 per cent c.i. 0.62 to 1.94); P = 0.76), in hip surgery, and no significant differences in knee surgery. When ximelagatran was started immediately before surgery, LMWH had a significantly higher rate of VTE in both hip (OR 1.87 (95 per cent c.i. 1.20 to 2.92); P = 0.006) and knee (OR 1.49 (95 per cent c.i. 1.14 to 1.93); P = 0.003) surgery, but less bleeding: hip OR 0.30 (95 per cent c.i. 0.17 to 0.53; P < 0.001); knee OR 0.71 (95 per cent c.i. 0.30 to 1.67; P = 0.43). CONCLUSION: This review demonstrated no overall advantage for either LMWH or ximelagatran in thromboprophylaxis following orthopaedic surgery. Benefits in VTE prevention with ximelagatran were gained at the expense of an increased risk of serious bleeding.     

Venous thromboembolism prophylaxis with low molecular weight heparin versus unfractionated heparin for patients undergoing operative treatment of closed femoral shaft fractures

BackgroundThe objective of this study was to compare inpatient mortality rates for patients with operatively treated closed femoral shaft fractures (AO/OTA 32 A-C) who received venous thromboembolism (VTE) prophylaxis with either low molecular weight heparin (LMWH) or unfractionated heparin.MethodsThis was a retrospective cohort study of a national database of patients presenting to Level I through IV trauma centers in the United States. All patients ≥18 years of age who sustained an operatively treated closed femoral shaft fracture were included. The primary outcome of inpatient mortality was compared between two groups: those who received LMWH or unfractionated heparin for VTE prophylaxis. Secondary outcomes were complications including VTE and bleeding events. Groups were compared using a multivariate regression model.ResultsThere were 2058 patients included in the study. Patients who received VTE prophylaxis with LMWH had lower odds of inpatient mortality compared to patients who received VTE prophylaxis with unfractionated heparin (OR 0.19; 95% CI 0.05 to 0.68, p = 0.011).ConclusionsVTE prophylaxis with LMWH is associated with lower inpatient mortality compared to VTE prophylaxis with unfractionated heparin for patients undergoing operative treatment of closed femoral shaft fractures. To our knowledge this is the first study to report these associations for a specific subset of orthopedic trauma patients.     

Dalteparin Vs Low-Dose Unfractionated Heparin for Prophylaxis Against Clinically Evident Venous Thromboembolism in Acute Traumatic Spinal Cord Injury: A Retrospective Cohort Study

Background: When venous thromboembolism (VTE) includes deep-vein thrombosis (DVT) and pulmonary embolism (PE), patients with acute traumatic spinal cord injury (SCI) have the highest incidence of VTE among all hospitalized groups, with PE the third most common cause of death. Although low-molecular-weight heparin (LMWH) outperforms low-dose unfractionated heparin (LDUH) in other patient populations, the evidence in SCI remains less robust.

Objective: To determine whether the efficacy for LMWH shown in previous SCI surveillance studies (eg, routine Doppler ultrasound) would translate into real-world effectiveness in which only clinically evident VTE is investigated (ie, after symptoms or signs present).

Methods: A retrospective cohort study was conducted of 90 patients receiving LMWH dalteparin (5,000 U daily) or LDUH (5,000 U twice daily) for VTE prophylaxis after acute traumatic SCI. The incidence of radiographically confirmed VTE was primarily analyzed, and secondary outcomes included complications of bleeding and heparin-induced thrombocytopenia.

Results: There was no statistically significant association (p = 0.7054) between the incidence of VTE (7.78% overall) and the type of prophylaxis received (LDUH 3/47 vs dalteparin 4/43). There was no significant differences in complications, location of VTE, and incidence of fatal PE. Paraplegia (as opposed to tetraplegia) was the only risk factor identified for VTE.

Conclusions: There continues to be an absence of definitive evidence for dalteparin (or other LMWH) over LDUH as the choice for VTE prophylaxis in patients with SCI. Novel approaches to VTE prophylaxis are urgently required for this population, whose risk of fatal PE has not decreased over the last 25 years.     

