Thromboprophylaxis In Medical Patients Research Articles

Incidence of thromboembolism and thromboprophylaxis in medical patients admitted to specialized hospital in Ethiopia using Padua prediction score.

Introduction:Venous thromboembolism is a major cause of mortality and morbidity among hospitalized patients and thromboprophylaxis is one of the key strategies to reduce such events. We aimed to assess venous thromboembolism risk using Padua prediction score, thromboprophylaxis practice, and outcomes in hospitalized medical patients at Tibebe Ghion Specialized Hospital, Bahir Dar, Ethiopia.Methods:A cross-sectional study was conducted among 219 patients admitted to Tibebe Ghion Specialized Hospital from 1 December 2018 to 31 May 2019. Data were collected from patients’ medical records using a pre-tested data abstraction format to collect patients’ clinical information and venous thromboembolism risk using the Padua prediction score. We used Statistical Package for the Social Sciences version 26 for data analysis. Descriptive statistics was used to summarize the findings, and binary logistic regression analysis was used to assess association between the variables of interest.Results:Reduced mobility, recent trauma and/or surgery, heart and/or respiratory failure, and active cancer were the frequently identified venous thromboembolism risk factors. Based on Padua prediction score, 48.4% of patients were at high risk of developing venous thromboembolism. The venous thromboembolism prophylaxis was given only for 55 (25.1%) patients and 15 of them were at low risk of developing venous thromboembolism (<4 Padua score) and were ineligible for thromboprophylaxis. Fifteen (6.84%) patients developed venous thromboembolism events during their stay at the hospital and 80% of them were from high risk group. The odds of females to develop venous thromboembolism were more than 14 times higher (adjusted odds ratio = 14.51; 95% confidence interval: 2.52–83.39, p = 0.003) than males. Reduced mobility (adjusted odds ratio = 10.00; 95% confidence interval: 1.70–58.70), <1 month trauma and/or surgery (adjusted odds ratio = 18.93; 95% confidence interval: 2.30–155.56), active cancer (adjusted odds ratio = 6.00; 95% confidence interval: 1.05–34.27), chronic kidney diseases (adjusted odds ratio = 61.790; 95% confidence interval: 2.627–1453.602), and hypertension (adjusted odds ratio = 7.270; 95% confidence interval: 1.105–47.835) were significantly associated with the risk of developing venous thromboembolism.Conclusion:Nearly half of the patients were at risk of developing venous thromboembolism. Underutilization of thromboprophylaxis and inappropriate use of prophylaxis were commonly seen in Tibebe Ghion Specialized Hospital.

Association Between Asymptomatic Proximal Deep Vein Thrombosis and Mortality in Acutely Ill Medical Patients.

BackgroundAsymptomatic proximal deep vein thrombosis (DVT) is an end point frequently used to evaluate the efficacy of anticoagulant thromboprophylaxis in medical patients. Recently, the clinical relevance of asymptomatic DVT has been challenged.Methods and ResultsThe objective of this study was to evaluate the relationship between asymptomatic proximal DVT and all‐cause mortality (ACM) using a cohort analysis of a randomized trial for the prevention of venous thromboembolism (VTE) in acutely ill medical patients. Patients who received at least 1 dose of study drug and had an adequate compression ultrasound examination of the legs on either day 10 or day 35 were categorized into 1 of 3 cohorts: no VTE, asymptomatic proximal DVT, or symptomatic DVT. Cox proportional hazards model, with adjustment for significant independent predictors of mortality, were used to compare the incidences of ACM. Of the 7036 patients, 6776 had no VTE, 236 had asymptomatic DVT, and 24 had symptomatic VTE. The incidence of ACM was 4.8% in patients without VTE. Both asymptomatic proximal DVT (mortality, 11.4%; hazard ratio [HR], 2.31; 95% CI, 1.52–3.51; P<0.0001) and symptomatic VTE (mortality, 29.2%; HR, 9.42; 95% CI, 4.18–21.20; P<0.0001) were independently associated with significant increases in ACM. The analysis was post hoc, and ultrasound results were not available for all patients. Adjustment for baseline variables significantly associated with ACM may not fully compensate for differences.ConclusionsAsymptomatic proximal DVT is associated with higher ACM than no VTE and remains a relevant end point to evaluate the efficacy of anticoagulant thromboprophylaxis in medical patients.RegistrationURL: https://www.clinicaltrials.gov; Unique identifier: NCT00571649.

