Rate Of Symptomatic Venous Thromboembolism Research Articles

Thromboprophylaxis Strategies in Acute Medically Ill Patients

We review pivotal clinical trials of extended-duration venous thromboembolism (VTE) prophylaxis strategies in acute medically ill patients. For VTE prophylaxis in medically ill patients, current guidelines recommend the use of parenteral anticoagulants during hospitalization but not for extended duration prophylaxis. In 2017, betrixaban was approved for VTE prophylaxis in acute medically ill patients based on the results of the APEX trial. The MARINER trial missed its primary endpoint of reducing the composite of symptomatic VTE and VTE-related mortality with rivaroxaban compared with placebo. It did show that rivaroxaban halved the symptomatic VTE rate compared with placebo and did achieve its secondary endpoint. The EXCLAIM, ADOPT, and MAGELLAN trials did not demonstrate a net clinical benefit in reduction of VTE events due to an increase in bleeding events. The risk of VTE remains high in acute medically ill patients after hospital discharge. Based on the results of the APEX trial which showed a reduction in VTE, the FDA approved betrixaban for use in acute medically ill patients for extended duration VTE prophylaxis. Next steps are to implement the findings from APEX and MARINER into clinical practice to reduce recurrent VTE, lower healthcare cost, and reduce rehospitalization.

A ten-year retrospective study investigating the rate of venous thromboembolism in patients who require immobilization in a total contact lower limb cast

To our knowledge, there is currently no information available about the rate of venous thromboembolism (VTE) or recommendations regarding chemoprophylaxis for patients whose lower limb is immobilized in a plaster cast. We report a retrospective case series assessing the rate of symptomatic VTE in patients treated with a lower limb cast. Given the complex, heterogeneous nature of this group of patients, with many risk factors for VTE, we hypothesized that the rate of VTE would be higher than in the general population. Patients treated with a lower limb cast between 2006 and 2018 were identified using plaster room records. Their electronic records and radiological reports were reviewed for details about their cast, past medical history, and any VTE recorded in our hospital within a year of casting. There were 136 episodes of casting in 100 patients. The mean age was 55 years (22 to 91). The mean time in a cast was 45 days (five days to eight months). A total of 76 patients had neuropathy secondary to diabetes. No patient received chemical thromboprophylaxis while in a cast. One VTE (0.7% of casting episodes) was documented. This was confirmed by Doppler scan nine days after removing the cast. The frequency of VTE was higher than that of the general population (0.05%); this is most likely attributable to our patients' apparent increase in VTE risk as suggested by The National Institute for Health and Care Excellence (NICE). These findings suggest that thromboprophylaxis is not routinely indicated in patients who undergo immobilization of the lower limb in a cast, although the risks of VTE should be assessed. While the cast itself does not pose an increased risk, other pathologies, such as active cancer, mean that each individual case needs to be considered on their merit. Cite this article: Bone Joint J 2019;101-B:691-694.

Direct oral anticoagulants for extended treatment of venous thromboembolism: insights from the EINSTEIN CHOICE study.

The risk of recurrence of venous thromboembolism (VTE) persists after interruption of the initial anticoagulation therapy. New evidence shows that direct oral anticoagulants are effective for extended treatment of VTE and may reduce the risk of all-cause mortality. The optimal duration of anticoagulation after VTE is, however, controversial and complicated by the need for individualised assessment and balance between thrombosis and bleeding risks. Three direct oral anticoagulants (rivaroxaban, apixaban and dabigatran) have been studied for extended treatment of VTE. Dabigatran was shown to be safer than vitamin K antagonists and similarly effective for the prevention of recurrent VTE. Dabigatran, apixaban and rivaroxaban resulted in significant decreases in the rate of recurrent symptomatic VTE when compared to placebo, without a statistically significant difference in the risk of major bleeding. The latest guidelines of the American College of Chest Physicians suggest the use of low-dose aspirin to prevent VTE recurrence in patients who want to stop anticoagulation. In the randomised, double-blind, phase 3 EINSTEIN CHOICE trial, once-daily rivaroxaban at doses of 20 mg or 10 mg and 100 mg of aspirin were compared in VTE patients for whom there was clinical equipoise for extended anticoagulation. Either a treatment dose (20 mg) or a prophylactic dose (10 mg) of rivaroxaban significantly reduced the risk of VTE recurrence without a significant increase in bleeding risk compared with aspirin. The EINSTEIN CHOICE trial included patients with provoked or unprovoked VTE. Patients with VTE provoked by minor persistent or minor transient risk factors enrolled in this trial had not-negligible VTE recurrence rates. These new findings on extended therapy suggest the possibility of anticoagulation regimens at intensities tailored to the patients' risk profiles and VTE characteristics, with a shift of the risk-benefit balance in favour of extended treatment.