Chemoprophylaxis for venous thromboembolism in pelvic and/or acetabular fractures: A systematic review

BackgroundIt is unclear which pharmacological agents, and at what dosage and timing, are most effective for venous thromboembolism (VTE) prophylaxis in patients with pelvic/acetabular fractures.MethodsWe searched the Cochrane Database of Systematic Reviews, Embase, Web of Science, EBSCO, and PubMed on October 3, 2020, for English-language studies of VTE prophylaxis in patients with pelvic/acetabular fractures. We applied no date limits. We included studies that compared efficacy of pharmacological agents for VTE prophylaxis, timing of administration of such agents, and/or dosage of such agents. We recorded interventions, sample sizes, and VTE incidence, including deep vein thrombosis (DVT) and pulmonary embolism.ResultsTwo studies (3604 patients) compared pharmacological agents, reporting that patients who received direct oral anticoagulants (DOACs) were less likely to develop DVT than those who received low molecular weight heparin (LMWH) (p < 0.01). Compared with unfractionated heparin (UH), LMWH was associated with lower odds of VTE (odds ratio [OR] = 0.37, 95% confidence interval [CI]: 0.22–0.63) and death (OR = 0.27, 95% CI: 0.10–0.72). Three studies (3107 patients) compared timing of VTE prophylaxis, reporting that late prophylaxis was associated with higher odds of VTE (OR = 1.9, 95% CI: 1.2–3.2) and death (OR = 4.0, 95% CI: 1.5–11) and higher rates of symptomatic DVT (9.2% vs. 2.5%, p = 0.03; and 22% vs. 3.1%, p = 0.01). One study (31 patients) investigated dosage of VTE prophylaxis, reporting that a higher proportion of patients with acetabular fractures were underdosed (23% of patients below range of anti–Factor Xa [aFXa] had acetabular fractures vs. 4.8% of patients within adequate range of aFXa, p<0.01).Conclusions: Early VTE chemoprophylaxis (within 24 or 48 h after injury) was better than late administration in terms of VTE and death. Many patients with acetabular fractures are underdosed with LMWH, with inadequate aFXa levels. Compared with UH, LMWH was associated with lower odds of VTE and death. DOACs were associated with lower risk of DVT compared with LMWH.Level of Evidence: III, systematic review of retrospective cohort studies.     

Low-Dose Aspirin Administered for Venous Thromboembolism Prophylaxis Reduces the Incidence of Heterotopic Ossification in Total Joint Arthroplasty

BackgroundHeterotopic ossification (HO) is a common complication following total joint arthroplasty (TJA). However, the pathophysiology of HO is not entirely understood. Inflammation may play a significant role in the pathogenesis of HO as nonsteroidal anti-inflammatory drugs are effective in the prevention of HO. The purpose of this study is to examine if aspirin (ASA), when used as venous thromboembolism (VTE) prophylaxis, influenced the rate of HO formation following TJA.MethodsWe queried our longitudinally maintained database to identify all patients who underwent primary total hip arthroplasty (THA) or total knee arthroplasty (TKA) for osteoarthritis between January 2016 and June 2018 with at least 3-month radiographic follow-up. In total, 1238 THAs and 1051 TKAs were included for analysis. Radiographs were reviewed and HO formation graded according to the Brooker classification. Patient demographic and VTE prophylaxis data were collected and reviewed for accuracy. Univariate and multivariate analysis was performed to evaluate the effect of ASA on HO formation.ResultsThe overall rate of HO was 37.5% after THA and 17.4% after TKA. Patients receiving ASA were less likely to develop HO after THA (34.8% vs 45.5%; P < .001), as well as HO after TKA (13.4% vs 18.4%; P = .047) compared to patients receiving non-ASA VTE prophylaxis. The rate of HO formation trended to be lower, albeit not statistically significantly, in patients receiving low-dose ASA (81 mg) vs high-dose ASA (325 mg).ConclusionPatients undergoing primary TJA receiving ASA for VTE prophylaxis were less likely to develop HO compared to patients who were administered non-ASA VTE prophylaxis.     

