Treating venous thromboembolic events in the pediatric population

In the pediatric population, the risk of venous thromboembolism (VTE) is lower and less defined than in adults, making the diagnosis easy to overlook. Signs and symptoms in children are usually vague, so nurse practitioners need to be aware of what to look for and how to manage VTE in children.     

New oral anticoagulants in the ED setting: a review

Background

Emergency department (ED) clinicians are not typically involved in the long-term management of patients' anticoagulation therapy, but they are responsible for decision making for emergency conditions requiring anticoagulation, such as acute venous thromboembolism (VTE). In addition, emergency physicians are often faced with patients who present first to the ED with conditions that may prompt long-term anticoagulation upon hospital discharge, such as atrial fibrillation (AF), or who have acute or potential bleeding complications from anticoagulation.

Objective

In this review, clinical trials of new oral anticoagulants evaluated for treatment of VTE and stroke prophylaxis in AF, as well as practical management aspects, will be discussed. In addition, clinical trials evaluating the adjunctive use of the new oral anticoagulants with antiplatelet therapy in patients who have experienced acute coronary syndrome will be explored.

Discussion

Both dabigatran etexilate and rivaroxaban have successfully completed phase III trials for acute VTE treatment and are currently approved for the reduction of risk of stroke and systemic embolism in patients with nonvalvular AF. In a recently completed phase III trial, apixaban also demonstrated promising efficacy and safety in that indication. Rivaroxaban represents the only new anticoagulant to date to have shown promising phase III results as an adjunct to antiplatelet therapy after acute coronary syndrome.

Conclusion

Knowledge of the appropriate clinical use and safety concerns of the new anticoagulants is imperative as they become more frequently prescribed, and their potential uses in the ED setting represent an important aspect of continuing education for emergency physicians.     

Understanding the new emerging oral anticoagulants for venous thromboembolism prophylaxis

Patients who have major orthopaedic surgery are at high risk for developing venous thromboembolism (VTE). Assessment of risk and treatment to prevent VTE are considered standard of care due to its significant morbidity, potential mortality, and clinical burden and cost. Guidelines are available aiding orthopaedic surgeons to choose the best methods of VTE prophylaxis. Optimal VTE prevention has not been achieved. Recent advances in the understanding of the coagulation cascade have evolved because of a novel understanding of the molecular influences on the coagulation pathway. Subsequently, new anticoagulants have been developed that target specific factors within the coagulation cascade that are contrasted to the currently used agents that have a broad effect on the coagulation pathway. Multiple clinical trials have tested the new anticoagulants within the orthopaedic total knee and total hip arthroplasty arena. In addition, research to find new ways to prevent VTE was driven by limitations of the currently available agents. The new oral anticoagulants extensively trialed in orthopaedics are dabigatran, rivaroxaban, and apixaban. Clinical trials indicate that the new oral agents have the potential to impact VTE prophylaxis in regard to efficacy, predicta bility and consistency, clinical monitoring, adherence as to use and duration, and convenience. Concerns persist regarding issues of bleeding complications, liver enzyme elevation, patients with renal disease, and drug-to-drug interactions. The new oral agents do not have an antidote to reverse bleeding effect and have no reliable assay to measure effect. Nurses need to be aware of these new VTE prophylactic choices and their implications in order to provide the best outcomes for their patients.     

The use of low molecular weight heparins in the prevention of venous thromboembolic disease

Deep vein thrombosis (DVT) and pulmonary embolism (PE) are leading causes of morbidity and mortality in the United States. Estimates range between 300,000 and 600,000 hospitalizations a year, with approximately 50,000 deaths related to PE. The incidence of the complication of DVT following total joint replacement is reported to occur in 50% to 75% of all unprotected patients. The increasing number of adults who undergo a total joint replacement dictates that orthopaedic nurses become a vital part of the development team that (1) identifies contributing factors to each patient's risk profile, (2) decreases this risk, and (3) refines the patient's transition through the acute hospitalization into the home or rehabilitation environment. The results of recent studies with a new class of heparins, the low molecular weight heparins, suggest their superiority and demonstrate improvement in decreasing the risk of developing DVT and subsequent PE in the total hip and knee patient population.     

