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1.  An Economic Evaluation of Venous Thromboembolism Prophylaxis Strategies in Critically Ill Trauma Patients at Risk of Bleeding 
PLoS Medicine  2009;6(6):e1000098.
Using decision analysis, Henry Stelfox and colleagues estimate the cost-effectiveness of three venous thromboembolism prophylaxis strategies in patients with severe traumatic injuries who were also at risk for bleeding complications.
Critically ill trauma patients with severe injuries are at high risk for venous thromboembolism (VTE) and bleeding simultaneously. Currently, the optimal VTE prophylaxis strategy is unknown for trauma patients with a contraindication to pharmacological prophylaxis because of a risk of bleeding.
Methods and Findings
Using decision analysis, we estimated the cost effectiveness of three VTE prophylaxis strategies—pneumatic compression devices (PCDs) and expectant management alone, serial Doppler ultrasound (SDU) screening, and prophylactic insertion of a vena cava filter (VCF)—in trauma patients admitted to an intensive care unit (ICU) with severe injuries who were believed to have a contraindication to pharmacological prophylaxis for up to two weeks because of a risk of major bleeding. Data on the probability of deep vein thrombosis (DVT) and pulmonary embolism (PE), and on the effectiveness of the prophylactic strategies, were taken from observational and randomized controlled studies. The probabilities of in-hospital death, ICU and hospital discharge rates, and resource use were taken from a population-based cohort of trauma patients with severe injuries (injury severity scores >12) admitted to the ICU of a regional trauma centre. The incidence of DVT at 12 weeks was similar for the PCD (14.9%) and SDU (15.0%) strategies, but higher for the VCF (25.7%) strategy. Conversely, the incidence of PE at 12 weeks was highest in the PCD strategy (2.9%), followed by the SDU (1.5%) and VCF (0.3%) strategies. Expected mortality and quality-adjusted life years were nearly identical for all three management strategies. Expected health care costs at 12 weeks were Can$55,831 for the PCD strategy, Can$55,334 for the SDU screening strategy, and Can$57,377 for the VCF strategy, with similar trends noted over a lifetime analysis.
The attributable mortality due to PE in trauma patients with severe injuries is low relative to other causes of mortality. Prophylactic placement of VCF in patients at high risk of VTE who cannot receive pharmacological prophylaxis is expensive and associated with an increased risk of DVT. Compared to the other strategies, SDU screening was associated with better clinical outcomes and lower costs.
Please see later in the article for Editors' Summary
Editors' Summary
For patients who have been seriously injured in an accident or a violent attack (trauma patients), venous thromboembolism (VTE)—the formation of blood clots that limit the flow of blood through the veins—is a frequent and potentially fatal complication. The commonest form of VTE is deep vein thrombosis (DVT). “Distal” DVTs (clots that form in deep veins below the knee) affect about half of patients with severe trauma; “proximal” DVTs (clots that form above the knee) develop in one in five trauma patients. DVTs cause pain and swelling in the affected leg and can leave patients with a painful condition called post-thrombotic syndrome. Worse still, part of the clot can break off and travel to the lungs where it can cause a life-threatening pulmonary embolism (PE). Distal DVTs rarely embolize but, if untreated, half of patients who present with a proximal DVT will develop a PE, and 2%–3% of them will die as a result.
Why Was This Study Done?
VTE is usually prevented by using heparin, a drug that stops blood clotting, but clinicians treating critically ill trauma patients have a dilemma. Many of these patients are at high risk of serious bleeding complications so cannot be given heparin to prevent VTE. Nonpharmacological ways to prevent VTE include the use of pneumatic compression devices to keep the blood moving in the legs (clots often form in patients confined to bed because of the sluggish blood flow in their legs), repeated screening for blood clots using Doppler ultrasound, and the insertion of a “vena cava filter” into the vein that takes blood from the legs to the heart. This last device catches blood clots before they reach the lungs but increases the risk of DVT. Unfortunately, no-one knows which VTE prevention strategy works best in trauma patients who cannot be given heparin. In this study, therefore, the researchers use decision analysis (the systematic evaluation of the most important factors affecting a decision) to estimate the costs and likely clinical outcomes of these strategies.
What Did the Researchers Do and Find?
The researchers used cost and clinical data from patients admitted to a Canadian trauma center with severe head/neck and/or abdomen/pelvis injuries (patients with a high risk of bleeding complications likely to make heparin therapy dangerous for up to two weeks after the injury) to construct a Markov decision analysis model. They then fed published data on the chances of patients developing DVT or PE, and on the effectiveness of the three VTE prevention strategies, into the model to obtain estimates of the costs and clinical outcomes of the strategies at 12 weeks after the injury and over the patients' lifetime. The estimated incidence of DVT at 12 weeks was 15% for the pneumatic compression device and Doppler ultrasound strategies, but 25% for the vena cava filter strategy. By contrast, the estimated incidence of PE was 2.9% with the pneumatic compression device, 1.5% with Doppler ultrasound, but only 0.3% with the vena cava filter. The expected mortality with all three strategies was similar. Finally, the estimated health care costs per patient at 12 weeks were Can$55,334 and Can$55,831 for the Doppler ultrasound and pneumatic compression device strategies, respectively, but Can$57,377 for the vena cava filter strategy; similar trends were seen for lifetime health care costs.
What Do These Findings Mean?
As with all mathematical models, these findings depend on the data fed into the model and on the assumptions included in it. For example, because data from one Canadian trauma unit were used to construct the model, these findings may not be generalizable. Nevertheless, these findings suggest that, although VTE is common among patients with severe injuries, PE is not a major cause of death among these patients. They also suggest that the use of vena cava filters for VTE prevention in patients who cannot receive heparin should not be routinely used because it is expensive and increases the risk of DVT. Finally, these results suggest that, compared with the other strategies, serial Doppler ultrasound is associated with better clinical outcomes and lower costs.
Additional Information
Please access these Web sites via the online version of this summary at
The US National Heart Lung and Blood Institute provides information (including an animation) on deep vein thrombosis and pulmonary embolism
MedlinePlus provides links to more information about deep vein thrombosis and pulmonary embolism (in several languages)
The UK National Health Service Choices Web site has information on deep vein thrombosis and on embolism (in English and Spanish)
The Eastern Association for the Surgery of Trauma working group document Practice Management Guidelines for the Management of Venous Thromboembolism in Trauma Patients can be downloaded from the Internet
PMCID: PMC2695771  PMID: 19554085
2.  Risk of Venous Thromboembolism in Patients with Cancer: A Systematic Review and Meta-Analysis 
PLoS Medicine  2012;9(7):e1001275.
Venous thromboembolism in patients with cancer is common, but precise incidence rates in different cancers are not known, making it difficult to target prevention strategies. This study summarizes the existing literature to determine the risk of venous thromboembolism in high- and average-risk groups of patients with different cancers.
People with cancer are known to be at increased risk of venous thromboembolism (VTE), and this risk is believed to vary according to cancer type, stage of disease, and treatment modality. Our purpose was to summarise the existing literature to determine precisely and accurately the absolute risk of VTE in cancer patients, stratified by malignancy site and background risk of VTE.
Methods and Findings
We searched the Medline and Embase databases from 1 January 1966 to 14 July 2011 to identify cohort studies comprising people diagnosed with one of eight specified cancer types or where participants were judged to be representative of all people with cancer. For each included study, the number of patients who developed clinically apparent VTE, and the total person-years of follow-up were extracted. Incidence rates of VTE were pooled across studies using the generic inverse variance method. In total, data from 38 individual studies were included. Among average-risk patients, the overall risk of VTE was estimated to be 13 per 1,000 person-years (95% CI, 7 to 23), with the highest risk among patients with cancers of the pancreas, brain, and lung. Among patients judged to be at high risk (due to metastatic disease or receipt of high-risk treatments), the risk of VTE was 68 per 1,000 person-years (95% CI, 48 to 96), with the highest risk among patients with brain cancer (200 per 1,000 person-years; 95% CI, 162 to 247). Our results need to be considered in light of high levels of heterogeneity, which exist due to differences in study population, outcome definition, and average duration of follow-up between studies.
VTE occurs in greater than 1% of cancer patients each year, but this varies widely by cancer type and time since diagnosis. The absolute VTE risks obtained from this review can aid in clinical decision-making about which people with cancer should receive anticoagulant prophylaxis and at what times.