Joint 2022 European Society of Thoracic Surgeons and The American Association for Thoracic Surgery guidelines for the prevention of cancer-associated venous thromboembolism in thoracic surgery

BackgroundVenous thromboembolism (VTE), which includes deep vein thrombosis and pulmonary embolism, is a potentially fatal but preventable postoperative complication. Thoracic oncology patients undergoing surgical resection, often after multimodality induction therapy, represent among the highest risk groups for postoperative VTE. Currently there are no VTE prophylaxis guidelines specific to these thoracic surgery patients. Evidenced-based recommendations will help clinicians manage and mitigate risk of VTE in the postoperative period and inform best practice.ObjectiveThese joint evidence-based guidelines from The American Association for Thoracic Surgery and the European Society of Thoracic Surgeons aim to inform clinicians and patients in decisions about prophylaxis to prevent VTE in patients undergoing surgical resection for lung or esophageal cancer.MethodsThe American Association for Thoracic Surgery and the European Society of Thoracic Surgeons formed a multidisciplinary guideline panel that included broad membership to minimize potential bias when formulating recommendations. The McMaster University GRADE Centre supported the guideline development process, including updating or performing systematic evidence reviews. The panel prioritized clinical questions and outcomes according to their importance for clinicians and patients. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used, including GRADE Evidence-to-Decision frameworks, which were subject to public comment.ResultsThe panel agreed on 24 recommendations focused on pharmacological and mechanical methods for prophylaxis in patients undergoing lobectomy and segmentectomy, pneumonectomy, and esophagectomy, as well as extended resections for lung cancer.ConclusionsThe certainty of the supporting evidence for the majority of recommendations was judged as low or very low, largely due to a lack of direct evidence for thoracic surgery. The panel made conditional recommendations for use of parenteral anticoagulation for VTE prevention, in combination with mechanical methods, over no prophylaxis for cancer patients undergoing anatomic lung resection or esophagectomy. Other key recommendations include: conditional recommendations for using parenteral anticoagulants over direct oral anticoagulants, with use of direct oral anticoagulants suggested only in the context of clinical trials; conditional recommendation for using extended prophylaxis for 28 to 35 days over in-hospital prophylaxis only for patients at moderate or high risk of thrombosis; and conditional recommendations for VTE screening in patients undergoing pneumonectomy and esophagectomy. Future research priorities include the role of preoperative thromboprophylaxis and the role of risk stratification to guide use of extended prophylaxis.     

Aspirin Thromboprophylaxis Is Associated With Less Major Bleeding Events Following Total Joint Arthroplasty

BackgroundThere is ongoing debate on what is optimal prophylactic agent to reduce venous thromboembolism (VTE) following total joint arthroplasty (TJA). Although many studies assess the efficacy of these agents in VTE prevention, no attention is given to their adverse effect on major bleeding events (MBEs). This study compared the incidence of MBE in patients receiving aspirin as VTE prophylaxis vs other chemoprophylaxis.MethodsA single-institution, retrospective study of 35,860 patients undergoing TJA between 2009 and 2020 was conducted. Demographic variables, co-morbidities, type of chemoprophylaxis, and intraoperative factors were collected. MBE was defined using the 2010 criteria for major bleeding in surgical patients presented by the Scientific and Standardization Committee of the International Society on Thrombosis and Haemostasis. To enhance capture rate, comprehensive queries utilizing MBE keywords were conducted in clinical notes, physician dictations, and phone call logs. Univariate followed by multivariate regression was performed as well as propensity score matched analysis.ResultsOverall, 270 patients (0.75%) in this cohort developed MBE. The MBE rate was 0.5% in the aspirin group and 1.2% in the non-aspirin group. After adjusting for confounders, multiple logistic regression and propensity score matched analysis revealed almost 2 times lower odds of MBE in patients who received aspirin. Variables independently associated with increased MBE risk included increasing age, body mass index, American Society of Anesthesiologists score, revision surgery, peptic ulcer disease, coagulopathy, intraoperative blood transfusion, and active smoking.ConclusionAdministration of aspirin for VTE prophylaxis, compared to other chemoprophylaxis agents may have an association with lower risk of major bleeding following TJA. Future randomized controlled trials should examine these findings.     