Potent Anticoagulation Does Not Reduce Venous Thromboembolism in High-Risk Patients.

Based on current guidelines from the American Academy of Orthopaedic Surgeons (AAOS), a number of prophylactic modalities for the prevention of venous thromboembolism in total joint arthroplasty may be used. It is common practice that more potent prophylactic agents are used for patients at higher risk of venous thromboembolism. However, we are aware of no studies that have investigated the efficacy of potent anticoagulation in higher-risk individuals. Therefore, the purpose of our study was to test the hypothesis that low-molecular-weight heparin and warfarin result in a reduction in venous thromboembolism events in high-risk patients. A retrospective, multi-institutional study of 60,467 primary and revision total joint arthroplasties from 2000 to 2015 was performed. Identified medications were classified as aspirin, low-molecular-weight heparin, or warfarin. Patients with unavailable venous thromboembolism prophylaxis information or those not receiving the aforementioned prophylaxis were excluded. Information pertinent to the objective of this study was collected and a venous thromboembolism risk score was calculated based on 26 variables. Treatment outcomes assessed included 90-day rate of symptomatic venous thromboembolism and periprosthetic joint infection. Propensity score matching was performed (1:1), as well as logistic regression analysis on the total sample. Aspirin prophylaxis demonstrated a lower rate of deep vein thrombosis, pulmonary embolism, and venous thromboembolism than warfarin and low-molecular-weight heparin alone throughout all risk scores. In the matched propensity score analysis, low-molecular-weight heparin and warfarin demonstrated increased odds of venous thromboembolism for both standard-risk and high-risk patients undergoing total knee arthroplasties compared with aspirin. For primary total hip arthroplasty, warfarin demonstrated an increased risk for high-risk patients and low-molecular-weight heparin demonstrated an increased risk for standard-risk patients. The prevalence of periprosthetic joint infection was higher in patients receiving warfarin (p < 0.001 for both comparisons of warfarin with aspirin and low-molecular-weight heparin). The results of this multi-institutional study demonstrate that the use of warfarin and low-molecular-weight heparin in higher-risk patients does not necessarily result in a reduction in symptomatic venous thromboembolism. Aspirin administered to higher-risk patients seems to be as effective as potent anticoagulation and more effective than warfarin. Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Extended anticoagulation for the secondary prevention of venous thromboembolic events: An updated network meta-analysis.

BackgroundExtended treatment is preconized in a significant proportion of patients with unprovoked venous thromboembolism (VTE). However, limited direct/indirect comparisons are available to appropriately weight the benefit/risk ratio of the diverse treatments available. We aimed to compare the rate of symptomatic recurrent VTE and major bleeding (MB), the net clinical benefit (VTE+MB) and death on vitamin-K antagonist (VKA), direct oral anticoagulants (DOAC) and antiplatelet drugs for extended anticoagulation.MethodsA systematic literature search through September 2018 identified randomized trials studying these pharmacologic therapies for extended anticoagulation following VTE. Treatment effects were calculated using network meta-analysis with frequentist fixed-effects model.Results18 trials (18,221 patients) were included in the analysis. All treatments reduced the risk of recurrence compared to placebo/observation. Nonetheless, VKA (RR 0.22; 95%CI 0.13–0.39) and DOAC (RRs ranging from 0.25–0.32; 95%CI ranging from 0.13–0.52) were more effective than aspirin, whereas low-dose VKA was less effective than standard-dose VKA (RR 2.47; 95%CI 1.34–4.55). The efficacy of DOAC was globally comparable to standard-adjusted dose VKA. Low- (RR 3.13; 95%CI 1.37–7.16) and standard-dose (RR 3.23; 95%CI 1.16–8.99) VKA also increased the risk of MB, which was not the case for any DOAC. Low-dose VKA and low-dose DOAC had similar effects on MB compared to standard-doses. Although there was a trend for reduced MB and enhanced net clinical benefit for DOAC compared to VKA, this was not statistically significant. The specific anticoagulant therapies had no significant effects on deaths.ConclusionStandard-dose VKA and low/standard-dose DOAC share similar effects on VTE recurrence and MB, whereas aspirin and low-dose VKA were associated with lower benefit/risk ratio.