Please see later in the article for the Editors' Summary.
Editors' Summary
A venous thrombosis is the medical term for a blood clot that forms in a vein, often completely blocking the vessel. The most common type is a deep vein thrombosis of the lower leg, which apart from causing pain and immobility, can break off (embolize), flow through the blood stream back to the heart, get caught in one of the blood vessels supplying the lungs, and cause a life-threatening pulmonary embolism. The term venous thromboembolism (VTE) refers to both a deep venous thrombosis and a pulmonary embolism and is a common cause of death, responsible for at least 300,000 deaths a year in the United States alone. There are many risk factors for developing a VTE, including age, immobility, certain medications, and some conditions, such as cancer: an estimated 20% of deaths from VTE occur among patients with cancer, and importantly, cancer patients with VTE have a much higher risk of death than those who do not have a VTE. The increased risk of developing a VTE is due to the treatments and surgery involved in the management of cancer, in addition to the risks associated with the condition itself.
Why Was This Study Done?
Previous studies have suggested that certain types of cancer, such as brain and pancreatic cancer, are associated with an increased risk of developing a VTE, but to date, clinical guidelines recommend preventative treatment of VTE only for cancer patients during hospital admissions for medical treatment and surgery, not for those patients receiving outpatient care. In this study, the researchers systematically reviewed the available published evidence to quantify the risks of developing a VTE in patients with cancer according to the type of cancer, and to determine whether certain patient groups are at particularly high risk of developing a VTE.
What Did the Researchers Do and Find?
The researchers used a comprehensive keyword search of two medical literature databases to identify relevant studies published between 1966 and 2011. Then they examined these studies according to certain criteria, such as the type of study and the type of cancer: the researchers were specifically looking for cohort studies of adult patients with one of eight cancer types—breast, lung, colorectal, prostate, brain, bone, pancreatic, and hematologic (including all leukemias, lymphomas, and multiple myeloma). The selected studies also had to include follow-up of more than 30 days and VTE outcomes. Then the researchers categorized selected studies according to the risk of developing a VTE—the researchers judged high-risk patients to be those with metastatic disease or receiving certain types of high-risk treatments, and judged average-risk patients to be representative of all patients with a cancer diagnosis. The researchers then pooled all the data from these studies and did a separate statistical analysis for high and average risk and for each cancer type.
Using these methods, the researchers identified 7,274 potentially relevant articles, of which 46 reports from 38 individual cohorts met the criteria to be included in their review. Of the 38 cohorts, the researchers categorized 31 as high risk and seven as average risk. In the pooled analysis the researchers found that among average-risk patients, the overall risk of VTE was 13 per 1,000 person-years, with the highest risk among patients with cancers of the pancreas, brain, and lung. Among patients judged to be at high risk, the researchers found that the risk of VTE was 68 per 1,000 person-years, with the highest risk among patients with brain cancer (200 per 1,000 person-years).
What Do These Findings Mean?
These findings suggest that the annual incidence rate of VTE in patients with cancer is between 0.5% and 20%, depending on the cancer type, background risk, and time since diagnosis. Cancers of the brain and pancreas have the highest risk of VTE for both high- and average-risk patient groups. Based on these more accurate data on the risks of VTE in different groups of cancer patients, future updates of clinical guidelines can now include more information about categories of risk to help guide clinicians when they make decisions about which patients should receive preventative treatment for VTE and when they should receive such treatment.
Additional Information
Please access these websites via the online version of this summary at 1371/journal.pmed.1001275.
Wikipedia gives more information about VTE (note that Wikipedia is a free online encyclopedia that anyone can edit)
Information about VTE for patients and health professionals is available from the American Cancer Society, the US National Cancer Institute, and the UK-based thrombosis charity Lifeblood
PMCID: PMC3409130  PMID: 22859911
3.  Diet as prophylaxis and treatment for venous thromboembolism? 
Both prophylaxis and treatment of venous thromboembolism (VTE: deep venous thrombosis (DVT) and pulmonary emboli (PE)) with anticoagulants are associated with significant risks of major and fatal hemorrhage. Anticoagulation treatment of VTE has been the standard of care in the USA since before 1962 when the U.S. Food and Drug Administration began requiring randomized controlled clinical trials (RCTs) showing efficacy, so efficacy trials were never required for FDA approval. In clinical trials of 'high VTE risk' surgical patients before the 1980s, anticoagulant prophylaxis was clearly beneficial (fatal pulmonary emboli (FPE) without anticoagulants = 0.99%, FPE with anticoagulants = 0.31%). However, observational studies and RCTs of 'high VTE risk' surgical patients from the 1980s until 2010 show that FPE deaths without anticoagulants are about one-fourth the rate that occurs during prophylaxis with anticoagulants (FPE without anticoagulants = 0.023%, FPE while receiving anticoagulant prophylaxis = 0.10%). Additionally, an FPE rate of about 0.012% (35/28,400) in patients receiving prophylactic anticoagulants can be attributed to 'rebound hypercoagulation' in the two months after stopping anticoagulants. Alternatives to anticoagulant prophylaxis should be explored.
Methods and Findings
The literature concerning dietary influences on VTE incidence was reviewed. Hypotheses concerning the etiology of VTE were critiqued in relationship to the rationale for dietary versus anticoagulant approaches to prophylaxis and treatment.
Epidemiological evidence suggests that a diet with ample fruits and vegetables and little meat may substantially reduce the risk of VTE; vegetarian, vegan, or Mediterranean diets favorably affect serum markers of hemostasis and inflammation. The valve cusp hypoxia hypothesis of DVT/VTE etiology is consistent with the development of VTE being affected directly or indirectly by diet. However, it is less consistent with the rationale of using anticoagulants as VTE prophylaxis. For both prophylaxis and treatment of VTE, we propose RCTs comparing standard anticoagulation with low VTE risk diets, and we discuss the statistical considerations for an example of such a trial.
Because of (a) the risks of biochemical anticoagulation as anti-VTE prophylaxis or treatment, (b) the lack of placebo-controlled efficacy data supporting anticoagulant treatment of VTE, (c) dramatically reduced hospital-acquired FPE incidence in surgical patients without anticoagulant prophylaxis from 1980 - 2010 relative to the 1960s and 1970s, and (d) evidence that VTE incidence and outcomes may be influenced by diet, randomized controlled non-inferiority clinical trials are proposed to compare standard anticoagulant treatment with potentially low VTE risk diets. We call upon the U. S. National Institutes of Health and the U.K. National Institute for Health and Clinical Excellence to design and fund those trials.
PMCID: PMC2925348  PMID: 20701748
4.  Patient-Centered Research 
Recent studies have shown that symptomatic venous thromboembolism (VTE) frequently develops after hospital discharge following total hip arthroplasty (THA). Risk factors associated with the development of symptomatic VTE, and the efficacy of extended medical prophylaxis to prevent late VTE, are not well defined.
Using California Medicare discharge data from 1995 through 1997, we identified 298 individuals ≥65 years who were re-hospitalized for symptomatic VTE <91 days after elective unilateral THA. We compared these cases with 599 unmatched controls. Hospital records of the surgical admission were carefully abstracted to obtain information about demographic, surgical and medical variables potentially associated with the development of VTE. Outcomes were confirmed by review of the hospitalization for VTE.
Alone or in combination, 70% of control patients were treated with pneumatic compression, 43% with warfarin, 28% with enoxaparin and 6% with unfractionated heparin. Warfarin was given to 29% after discharge. In bivariate analysis, a body mass index (BMI) of ≥25 was strongly associated with rehospitalization for VTE [OR = 2.5, CI 1.8–3.5]. In a risk-adjusted model, independent predictors of VTE included: age over 85 years (vs 65–74) [OR = 2.3, CI 1.2–4.5], female sex [OR = 1.4, CI 1.0–1.9], ambulating before the second post-operative day [OR = 0.7, CI 0.5–0.9], and prior VTE [OR = 3.7, CI 1.8–8.0]. Using patients with a BMI <25 who received no form of prophylaxis (except TED stockings) as the referent group, the only patients who had significantly lower odds of VTE were patients with a BMI <25 who received the following forms of prophylaxis: pneumatic compression alone [OR = 0.4, CI 0.1–1.0], pneumatic compression with enoxaparin [OR = 0.35, CI 0.1–0.9] and pneumatic compression with warfarin [OR = 0.19, CI 0.1–0.5]. Similarly, warfarin use after hospital discharge was associated with absence of VTE, but this was significant only among patients with a BMI <25 [OR = 0.5, CI 0.2–0.8]; for BMI>25 [OR = 0.7, CI 0.5–1.1].
