How to avoid venous thromboembolism in women at increased risk--with special focus on low-risk periods

Venous thromboembolism (VTE) is a major cause of mortality during Western women's fertile life. Although half of thromboembolic events occur during times of low-risk situations, almost all our knowledge is focused on medical thromboprophylaxis during high-risk situations. Thus, since we only use medical thromboprophylaxis at high-risk periods, lifestyle advice could be an attractive complement both during high- and low-risk situations. The knowledge of how lifestyle factors affect VTE risk has grown in recent years, and women at high risk are often highly motivated to make changes in order to reduce their risk. This review is focused on modifiable risk factors for VTE and advice that may be given to women at increased risk of VTE.

Association between thyroid dysfunction and venous thromboembolism in the elderly: a prospective cohort study.

BACKGROUND Venous thromboembolism (VTE) and subclinical thyroid dysfunction (SCTD) are both common in elderly patients. SCTD has been related to a hypercoagulable state and increased thromboembolic risk. However, prospective data on the relationship between SCTD and VTE are lacking. OBJECTIVES To investigate the relationship between SCTD and recurrent VTE (rVTE), all-cause mortality, and thrombophilic biomarkers. PATIENTS Elderly participants with VTE. METHODS In a prospective multicenter cohort, thyroid hormones and thrombophilic biomarkers were measured 1 year after acute VTE, as both may be influenced by acute thrombosis. We defined subclinical hypothyroidism (SHypo) as elevated thyroid stimulating hormone levels (TSH=4.50-19.99 mIU/l), and subclinical hyperthyroidism (SHyper) as TSH<0.45, both with normal free thyroxine levels. Outcomes were incidence of rVTE and overall mortality during follow-up starting after the 1-year blood sampling. RESULTS Of 561 participants (58% with anticoagulation), 6% had SHypo and 5% SHyper. After 20.8 months of mean follow-up, 9% developed rVTE and 10% died. rVTE incidence rate was 7.2 (95% confidence interval:2.7-19.2) per 100 patient-years in SHypo, 0.0 (0.0-7.6) in SHyper and 5.9 (4.4-7.8) in euthyroid participants. In multivariate analyses, the sub-hazard ratio [SHR] for rVTE was 0.00 (0.00-0.58) in SHyper and 1.50 (0.52-4.34) in SHypo compared to euthyroids, without increased thrombophilic biomarkers. SHyper (HR 0.80,0.23-2.81) and SHypo (HR 0.99,0.30-3.29) were not associated with mortality. CONCLUSION In elderly patients, SHyper may be associated with lower rVTE risks. SHypo showed a non-statistically significant pattern of an association with rVTE, without increased mortality or differences in thrombophilic biomarkers. This article is protected by copyright. All rights reserved.

A Case of Internal Carotid Artery Thrombosis associated with Thalidomide Administration in Multiple Myeloma

Thalidomide is an effective chemotherapeutic agent used to achieve remission in multiple myeloma. However, its administration is associated with several adverse effects including venous thromboembolism, while arterial thrombosis has also, although rarely, been described in the literature. We report a case of internal carotid artery occlusion within 1 week of starting thalidomide with prophylactic low molecular weight heparin in a patient who had no other prothrombotic risk factors. It is not known why this complication occurs despite the administration of anticoagulant prophylaxis. The role of factor VIII, von Willebrand factor antigen levels and fibrinogen in multiple myeloma patients should be studied in order to determine if these factors should be targeted in future prophylactic treatment.