Venous Thromboembolism and Bleeding Adverse Events in Lower Leg, Ankle, and Foot Orthopaedic Surgery with and without Anticoagulants.

Currently, there is insufficient knowledge about the benefits of anticoagulant use for primary prevention of venous thromboembolism (VTE) and its inherent risk of bleeding adverse events in patients undergoing surgery distal to the knee. The study included patients who had undergone an orthopaedic procedure distal to the tibial articular surface when they were 18 years of age or older. Using retrospective information from a tertiary care referral center, we compared patient demographics, clinical findings, diagnostic reports, procedures performed, and the rate of symptomatic VTE and bleeding adverse events between patients who had and those who had not received anticoagulant prophylaxis. Propensity score matching was used to minimize selection bias due to prophylactic treatment allocation. A total of 5,286 patients who had received anticoagulant prophylaxis for below-the-knee surgery were successfully matched with 5,286 patients who had not received anticoagulant prophylaxis for such surgery. After propensity score matching, the standardized difference between the groups was <0.1 for all baseline characteristics, indicating a negligible difference between the groups. Patients who received anticoagulant prophylaxis had a significantly lower risk of developing a VTE compared with patients who did not (39 patients [0.7%] versus 99 patients [1.9%]), with an odds ratio (OR) of 0.38 (95% confidence interval [CI], 0.25 to 0.56; p < 0.001). In contradistinction, patients who received anticoagulant prophylaxis had a significantly higher risk of developing a bleeding adverse event than those who did not (115 [2.2%] versus 55 [1.0%]; OR, 2.18 [95% CI, 1.55 to 3.09]; p < 0.001). Anticoagulant prophylaxis reduced the risk of VTE after surgery distal to the tibial articular surface by 3-fold but resulted in a concomitant 2-fold increase in the risk of a bleeding adverse event. Large-scale, prospective studies are necessary to better understand the true incidence of such events, associated patient-specific risk factors, efficacy of various thromboprophylactic regimens, and patient-reported implications of such events. Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Apixaban for Primary Prevention of Venous Thromboembolism in Patients With Multiple Myeloma Receiving Immunomodulatory Therapy.

Immunomodulatory drugs (IMiDs), including thalidomide, lenalidomide, and pomalidomide, have improved survival of patients with multiple myeloma (MM). However, these therapies are associated with an increased risk of venous thromboembolism (VTE). Apixaban has been approved for treatment of acute VTE and for risk reduction of recurrent VTE following initial therapy. In this phase IV single-arm study (NCT02958969), we aim to prospectively evaluate the safety and efficacy of apixaban for primary prevention of VTE in patients with MM. The primary efficacy objective of this trial is to determine the rate of symptomatic VTE, including deep vein thrombosis (DVT) and pulmonary embolism (PE), over 6 months. The primary safety objective is to determine the rate of major bleeding in MM patients receiving apixaban prophylaxis. If proven safe and effective, apixaban will emerge as a promising option for oral VTE prophylaxis in MM patients.

Individual risk factors predictive of venous thromboembolism in patients with temporary lower limb immobilization due to injury: a systematic review

Essentials Thromboprophylaxis after lower limb injury is often based on complex risk stratification.Our systematic review identified variables predicting venous thromboembolism (VTE) in this group.Age and injury type were commonly reported to increase the odds of VTE (odds ratio 1.5–3.48).We found limited evidence to support the use of other risk factors within prediction models. SummaryBackgroundPatients immobilized after lower limb injury are at risk of venous thromboembolism (VTE). There is international variation in the use of thromboprophylaxis for such patients. Risk‐based strategies have been adopted to aid decision making in many settings. The accuracy of these strategies is unclear.ObjectivesA systematic review was undertaken to identify all individual patient‐identifiable risk factors linked to any VTE outcome following lower limb immobilization.MethodsSeveral electronic databases were searched from inception to May 2017. Any studies that included a measurement of VTE as a patient outcome in adults requiring temporary immobilization (e.g. leg cast or brace in an ambulatory setting) for an isolated lower limb injury and reported risk factor variables were included. Descriptive statistics and thematic analysis were used to synthesize the evidence.ResultsOur database search returned 4771 citations, of which 15 studies reporting outcome data on 80 678 patients were eligible for analysis. Risk‐factor associations were reported through regression analyses, non‐parametric tests and descriptive statistics. All studies were assessed as at moderate or serious risk of bias using the ROBINS‐I risk of bias tool.Advancing age and injury type were the only individual risk factors demonstrating a reproducible association with increased symptomatic and/or asymptomatic VTE rates. Several risk factors currently used in scoring tools did not appear to be robustly evaluated for subsequent association with VTE within these studies.ConclusionsClinicians should be aware of the limited evidence to support individual risk factors in guiding thromboprophylaxis use for this patient cohort.