Higher BMI was strongly associated with rehospitalization for symptomatic VTE after total hip arthroplasty. Pneumatic compression and oral anticoagulation after hospital discharge were both associated with significantly lower odds of developing VTE, but only among patients with a BMI <25. Further studies are clearly needed to confirm our findings. In order to further reduce the incidence of symptomatic VTE after THA, efforts should focus on improving the effectiveness of in-hospital as well as extended medical prophylaxis among overweight and obese patients.
PMCID: PMC1495729
5.  The effect of a continuing medical education program on Venous thromboembolism prophylaxis utilization and mortality in a tertiary-care hospital 
Thrombosis Journal  2014;12:9.
Venous thromboembolism (VTE) prophylaxis is underutilized for hospitalized patients. The primary objective of this study was to assess the impact of a continuing medical education (CME) program on thromboprophylaxis and VTE-associated mortality in a tertiary-care hospital.
This was a retrospective study of all patients admitted to a tertiary-care hospital from 01/07/2009 to 30/06/2010 (after a CME program that aimed at improving VTE prophylaxis) and had confirmed VTE during stay. VTE prophylaxis utilization and associated mortality were assessed in them and compared to those of a similar cohort of patients hospitalized in the previous 12 months.
There were 147 confirmed VTE cases in the study period (surgical: 26.5% and medical: 73.5%). Most (63.9%) VTE patients received prophylaxis after the CME program compared with 36.5% in the previous 12 months (relative risk 1.73; 95% confidence interval, 1.38-2.18; P < 0.001). More surgical (82.1%) than medical (57.4%) patients received prophylaxis (P < 0.01). VTE-associated mortality rate was 10.9% with a significant decrease after the CME program (relative risk, 0.52; 95% confidence interval, 0.30-0.90). This mortality was lower for those who received VTE prophylaxis compared to those who didn’t (4.3% and 22.6%, respectively; P < 0.01). Additionally, VTE-associated deaths represented 1.1% of total hospital mortality compared to 1.9% in the 12 months before CME program (relative risk, 0.58; 95% confidence interval, 0.32-1.04; P = 0.07).
A CME educational program to improve VTE prophylaxis in a tertiary-care hospital was associated with improvement in VTE prophylaxis utilization and VTE-associated mortality. Such programs are highly recommended.
PMCID: PMC4041361  PMID: 24891840
Venous thromboembolism; Deep venous thrombosis; Pulmonary embolism; Thromboprophylaxis; Continuing medical education
6.  Venous thromboprophylaxis in gastrointestinal bleeding 
Individuals who experience gastrointestinal (GI) bleeding often have an unpredictable clinical course, which may include emergency surgery and intensive care unit admission. Hospitalization for acute illnesses is additionally associated with increased risk for venous thromboembolism (VTE), which, in turn, is not self-limiting and can lead to further complications such as pulmonary embolism. Consequently, pharmacological prophylaxis for VTE has been strongly recommended if the benefits are deemed to outweigh risk. However, physicians must be especially cautious about prophylaxis in patients with GI bleeds; accordingly, this retrospective study investigated the use of VTE prophylaxis and the subsequent incidence of complications in a group of inpatients with GI bleed from a tertiary centre in London, Ontario.
To study the use of venous thromboembolism (VTE) prophylaxis and the incidence of thrombotic events in patients with acute gastrointestinal (GI) bleeding.
Individuals admitted with a primary diagnosis of a GI bleed along with any endoscopically confirmed source (over a two-year period) were included. Patient comorbidity and data regarding anticoagulation or antiplatelet agent use before hospitalization were collected, in addition to type of VTE prophylaxis and duration of treatment. The primary end point was the development of VTE (deep vein thrombosis or pulmonary embolism) within one year of presentation.
Data from 504 patients admitted with GI bleeding were eligible for review. The total number of VTE events was 20 (4%) while the mortality rate during hospitalization was 4.6%; 397 patients were not given VTE prophylaxis during their hospitalization. Of the patients who were given VTE prophylaxis, 68 received prophylactic heparin or heparin derivatives during their admission. One hundred sixty-five patients had at least one other significant risk factor for VTE including recent or subsequent surgery, past thrombotic event or malignancy. The incidence of thrombosis in those with significant risk factors for VTE was significantly higher than those without (8.5% versus 1.8%; P=0.0009). Overall, there was no significant difference in thrombotic events between individuals receiving pharmacological prophylaxis (1.2%) and those who did not (2.8%) (P=0.4).
Overall, VTE prophylaxis did not significantly affect thrombotic events in patients admitted for an active GI bleed.
PMCID: PMC4399374  PMID: 25855878
Gastrointestinal bleeding; Venous thromboembolism prophylaxis
7.  Venous Thromboembolism in Patients with 
Inflammatory bowel diseases  2014;20(4):631-636.
Inflammatory bowel disease is a well known risk factor for venous thromboembolism (VTE). Existing guidelines for thromboprophylaxis in hospitalized patients do not extend to other clinical scenarios that may also be associated with VTE risk. Our aim was to estimate the fraction of VTE events in IBD patients that could be prevented.
A retrospective analysis assessed all IBD patients diagnosed with VTE at a single academic medical center from 2002–2012. Confirmed cases were analyzed for VTE risk factors, inpatient status, the use of DVT prophylaxis, and when applicable the reason for omission of prophylaxis. IBD VTE cases were compared with age- and sex-matched non-IBD VTE controls with regards to risk factors and potential opportunities for VTE prevention.
There were 204 IBD patients (108 UC, 96 CD) diagnosed with VTE (110 DVT, 66 PE, 27 intra-abdominal thromboses, 1 other). One third of the VTE events occurred in hospitalized patients. Two-third of the medical inpatients and 44% of surgical in-patients who developed VTE did not receive prophylaxis. Importantly, 129 VTE events occurred in outpatients. The proportion of outpatients hospitalized within 4 weeks of developing venous thrombosis was higher in IBD patients than non-IBD controls (33 vs. 15%, p=0.0003). One-third of patients (36%) were experiencing ambulatory disease flares at the time of VTE diagnosis.
A substantial portion of VTE events in IBD patients occurred in clinical scenarios not routinely recommended for thromboprophylaxis. Further investigation of primary prophylaxis for IBD patients in high risk outpatients may be warranted.
PMCID: PMC4116613  PMID: 24552828
celiac disease; Crohn’s disease; ulcerative colitis; thrombosis; prophylaxis
8.  Venous thromboembolic events in isolated severe traumatic brain injury 
The purpose of this study was to investigate the effect of prophylactic anticoagulation on the incidence of venous thromboembolic events (VTE) in patients suffering from isolated severe traumatic brain injury (TBI).
Materials and Methods:
Retrospective matched case-control study in adult patients sustaining isolated severe TBI (head AIS ≥3, with extracranial AIS ≤2) receiving VTE prophylaxis while in the surgical intensive care unit from 1/2007 through 12/2009. Patients subjected to VTE prophylaxis were matched 1:1 by age, gender, glasgow coma scale (GCS) score at admission, presence of hypotension on admission, injury severity score, and head abbreviated injury scale (AIS) score, with patients who did not receive chemical VTE prophylaxis. The primary outcome measure was VTE. Secondary outcomes were SICU and hospital length of stay (HLOS), adverse effects of anticoagulation, and mortality.
After propensity matching, 37 matched pairs were analysed. Cases and controls had similar demographics, injury characteristics, rate of craniotomies/craniectomies, SICU LOS, and HLOS. The median time of commencement of VTE prophylaxis was 10 days. The incidence of VTE was increased 3.5-fold in the controls compared to the cases (95% CI 1.0-12.1, P=0.002). The mortality was higher in patients who did not receive anticoagulation (19% vs. 5%, P=0.001). No adverse outcomes were detected in the anticoagulated patients.