Low-Dose Aspirin Is Safe and Effective for Venous Thromboembolism Prevention in Patients Undergoing Revision Total Hip Arthroplasty: A Retrospective Cohort Study

BackgroundCurrently, there is no established universal standard of care for prophylaxis against venous thromboembolism (VTE) in orthopedic patients undergoing revision total hip arthroplasty (rTHA). The aim of this study is to determine whether a protocol of 81-mg aspirin (ASA) bis in die (BID) is safe and/or effective in preventing VTE in patients undergoing rTHAs vs 325-mg ASA BID.MethodsIn 2017, a large academic medical center adopted a new protocol for VTE prophylaxis in arthroplasty patients at standard risk. Initially, patients received 325-mg ASA BID but switched to 81-mg ASA BID. A retrospective review (2011-2019) was performed to identify 1361 consecutive rTHA patients and their associated 90-day postoperative complications such as VTE, including pulmonary embolism (PE) and/or deep vein thrombosis (DVT), as the primary outcome; and gastrointestinal and wound bleeding, acute periprosthetic joint infection, and mortality as the secondary outcome.ResultsFrom 2011 to 2017, 973 rTHAs were performed and 13 total VTE cases were diagnosed (1.34%). From 2017 to 2019, 388 rTHAs were performed with 3 total VTE cases identified (0.77%). Chi-squared analyses and logistic regression models showed no differences in rates or odds in postoperative PE (P = .09), DVT (P = .79), PE and DVT (P = .85), and total VTE (P = .38) using either dose. There were also no differences between bleeding complications (P = .14), infection rate (P = .46), and mortality (P = .53).ConclusionUsing a protocol of 81-mg of ASA BID is noninferior to 325-mg ASA BID and may be safe and effective in maintaining low rates of VTE in patients undergoing rTHA.     

Routine use of LMWH prophylaxis is associated with a lower incidence of venous thromboembolic events following an ankle fracture

BackgroundVenous thromboembolic events (VTE) are well-known and serious complications following a trauma to the lower extremities. There is an ongoing debate on the benefit of low-molecular-weight heparin (LMWH) as prophylaxis following ankle fracture treatment. We examined the association between the incidence of VTE and the use of LMWH-prophylaxis following an ankle fracture, as well as factors affecting the risk of VTE.MethodsIn this retrospective cohort study, data on ankle fractures and fracture treatment from the Swedish Fracture Register was linked to data from the Swedish National Patient Register and the Swedish Prescribed Drug Register. Patients with VTE and patients who received LMWH prophylaxis were identified. The treating orthopedic departments were sent a questionnaire about their guidelines regarding the use of LMWH prophylaxis.Results222 cases of diagnosed VTE were identified among 14,954 ankle fractures. Orthopedic departments with higher-than-average use of LMWH prophylaxis among non-operatively treated ankle fractures had a lower incidence of VTE (OR 0.60, CI 0.39–0.92). Among operatively treated patients, departments with a guideline for the routine use of LMWH prophylaxis also had lower incidence of VTE (OR 0.56, CI 0.37–0.86). A later onset of VTE was seen among patients prescribed LMWH prophylaxis, with a mean of 56 days to onset (CI 44–67), compared to 39 days (CI 33–45) in patients without prescribed prophylaxis. During the first two weeks following injury, there was only one case of VTE in patients with prescribed LMWH, compared to 39 cases of VTE among patients without prescribed prophylaxis.ConclusionsRoutine use of LMWH in patients with operatively treated ankle fractures was associated with a lower incidence of VTE. A more frequent use of LMWH among patients with non-operatively treated ankle fractures were associated with a lower incidence of VTE. The onset occurred later among patients with LMWH-prophylaxis who still suffered a VTE.     