Prospective Study of Apixaban for Primary Prevention of Venous Thromboembolism in Patients with Multiple Myeloma Receiving Immunomodulatory Therapy

IntroductionImmunomodulatory/cereblon-binding drugs (IMiDs), including lenalidomide and pomalidomide, have improved survival of patients with multiple myeloma (MM) and comprise the therapeutic foundation at all phases of therapy. While these agents are generally well-tolerated, their increased risk of venous thromboembolism (VTE), in particular deep vein thrombosis and pulmonary embolism, presents a major clinical challenge for the treatment of MM. Apixaban, a direct oral anticoagulant which directly blocks Factor Xa, has been approved for treatment in patients with VTE. Apixaban has not been prospectively evaluated for thromboprophylaxis in MM in the US. In this phase IV single-arm study (NCT02958969), we prospectively evaluate the safety and efficacy of apixaban for primary prevention of VTE in patients with MM receiving IMiD therapy.MethodsFifty patients with MM on IMiD therapy received apixaban 2.5 mg orally twice daily for primary prevention of VTE and were prospectively monitored for 6 months. Patients requiring therapeutic anticoagulation or with history of prior VTE were excluded. Patients stopped aspirin while on apixaban. Primary safety outcomes were rates of major hemorrhage and clinically relevant non-major hemorrhage over 6 months. Major bleeding was defined as overt bleeding associated with a decrease in hemoglobin of ≥ 2 g/dL, requiring transfusion of ≥ 2 units of blood, occurring in a critical site, or contributing to death. Clinically relevant non-major bleeding was defined as overt bleeding not meeting the criteria for major bleeding but associated with medical intervention, surgical intervention, or interruption of the study drug. The primary efficacy outcome was the rate of symptomatic VTE over 6 months.ResultsBaseline characteristics are listed (Table). Median age was 63 years (range 51-74) with 50% of patients being male. Patients had received a median of 2 lines of therapy (range 0-8), and the majority (82%) had received prior autologous stem cell transplantation (AutoSCT). Patients received apixaban thromboprophylaxis in combination with lenalidomide (58%) or pomalidomide (42%). The majority (66%) received IMiDs for post-autoSCT consolidation or maintenance therapy. Most (80%) had traditional cardiovascular (CV) risk factors prior to initiation of apixaban, including hypertension (50%), obesity (46%), history of smoking (34%) and hyperlipidemia (32%).At planned interim analysis at 3 months (range 23-149 days) with data still being collected for planned 6 month study duration, no patients had experienced major hemorrhage or VTE. Two patients experienced clinically relevant, non-major hemorrhage, including one patient with unprovoked epistaxis lasting more than 5 minutes and another patient with mechanical trauma. These events were medically managed, and both patients were able to resume apixaban. One patient stopped therapy shortly after initiation due to allergic reaction to apixaban manifesting as generalized edema. No patients experienced stroke, myocardial infarction (MI), or death.ConclusionsIn this pilot study of 50 patients, low-dose apixaban was safe and well tolerated as thromboprophylaxis for patients with MM receiving IMiDs. No patients experienced VTE, major hemorrhage, stroke, or MI. Further randomized studies are needed to validate apixaban as a standard primary prevention anti-thrombotic strategy for patients with MM receiving IMiDs. [Display omitted] DisclosuresMoslehi:Bristol-Myers Squibb: Consultancy, Research Funding. Jagasia:Incyte Corporation: Membership on an entity's Board of Directors or advisory committees.

Venous thromboembolism after total knee and hip arthroplasty. A retrospective study.

Objectives:To evaluate the incidence and risk factors of Venous thromboembolism (VTE) among total knee arthroplasty (TKA) and total hip arthroplasty (THA) patients following surgery.Methods:We conducted a retrospective review of electronic medical records of consecutive patients between January 2010 and January 2015 who underwent TKA or THA at King Abdulaziz Medical City (KAMC), Riyadh, Saudi Arabia.Results:The incidence of symptomatic VTE was 1.9% (17 events, 95% CI: 1.1–2.8) in 756 patients who underwent 889 surgeries. All VTE cases developed before hospital discharge. Twelve (1.4%) patients developed pulmonary embolism, and 5 (0.6%) patients developed deep vein thrombosis. The majority of patients (n=557, 62.7%) underwent surgery for single TKA, and 138 (15.5%) patients underwent bilateral arthroplasty. Based on univariate risk analysis, bilateral arthroplasty was the only potential predictor for VTE after surgery.Conclusion:The rate of symptomatic VTE in a Saudi population following arthroplasty is low and comparable to the international data. However, efforts and more trials are needed to further improve in-hospital thromboprophylaxis measures.