Prevalence of deep vein thrombosis and associated factors in adult medical patients admitted to the University Teaching Hospital, Lusaka, Zambia

&#x0D; &#x0D; &#x0D; &#x0D; &#x0D; &#x0D; &#x0D; &#x0D; Background: Deep vein thrombosis (DVT) and pulmonary embolism (PE) collectively referred to as venous thromboembolism (VTE) are associated with significant morbidity and mortality worldwide.&#x0D; DVT is common in hospitalized patients with acute medical illness. Routine use of thromboprophylaxis has been shown to reduce prevalence of DVT in hospitalized patients with acute medical illness. Thromboprophylaxis is not routinely given to hospitalized medical patients in most hospitals in Zambia.&#x0D; Objectives: The objectives of this study were: todetermine the prevalence and anatomical distribution of DVT in medical patients admitted to the UTH for at least 7 days; establish demographic and clinical characteristics of medical patients with DVT and finally determine the accuracy of the Well's score for DVT.&#x0D; Methods: This was a descriptive, cross sectional analytical study. The sample size comprised 296 medical patients admitted for at least 7 days. A questionnaire was used to obtain demographic characteristics and relevant clinical history. A focused detailed physical examination was conducted to screen for DVT of the lower limbs and Well's score for DVT computed. Laboratory tests including HIV test and full blood count were done. Biochemical and genetic studies to evaluate for inherited and acquired thrombophilias could not be done due limited financial resources. Compression ultrasound scans (USS) were done on lower limbs of recruited patients to determine the presence of DVT. Variables of interest were compared by chi-square, Kruskal-wallis and t-tests. Multivariate and univariate logistic regression analysis were used to assess for associations between DVT and independent variables of interest.&#x0D; Results: The Prevalence of DVT of the lower limbs was 11.1 % (33/296). Prevalence of proximal lower limb DVT was 9.1%. Eighty two percent (27/33) of all patients with DVT had proximal lower limb DVT. Asymptomatic lower limb DVT was noted in 85 % (28/33) of all patients with DVT.&#x0D; The Mean age of patients with DVT was 42.12 years (SD 12.71).The mean duration of hospital admission was 11.91 (SD 7.77) days. Seventy six percent (25/33) of all patients with DVT had an infectious disease as a primary diagnosis. Tuberculosis was the most common infectious disease among patients with DVT accounting for 60.6 % (20/33) of all infections. Up to 70 % (23/33) of all patients with DVT were HIV positive.&#x0D; The specificity for the Wells score specificity for DVT was 73.4% while the sensitivity was 100%. The accuracy was 76.3%.The positive and negative predictive values were 32% and 100% respectively.&#x0D; Conclusion: Proximal Lower limb DVT is common among HIV positive medical patients admitted for at least 7 days at the UTH. In our study, lower extremity proximal DVT was more common in patients with Tuberculosis and a low BMI. Up to 85% of lower limb DVT was asymptomatic. Without a high index of suspicion, lower limb DVT is likely to be missed. The pretest Wells score correlated well with the USS findings and could be used as a rule out test for those with suspected DVT.A follow up study to evaluate for genetic and biochemical factors that predispose to DVT need to be undertaken in the near future. There is need to advocate for thromboprophylaxis in medical patients with acute illness and prolonged hospital stay.&#x0D; &#x0D; &#x0D; &#x0D; &#x0D; &#x0D; &#x0D; &#x0D;

Prevalence of deep vein thrombosis and associated factors in adult medical patients admitted to the University Teaching Hospital, Lusaka, Zambia