Prophylactic anticoagulation decreases the overall risk for clinically significant VTE in patients with severe isolated TBI. Prospective validation of the timing and safety of chemical VTE prophylaxis in these instances is warranted.
PMCID: PMC3299146  PMID: 22416148
Anticoagulation; isolated severe head injury; mortality; traumatic brain injury; venous thromboembolic event
9.  Venous thromboembolism risk and prophylaxis in the acute hospital care setting: report from the ENDORSE study in Egypt 
Thrombosis Journal  2012;10:20.
Venous thromboembolism (VTE) is a leading cause of hospital-related deaths worldwide. However, the proportion of patients at risk of VTE who receive appropriate prophylaxis in Egypt is unknown. The ENDORSE study in Egypt is part of a global initiative to uncover the incidence of high-risk surgical and medical patients and determine what proportion of these patients receive appropriate VTE prophylaxis.
Ten Egyptian hospitals participated in this observational study, enrolling all surgical and medical patients that met the study criteria. This resulted in a cohort of 1,008 patients in acute care facilities who underwent a retrospective chart review. Each patient’s VTE risk status and the presence or absence of appropriate prophylactic care was assessed according to the American College of Chest Physicians (ACCP) guidelines 2004.
Of the 1,008 patients enrolled, 395 (39.2%) were found to be at high-risk for VTE. Overall, 227 surgical patients were at high-risk, although only 80 (35.2%) received ACCP-recommended prophylaxis. Similarly, 55/268 (32.75%) of high-risk medical patients received appropriate VTE prophylaxis. Low molecular weight heparin was the most commonly used anticoagulant, while mechanical prophylactic use was quite low (1.5%) in high-risk patients.
In Egypt, more than one-third of all patients hospitalized for surgery or acute medical conditions are at high risk for developing VTE. However, only a small fraction of these patients receive appropriate VTE prophylaxis. Corrective measures are necessary for preventing VTE morbidity and mortality in these high risk patients.
PMCID: PMC3502290  PMID: 22950681
Venous thromboembolism; Egypt; Thromboprophylaxis; Risk factors
10.  Current and Former Smoking and Risk for Venous Thromboembolism: A Systematic Review and Meta-Analysis 
PLoS Medicine  2013;10(9):e1001515.
In a meta-analysis of 32 observational studies involving 3,966,184 participants and 35,151 events, Suhua Wu and colleagues found that current, ever, and former smoking was associated with risk of venous thromboembolism.
Please see later in the article for the Editors' Summary
Smoking is a well-established risk factor for atherosclerotic disease, but its role as an independent risk factor for venous thromboembolism (VTE) remains controversial. We conducted a meta-analysis to summarize all published prospective studies and case-control studies to update the risk for VTE in smokers and determine whether a dose–response relationship exists.
Methods and Findings
We performed a literature search using MEDLINE (source PubMed, January 1, 1966 to June 15, 2013) and EMBASE (January 1, 1980 to June 15, 2013) with no restrictions. Pooled effect estimates were obtained by using random-effects meta-analysis. Thirty-two observational studies involving 3,966,184 participants and 35,151 VTE events were identified. Compared with never smokers, the overall combined relative risks (RRs) for developing VTE were 1.17 (95% CI 1.09–1.25) for ever smokers, 1.23 (95% CI 1.14–1.33) for current smokers, and 1.10 (95% CI 1.03–1.17) for former smokers, respectively. The risk increased by 10.2% (95% CI 8.6%–11.8%) for every additional ten cigarettes per day smoked or by 6.1% (95% CI 3.8%–8.5%) for every additional ten pack-years. Analysis of 13 studies adjusted for body mass index (BMI) yielded a relatively higher RR (1.30; 95% CI 1.24–1.37) for current smokers. The population attributable fractions of VTE were 8.7% (95% CI 4.8%–12.3%) for ever smoking, 5.8% (95% CI 3.6%–8.2%) for current smoking, and 2.7% (95% CI 0.8%–4.5%) for former smoking. Smoking was associated with an absolute risk increase of 24.3 (95% CI 15.4–26.7) cases per 100,000 person-years.
Cigarette smoking is associated with a slightly increased risk for VTE. BMI appears to be a confounding factor in the risk estimates. The relationship between VTE and smoking has clinical relevance with respect to individual screening, risk factor modification, and the primary and secondary prevention of VTE.
Please see later in the article for the Editors' Summary
Editors' Summary
Blood normally flows throughout the human body, supplying its organs and tissues with oxygen and nutrients. But, when an injury occurs, proteins called clotting factors make the blood gel (coagulate) at the injury site. The resultant clot (thrombus) plugs the wound and prevents blood loss. Occasionally, a thrombus forms inside an uninjured blood vessel and partly or completely blocks the blood flow. Clot formation inside one of the veins deep within the body, usually in a leg, is called deep vein thrombosis (DVT) and can cause pain, swelling, and redness in the affected limb. DVT can be treated with drugs that stop the blood clot from getting larger (anticoagulants) but, if left untreated, part of the clot can break off and travel to the lungs, where it can cause a life-threatening pulmonary embolism. DVT and pulmonary embolism are collectively known as venous thromboembolism (VTE). Risk factors for VTE include having an inherited blood clotting disorder, oral contraceptive use, prolonged inactivity (for example, during a long-haul plane flight), and having surgery. VTEs are present in about a third of all people who die in hospital and, in non-bedridden populations, about 10% of people die within 28 days of a first VTE event.
Why Was This Study Done?
Some but not all studies have reported that smoking is also a risk factor for VTE. A clear demonstration of a significant association (a relationship unlikely to have occurred by chance) between smoking and VTE might help to reduce the burden of VTE because smoking can potentially be reduced by encouraging individuals to quit smoking and through taxation policies and other measures designed to reduce tobacco consumption. In this systematic review and meta-analysis, the researchers examine the link between smoking and the risk of VTE in the general population and investigate whether heavy smokers have a higher risk of VTE than light smokers. A systematic review uses predefined criteria to identify all the research on a given topic; meta-analysis is a statistical method for combining the results of several studies.
What Did the Researchers Do and Find?
The researchers identified 32 observational studies (investigations that record a population's baseline characteristics and subsequent disease development) that provided data on smoking and VTE. Together, the studies involved nearly 4 million participants and recorded 35,151 VTE events. Compared with never smokers, ever smokers (current and former smokers combined) had a relative risk (RR) of developing VTE of 1.17. That is, ever smokers were 17% more likely to develop VTE than never smokers. For current smokers and former smokers, RRs were 1.23 and 1.10, respectively. Analysis of only studies that adjusted for body mass index (a measure of body fat and a known risk factor for conditions that affect the heart and circulation) yielded a slightly higher RR (1.30) for current smokers compared with never smokers. For ever smokers, the population attributable fraction (the proportional reduction in VTE that would accrue in the population if no one smoked) was 8.7%. Notably, the risk of VTE increased by 10.2% for every additional ten cigarettes smoked per day and by 6.1% for every additional ten pack-years. Thus, an individual who smoked one pack of cigarettes per day for 40 years had a 26.7% higher risk of developing VTE than someone who had never smoked. Finally, smoking was associated with an absolute risk increase of 24.3 cases of VTE per 100,000 person-years.
What Do These Findings Mean?
These findings indicate that cigarette smoking is associated with a statistically significant, slightly increased risk for VTE among the general population and reveal a dose-relationship between smoking and VTE risk. They cannot prove that smoking causes VTE—people who smoke may share other unknown characteristics (confounding factors) that are actually responsible for their increased risk of VTE. Indeed, these findings identify body mass index as a potential confounding factor that might affect the accuracy of estimates of the association between smoking and VTE risk. Although the risk of VTE associated with smoking is smaller than the risk associated with some well-established VTE risk factors, smoking is more common (globally, there are 1.1 billion smokers) and may act synergistically with some of these risk factors. Thus, smoking behavior should be considered when screening individuals for VTE and in the prevention of first and subsequent VTE events.