Electronic alerts, comparative practitioner metrics, and education improve thromboprophylaxis and reduce venous thrombosis in community hospitals

BackgroundVenous thromboembolism prophylaxis remains underutilized in hospitalized medical patients at high risk for venous thromboembolism. We previously reported that a multifaceted intervention was associated with a sustained increase in appropriate thromboprophylaxis and reduced symptomatic venous thromboembolism among medical patients hospitalized in two urban teaching hospitals. The effectiveness of this intervention in community hospitals is unknown. MethodsWe performed a prospective multicenter cohort study in three community hospitals. All medical patients admitted from February 1, 2011 to January 31, 2014 were eligible. Consecutive eligible patients were enrolled into the 12‐month “control,” 12‐month “intervention,” or 12‐month “maintenance” group. We provided electronic alerts, physician performance feedback, and targeted medical education for the intervention group. Only the alert component of the intervention continued in the maintenance group. The primary outcome was the rate of appropriate thromboprophylaxis among patients at high risk for venous thromboembolism defined as the prescription of guideline recommended chemoprophylaxis, or identification of a chemoprophylaxis contraindication. Secondary outcomes included rates of symptomatic venous thromboembolism, major bleeding, all‐cause mortality, heparin‐induced thrombocytopenia, physician satisfaction, and alert fatigue. ResultsAppropriate thromboprophylaxis when compared to the control group rate of 67% was higher for the intervention group (85%) and for the maintenance group (77%; P<.001 for each comparison). A reduction of 90‐day symptomatic venous thromboembolism accompanied the intervention (control 4.5%, intervention 3.4%, maintenance 3.0%, P=.04). ConclusionsThis multifaceted intervention was associated with an overall increase in appropriate thromboprophylaxis of medical patients compared with the control period. Hospital‐associated venous thrombosis rates decreased.

Efficacy and safety of low-molecular-weight heparin after knee arthroscopy: A meta-analysis.

BackgroundVenous thromboembolism (VTE) is considered a potentially serious complication of knee arthroscopy and leads to conditions such as deep venous thrombosis (DVT) and pulmonary embolism (PE). Low-molecular-weight heparin (LMWH) is widely employed in knee arthroscopy to reduce perioperative thromboembolic complications. However, the efficacy and safety of LMWH in knee arthroscopy remains unclear.MethodsSeven randomized controlled clinical trials on LMWH in knee arthroscopy were identified and included in this meta-analysis. The main outcomes of the effectiveness (prevention of DVT and PE) and complications (death, major bleeding, and minor bleeding) of LMWH in knee arthroscopic surgery were assessed using Review Manager 5.3 software.ResultsThe meta-analysis indicated that LMWH prophylaxis comprised 79% of asymptomatic DVT. No association was found in symptomatic VTE (RR: 0.90; 95% confidence interval [CI]: 0.39–2.08; P = 0.80), symptomatic DVT (RR: 0.79; 95% CI: 0.28–2.23; P = 0.66), symptomatic PE (RR: 1.36; 95% CI: 0.37–4.97; P = 0.64) and major bleeding (RR: 0.70; 95% CI: 0.12–3.95; P = 0.68) risk during LMWH prophylaxis were identified. Death was not reported in these studies. Moreover, there was a lower incidence of minor bleeding (RR: 0.64; 95% CI: 0.49 to 0.83; P = 0.001) in the control group than in the LMWH group.ConclusionCompared with the control group, the group treated with LMWH after knee arthroscopy was no association in reducing the symptomatic VTE rate, symptomatic DVT rate or symptomatic PE rate. The symptomatic VTE rate was 0.5% (11/2,166) in the LMWH group versus 0.6% (10/1,713) in the control group. Although the limitations of this meta-analysis cannot be ignored, the results of our study show that LMWH after knee arthroscopy is ineffective. We recommend that LMWH should not be routinely provided for knee arthroscopy.Trial registrationClinicalTrials.gov NCT03164746