Background: Deep vein thrombosis (DVT) and pulmonary embolism (PE) collectively referred to as venous thromboembolism (VTE) are associated with significant morbidity and mortality worldwide. DVT is common in hospitalized patients with acute medical illness. Routine use of thromboprophylaxis has been shown to reduce prevalence of DVT in hospitalized patients with acute medical illness. Thromboprophylaxis is not routinely given to hospitalized medical patients in most hospitals in Zambia. Objectives: The objectives of this study were: todetermine the prevalence and anatomical distribution of DVT in medical patients admitted to the UTH for at least 7 days; establish demographic and clinical characteristics of medical patients with DVT and finally determine the accuracy of the Well's score for DVT. Methods: This was a descriptive, cross sectional analytical study. The sample size comprised 296 medical patients admitted for at least 7 days. A questionnaire was used to obtain demographic characteristics and relevant clinical history. A focused detailed physical examination was conducted to screen for DVT of the lower limbs and Well's score for DVT computed. Laboratory tests including HIV test and full blood count were done. Biochemical and genetic studies to evaluate for inherited and acquired thrombophilias could not be done due limited financial resources. Compression ultrasound scans (USS) were done on lower limbs of recruited patients to determine the presence of DVT. Variables of interest were compared by chi-square, Kruskal-wallis and t-tests. Multivariate and univariate logistic regression analysis were used to assess for associations between DVT and independent variables of interest. Results: The Prevalence of DVT of the lower limbs was 11.1 % (33/296). Prevalence of proximal lower limb DVT was 9.1%. Eighty two percent (27/33) of all patients with DVT had proximal lower limb DVT. Asymptomatic lower limb DVT was noted in 85 % (28/33) of all patients with DVT. The Mean age of patients with DVT was 42.12 years (SD 12.71).The mean duration of hospital admission was 11.91 (SD 7.77) days. Seventy six percent (25/33) of all patients with DVT had an infectious disease as a primary diagnosis. Tuberculosis was the most common infectious disease among patients with DVT accounting for 60.6 % (20/33) of all infections. Up to 70 % (23/33) of all patients with DVT were HIV positive. The specificity for the Wells score specificity for DVT was 73.4% while the sensitivity was 100%. The accuracy was 76.3%.The positive and negative predictive values were 32% and 100% respectively. Conclusion: Proximal Lower limb DVT is common among HIV positive medical patients admitted for at least 7 days at the UTH. In our study, lower extremity proximal DVT was more common in patients with Tuberculosis and a low BMI. Up to 85% of lower limb DVT was asymptomatic. Without a high index of suspicion, lower limb DVT is likely to be missed. The pretest Wells score correlated well with the USS findings and could be used as a rule out test for those with suspected DVT.A follow up study to evaluate for genetic and biochemical factors that predispose to DVT need to be undertaken in the near future. There is need to advocate for thromboprophylaxis in medical patients with acute illness and prolonged hospital stay.

The overuse of thromboprophylaxis in medical patients: main clinical aspects

Overuse of thromboprophylaxis is not an infrequent behavior in internal medicine. However, differently from underuse, overuse of thromboprophylaxis is rarely taken into account, and only few studies have addressed this issue. The purpose of our study was to try to understand the reasons behind this phenomenon. Using data from the TEVERE study, we evaluated 279 patients hospitalized in 21 hospitals of the Lazio Region in Italy. Only patients who were negative to major risk scores as established in the scientific literature were included. We assessed the frequency of thromboprophylaxis in acutely ill medical patients hospitalized in emergency and internal medicine wards, and we performed a comparative analysis for each risk factor among patients who received or not received thromboprophylaxis. Forty-seven patients (16.5%) with negative risk scores were given thromboprophylaxis during hospitalization. On backward stepwise logistic regression analysis, severe infection (odds ratio [OR] 2.31; 95% confidence interval [CI] 1.25-4.35) and chronic venous insufficiency (OR 3.02; 95% CI 1.96-4.67) were found to be the strongest predictors of the use of thromboprophylactic treatment with heparin. The subgroup of patients who did not exhibit risk factors was also analyzed, and age was found to be the main factor in the decision-making process regarding heparin administration in the absence of other risk factors (74.9 ± 11.8 vs 63.7 ± 18.1, p=0.002). Our findings suggest that thromboprophylaxis is associated with considerable uncertainty, which results in its overuse. Further research is needed to better understand thromboembolic risk factors in hospitalized medical patients.