Meta-analysis of low molecular weight heparin in the prevention of venous thromboembolism in general surgery.

BACKGROUND: Low molecular weight heparins (LMWHs) have become routine thromboprophylaxis in general surgery. However, their actual clinical effect, its magnitude relative to that of unfractionated heparin (UFH), and the optimal dose are still debated. METHODS: A meta-analysis was performed of all available randomized trials in general surgery comparing LMWH with placebo or no treatment, or with UFH. RESULTS: Comparison versus placebo or no treatment confirmed that the significant reduction in asymptomatic deep vein thrombosis (DVT) obtained with LMWH (n = 513; relative risk (RR) 0.28 (95 per cent confidence interval 0.14-0.54)) was associated with a significant reduction in clinical pulmonary embolism (n = 5456; RR 0.25 (0.08-0.79)) and clinical venous thromboembolism (VTE) (n = 4890; RR 0.29 (0.11-0.73)), and a trend towards a reduction in overall mortality rate. Comparison versus UFH showed a trend in favour of LMWH, with a significant reduction in clinical VTE (P = 0.049), a trend also found for cancer surgery. LMWH at doses below 3400 anti-Xa units seemed to be as effective as, and safer than, UFH, while higher doses yielded slightly superior efficacy but increased haemorrhagic risk, including that of major haemorrhage. CONCLUSION: Asymptomatic DVT may be regarded as a reliable surrogate endpoint for clinical outcome in studies investigating thromboprophylaxis in general surgery. LMWH seems to be as effective and safe as UFH. Determination of the optimal dose regimen of LMWH for this indication requires further investigation.     

Low-Dose vs Regular-Dose Aspirin for Venous Thromboembolism Prophylaxis in Primary Total Joint Arthroplasty

BackgroundConsensus on whether low-dose (81 mg) or regular-dose (325 mg) aspirin (ASA) is more effective for venous thromboembolism (VTE) chemoprophylaxis in primary total joint arthroplasties (TJAs) is not reached. The goal of this study is to evaluate the efficacy of low-dose and regular-dose ASA for VTE chemoprophylaxis in primary total hip arthroplasties and total knee arthroplasties.MethodsWe retrospectively identified 3512 primary TJAs (2344 total hip arthroplasties and 1168 total knee arthroplasties) with ASA used as VTE chemoprophylaxis between 2000 and 2019. Patients received ASA twice daily for 4-6 weeks after surgery with 961 (27%) receiving low-dose ASA and 2551 (73%) receiving regular-dose ASA. The primary endpoint was 90-day incidence of symptomatic VTEs. Secondary outcomes were gastrointestinal (GI) bleeding events and mortality. The mean age at index TJA was 66 years, 54% were female, and mean body mass index was 31 kg/m². The mean Charlson Comorbidity Index was 3.5. Mean follow-up was 3 years.ResultsThere was no difference in 90-day incidence of symptomatic VTEs between low-dose and regular-dose ASA (0% vs 0.1%, respectively; P = .79). There were no GI bleeding events in either group. There was no difference in 90-day mortality between low-dose and regular-dose ASA (0.3% vs 0.1%, respectively; P = .24).ConclusionIn 3512 primary TJA patients treated with ASA, we found a cumulative incidence of VTE <1% at 90 days. Although this study is underpowered, it appears that twice daily low-dose ASA was equally effective to twice daily regular-dose ASA for VTE chemoprophylaxis, with no difference in risk of GI bleeds or mortality.Level of EvidenceIII, retrospective cohort study.     