Improving Pharmacologic Prevention of VTE in Trauma: IMPACT-IT QI Project

Enoxaparin regimens commonly used for prophylaxis fail to achieve optimal anti-factor Xa levels in up to 70 per cent of trauma patients. Accordingly, trauma services at the study institution endeavored to develop a standardized approach to optimize pharmacologic prevention with enoxaparin. An enoxaparin venous thromboembolism (VTE) prophylaxis protocol implemented in October 2015 provided weight-adjusted initial dosing parameters with subsequent dose titration to achieve targeted anti-factor Xa levels. Symptomatic VTE rate was evaluated 12 months pre- and post-implementation. Data were obtained from the trauma registry and charts were reviewed from electronic medical records. The rate of symptomatic VTE significantly declined post-implementation (2.0% vs 0.9%, P = 0.009). Enoxaparin use was comparable in these two phases validating that the decline in symptomatic VTEs was not due to an increase in enoxaparin use. Symptomatic VTE rate for patients who received enoxaparin in the post-implementation cohort decreased from 3.2 to 1.0 per cent (P = 0.023, 95% confidence interval = 0.124-0.856). There was also a significant decrease in the rate of symptomatic deep vein thrombosis (2.8% vs 0.9%, P = 0.040, 95% confidence interval = 0.117-0.950). This approach to VTE prophylaxis with enoxaparin resulted in a significant reduction in symptomatic VTE rates. Implementation of similar practices may be equally impactful in other institutions that use enoxaparin.

Incidence of clinically suspected venous thromboembolism in British Indian patients.

Introduction Venous thromboembolism (VTE) remains a major public health issue around the world. Ethnicity is known to alter the incidence of VTE. To our knowledge, there are no reports in the literature investigating the incidence of VTE in British Indians. The aim of this study was to investigate the rates of symptomatic VTE in British Indian patients in the UK. Methods Patients referred to our institution between January 2011 and August 2013 with clinically suspected VTE were eligible for inclusion in the study. Those not of British Indian or Caucasian ethnicity were excluded. A retrospective review of these two cohorts was conducted. Results Overall, 15,529 cases were referred to our institution for suspected VTE. This included 1,498 individuals of British Indian ethnicity. Of these, 182 (12%) had confirmed VTE episodes. A further 13,159 of the patients with suspected VTE were coded as Caucasian, including 2,412 (16%) who had confirmed VTE events. VTE rates were a third lower in British Indians with clinically suspected VTE than in the equivalent Caucasian group. The British Indian cohort presented with VTE at a much earlier age than Caucasians (mean 57.0 vs 68.0 years). Conclusions This study suggests that British Indian patients have a lower incidence of VTE and are more likely to present at an earlier age than Caucasians. There was no significant difference in VTE type (deep vein thrombosis vs pulmonary embolism) among the ethnic groups. Clinicians should be aware of variations within ethnicities but should continue to adhere to existing VTE prevention guidance.

Interventions for implementation of thromboprophylaxis in hospitalized patients at risk for venous thromboembolism.

Background Venous thromboembolism (VTE) is a leading cause of morbidity and mortality in hospitalized patients. While numerous randomized controlled trials (RCTs) have shown that the appropriate use of thromboprophylaxis in hospitalized patients at risk for VTE is safe, effective, and cost‐effective, thromboprophylaxis remains underused or inappropriately used. Our previous review suggested that system‐wide interventions, such as education, alerts, and multifaceted interventions were more effective at improving the prescribing of thromboprophylaxis than relying on individual providers’ behaviors. However, 47 of the 55 included studies in our previous review were observational in design. Thus, an update to our systematic review, focused on the higher level of evidence of RCTs only, was warranted.

Thromboembolism prophylaxis in orthopaedics: an update.

Venous thromboembolism (VTE) is a serious complication during and after hospitalization, yet is a preventable cause of in-hospital death.Without VTE prophylaxis, the overall VTE incidence in medical and general surgery hospitalized patients is in the range of 10% to 40%, while it ranges up to 40% to 60% in major orthopaedic surgery. With routine VTE prophylaxis, fatal pulmonary embolism is uncommon in orthopaedic patients and the rates of symptomatic VTE within three months are in the range of 1.3% to 10%.VTE prophylaxis methods are divided into mechanical and pharmacological. The former include mobilization, graduated compression stockings, intermittent pneumatic compression device and venous foot pumps; the latter include aspirin, unfractionated heparin, low molecular weight heparin (LMWH), adjusted dose vitamin K antagonists, synthetic pentasaccharid factor Xa inhibitor (fondaparinux) and newer oral anticoagulants. LMWH seems to be more efficient overall compared with the other available agents. We remain sceptical about the use of aspirin as a sole method of prophylaxis in total hip and knee replacement and hip fracture surgery, while controversy still exists regarding the use of VTE prophylaxis in knee arthroscopy, lower leg injuries and upper extremity surgery.Cite this article: EFORT Open Rev 2018;3:136-148. DOI: 10.1302/2058-5241.3.170018

Low rates of symptomatic venous thromboembolism in patients with gastrointestinal cancer: an Iranian study.