Profile of betrixaban and its potential in the prevention and treatment of venous thromboembolism.

Venous thromboembolism (VTE), which includes deep vein thrombosis and pulmonary embolism, is a common and potentially preventable cause of morbidity and mortality. Unfractionated heparin, low-molecular-weight heparin, and warfarin have been the cornerstone of VTE prevention and treatment but are being replaced by recently approved non-vitamin K antagonist oral anticoagulants (NOACs): dabigatran, rivaroxaban, apixaban, and edoxaban. The NOACs are at least as effective and as safe as heparins and warfarin for VTE prevention and treatment and are more convenient because they have a low propensity for food and drug interactions and are given in fixed doses without routine coagulation monitoring. The remaining limitations of currently available NOACs include their dependence on renal and hepatic function for clearance, and the lack of an approved antidote. Betrixaban is a new NOAC with distinct pharmacological characteristics: minimal renal clearance, minimal hepatic metabolism, and long half-life. It has undergone successful Phase II studies in orthopedic thromboprophylaxis, and in stroke prevention in atrial fibrillation. Currently, it is being evaluated in a Phase III trial of extended thromboprophylaxis in medical patients (APEX study). In this article, we describe the development of betrixaban, review its pharmacological profile, discuss the results of clinical trials, and examine its potential for VTE prevention and treatment.

Assessment of thromboprophylaxis in medical patients hospitalized in Andalusia. A multicenter study

Background and objectivesHospitalized patients are a population at risk for venous thromboembolism (VTE). The PRETEMED-2007 clinical practice guidelines help identify high-risk medical patients who are suited to thromboprophylaxis. These guidelines therefore provide a standard for prophylaxis in such patients. We evaluated the risk of VTE and the adjustment of thromboprophylaxis to the standards of the PRETEMED-2007 guidelines in patients hospitalized in internal medicine departments. Patients and methodsAn observational, cross-sectional multicenter study was performed in 2010 in 16 hospitals in Andalusia and included 20 consecutive patients per center. The study variables were age, sex, risk factors for VTE and hemorrhage, the risk-adjusted PRETEMED of VTE, adjustment of thromboembolic prophylaxis at admission and at discharge and hospital mortality. ResultsThe study included 293 patients (57.8% men) with a mean age of 69 (±15) years. The most common triggers for VTE were acute severe infection (27.3%) and neoplasia (16.4%). Some 43.4% of the patients presented a risk of hemorrhage. The risk of VTE at admission and discharge was high in 47.8% and 31% and moderate in 8.2% and 10.6%, respectively. A total of 91.7% and 17.3% of the patients underwent prophylaxis with low-molecular-weight heparin on admission and at discharge, respectively. The prescription was appropriate for 59.9% of the patients at admission (overutilization 38.4%, underutilization 1.7%) and for 74.7% at discharge (overutilization 5.4%, underutilization 19.9%). The adjustment was greater in patients older than 60 years and with greater hemorrhagic risk. ConclusionsFor 60% of the patients admitted to the departments of internal medicine in Andalusia, the thromboprophylaxis was appropriate. The inadequacy of thromboprophylaxis (40%) is mostly due to overutilization. These results suggest significant space for improvement.

Thromboprophylaxis for medical patients with cancer: what do the guidelines say?

Venous thromboembolism (VTE) is frequent in cancer patients and is one of the leading causes of death in this population. Hospitalized cancer patients and those receiving chemotherapy are at the greatest risk of developing VTE. Many randomized controlled trials in a variety of patient populations have demonstrated that primary prophylaxis is effective in reducing the risk of VTE among cancer patients. Pharmacological thromboprophylaxis is recommended in all hospitalized medically ill cancer patients without a contraindication to anticoagulant therapy. Thromboprophylaxis in ambulatory patients undergoing chemotherapy is only considered in those at high risk of VTE. In this article, we evaluate the different clinical practice guideline recommendations for primary VTE prophylaxis in hospitalized medically ill patients with cancer and ambulatory patients undergoing chemotherapy.