Venous Thromboembolism in Cancer Patients Undergoing Major Surgery

Background  Cancer patients undergoing major abdominal or pelvic surgery are at considerable risk of venous thromboembolism (VTE). The genesis of thromboses in malignancy is complicated, and reflects the interaction and derangement of multiple molecular pathways. Furthermore, the nature and location of the cancer, as well as the type surgery involved, are thought to affect the level of VTE risk. These considerations may therefore affect treatment decisions. Methods  We performed multiple Medline searches with terms including but not limited to VTE, cancer, surgery, abdominal, colorectal, unfractionated heparin (UFH), and low-molecular-weight heparin (LMWH) to identify reviews, meta-analyses, nonrandomized and randomized controlled trials, and clinical guidelines relating to management of VTE in patients with abdominal cancer. Results  VTE incidence in patients with malignancy varied according to cancer type, location, stage of progression, and the use of catheters and/or chemotherapy. Thromboprophylaxis with UFH or LMWH reduces the risk of developing VTE in these patients. However, LMWHs have a favorable risk-benefit profile over UFH and extending the duration prophylaxis may improve outcomes. Conclusion  A number of recommendations can be made for the prevention of VTE in patients undergoing abdominal or pelvic surgery for cancer: (1) risk-stratify all patients according to defined evidence-based guidelines; (2) for most abdominal surgical oncology patients at risk, use of both an anticoagulant and mechanical means are indicated and beneficial; and (3) consider extended-duration prophylaxis (up to 28 days) in those patients with major abdominal/pelvic operations and impaired mobility, preferably with LMWH.     

Venous thromboembolism after laparoscopic bariatric surgery for morbid obesity: clinical burden and prevention

BackgroundThe clinical benefit of prophylaxis for venous thromboembolism (VTE) in laparoscopic bariatric surgery is unclear. Our objective was to assess the clinical burden of VTE after laparoscopic bariatric surgery.MethodsWe performed a systematic review and meta-analysis. Studies were considered for the review if they reported on the methods used for antithrombotic prophylaxis and on the incidence of objectively confirmed VTE in patients who had undergone laparoscopic bariatric surgery.ResultsOverall, 19 studies were included in the analysis. The weighted mean incidence (WMI) of pulmonary embolism was .5% (12 events in 3991 patients, 12 studies; 95% confidence interval [CI] .2–.9%; I² 38%) with unfractionated heparin (5000 UI twice or 3 times daily) or low-molecular-weight heparin (30 mg twice daily or 40 mg once daily). The WMI of major bleeding as originally reported in 7 of these studies was 3.6% (2741 patients; 95% CI .9–7.95; I² 94%). The WMI of screened VTE in 3 high-quality studies with different regimens of heparin prophylaxis was 2.0% (8 events in 458 patients; 95% CI .9–3.5%; I² 0%). The WMI of symptomatic VTE was .6% (4 studies; 7 events in 1328 patients; 95% CI .3–1.1%; I² 0%) and that of major bleeding was 2.0% (95% CI 1.0–3.4%; I² 55%), with weight-adjusted doses of heparin prophylaxis.ConclusionThe rate of VTE after laparoscopic bariatric surgery seems to be relatively low with standard regimens for antithrombotic prophylaxis. The incidence of major bleeding seems to increase using weight-adjusted doses of heparin with no advantage in terms of VTE reduction.     

The Prognostic Value of Impaired Walking Distance on Long-term Outcome in Patients with Known or Suspected Peripheral Arterial Disease

IntroductionVenous thrombo-embolism (VTE) has traditionally been considered rare in Asia. Recent reports from Hong Kong and Singapore indicate an increasing incidence of VTE.ObjectivesTo determine the incidence of VTE among hospitalised patients and study the predisposing factors and hence to increase the awareness of the need for VTE prophylaxis.MethodsThis is a retrospective study carried out on all patients diagnosed with VTE between 1996 and 2005 at our hospital. In-patient records were used to collect data while out-patient records were used for follow-up outcomes.ResultsThe incidence of VTE was 17.46 per 10 000 admissions. Malignancy (31%) was the most common predisposing factor, followed by postoperative status (30%). The incidence following surgery was five per 10 000 operations. General surgery patients had the highest incidence of deep vein thrombosis (DVT; 40.3%), while the incidence in orthopaedic patients was 20.1%. Low-molecular-weight heparin (LMWH) has been increasingly used therapeutically over the years. Pulmonary embolism was diagnosed in 14.9% of the study patients. Mortality in those with confirmed pulmonary embolism was 13.5%.ConclusionVTE is no longer a rarity in India. General surgical operations are the most common causes of postoperative DVT. Pulmonary embolism continues to be ‘suspected’ more often than it is diagnosed.     