Cost-effectiveness analysis of apixaban compared to low-molecular-weight heparins and vitamin k antagonists for treatment and secondary prevention of venous thromboembolism

Objective: Cost-effectiveness analysis of a 6-month treatment of apixaban (10 mg/12h, first 7 days; 5 mg/12h afterwards) for the treatment of the first event of venous thromboembolism (VTE) and prevention of recurrences, versus low-molecular-weight heparins/vitamin K antagonists treatment (LMWH/VKA). Material and methods: A lifetime Markov model with 13 health states was used for describing the course of the disease. Efficacy and safety data were obtained from AMPLIFY and AMPLIFY-EXT clinical trials; health outcomes were measured as life years gained (LYG) and quality-adjusted life years (QALY). The chosen perspective of this analysis has been the Spanish National Health System (NHS). Drugs, management of VTE and complications costs were obtained from several Spanish data sources (€, 2014). A 3% discount rate was applied to health outcomes and costs. Univariate and probabilistic sensitivity analyses (SA) were performed in order to assess the robustness of the results. Results: Apixaban was the most effective therapy with 7.182 LYG and 5.865 QALY, versus 7.160 LYG and 5.838 QALYs with LMWH/VKA. Furthermore, apixaban had a lower total cost (€13,374.70 vs €13,738.30). Probabilistic SA confirmed dominance of apixaban (led to better health outcomes with less associated costs) in 89% of the simulations. Conclusions: Apixaban 5 mg/12h versus LMWH/VKA was an efficient therapeutic strategy for the treatment and prevention of recurrences of VTE from the NHS perspective.

Clinically indicated replacement versus routine replacement of peripheral venous catheters (Review)

Background Centers for Disease Control Guidelines recommend replacement of peripheral intravenous (IV) catheters every 72 to 96 hours. Routine replacement is thought to reduce the risk of phlebitis and bacteraemia. Catheter insertion is an unpleasant experience for patients and replacement may be unnecessary if the catheter remains functional and there are no signs of inflammation. Costs associated with routine replacement may be considerable. Objectives To assess the effects of removing peripheral IV catheters when clinically indicated compared with removing and re-siting the catheter routinely.

Ticagrelor, a platelet aggregation inhibitor for the potential prevention and treatment of arterial thrombosis and acute coronary syndromes

Ticagrelor is an orally active ADP P2Y12 receptor antagonist in development by AstraZeneca plc for the reduction of recurrent ischemic events in patients with acute coronary syndromes (ACS). Prior to the development of ticagrelor, thienopyridine compounds, such as clopidogrel, were the focus of research into therapies for ACS. Although the thienopyridines are effective platelet aggregation inhibitors, they are prodrugs and, consequently, exert a slow onset of action. In addition, the variability in inter-individual metabolism of thienopyridine prodrugs has been associated with reduced efficacy in some patients. Ticagrelor is not a prodrug and exhibits a more rapid onset of action than the thienopyridine prodrugs. In clinical trials conducted to date, ticagrelor was a potent inhibitor of ADP-induced platelet aggregation and demonstrated effects that were comparable to clopidogrel. In a phase II, short-term trial, the bleeding profile of participants treated with ticagrelor was similar to that obtained with clopidogrel; however, an increased incidence of dyspnea was observed - an effect that has not been reported with the thienopyridines. Considering the occurrence of dyspnea, and the apparent non-superiority of ticagrelor to clopidogrel, it is difficult to justify a clear benefit to the continued development of ticagrelor. Outcomes from an ongoing phase III trial comparing ticagrelor with clopidogrel in 18,000 patients with ACS are likely to impact on the future development of ticagrelor.

Factors associated with recurrence of venous leg ulcers : a survey and retrospective chart review