Guidelines for the use of imaging techniques for the investigation of venous thromboembolic disease

The diagnosis of venous thromboembolic disease remains a difficult challenge. Chest radiography, ventilation/perfusion lung scanning, noninvasive leg testing, and pulmonary angiography were evaluated with regard to sensitivity, specificity, positive and negative predictive values. The need for treatment, observation, or serial testing with respect to risks and benefits of treatment and likelihood of serious outcomes was evaluated. The evidence for conclusions was based on the methodology and values of the Canadian Task Force on the Periodic Health Examination. The Diagnostic Imaging Advisory Group of the Canadian Association of Emergency Physicians developed eight recommendations.     

Low-molecular-weight heparin for the long-term treatment of symptomatic venous thromboembolism: meta-analysis of the randomized comparisons with oral anticoagulants

Summary. Background: The management of venous thromboembolism (VTE) requires an initial treatment with unfractionated heparin (UFH) or low‐molecular‐weight heparin (LMWH), followed by oral anticoagulants (OA) for at least 3 months. OA treatment however, requires laboratory monitoring of anticoagulation, carries a definite risk of bleeding, and may be contraindicated in some patients. As an alternative to vitamin K antagonists, subcutaneous LMWH has been proposed and evaluated in randomized clinical trials, but they are all small studies that lack the power to establish if these two treatment modalities are equivalent in efficacy or safety. Objectives: The objective of this review was to evaluate the efficacy (VTE recurrence) and safety (bleeds and deaths) of long‐term treatment of VTE with LMWH compared with OA. A secondary endpoint was to evaluate the effect of LMWH on cancer mortality. Methods: Computerized searches of MedLine and EmBase were performed. In addition, randomized clinical trials were located through personal communication with colleagues, and through the manual scanning of meeting proceedings and reference lists of relevant studies. When necessary, the authors of the selected papers were called to obtain additional information. Two reviewers (AI and FG) reviewed and extracted data independently using a standard form. The primary analysis was performed for efficacy and safety endpoints on an intention‐to‐treat basis for the study period of randomized treatment. A meta‐regression analysis was used to investigate the relationship between daily dose and clinical outcome. Results: Seven studies that fulfillled our predefined criteria were identified, for a total of 1379 patients. When all studies were combined, a statistically non‐significant reduction in the risk of VTE (OR 0.66; 95% confidence interval [CI] 0.41, 1.07) and in the risk of major bleeding (OR 0.45; 95% CI 0.18, 1.11) in favor of LMWH treatment was found. No difference in total mortality (OR 1.19; 95% CI 0.78, 1.83) or in cancer‐related mortality was observed between the LMWH and the OA treatment. Conclusions: The results of this meta‐analysis indicate that a 3‐month course of LMWH is as effective and safe as a corresponding period of OA treatment, and may thus be considered as a valuable alternative option for patients in whom OA treatment appears contraindicated or problematic.     

Long-term use of oral anticoagulants. Current recommendations

In many patients receiving long-term oral anticoagulation therapy, hemorrhagic complications occur less often when prothrombin time is maintained within a lower range than that required by a traditional regimen. A target prothrombin time ratio of 1.3 to 1.5 has been recommended for all circumstances except (1) prevention of thromboembolism in patients with mechanical heart valves and (2) prevention of recurrent systemic embolism. Because primary care physicians often monitor the overall treatment program of patients receiving oral anticoagulants, they need to be familiar with the indications, contraindications, and practical considerations that are associated with the use of these drugs.     

Recent advances in the treatment of thromboembolic diseases: venous thromboembolism

Venous thromboembolic diseases are the major concern of rising cost of healthcare and are commonest health problem across the globe. Both genetic and acquired risk factors are believed to be strongly linked with these diseases. Commonly encountered problems to the therapy include dose fixing and routine monitoring, yet some serious problems of bleeding also necessitate the immediate need to develop new agents. The review is primarily concerned with the new developments in the treatment of thromboembolic diseases. Therapeutic applications of anticoagulants, antiplatelets, and thrombolytics have been discussed in enough detail.     