Enoxaparin Versus Direct Oral Anticoagulants for Venous Thromboembolism in Asians Undergoing Total Knee Arthroplasty: A Meta-Analysis and Systematic Review

BackgroundThe introduction of direct oral anticoagulants (DOACs) shows promise for their role as a chemoprophylaxis agent after total knee arthroplasty (TKA) for the prevention of venous thromboembolism (VTE). However, existing studies are largely based on Western populations that do not account for the different risk profiles and lower rates of VTE in Asians. This systematic review and meta-analysis aimed to evaluate the efficacy of DOACs compared with enoxaparin in an Asian-based population study.MethodsThe review was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. All studies that compared outcomes between enoxaparin and DOACs as VTE prophylaxis after TKA in the Asian population were included.ResultsFive studies with 121,153 patients were included. DOACs demonstrated a convincing benefit over enoxaparin in overall VTE prevention (odds ratio [OR] = 0.42, 95% confidence interval [CI]: 0.24-0.74). However, although the OR trended in favor of DOACs for the reduction of deep vein thrombosis events (OR = 0.54, 95% CI: 0.20-1.48) and pulmonary embolism (OR = 0.75, 95% CI: 0.07-8.20), statistical significance was not reached. In terms of bleeding complications, both arms had similar rates of major (0.91% vs 0.20%), clinically relevant nonmajor (3.28% vs 2.94%), and minor bleeding complications (12.8 vs 13.3%). A nonsignificance advantage of enoxaparin over DOACs was revealed in the OR for major bleeding (OR = 3.17; 95% CI: 0.81-12.43), whereas DOACs were favored to reduce risk of clinically relevant nonmajor (OR = 0.82; 95% CI: 0.01-91.51) and minor bleeding (OR = 0.76; 95% CI: 0.11-5.33).ConclusionDOACs confer a significantly reduced rate of overall VTE compared with enoxaparin in Asians after TKA. No significant differences in deep vein thrombosis, pulmonary embolism, and rates of bleeding complications exist.     

A Prospective Cohort Comparative Study of Rivaroxaban,Dabigatran, and Apixaban Oral Thromboprophylaxis in 2431 Hip and Knee Arthroplasty Patients: Primary Efficacy Outcomes and Safety Profile

BackgroundDirect oral anticoagulants (DOACs) have promised superior efficacy to low molecular weight heparins in the prevention of venous thromboembolism (VTE) in total hip and knee arthroplasty. However, there are concerns about raised associated bleeding and wound problems with these agents. This study aims to evaluate and compare the efficacy and safety of the 3 DOAC drugs: rivaroxaban, dabigatran and apixaban.MethodsThe primary outcome measures were rate of symptomatic VTE and major bleeding. Secondary outcome measures were wound healing problems and requirement for return to theater. A total of 2431 patients received one of the DOAC drugs as thromboprophylaxis following total hip arthroplasty (35 days) or total knee arthroplasty (14 days) between 2011 and 2015. Binary variables were compared between the 3 groups by using the chi-squared test or Fisher’s exact test. Relative risks of selected primary and secondary end points were also calculated for the prespecified pairwise comparison.ResultsThe overall symptomatic VTE rate was 2%. Rivaroxaban had a statistically significant superior efficacy for overall VTE prevention (0.8% vs 2.6%) compared with dabigatran (P < .01) and apixaban (P < .01), and deep vein thrombosis prevention (0.3% vs 2.2%) over dabigatran (P < .01). The overall rate of major bleeding was 1.2% with no significant difference observed between the 3 studied drugs.ConclusionAll 3 drugs had symptomatic VTE rates comparable with low molecular weight heparin from the published literature. Rivaroxaban appears to have superior efficacy in VTE prevention over apixaban and dabigatran. No statistical difference was observed for major bleeding with any of the 3 agents.