Background: Chronic venous leg ulcers have a significant impact on older individuals’ well-being and health care resources. Unfortunately after healing, up to 70% recur. ----- Objective: To examine the relationships between leg ulcer recurrence and physical activity, compression, nutrition, health, psychosocial indicators and self-care activities in order to provide information for preventive strategies. ----- Design: Survey and retrospective chart review Settings: Two metropolitan hospital and three community-based leg ulcer clinics. ----- Subjects: A sample of 122 community living patients with leg ulcer of venous aetiology which had healed between 12 and 36 months prior to the survey. ---- Methods: Data were collected from medical records on demographics, medical history and previous ulcer history and treatments; and from self-report questionnaires on physical activity, nutrition, psychosocial measures, ulcer recurrences and history, compression and other self-care activities. All variables significantly associated with recurrence at the bivariate level were entered into a logistic regression model to determine their independent influences on recurrence. ----- Results: Median follow-up time was 24 months (range 12–40 months). Sixty-eight percent of participants had recurred. Bivariate analysis found recurrence was positively associated with ulcer duration, cardiac disease, a Body Mass Index ≤20, scoring as at-risk of malnutrition and depression; and negatively associated with increased physical activity, leg elevation, wearing Class 2 (20–25mmHg) or Class 3 (30–40mmHg) compression hosiery, and higher self-efficacy scores. After adjusting for all variables, an hour/day of leg elevation (OR=0.04, 95% CI=0.01–0.17), days/week in Class 2 or 3 compression hosiery (OR=0.53, 95% CI=0.34–0.81), Yale Physical Activity Survey score (OR=0.95, 95% CI=0.92–0.98), cardiac disease (OR=5.03, 95% CI=1.01–24.93) and General Self-Efficacy scores (OR=0.83, 95% CI=0.72–0.94) remained significantly associated (p<0.05) with recurrence. ----- Conclusions: Results indicate a history of cardiac disease is a risk factor for recurrence; while leg elevation, physical activity, compression hosiery and strategies to improve self-efficacy are likely to prevent recurrence.

Can venous occlusion plethysmography be used to measure high rates of arterial inflow?

To investigate whether venous occlusion plethysmography (VOP) may be used to measure high rates of arterial inflow associated with exercise, venous occlusions were performed at rest, and following dynamic handgrip exercise at 15, 30, 45, and 60 % of maximum voluntary contraction (MVC) in seven healthy males. The effect of including more than one cardiac cycle in the calculation of blood flow was assessed by comparing the cumulative blood flow over one, two, three, or four cardiac cycles. The inclusion of more than one cardiac cycle at 30 and 60 % MVC, and more than two cardiac cycles at 15 and 45 % MVC resulted in a lower blood flow compared to using only the first cardiac cycle (P < 0.05). Despite the small time interval over which arterial inflow was measured (~1 second), this did not affect the reproducibility of the technique. Reproducibility (coefficient of variation for arterial inflow over three trials) tended to be poorer at the higher workloads, although this was not significant (12.7 ± 6.6 %, 16.2 ± 7.3 %, and 22.9 ± 9.9 % for the 15, 30, and 45 % MVC workloads; P=0.102). There was also a tendency for greater reproducibility with the inclusion of more cardiac cycles at the highest workload, but this did not reach significance (P=0.070). In conclusion, when calculated over the first cardiac cycle only during venous occlusion, high rates of FBF can be measured using VOP, and this can be achieved without a significant decrease in the reproducibility of the measurement.

Plasma ATP concentration and venous oxygen content in the forearm during dynamic handgrip exercise

Background: It has been proposed that adenosine triphosphate (ATP) released from red blood cells (RBCs) may contribute to the tight coupling between blood flow and oxygen demand in contracting skeletal muscle. To determine whether ATP may contribute to the vasodilatory response to exercise in the forearm, we measured arterialised and venous plasma ATP concentration and venous oxygen content in 10 healthy young males at rest, and at 30 and 180 seconds during dynamic handgrip exercise at 45% of maximum voluntary contraction (MVC). Results: Venous plasma ATP concentration was elevated above rest after 30 seconds of exercise (P < 0.05), and remained at this higher level 180 seconds into exercise (P < 0.05 versus rest). The increase in ATP was mirrored by a decrease in venous oxygen content. While there was no significant relationship between ATP concentration and venous oxygen content at 30 seconds of exercise, they were moderately and inversely correlated at 180 seconds of exercise (r = -0.651, P = 0.021). Arterial ATP concentration remained unchanged throughout exercise, resulting in an increase in the venous-arterial ATP difference. Conclusions: Collectively these results indicate that ATP in the plasma originated from the muscle microcirculation, and are consistent with the notion that deoxygenation of the blood perfusing the muscle acts as a stimulus for ATP release. That ATP concentration was elevated just 30 seconds after the onset of exercise also suggests that ATP may be a contributing factor to the blood flow response in the transition from rest to steady state exercise.