: Venous thromboembolism (VTE), which mostly includes deep vein thrombosis (DVT) and pulmonary embolism (PE), is associated with considerable morbidity and mortality in patients with cancer. As little is known about VTE associated with gastrointestinal cancers among the populations in the Middle East. This study aimed to determine the relative frequency of symptomatic VTE in patients with gastrointestinal malignancies in Iran. The charts of patients with gastrointestinal cancers in our institute from April 2010 to March 2015 were investigated for symptomatic VTE in a retrospective study. In this study, all of the patients received chemotherapy. The data included the site of cancer, time of therapies initiation, patient's characteristics, type of VTE, the time of developing symptomatic VTE of patients with gastrointestinal cancer and the stage which VTE occurred. All of DVTs and pulmonary embolism were confirmed by Doppler ultrasonography and computed tomography angiography. A total of 614 consecutive patients with gastrointestinal cancer were included in study. In total, 22 patients (3.6%) were found to have experienced symptomatic VTE (confidence interval 95%: 2.1-5.1%) which included: 19 patients who suffered from DVT and three of them detected pulmonary embolism, and other types of VTE were not reported. Out of 22 patients with VTE, 17 of them have been occurred after chemotherapy (77%) within 6.17 ± 5.17 (range, 1-19) month after starting chemotherapy. The distribution of frequency of stage in which the VTE occurred, was more in stage III and IV. The rate of symptomatic VTE in patients with gastrointestinal cancer in Iran is relatively lower than other studies done in the west. Therefore, it seems the rate of VTE differs in different ethnic groups.

Risk of Venous Thromboembolism after a Single Normal Proximal Lower Extremity Venous Ultrasound.

The optimal lower extremity venous ultrasound (US) protocol to diagnose deep venous thrombosis of the popliteal and more proximal veins is unclear. To determine the three-month rate of symptomatic venous thromboembolism (VTE) and clinical outcomes of inpatients and ambulatory patients with normal findings on single venous ultrasound of the popliteal and more proximal veins (single proximal US). Single proximal US results and clinical data of all inpatient and ambulatory patients with suspected acute deep venous thrombosis were retrospectively reviewed during a 12-month period between January and December 2014. Three-month follow-up data were reviewed for all these patients, who received all their care from a single geographically isolated health maintenance organization. Three-month rate of symptomatic VTE and clinical outcomes after an initially normal single proximal US result. Of 1295 patients, 111 (8.6%) were found to have acute deep venous thrombosis on the initial proximal US. Of the remaining 1184 patients with initially normal results on proximal US who were sampled at 3-month follow-up, 1075 patients (90.8%) had no venous thromboembolic event. Among the others, 11 (0.9%) had a subsequent imaging-confirmed venous thromboembolic event, 53 (4.5%) died (none owing to venous thromboembolism), and 45 (3.8%) did not complete follow-up. Symptomatic VTE after an initially normal single proximal US result occurred in less than 1% of this cohort. Therefore, serial proximal US is unnecessary for most of our patients, and its elimination will save time and out-of-pocket expenses.

Asymptomatic Lower Extremity Deep Vein Thrombosis - Clinical Characteristics, Management Strategies, and Long-Term Outcomes.