Betrixaban (PRT054021): pharmacology, Dose Selection and Clinical Studies

The recently introduced oral anticoagulants, dabigatran, rivaroxaban and apixaban, were shown, in randomized controlled trials, to be at least as effective and safe as monitored warfarin therapy for the treatment of venous thromboembolism and stroke prevention in atrial fibrillation. These new oral anticoagulants have predictable pharmacology, less variability in anticoagulant effect and fewer drug and food interactions than warfarin, allowing unmonitored and fixed dosing, which renders their use appealing. The remaining limitations of currently available new oral anticoagulants include their dependence on renal and hepatic clearance, and the lack of an antidote, which is problematic in bleeding patients and those requiring urgent surgery. Betrixaban is a new direct factor Xa inhibitor with distinct pharmacological characteristics, including a long half-life, minimal renal clearance and minimal hepatic metabolism. Betrixaban was tested in Phase II studies in orthopedic thromboprophylaxis (EXPERT) and atrial fibrillation (EXPLORE-Xa), and is being evaluated in a Phase III trial of extended thromboprophylaxis in medical patients (APEX). This article details the pharmacology, preclinical and clinical development of betrixaban.

Prevention of venous thromboembolism in acutely ill medical patients after the results of recent trials with the new oral anticoagulants

Venous thromboembolism (VTE) is a common potentially life-threatening complication in acutely ill medical patients; over 70 % of the fatal episodes of pulmonary embolism during hospitalization occur in non-surgical patients. In the absence of thromboprophylaxis, the incidence of venographically detected deep vein thrombosis is about 15 % in medical patients. Several trials and meta-analyses have clearly demonstrated the prophylactic role of unfractionated heparin, low molecular weight heparin and fondaparinux. Although over the past few years the knowledge of epidemiology, clinical features and prophylaxis in medical patients has significantly improved, there remain a number of controversial areas that require further investigation. Newer VTE risk assessment models have been proposed to select high risk hospitalized medical patients, but they still require external validation; scarce data are available to stratify patients to identify their individual bleeding risk. The optimal duration of thromboprophylaxis in medical patients is still a matter of debate; currently, extended prophylaxis after discharge is not recommended, but it may be required for subgroup of patients with persistently high VTE risk and a negligible risk of bleeding. Based on the results of recent studies, the new oral anticoagulants appear to have a very limited role, if any. However, a better risk stratification of patients who have a persistently increased risk of VTE is warranted to improve the risk to benefit profile of any anticoagulant drug to be used in this setting.

Routine pharmacological venous thromboembolism prophylaxis in frail older hospitalised patients: where is the evidence?

It has been claimed that there are over 25,000 preventable in-hospital deaths from venous thromboembolism annually in the UK. NICE and SIGN guidelines therefore recommend that all hospitalised patients are risk assessed for venous thromboembolism. The guidelines would recommend using pharmacological thromboprophylaxis for all patients aged 60 and above with reduced mobility and acute medical illness unless obvious contra-indications exist. Meta-analysis data regarding pharmacological thromboprophylaxis for medical patients demonstrate reductions in asymptomatic deep vein thrombosis (DVT) rather than fatal pulmonary embolism and mortality. There is also the potential for increased bleeding risk with this approach. Evidence for older medical in-patients, particularly those aged over 75, is more limited being derived from subgroup analyses of larger clinical trials. In addition, based on exclusion criteria such as increased bleeding risk, frailer older adults were unlikely to have been included within such trials. This commentary will (i) critically appraise available data on the incidence of DVT and PE in older hospitalised patients; (ii) review the evidence available from meta-analyses and subgroup analyses in older medical in-patients for the use of venous thromboembolism prophylaxis; (iii) discuss those situations out-with the guidelines where venous thromboprophylaxis may not be appropriate and even potentially harmful in this patient group and (iv) suggest future research directions.