Central venous oxygen saturation monitoring

It has been established that mixed venous oxygen saturation (SvO2) reflects the balance between systemic oxygen deliver y and consumption. Literature indicates that it is a valuable clinical indicator and has good prognostic value early in patient course. This article aims to establish the usefulness of SvO2 as a clinical indicator. A secondary aim was to determine whether central venous oxygen saturation (ScvO2) and SvO2 are interchangeable. Of particular relevance to cardiac nurses is the link between decreased SvO2 and cardiac failure in patients with myocardial infarction, and with decline in myocardial function, clinical shock and arrhythmias. While absolute values ScvO2 and SvO2 are not interchangeable, ScvO2 and SvO2are equivalent in terms of clinical course. Additionally, ScvO2 monitoring is a safer and less costly alternative to SvO2 monitoring. It can be concluded that continuous ScvO2 monitoring should potentially be undertaken in patients at risk of haemodynamic instability.

Compression for preventing recurrence of venous ulcers

Background: Up to 1% of adults will suffer from leg ulceration at some time. The majority of leg ulcers are venous in origin and are caused by high pressure in the veins due to blockage or weakness of the valves in the veins of the leg. Prevention and treatment of venous ulcers is aimed at reducing the pressure either by removing / repairing the veins, or by applying compression bandages / stockings to reduce the pressure in the veins. The vast majority of venous ulcers are healed using compression bandages. Once healed they often recur and so it is customary to continue applying compression in the form of bandages, tights, stockings or socks in order to prevent recurrence. Compression bandages or hosiery (tights, stockings, socks) are often applied for ulcer prevention. Objectives To assess the effects of compression hosiery (socks, stockings, tights) or bandages in preventing the recurrence of venous ulcers. To determine whether there is an optimum pressure/type of compression to prevent recurrence of venous ulcers. Search methods The searches for the review were first undertaken in 2000. For this update we searched the Cochrane Wounds Group Specialised Register (October 2007), The Cochrane Central Register of Controlled Trials (CENTRAL) - The Cochrane Library 2007 Issue 3, Ovid MEDLINE - 1950 to September Week 4 2007, Ovid EMBASE - 1980 to 2007 Week 40 and Ovid CINAHL - 1982 to October Week 1 2007. Selection criteria Randomised controlled trials evaluating compression bandages or hosiery for preventing venous leg ulcers. Data collection and analysis Data extraction and assessment of study quality were undertaken by two authors independently. Results No trials compared recurrence rates with and without compression. One trial (300 patients) compared high (UK Class 3) compression hosiery with moderate (UK Class 2) compression hosiery. A intention to treat analysis found no significant reduction in recurrence at five years follow up associated with high compression hosiery compared with moderate compression hosiery (relative risk of recurrence 0.82, 95% confidence interval 0.61 to 1.12). This analysis would tend to underestimate the effectiveness of the high compression hosiery because a significant proportion of people changed from high compression to medium compression hosiery. Compliance rates were significantly higher with medium compression than with high compression hosiery. One trial (166 patients) found no statistically significant difference in recurrence between two types of medium (UK Class 2) compression hosiery (relative risk of recurrence with Medi was 0.74, 95% confidence interval 0.45 to 1.2). Both trials reported that not wearing compression hosiery was strongly associated with ulcer recurrence and this is circumstantial evidence that compression reduces ulcer recurrence. No trials were found which evaluated compression bandages for preventing ulcer recurrence. Authors' conclusions No trials compared compression with vs no compression for prevention of ulcer recurrence. Not wearing compression was associated with recurrence in both studies identified in this review. This is circumstantial evidence of the benefit of compression in reducing recurrence. Recurrence rates may be lower in high compression hosiery than in medium compression hosiery and therefore patients should be offered the strongest compression with which they can comply. Further trials are needed to determine the effectiveness of hosiery prescribed in other settings, i.e. in the UK community, in countries other than the UK.