The prognosis of asymptomatic deep vein thrombosis (DVT) is uncertain and there is no consensus on the necessity of detection and treatment.Methods and Results:We retrospectively evaluated 300 patients with asymptomatic lower extremity DVT screened from 4,514 consecutive patients on ultrasound at Kyoto University Hospital between January 2010 and September 2015. The subjects had concomitant active cancer in 40%, unprovoked DVT in 59%, and distal DVT in 70%. The cumulative 5-year incidences of symptomatic recurrent venous thromboembolism (VTE); major bleeding; and all-cause death were 14.5%, 16.6%, and 34.1%, respectively. Among 232 patients (77%) with prolonged anticoagulant therapy, anticoagulants were discontinued in 48.4% at 1 year. Anticoagulant therapy was associated with a significantly higher incidence of major bleeding compared with the non-anticoagulant group (20.5% vs. 1.5%, P=0.01) with no significant effect on the incidence of VTE. In patients with active cancer, the favorable effect of anticoagulants relative to no anticoagulants for VTE was significant (HR, 0.22; 95% CI: 0.05-0.95). Prolonged anticoagulants therapy was implemented in the majority of patients with asymptomatic DVT, but was associated with a significantly higher risk for major bleeding. On subgroup analysis in patients with active cancer, however, there appeared to be a benefit of prolonged anticoagulant therapy in decreasing the rate of symptomatic recurrent VTE.

A Systematic Review and Meta-Analysis of Randomized Trials Examining Extended Thromboprophylaxis with Direct Oral Anticoagulants in Hospitalized Medical Patients

▪INTRODUCTION:Thromboprophylaxisduring hospitalization is an accepted intervention to prevent hospital related venous thromboembolism (VTE), however VTE still occurs post discharge. Recently, several randomized trials have compared extended prophylaxis with a direct oral anticoagulant (DOAC) for a prolonged period after hospital discharge to standard short-course prophylaxis with low molecular weight heparin (LMWH) in acutely-ill medical patients. While DOACs offer a convenient means to prevent post-hospitalization VTE, it remains unclear if this intervention has a positive risk-benefit ratio in the overall population of acutely hospitalized medical patients. To better answer this, we performed the following systematic review and meta-analysis.METHODS:We performed a systematic literature search in Medline using PUBMED in an attempt to identify all relevant randomized clinical trials comparing extended prophylaxis with any DOAC to standard course prophylaxis in hospitalized medical (non-surgical) patients. We extracted data on study design and characteristics, total VTE, symptomatic VTE, total bleeding, and major bleeding. Pooled relative risk (RR) was calculated with a corresponding 95% confidence interval (CI) using a Mantel-Haneszelrandom-effects model. Absolute risk differences and the number needed to treat (NNT) or number needed to harm (NNH) were generated along with Forest plots.RESULTS:Our search identified 338 individual publications, of which 313 were excluded on initial screening by title and abstract. Full text were obtained of the remaining 25 studies and independently reviewed by two physicians, of which 22 were excluded for the following reasons: Comments on other articles (12), Study Protocol (1), Review article (8), Data unavailable (1).A total of three trials, enrolling 22,142 patients, were included. Apixaban, rivaroxaban, andbetrixabanwere each evaluated by one study. Among the studies, 11,064 patients were randomized to extended DOAC prophylaxis, while 11,078 were randomized to standard course LMWH prophylaxis.In pooled analysis, VTE (including screened asymptomatic VTE) occurred in 4.30% of the patients receiving extended DOAC prophylaxis and 5.61% of patients treated with standard course LMWH (RR 0.76 [95% CI, 0.67-0.87], P = <0.0001, I2 = 0%). The NNT was 76. Symptomatic VTE occurred in 1.11% of patients treated with extended course DOACs and 1.68% patients treated with standard course LMWH. DOAC extended prophylaxis was associated with a significant reduction in symptomatic VTE (RR 0.66 [95% CI, 0.51-0.86], P = 0.002, I2 = 0%). The pooled absolute risk reduction was 0.57%, with a NNT of 176.A bleeding event occurred in 4.82% of patients receiving extended course DOACs compared to 3.16% of patients receiving standard course LMWH. The pooled analysis demonstrates a statistically relevant increase in bleeding (RR 1.74 [95% CI, 1.05-2.90], P < 0.001, I2 = 92%), with an absolute risk difference of 1.67% and a NNH of 60. A major bleeding event occurred in 0.59% of patients treated with extended course DOACs and 0.35% of patients treated with standard course LMWH. DOAC extended prophylaxis was associated with a significantly increased rate of major bleeding (RR 1.71 [95% CI, 1.07-2.75], P = 0.03, I2 = 23%). The pooled absolute risk difference is 0.24% with a NNH of 417.CONCLUSIONS:In this pooled analysis, extendedthromboprophylaxiswith DOACs was associated with a significant decrease in total and symptomatic VTEin medical patientsas compared to standard course LMWH. However, the low rate of symptomatic VTE, low absolute risk reduction, and significantly increased rate of bleeding with extended prophylaxis calls into questions if this intervention should be used. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.