Impact of age on the efficacy and safety of extended-duration thromboprophylaxis in medical patients

The EXCLAIM study enrolled hospitalised acutely ill medical patients with age >40years and recently-reduced mobility into a trial of extended-duration anticoagulant thromboprophylaxis. This post-hocanalysis evaluated the impact of age on patient outcomes. After completion of open-label therapy with enoxaparin 40 mg once-daily (10 ± 4 days), eligible patients underwent randomisation to receive double-blind therapy of enoxaparin (n=2,975) or placebo (n=2,988) for 28 ± 4 days. During follow-up, the venous thromboembolism (VTE) risk increased with age in both treatment groups. In patients with age >75 years, those who received extended-duration enoxaparin had lower incidence of VTE (2.5% vs 6.7%; absolute difference [AD] [95% confidence interval]: -4.2% [-6.5, -2.0]), proximal deep-vein thrombosis (2.5% vs 6.6%; AD -4.1% [-6.2, -2.0]), and symptomatic VTE (0.3% vs 1.5%; AD -1.2% [-2.2, -0.3]), in comparison to those who received placebo. In patients with age ≤75years, those who received enoxaparin had reduced VTE (2.4% vs 2.8%; AD -0.4% [-1.5, 0.7]) and symptomatic VTE (0.2% vs 0.7%; AD -0.6% [-1.0, -0.1]) in comparison to those who received placebo. In both age subgroups, patients who received enoxaparin had increased rates of major bleeding versus those who received placebo: age >75 years (0.6% vs 0.2%; AD +0.3% [-0.2, 0.9], respectively); age ≤75 years (0.7% vs 0.2%; AD +0.5% [0.1, 0.9]). Patients in both age subgroups that received enoxaparin had similar low bleeding rates (0.6% and 0.7%, respectively). VTE risk increased with age, though the bleeding risk did not. Patients with age >75 years had a more favourable benefit-to-harm profile than younger patients.

Venous thromboprophylaxis in medical patients: an application review

ObjectiveRoutine thromboprophylaxis, despite its well-known effectiveness and the fact that venous thromboembolism is a potentially avoidable condition, is not fully established in clinical practice. The objectives of the present study were to determine how often thromboprophylaxis is used and the presence of thromboembolism risk factors, and to verify the appropriateness of its use in medical inpatients, assuming a long-standing national guideline as a parameter. MethodsThis was a retrospective cross-sectional study, involving inpatients with medical conditions in the adult general ward of a faculty hospital. The review was based on a defined guideline. Results146 patients were included in the review. At least one risk factor for venous thrombo embolism was found in 94.5%. In 130 (89%) patients, prophylactic heparin was indicated, and some kind of heparin was prescribed in 73.3%. Regarding the adequacy of prophylaxis, 53.4% of prescriptions were correct regarding prophylaxis indication and dose; 24% had incorrect dose or frequency of use; 19.2% had no prophylaxis prescription, although it was indicated; and in five cases (3.4%), the drug was prescribed, even though it was not indicated. ConclusionThromboprophylaxis is underused in this population, and an inappropriate dose was prescribed in 50% of cases. Therefore, future studies and interventions should include an educational program started from the emergency department care, an essential step to bring evidence closer to clinical practice.

Venous thromboembolism prophylaxis in medical ICU patients in Asia (VOICE Asia): A multicenter, observational, cross-sectional study

ObjectivesThe VOICE Asia study aimed to establish the mode of thromboprophylaxis in medical patients admitted to intensive care units (ICU), and to describe the epidemiology of patients at high-risk of venous thromboembolism (VTE) and of patients who were prescribed low molecular weight heparin (LMWH). MethodsThis multinational, observational, cross-sectional study recruited medical patients admitted to ICU in whom a decision to give VTE prophylaxis had been taken. The treating physicians decided patient management. We recorded demographics, VTE risk factors, VTE risk assessment, thromboprophylaxis, and compliance to the American College of Chest Physicians (ACCP) guidelines. ResultsThe study enrolled 2969 patients from 113 centers in 5 Asian countries. The most common VTE risk factors were age >60years (57.1%), prolonged immobility (50.6%), respiratory diseases (41.3%), and acute infectious disease (36.2%). There was a wide gap between physicians’ assessment of ‘very high’ risk for VTE (8.4%) and Caprini ‘very high’ risk stratification (54.9%). 2919 (98.3%) patients received prophylaxis (22.9%-only mechanical, 31.2%-only pharmacological, 44.2%-both, mechanical and pharmacological and 1.7%- no prophylaxis). Early mobilization (44.3%) and LMWH (66.2%, mean duration of prophylaxis-8.6days) were the most common mechanical and pharmacological prophylaxis, respectively. 80.6% of patients were given thromboprophylaxis as per the ACCP guidelines (and 4.7% per Japanese guidelines). ConclusionsThere is substantial underestimation of VTE risk and non-adherence to guidelines for thromboprophylaxis in medical ICU patients in participating Asian countries. This emphasizes the need for increasing awareness about optimum VTE risk assessment and improved implementation of appropriate thromboprophylaxis in at-risk medical ICU patients.