The impact of psychosocial factors on adherence to compression therapy to prevent recurrence of venous leg ulcers

Aims To identify self-care activities undertaken and determine relationships between self-efficacy, depression, quality of life, social support and adherence to compression therapy in a sample of patients with chronic venous insufficiency. Background Up to 70% of venous leg ulcers recur after healing. Compression hosiery is a primary strategy to prevent recurrence, however, problems with adherence to this strategy are well documented and an improved understanding of how psychosocial factors influence patients with chronic venous insufficiency will help guide effective preventive strategies. Design Cross-sectional survey and retrospective medical record review. Method All patients previously diagnosed with a venous leg ulcer which healed between 12–36 months prior to the study were invited to participate. Data on health, psychosocial variables and self-care activities were obtained from a self-report survey and data on medical and previous ulcer history were obtained from medical records. Multiple linear regression modelling was used to determine the independent influences of psychosocial factors on adherence to compression therapy. Results In a sample of 122 participants, the most frequently identified self-care activities were application of topical skin treatments, wearing compression hosiery and covering legs to prevent trauma. Compression hosiery was worn for a median of 4 days/week (range 0–7). After adjustment for all variables and potential confounders in a multivariable regression model, wearing compression hosiery was found to be significantly positively associated with participants’ knowledge of the cause of their condition (p=0.002), higher self-efficacy scores (p=0.026) and lower depression scores (p=0.009). Conclusion In this sample, depression, self-efficacy and knowledge were found to be significantly related to adherence to compression therapy. Relevance to clinical practice These findings support the need to screen for and treat depression in this population. In addition, strategies to improve patient knowledge and self-efficacy may positively influence adherence to compression therapy.

Cost-effectiveness of a central venous catheter care bundle

Background: A bundled approach to central venous catheter care is currently being promoted as an effective way of preventing catheter-related bloodstream infection (CR-BSI). Consumables used in the bundled approach are relatively inexpensive which may lead to the conclusion that the bundle is cost-effective. However, this fails to consider the nontrivial costs of the monitoring and education activities required to implement the bundle, or that alternative strategies are available to prevent CR-BSI. We evaluated the cost-effectiveness of a bundle to prevent CR-BSI in Australian intensive care patients. ---------- Methods and Findings: A Markov decision model was used to evaluate the cost-effectiveness of the bundle relative to remaining with current practice (a non-bundled approach to catheter care and uncoated catheters), or use of antimicrobial catheters. We assumed the bundle reduced relative risk of CR-BSI to 0.34. Given uncertainty about the cost of the bundle, threshold analyses were used to determine the maximum cost at which the bundle remained cost-effective relative to the other approaches to infection control. Sensitivity analyses explored how this threshold alters under different assumptions about the economic value placed on bed-days and health benefits gained by preventing infection. If clinicians are prepared to use antimicrobial catheters, the bundle is cost-effective if national 18-month implementation costs are below $1.1 million. If antimicrobial catheters are not an option the bundle must cost less than $4.3 million. If decision makers are only interested in obtaining cash-savings for the unit, and place no economic value on either the bed-days or the health benefits gained through preventing infection, these cost thresholds are reduced by two-thirds.---------- Conclusions: A catheter care bundle has the potential to be cost-effective in the Australian intensive care setting. Rather than anticipating cash-savings from this intervention, decision makers must be prepared to invest resources in infection control to see efficiency improvements.