Additional Information
Please access these Web sites via the online version of this summary at
The US National Heart Lung and Blood Institute provides information on deep vein thrombosis (including an animation about how DVT causes pulmonary embolism), and information on pulmonary embolism
The UK National Health Service Choices website has information on deep vein thrombosis, including personal stories, and on pulmonary embolism; SmokeFree is a website provided by the UK National Health Service that offers advice on quitting smoking
The non-profit organization US National Blood Clot Alliance provides detailed information about deep vein thrombosis and pulmonary embolism for patients and professionals and includes a selection of personal stories about these conditions
The World Health Organization provides information about the dangers of tobacco (in several languages), from the US National Cancer Institute, offers online tools and resources to help people quit smoking
MedlinePlus has links to further information about deep vein thrombosis, pulmonary embolism, and the dangers of smoking (in English and Spanish)
PMCID: PMC3775725  PMID: 24068896
11.  Utilization of Parenteral Anticoagulants and Warfarin: Impact on the Risk of Venous Thromboembolism Recurrence in the Outpatient Setting 
American Health & Drug Benefits  2014;7(8):444-451.
Clinical guidelines recommend parenteral anticoagulation therapy with an early initiation of warfarin therapy for the treatment of patients with acute venous thromboembolism (VTE) and the prevention of recurrence.
To evaluate the outpatient utilization of parenteral anticoagulant therapy and warfarin among patients with VTE, and to examine the effects of parenteral anticoagulant use and the time to warfarin initiation from VTE diagnosis on the risk for VTE recurrence.
The Truven Health MarketScan Commercial Claims Database was used to identify patients aged 18 to 64 years who had an outpatient claim for deep-vein thrombosis or pulmonary embolism between January 2010 and December 2011 (ie, index date) and had no VTE diagnosis or treatment during the 12 months before the index date, had no hospital or emergency department VTE claim within 7 days after the index outpatient VTE claim, and had received warfarin <30 days after the index date. A recurrent VTE event was defined as a VTE-related emergency department visit or hospitalization within 8 to 365 days after the index date. A Cox proportional hazards model was used to estimate the adjusted hazard ratio (HR) associated with VTE recurrence risk related to parenteral anticoagulant use and warfarin initiation timing.
A total of 5820 patients were included in the study (mean age, 50.5 years); of these, 45% were female. A total of 75.7% (4403) of the patients receiving warfarin also received a parenteral anticoagulant, and the median time from VTE diagnosis to warfarin initiation was 5 days for parenteral anticoagulant users compared with 11 days for nonusers. Parenteral anticoagulant use was associated with a 49% recurrent VTE risk reduction (HR, 0.51; 95% confidence interval [CI], 0.43–0.60; P <.001). Each day of delayed warfarin initiation from the diagnosis of acute VTE was associated with a 1% increase in the risk for VTE recurrence (HR, 1.01; 95% CI, 1.01–1.02; P = .003).
Overall, 1 in 4 patients with VTE who had received warfarin in the outpatient setting did not receive parenteral anticoagulation therapy. Among those who received warfarin, its initiation was not always timely, despite its positive effects on reducing VTE recurrence. These findings highlight the potential quality-of-care concerns associated with the failure to use or the delayed implementation of guideline-recommended VTE treatment, and the need to improve compliance with clinical guidelines in the treatment of patients with VTE.
PMCID: PMC4280521  PMID: 25558306
12.  Colectomy is a risk factor for venous thromboembolism in ulcerative colitis 
AIM: To compare venous thromboembolism (VTE) in hospitalized ulcerative colitis (UC) patients who respond to medical management to patients requiring colectomy.
METHODS: Population-based surveillance from 1997 to 2009 was used to identify all adults admitted to hospital for a flare of UC and those patients who underwent colectomy. All medical charts were reviewed to confirm the diagnosis and extract clinically relevant information. UC patients were stratified by: (1) responsive to inpatient medical therapy (n = 382); (2) medically refractory requiring emergent colectomy (n = 309); and (3) elective colectomy (n = 329). The primary outcome was the development of VTE during hospitalization or within 6 mo of discharge. Heparin prophylaxis to prevent VTE was assessed. Logistic regression analysis determined the effect of disease course (i.e., responsive to medical therapy, medically refractory, and elective colectomy) on VTE after adjusting for confounders including age, sex, smoking, disease activity, comorbidities, extent of disease, and IBD medications (i.e., corticosteroids, mesalamine, azathioprine, and infliximab). Point estimates were presented as odds ratios (OR) with 95%CI.
RESULTS: The prevalence of VTE among patients with UC who responded to medical therapy was 1.3% and only 16% of these patients received heparin prophylaxis. In contrast, VTE was higher among patients who underwent an emergent (8.7%) and elective (4.9%) colectomy, despite greater than 90% of patients receiving postoperative heparin prophylaxis. The most common site of VTE was intra-abdominal (45.8%) followed by lower extremity (19.6%). VTE was diagnosed after discharge from hospital in 16.7% of cases. Elective (adjusted OR = 3.69; 95%CI: 1.30-10.44) and emergent colectomy (adjusted OR = 5.28; 95%CI: 1.93-14.45) were significant risk factors for VTE as compared to medically responsive UC patients. Furthermore, the odds of a VTE significantly increased across time (adjusted OR = 1.10; 95%CI: 1.01-1.20). Age, sex, comorbidities, disease extent, disease activity, smoking, corticosteroids, mesalamine, azathioprine, and infliximab were not independently associated with the development of VTE.
CONCLUSION: VTE was associated with colectomy, particularly, among UC patients who failed medical management. VTE prophylaxis may not be sufficient to prevent VTE in patients undergoing colectomy.
PMCID: PMC4306170  PMID: 25632199
Inflammatory bowel diseases; Ulcerative colitis; Deep vein thrombosis; Pulmonary embolism; Surgery
13.  Venous Thromboembolism in the Outpatient Setting 
Archives of internal medicine  2007;167(14):1471-1475.
There has been great interest in optimizing prophylaxis against venous thromboembolism (VTE) in the hospital setting. However, data from earlier studies suggest that the majority of VTE events occur in the outpatient setting. The purpose of this observational study was to describe the frequency of VTE events occurring in the outpatient setting, characterize the prevalence of previously identified risk factors for VTE, and to identify prior utilization of VTE prophylaxis.
The medical records of residents from the Worcester (MA) metropolitan area diagnosed with ICD-9 codes consistent with possible VTE during 1999, 2001, and 2003 were independently validated and reviewed by trained abstractors.
A total of 1,897 subjects had a confirmed episode of VTE. Approximately 74% of patients developed VTE in the outpatient setting – a substantial proportion of these patients had undergone surgery (23%) or hospitalization (37%) in the preceding 3 months. Among these patients, more than 50% experienced VTE within one month of the preceding hospital encounter. Other major risk factors for VTE in the outpatient setting included active malignancy (29%) or prior VTE (20%). Among patients with a recent hospitalization who subsequently developed VTE, less than 50% had received anticoagulant prophylaxis for VTE during that visit.
More VTE events were diagnosed in the 3 months following hospitalization than during hospitalization. Efforts to improve in-hospital utilization of VTE prophylaxis may help decrease the incidence of outpatient VTE. However, given shortening lengths of hospital stay, studies of extended VTE prophylaxis following hospital discharge are warranted.
PMCID: PMC2762787  PMID: 17646600
venous thromboembolism; deep vein thrombosis; pulmonary embolism; population-health
14.  Thromboprophylaxis with low-molecular-weight heparin in medical patients with cancer 
Cancer  2009;115(24):5637-5650.
Venous thromboembolism (VTE) is a frequent complication of cancer and cancer treatment and is associated with multiple clinical consequences including recurrent VTE, bleeding and an increase in risk of death. While the risks associated with VTE has been well recognized in surgical cancer patients, there is also considerable and increasing risk in medical cancer patients. VTE risk factors in medical cancer patients include the type and stage of cancer, major comorbid illnesses, current hospitalization, active chemotherapy, hormonal therapy, and antiangiogenic agents. Low-molecular-weight heparins (LMWHs) are commonly recommended for the prevention of VTE in hospitalized cancer patients and higher-risk ambulatory cancer patients due to their favorable risk-to-benefit profile. These agents have been shown to be effective in both the primary and secondary prevention of VTE in medical cancer patients. Extended-duration anticoagulant therapy is often recommended to reduce the risk of VTE recurrence in patients with cancer. LMWHs are often utilized for long-term prophylaxis due to a reduced need for coagulation monitoring, few major bleeding episodes, and once-daily dosing. Despite clinical and practical benefits, a substantial proportion of medical cancer patients do not receive VTE prophylaxis. To improve the appropriate prevention and treatment of VTE in cancer patients, guidelines have been published recently by the American Society of Clinical Oncology and the National Comprehensive Cancer Network. Widespread dissemination and application of these guidelines are encouraged to improve the appropriate use of these agents and improve clinical outcomes in medical cancer patients at risk for VTE and its complications.