Dosing Frequency of Unfractionated Heparin Thromboprophylaxis: A Meta-analysis

In medical patients, it is unclear whether thromboprophylaxis with low-dose unfractionated heparin (UFH) should be administered bid or tid. This study was a mixed-treatment comparison meta-analysis of randomized control trials that enrolled hospitalized nonsurgical patients at risk for VTE and compared UFH bid, UFH tid, or low-molecular-weight heparin (LMWH) to one another or to an inactive control subject. DVT, pulmonary embolism (PE), major bleeding, and death were measured. A Bayesian framework using a random-effects model was applied. Sixteen trials with moderate methodologic quality enrolling 27,667 patients contributed to this analysis. The relative risk and 95% credible intervals comparing UFH tid to UFH bid for DVT, PE, death, and major bleeding were 1.56 (0.64-4.33), 1.67 (0.49-208.09), 1.17 (0.72-1.95), and 0.89 (0.08-7.05), respectively. When compared with either dose of UFH, the use of LMWH has an effect similar to UFH on all four outcomes. Moderate-quality evidence suggests that subcutaneous UFH bid and UFH tid do not differ in effect on DVT, PE, major bleeding, and mortality. Either of the two dosing regimens of UFH or LMWH appears to be a reasonable strategy for thromboprophylaxis in medical patients. A future randomized trial comparing the two doses of UFH is very unlikely, considering the very large sample size that would be required to demonstrate a significant difference, which, if it exists, is undoubtedly small.

Venous thromboembolism prevention in medical patients: a framework for improving practice

Medical inpatients have been shown to be at risk of venous thromboembolism (VTE) including fatal pulmonary emboli. Several studies have shown that pharmacological thromboprophylaxis significantly reduces the rates of VTE, yet studies published to date have shown a considerable underuse of thromboprophylaxis in medical patients. This study assesses the current use of thromboprophylaxis in medical patients at our institution and aims to identify simple strategies to improve practice. A prospective study of thromboprophylaxis prescription was undertaken on three occasions over a 12-month period. Patients were stratified according to the number of risk factors and standards of thromboprophylaxis assessed according to risk. After the first round of data collection, results were presented, a local guideline was developed and a risk assessment was added to the clerking pro forma. There were 122 patients in the first round, 101 in the second and 163 in the third. Eligible moderate and high-risk patients receiving a low molecular weight heparin (LMWH) increased from 31% to 63% (P < 0.005) over the study period. Prescription of thromboembolic deterrent (TED) stockings in those contraindicated to LMWH increased from 23% to 35% although this was not statistically significant (P = 0.08), and the percentage of high-risk patients correctly receiving LMWH, TED stockings or both increased from 22% to 62% (P < 0.0005). Documentation of contraindications to thromboprophylaxis increased from 0% to 59% (P < 0.0005). This paper demonstrates an initial rate of thromboprophylaxis use considerably less than the ENDORSE trial. However the strategies employed following initial audit resulted in a significant increase in the prescription of both mechanical and pharmacological thromboprophylaxis. This example demonstrates the role of audit education and a risk assessment in stimulating change. Such strategies could be used to ensure compliance to recently published National Institute of Clinical Excellence VTE guidelines. Furthermore this example could be generalized to improve other aspects of care.