Differentiation of parenteral anticoagulants in the prevention and treatment of venous thromboembolism

Background

The prevention of venous thromboembolism has been identified as a leading priority in hospital safety. Recommended parenteral anticoagulant agents with different indications for the prevention and treatment of venous thromboembolism include unfractionated heparin, low-molecular-weight heparins and fondaparinux. Prescribing decisions in venous thromboembolism management may seem complex due to the large range of clinical indications and patient types, and the range of anticoagulants available.

Methods

MEDLINE and EMBASE databases were searched to identify relevant original articles.

Results

Low-molecular-weight heparins have nearly replaced unfractionated heparin as the gold standard antithrombotic agent. Low-molecular-weight heparins currently available in the US are enoxaparin, dalteparin, and tinzaparin. Each low-molecular-weight heparin is a distinct pharmacological entity with different licensed indications and available clinical evidence. Enoxaparin is the only low-molecular-weight heparin that is licensed for both venous thromboembolism prophylaxis and treatment. Enoxaparin also has the largest body of clinical evidence supporting its use across the spectrum of venous thromboembolism management and has been used as the reference standard comparator anticoagulant in trials of new anticoagulants. As well as novel oral anticoagulant agents, biosimilar and/or generic low-molecular-weight heparins are now commercially available. Despite similar anticoagulant properties, studies report differences between the branded and biosimilar and/or generic agents and further clinical studies are required to support the use of biosimilar low-molecular-weight heparins. The newer parenteral anticoagulant, fondaparinux, is now also licensed for venous thromboembolism prophylaxis in surgical patients and the treatment of acute deep-vein thrombosis; clinical experience with this anticoagulant is expanding.

Conclusions

Parenteral anticoagulants should be prescribed in accordance with recommended dose regimens for each clinical indication, based on the available clinical evidence for each agent to assure optimal safety and efficacy.     

The potential role of new oral anticoagulants in the prevention and treatment of thromboembolism

Thromboembolic disorders are among the major causes of morbidity and mortality, and anticoagulation remains the cornerstone of prevention and treatment of these disorders. Although effective, the well-established agents have significant drawbacks. Heparin, low molecular weight heparin, and fondaparinux must be given parenterally, which is inconvenient for long-term or home use. The orally administered vitamin K antagonists (such as warfarin) have a slow onset of action, thus requiring bridging therapy with a parenteral agent when immediate anticoagulation is needed (e.g. inpatients with acute deep vein thrombosis). Because vitamin K antagonists produce a variable anticoagulant response as a result of multiple drug-drug and food-drug interactions and genetic polymorphisms, frequent coagulation monitoring and dose adjustment are required to ensure a therapeutic level of anticoagulation, which is inconvenient for both patients and physicians. In the search for new agents to overcome the drawbacks associated with traditional agents, direct Factor Xa inhibitors (e.g. rivaroxaban, apixaban, and edoxaban) and direct thrombin inhibitors (e.g. dabigatran etexilate) have been developed and are undergoing late-stage clinical evaluation for the prevention and treatment of thromboembolic disorders. These new oral agents have already shown promise in large-scale clinical studies and data suggest that we have entered a new era with novel drugs that are closer than ever to the 'ideal anticoagulant'. Because these new oral agents have a rapid onset of action and can be given at fixed doses without the need for routine coagulation monitoring, they may simplify treatment paradigms and are expected to improve overall clinical outcome.     

Work-related stressors and occurrence of adverse events in an ED

ObjectiveThe purpose of this study was to investigate the relationship between 12 work-related stressors and the occurrence of adverse events in an emergency department (ED).MethodsNurses and physicians, working in an ED at a Danish regional hospital, filled out a questionnaire on occurrence and emotional impact of 12 work-related stressors after each shift during a 4-week period. The questionnaire also instructed the participants to describe any adverse events that they were involved in during the shift.ResultsTwo hundred fourteen adverse events were reported during the 979 studied shifts. During the same period, only 27 adverse events were reported to the mandatory national reporting system, and only 10 of these were duplicates. A high variability of stressors and emotional impact among the different groups of participants was found. Linear regression analysis showed an association between involvement in adverse events and the occurrence and emotional impact of stressors across groups, whereas no significant association was found for age, seniority, shift type, or length.ConclusionThe study showed an association between the occurrence and impact of 12 work-related stressors and involvement in adverse events across the groups of participants. Furthermore, the study showed that most adverse events were not reported to the mandatory national reporting system.