Condensed abstract
To improve appropriate prevention of venous thromboembolism in cancer patients and clinical outcomes widespread dissemination and utilization of evidence-based guidelines such as those from the American Society of Clinical Oncology and the National Comprehensive Cancer Network are needed. Low-molecular-weight heparins are commonly recommended for the prevention of venous thromboembolism in hospitalized cancer patients and higher-risk ambulatory cancer patients.
PMCID: PMC3714853  PMID: 19827150
venous thromboembolism; cancer; anticoagulation; low-molecular-weight heparin; prophylaxis
15.  Evaluating patient values and preferences for thromboprophylaxis decision making during pregnancy: a study protocol 
Pregnant women with prior venous thromboembolism (VTE) are at risk of recurrence. Low molecular weight heparin (LWMH) reduces the risk of pregnancy-related VTE. LMWH prophylaxis is, however, inconvenient, uncomfortable, costly, medicalizes pregnancy, and may be associated with increased risks of obstetrical bleeding. Further, there is uncertainty in the estimates of both the baseline risk of pregnancy-related recurrent VTE and the effects of antepartum LMWH prophylaxis. The values and treatment preferences of pregnant women, crucial when making recommendations for prophylaxis, are currently unknown. The objective of this study is to address this gap in knowledge.
We will perform a multi-center cross-sectional interview study in Canada, USA, Norway and Finland. The study population will consist of 100 women with a history of lower extremity deep vein thrombosis (DVT) or pulmonary embolism (PE), and who are either pregnant, planning pregnancy, or may in the future consider pregnancy (women between 18 and 45 years). We will exclude individuals who are on full dose anticoagulation or thromboprophylaxis, who have undergone surgical sterilization, or whose partners have undergone vasectomy. We will determine each participant's willingness to receive LMWH prophylaxis during pregnancy through direct choice exercises based on real life and hypothetical scenarios, preference-elicitation using a visual analog scale (“feeling thermometer”), and a probability trade-off exercise. The primary outcome will be the minimum reduction (threshold) in VTE risk at which women change from declining to accepting LMWH prophylaxis. We will explore possible determinants of this choice, including educational attainment, the characteristics of the women’s prior VTE, and prior experience with LMWH. We will determine the utilities that women place on the burden of LMWH prophylaxis, pregnancy-related DVT, pregnancy-related PE and pregnancy-related hemorrhage. We will generate a “personalized decision analysis” using participants’ utilities and their personalized risk of recurrent VTE as inputs to a decision analytic model. We will compare the personalized decision analysis to the participant’s stated choice.
The preferences of pregnant women at risk of VTE with respect to the use of antithrombotic therapy remain unexplored. This research will provide explicit, quantitative expressions of women's valuations of health states related to recurrent VTE and its prevention with LMWH. This information will be crucial for both guideline developers and for clinicians.
PMCID: PMC3495041  PMID: 22646475
16.  Effectiveness of a novel and scalable clinical decision support intervention to improve venous thromboembolism prophylaxis: a quasi-experimental study 
Venous thromboembolism (VTE) causes morbidity and mortality in hospitalized patients, and regulators and payors are encouraging the use of systems to prevent them. Here, we examine the effect of a computerized clinical decision support (CDS) intervention implemented across a multi-hospital academic health system on VTE prophylaxis and events.
The study included 223,062 inpatients admitted between April 2007 and May 2010, and used administrative and clinical data. The intervention was integrated into a commercial electronic health record (EHR) in an admission orderset used for all admissions. Three time periods were examined: baseline (period 1), and the time after implementation of the first CDS intervention (period 2) and a second iteration (period 3). Providers were prompted to accept or decline prophylaxis based on patient risk. Time series analyses examined the impact of the intervention on VTE prophylaxis during time periods two and three compared to baseline, and a simple pre-post design examined impact on VTE events and bleeds secondary to anticoagulation. VTE prophylaxis and events were also examined in a prespecified surgical subset of our population meeting the public reporting criteria defined by the Agency for Healthcare Research and Quality (AHRQ) Patient Safety Indicator (PSI).
Unadjusted analyses suggested that “recommended”, “any”, and “pharmacologic” prophylaxis increased from baseline to the last study period (27.1% to 51.9%, 56.7% to 78.1%, and 42.0% to 54.4% respectively; p < 0.01 for all comparisons). Results were significant across all hospitals and the health system overall. Interrupted time series analyses suggested that our intervention increased the use of “recommended” and “any” prophylaxis by 7.9% and 9.6% respectively from baseline to time period 2 (p < 0.01 for both comparisons); and 6.6% and 9.6% respectively from baseline to the combined time periods 2 and 3 (p < 0.01 for both comparisons). There were no significant changes in “pharmacologic” prophylaxis in the adjusted model. The overall percent of patients with VTE increased from baseline to the last study period (2.0% to 2.2%; p = 0.03), but an analysis excluding patients with VTE “present on admission” (POA) demonstrated no difference in events (1.3% to 1.3%; p = 0.80). Overall bleeds did not significantly change. An analysis examining VTE prophylaxis and events in a surgical subset of patients defined by the AHRQ PSI demonstrated increased “recommended”, “any”, and “pharmacologic” prophylaxis from baseline to the last study period (32.3% to 60.0%, 62.8% to 85.7%, and 47.9% to 63.3% respectively; p < 0.01 for all comparisons) as well as reduced VTE events (2.2% to 1.7%; p < 0.01).
The CDS intervention was associated with an increase in “recommended” and “any” VTE prophylaxis across the multi-hospital academic health system. The intervention was also associated with increased VTE rates in the overall study population, but a subanalysis using only admissions with appropriate POA documentation suggested no change in VTE rates, and a prespecified analysis of a surgical subset of our sample as defined by the AHRQ PSI for public reporting purposes suggested reduced VTE. This intervention was created in a commonly used commercial EHR and is scalable across institutions with similar systems.
PMCID: PMC3502442  PMID: 22938083
Electronic medical record; Electronic health record; Health information technology; Clinical decision support; Venous thrombosis; Deep venous thrombosis; Quasi-experimental study
17.  Efficacy and safety of venous thromboembolism prophylaxis with fondaparinux or low molecular weight heparin in a large cohort of consecutive patients undergoing major orthopaedic surgery – findings from the ORTHO-TEP registry 
In large randomized trials, thromboprophylaxis with fondaparinux in major orthopaedic surgery (MOS) has been shown to be superior to low molecular weight heparin (LMWH) prophylaxis with comparable safety. However, patients treated under trial conditions are different from unselected patients and efficacy and safety outcomes may be different in unselected patients in daily practice. We performed a retrospective cohort study to compare the efficacy and safety of venous thromboembolism (VTE) prophylaxis with fondaparinux or LMWH in 3896 consecutive patients undergoing major orthopaedic surgery at our centre.
All patients undergoing MOS between January 2006 and December 2009 were retrospectively analyzed using patient charts, hospital admission and discharge database, quality management database, transfusion unit database and VTE event documentation. VTE standard prophylaxis at our institution was LMWH (3000–6000 aXa units once daily) from January 2006 to December 2007 or fondaparinux 2.5 mg from January 2008 to December 2009. In these two large cohorts of unselected consecutive patients, in-hospital incidences of VTE, surgical complications, severe bleeding and death were evaluated.
Symptomatic VTE was found in 4.1% of patients in the LMWH group (62/1495 patients; 95% CI 0.032, 0.052) compared with 5.6% of patients receiving fondaparinux (112/1994 patients, 95% CI 0.047, 0.067; P= 0.047). Distal deep vein thrombosis (DVT) was significantly more frequent in the fondaparinux group (3.9%, 95% CI 0.031, 0.048; vs. 2.5%; 95% CI 0.018, 0.034; P= 0.021). No significant differences in the rates of major VTE or death were found. Rates of severe bleeding, transfusion of RBC concentrates, plasma and platelet concentrates were comparable between both treatment groups. However, patients receiving fondaparinux had significantly lower rates of surgical revisions (1.6%, 95% CI 0.011, 0.022 vs. 3.7%, 95% CI 0.028, 0.047; P < 0.001). Multivariate analysis revealed previous VTE (HR 18.2, 95% CI 11.6, 28.5; P < 0.001) and female gender (HR 1.9, 95% CI 1.3, 2.7; P < 0.001), but not fondaparinux prophylaxis (HR1.3, 95% CI 0.9, 1.7; P= 0.184) to be associated with significantly increased VTE risk.