Definition of immobility in studies of thromboprophylaxis in hospitalized medical patients: A systematic review

Venous thromboembolism (VTE) is a common, serious and preventable complication in hospitalized patients. Thromboprophylaxis in medical patients is safe, effective, and cost saving, but remains underutilized. Although immobility plays an important role in determining VTE risk in medical patients, no clear criteria exist to guide clinicians in assessing immobility when making decisions about thromboprophylaxis. A systematic review was conducted to determine how immobility is defined and operationalized in randomized controlled trials (RCTs) of thromboprophylaxis in medical inpatients. PubMed database was searched until September 2008 for RCTs of thromboprophylaxis in medical patients. Articles retrieved were further hand-searched to identify additional RCTs. Definitions of "immobility" were assessed. Twenty-one RCTs were retrieved, 18 were retained and 17 of these defined, to varying degrees, "immobility." Studies used several definition criteria, including the patient's degree of activity (14 studies), time spent immobile or mobile (13 studies), distance walked (4 studies) and underlying reason for immobility (4 studies); 14 studies used a combination of criteria. Definitions were clearly operationalized in 15 studies. The concept of "immobility" was utilized in study introductions (4 studies), inclusion/exclusion criteria (16 studies), as a stratification variable before randomization (1 study), in ongoing patient assessment (1 study), in treatment decisions (5 studies), as part of the study intervention (2 studies), as standard of care (2 studies), and in the results, discussion or conclusions (12 studies). There is a marked lack of consistency in how the concept of immobility is defined and utilized in RCTs of thromboprophylaxis in medical inpatients. This circumstance may contribute to the underutilization of thromboprophylaxis in clinical practice with medical inpatients.

VTE prophylaxis for the medical patient: where do we stand? – A focus on cancer patients

Acutely ill medical patients are at moderate to high risk of venous thromboembolism (VTE): approximately 10–30% of general medical patients may develop deep-vein thrombosis or pulmonary embolism, and the latter is a leading contributor to deaths in hospital. Medical conditions associated with a high risk of VTE include cardiac disease, cancer, respiratory disease, inflammatory bowel disease, rheumatological and infectious diseases. Pre-disposing risk factors in medical patients include a history of VTE, history of malignancy, complicating infections, increasing age, thrombophilia, prolonged immobility and obesity. Hence active cancer and a history of cancer are both strongly related to VTE in medical (non-surgical) patients. Heparins, both unfractionated (UFH) and low molecular weight (LMWH) and fondaparinux have been shown to be effective agents in prevention of VTE in this setting. However, it has not yet been possible to demonstrate a significant effect on mortality rates in this population. In medical patients, unfractionated heparin has a higher rate of bleeding complications than low molecular weight heparin. Thromboprophylaxis has been shown to be effective in medical patients with cancer and may have an effect on cancer outcomes. Thromboprophylaxis in patients receiving chemotherapy remains controversial and requires further investigation. There is no evidence for the use of aspirin, warfarin or mechanical methods. We recommend either low molecular weight heparin or fondaparinux as safe and effective agents in the thromboprophylaxis of medical patients.

Genesis of medical thromboprophylaxis guidelines in Australia: a need for transparency and standardisation in guideline development

Clinical guidelines are recommendations based on systematic identification and synthesis of the best available scientific evidence. The National Health and Medical Research Council (NHMRC) has published standards for guideline development. According to the NHMRC standards, guideline development must be a transparent and independent process, with full disclosure of any potential competing interests. Australian guidelines for prevention of venous thromboembolism have been published by an autonomous group. Several features of the processes used to produce and distribute these guidelines, such as pharmaceutical sponsorship, do not meet NHMRC endorsement standards. The guidelines may overstate the need for thrombo-prophylaxis in medical patients, and thus expose some patients to an unnecessary risk of bleeding complications. Despite this, these guidelines have been taken up avidly by national and state bodies responsible for safety and quality in health care, and mandated national application has been proposed.

Thromboprophylaxis in Medical Patients: An Update

Thromboprophylaxis in Medical Patients: An Update