Thromboprophylaxis with fondaparinux is less effective to prevent distal VTE than LMWH in unselected patients undergoing MOS, but is equally effective with regard to rates of major VTE and death. However, differences in efficacy of LMWH or fondaparinux are of little relevance compared with a history of VTE or female gender, which were found to be the main VTE risk factors in MOS. The safety profile of fondaparinux was comparable with LMWH with regard to rates of severe bleeding complications, but patients receiving fondaparinux had significantly less surgical complications requiring surgical revisions. Both our efficacy and safety findings differ from data derived from large phase III trials testing fondaparinux against LMWH in MOS, where overall rates of symptomatic VTE were lower and the safety profile of fondaparinux was different.
We conclude that the strict patient selection and surveillance in phase-III trials results in lower VTE and bleeding event rates compared with unselected routine patients. Consequently, the efficacy and safety profile of thromboprophylaxis regimens needs to be confirmed in large registries or phase IV trials of unselected patients.
PMCID: PMC3522808  PMID: 22515679
bleeding; deep vein thrombosis; fondaparinux; venous thromboembolism; VTE prophylaxis
18.  Prevention and treatment of venous thromboembolism in patients with cancer 
Canadian Pharmacists Journal : CPJ  2012;145(1):24-29.e1.
Background: Many patients who experience a venous thromboembolic event have cancer, and thrombosis is much more prevalent in patients with cancer than in those without it. Thrombosis is the second most common cause of death in cancer patients and cancer is associated with a high rate of recurrence of venous thromboembolism (VTE), bleeding, requirement for long-term anticoagulation and poorer quality of life.
Methods: A literature review was conducted to identify guidelines and evidence pertaining to anticoagulation prophylaxis and treatment for patients with cancer, with the goal of identifying opportunities for pharmacists to advocate for and become more involved in the care of this population.
Results: Many clinical trials and several guidelines providing guidance to clinicians in the treatment and prevention of VTE in patients with cancer were identified. Current clinical evidence and guidelines suggest that cancer patients receiving care in hospital with no contraindications should receive VTE prophylaxis with unfractionated heparin (UFH), a low-molecular-weight heparin (LMWH) or fondaparinux. Patients who require surgery for their cancer should receive prophylaxis with UFH, LMWH or fondaparinux. Cancer patients who have experienced a VTE event should receive prolonged anticoagulant therapy with LMWH (at least 3 months to 6 months). No routine prophylaxis is required for the majority of ambulatory patients with cancer who have not experienced a VTE event. Most publicly funded drug plans in Canada have developed criteria for funding of LMWH therapy for patients with cancer.
Conclusions: Evidence suggests that LMWH for 3 to 6 months is the preferred strategy for most cancer patients who have experienced a thromboembolic event and for hospital inpatients, but this is often not implemented in practice. Concerns about adherence with injectable therapy should not prevent use of these agents. Pharmacists should assess cancer patients for their risk of VTE and should advocate for optimal VTE pharmacotherapy as appropriate. If LMWH is the preferred agent, on the basis of the evidence, the pharmacist should educate the patients appropriately and work with the prescriber to ensure best care.
PMCID: PMC3567538  PMID: 23509484
19.  Venous thromboembolism prophylaxis in hospitalized elderly patients: Time to consider a ‘MUST’ strategy 
Venous thromboembolism (VTE) is the commonest cause of preventable death in hospitalized patients. Elderly patients have higher risk of VTE because of the high prevalence of predisposing co-morbidities and acute illnesses. Clinical diagnosis of VTE in the elderly patient is particularly difficult and, as such, adequate VTE prophylaxis is of pivotal importance in reducing the mortality and morbidities of VTE. Omission of VTE prophylaxis is, however, very common despite continuous education. A simple way to overcome this problem is to implement universal VTE prophylaxis for all hospitalized elderly patients instead of selective prophylaxis for some patients only according to individual's risk of VTE. Although pharmacological VTE prophylaxis is effective for most patients, a high prevalence of renal impairment and drug interactions in the hospitalized elderly patients suggests that a multimodality approach may be more appropriate. Mechanical VTE prophylaxis, including calf and thigh compression devices and/or an inferior vena cava filter, are often underutilized in hospitalized elderly patients who are at high-risk of bleeding and VTE. Because pneumatic compression devices and thigh length stockings are virtually risk free, mechanical VTE prophylaxis may allow early or immediate implementation of VTE prophylaxis for all hospitalized elderly patients, regardless of their bleeding and VTE risk. Although the cost-effectiveness of this Multimodality Universal STat (‘MUST’) VTE prophylaxis approach for hospitalized elderly patients remains uncertain, this strategy appears to offer some advantages over the traditional ‘selective and single-modal’ VTE prophylaxis approach, which often becomes ‘hit or miss’ or not implemented promptly in many hospitalized elderly patients. A large clustered randomized controlled trial is, however, needed to assess whether early, multimodality, universal VTE prophylaxis can improve important clinical outcomes of hospitalized elderly patients.
PMCID: PMC3390075  PMID: 22783295
age; bundle of care; deep vein thrombosis; prevention; pulmonary embolism
20.  Thromboprophylaxis use in medical and surgical inpatients and the impact of an electronic risk assessment tool as part of a multi-factorial intervention. A report on behalf of the elVis study investigators 
Venous thromboembolism (VTE) is a major source of morbidity and mortality for both surgical and medical hospitalised patients. Despite the availability of guidelines, thromboprophylaxis continues to be underutilised. This study aims to assess the effectiveness of an electronic VTE risk assessment tool (elVis) on VTE prophylaxis in hospitalised patients. A national, multicentre, prospective clinical audit collected information on VTE prophylaxis and risk factors for VTE in 2,400 hospitalised patients (comprising of equal numbers of medical, surgical and orthopaedic patients). After auditing the standard care use of VTE prophylaxis in 1,200 consecutive patients (audit 1, A1), the elVis system was installed and a second audit (A2) of VTE prophylaxis was performed in a further 1,200 patients. The use of the electronic VTE risk assessment tool was low with 20.5% of patients assessed with elVis. The intervention, elVis plus accompanying education, improved the use VTE prophylaxis to guidelines by 5.0% amongst all patients and by 10.7% amongst high risk patients (adjusted odds ratio (AOR) 1.27 and 1.65 respectively). The use of elVis in A2 varied between hospitals and specialties and this resulted in marked heterogeneity. Despite this heterogeneity, patients assessed with elVis had 1.44 times higher AOR of being treated to guidelines compared to those who were not (P < 0.05). The use of elVis accompanied by staff education improved VTE prophylaxis, especially amongst high risk patients. To optimise the effectiveness and support enduring practice change electronic systems, such as elVis, need to be completely integrated within the treatment pathway.
PMCID: PMC3170471  PMID: 21643821
Deep vein thrombosis; Venous thromboembolism; Pulmonary embolism; Guideline adherence; Prevention; Thromboprophylaxis
21.  Risk factors for perioperative venous thromboembolism: A retrospective study in Japanese women with gynecologic diseases 
Thrombosis Journal  2010;8:17.
Patients with gynecologic cancer have a high risk of venous thromboembolism (VTE) like patients with other cancers. However, there is little information on risk factors for VTE during gynecologic surgery and no uniform preventive strategy. Our objectives were to identify risk factors for perioperative VTE in gynecologic patients and establish methods for prevention.
We analyzed 1,232 patients who underwent surgery at the Department of Obstetrics and Gynecology of St. Marianna University School of Medicine between January 2005 and June 2008. We investigated (1) risk factors for preoperative VTE, (2) use of an inferior vena cava (IVC) filter, and (3) risk factors for postoperative VTE.
There were 39 confirmed cases of perioperative VTE (3.17%), including 25 patients with preoperative VTE and 14 with postoperative VTE. Thirty-two patients had cancer and seven patients had benign diseases. Twenty-two of the 32 cancer patients (68.7%) had preoperative VTE, while postoperative VTE occurred in 10 cancer patients. Multivariate analysis indicated that ovarian cancer, tumor diameter ≥10 cm, and previous of VTE were independent risk factors for preoperative VTE. Among ovarian cancer patients, multivariate analysis showed that an age ≥50 years, the presence of heart disease, clear cell adenocarcinoma, and tumor diameter ≥20 cm were independent risk factors for preoperative VTE. The factors significantly related to preoperative VTE in patients with benign disease included previous VTE, age ≥55 years, tumor diameter ≥20 cm, and a history of allergic-immunologic disease. Thirteen of the 25 patients (52%) with preoperative VTE had an IVC filter inserted preoperatively. Postoperative screening (interview and D-dimer measurement) revealed VTE in 14/1,232 patients (1.14%). Multivariate analysis indicated that cancer surgery, a history of allergic-immunologic disease, and blood transfusion ≥2,000 ml were independent risk factors for postoperative VTE.
Perioperative VTE is often fatal and preventive measures should be taken in the gynecologic field, especially when patients have the risk factors identified in this study. Since VTE is often present before surgery, preoperative screening is important and use of an IVC filter should be considered.
PMCID: PMC2989308  PMID: 21054901
22.  Current and emerging strategies in the management of venous thromboembolism: benefit–risk assessment of dabigatran 
Venous thromboembolism (VTE) is a disease state that carries significant morbidity and mortality, and is a known cause of preventable death in hospitalized and orthopedic surgical patients. There are many identifiable risk factors for VTE, yet up to half of VTE incident cases have no identifiable risk factor and carry a high likelihood of recurrence, which may warrant extended therapy. For many years, parenteral unfractionated heparin, low-molecular weight heparin, fondaparinux, and oral vitamin K antagonists (VKAs) have been the standard of care in VTE management. However, limitations in current drug therapy options have led to suboptimal treatment, so there has been a need for rapid-onset, fixed-dosing novel oral anticoagulants in both VTE treatment and prophylaxis. Oral VKAs have historically been challenging to use in clinical practice, with their narrow therapeutic range, unpredictable dose responsiveness, and many drug–drug and drug–food interactions. As such, there has also been a need for novel anticoagulant therapies with fewer limitations, which has recently been met. Dabigatran etexilate is a fixed-dose oral direct thrombin inhibitor available for use in acute and extended treatment of VTE, as well as prophylaxis in high-risk orthopedic surgical patients. In this review, the risks and overall benefits of dabigatran in VTE management are addressed, with special emphasis on clinical trial data and their application to general clinical practice and special patient populations. Current and emerging therapies in the management of VTE and monitoring of dabigatran anticoagulant-effect reversal are also discussed.
PMCID: PMC4455861  PMID: 26064057
novel oral anticoagulants; dabigatran; venous thromboembolism; deep venous thrombosis; pulmonary embolism; oral anticoagulation
23.  Cancer and venous thromboembolic disease: from molecular mechanisms to clinical management 
Current Oncology  2014;21(3):134-143.
Venous thromboembolism (vte) represents a major challenge in the management of patients with cancer. The malignant phenotype is associated with derangements in the coagulation cascade that can manifest as thrombosis, hemorrhage, or disseminated intravascular coagulation. The risk of vte is increased by a factor of approximately 6 in patients with cancer compared with non-cancer patients, and cancer patients account for approximately 20% of all newly diagnosed cases of vte. Postmortem studies have demonstrated rates of vte in patients with cancer to be as high as 50%. Despite that prevalence, vte prophylaxis is underused in hospitalized patients with cancer. Studies have demonstrated that hospitalized patients with cancer are less likely than their non-cancer counterparts to receive vte prophylaxis. Consensus guidelines address the aforementioned issues and emerging concepts in the area, including the use of risk-assessment models, biomarkers to identify patients at highest risk of vte, and use of anticoagulants as anticancer therapy. Despite those guidelines, a gulf exists between current recommendations and clinical practice; greater efforts are thus required to ensure effective implementation of strategies to reduce the incidence of vte in patients with cancer.
PMCID: PMC4059798  PMID: 24940094
Venous thromboembolism
24.  Venous thromboembolism risk & prophylaxis in the acute hospital care setting (ENDORSE), a multinational cross-sectional study: Results from the Indian subset data 
Background & objectives:
Venous thromboembolism (VTE) is a major health problem with substantial morbidity and mortality. It is often underdiagnosed due to lack of information on VTE risk and prophylaxis. The ENDORSE (Epidemiologic International Day for the Evaluation of Patients at Risk for Venous Thromboembolism in the Acute Hospital Care Setting) study aimed to assess the prevalence of VTE risk in acute hospital care setting and proportion of at-risk patients receiving effective prophylaxis. We present here the risk factor profile and prophylaxis pattern of hospitalized patients who participated in ENDORSE study in India.
In this cross-sectional study in India, all patients (surgical >18 yr, medical >40 yr) from 10 hospitals were retrospectively studied. Demographics, VTE risk factors and prophylaxis patterns were assessed according to the 2004 American College of Chest Physicians (ACCP) evidence-based consensus guidelines.
We recruited 2058 patients (1110 surgical, 948 medical) from 10 randomly selected hospitals in India between August 2006 and January 2007. According to the ACCP criteria, 1104 (53.6%) patients [surgical 680 (61.3%), medical 424 (44.7%)] were at-risk for VTE. Chronic pulmonary disease/heart failure and complete immobilization were the most common risk factors before and during hospitalization, respectively. In India, 16.3 per cent surgical and 19.1 per cent medical at-risk patients received ACCP-recommended thromboprophylaxis.
Interpretation & conclusions:
Despite a similar proportion of at-risk hospitalized patients in India and other participating countries, there was major underutilization of prophylaxis in India. It necessitates increasing awareness about VTE risk and ensuring appropriate thromboprophylaxis.
PMCID: PMC3461719  PMID: 22885265
India; thromboprophylaxis; venous thromboembolism (VTE); VTE risk
25.  Anticoagulation Bridging Therapy Patterns in Patients Undergoing Total Hip or Total Knee Replacement in a US Health Plan: Real-World Observations and Implications 
American Health & Drug Benefits  2011;4(4):240-248.
The necessity for anticoagulant bridging therapy after joint replacement surgery is widely understood, but treatment administration patterns in the prevention of venous thromboembolism (VTE) after total hip replacement (THR) or total knee replacement (TKR) surgery during the hospital stay have yet to be examined.
To investigate anticoagulation thromboprophylaxis patterns, especially the use of anticoagulant bridging therapy and/or nonbridged treatment strategies, in patients undergoing THR/TKR surgery.
This retrospective study was based on a large hospital database linked with outpatient claims from 2005 through 2007. The study population included 1770 patients who were admitted for either THR or TKR surgery and were aged ≥18 years on the date of the surgery, defined as the index date. Patients were required to have commercial insurance or Medicare coverage and be continuously enrolled in their health plan for at least 180 days before and 90 days after the index date. The data were analyzed retrospectively for risk-adjusted postsurgery VTE and major bleeding events among patients receiving anticoagulation thromboprophylaxis. Patterns of anticoagulant bridging therapy use were also assessed. A risk adjustment was performed using propensity score matching.
Of 1770 eligible patients, 1551 (88%) received anticoagulant VTE prophylaxis; 264 (15%) received combination low-molecular-weight heparin and warfarin. Of these, 105 (40%) patients were switched between the 2 monotherapies, and 159 (60%) received bridged (overlapping) prophylaxis. The overall rates of VTE and bleeding events were significantly lower with bridged therapy than with nonbridged therapy (5.8% vs 18.4%, respectively, for VTE, P <.02; 2.3% vs 4.60% for major bleeding, P = .41; 1.15% vs 8.05% for minor bleeding, P <.03).
Although existing guidelines recommend anticoagulant bridging therapy after THR or TKR surgery, the limited data regarding anticoagulant bridging practice patterns suggest that patients who undergo such surgery do not receive adequate anticoagulant thromboprophylaxis immediately after discharge. Our findings suggest that increased use of bridging therapy after THR or TKR surgery may help improve postsurgery patient outcomes by reducing VTE and bleeding rates.
PMCID: PMC4125758  PMID: 25126354

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