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1.  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.
doi:10.3724/SP.J.1263.2011.00114
PMCID: PMC3390075  PMID: 22783295
age; bundle of care; deep vein thrombosis; prevention; pulmonary embolism
2.  Venous Thromboembolism in the Patient with Cancer: Focus on Burden of Disease and Benefits of Thromboprophylaxis 
Cancer  2010;117(7):1334-1349.
Venous thromboembolism (VTE) is a significant cause of morbidity and mortality in patients with cancer. The risk of VTE varies over the natural history of cancer, with the highest risk occurring during hospitalization and following disease recurrence. Patient and disease characteristics are associated with further increased risk of VTE in this setting. Specific factors include cancer type (eg, pancreatic cancer, brain cancer, lymphoma) and the presence of metastatic disease at the time of diagnosis. VTE is a significant predictor of increased mortality during the first year among all types and stages of cancer, with metastatic disease the strongest predictor of mortality. VTE is also associated with early death in ambulatory patients with cancer. These data highlight the need for close monitoring, prompt treatment, and appropriate preventive strategies for VTE in patients with cancer. The American Society of Clinical Oncology and the National Comprehensive Cancer Network have issued guidelines regarding the prophylaxis and treatment of patients with cancer. This review summarizes the impact of VTE on patients with cancer, the effects of VTE on clinical outcomes, the importance of thromboprophylaxis in this population, relevant ongoing clinical trials examining the prevention of VTE, and new pharmacologic treatment options.
doi:10.1002/cncr.25714
PMCID: PMC3780385  PMID: 21425133
Venous thromboembolism; VTE; cancer; thromboprophylaxis; anticoagulant; chemotherapy; low–molecular weight heparin; LMWH
3.  Statin treatment and risk of recurrent venous thromboembolism: a nationwide cohort study 
BMJ Open  2013;3(11):e003135.
Objectives
Statins may decrease the risk of primary venous thromboembolism (VTE), that is, deep vein thrombosis (DVT) and pulmonary embolism (PE) but the effect of statins in preventing recurrent VTE is less clear. The aim of this study was therefore to investigate the association between statin therapy and risk of recurrent VTE.
Design
A prospective cohort study.
Setting
All hospitals in Denmark.
Participants
All patients with a hospital diagnosis of VTE in Denmark during 1997–2009 associated with a warfarin or heparin prescription were identified.
Main outcome measures
Adjusted HR of recurrent hospitalised VTE (ie, fatal or non-fatal DVT or PE) associated with use of statins.
Results
44 330 patients with VTE were included in the study. Of these 3914 were receiving statin therapy at baseline. Patients receiving statins were older (68±11 compared to 62±18 years), had more comorbidity and used more medications. The incidence rate for recurrent VTE was 24.4 (95% CI 22.8 to 26.2) per 1000 person-years among statin users and 48.5 (95% CI 47.4 to 49.7) per 1000 person-years among non-statin users. Statin use was associated with a significantly lower risk of a recurrent VTE, adjusted HR 0.74 (95% CI 0.68 to 0.80), compared with no statin use. The association between statin use and risk of recurrent VTE was significantly affected by age. Among younger individuals (≤80 years), statin use was associated with lower risk of recurrent VTE, HR 0.70 (95% CI 0.65 to 0.76) whereas in older individuals (>80 years) statin use was significantly associated with higher risk of recurrent VTE, HR 1.28 (95% CI 1.02 to 1.60), p for interaction=<0.0001.
Conclusions
Statin use was associated with a decreased risk of recurrent VTE.
doi:10.1136/bmjopen-2013-003135
PMCID: PMC3822311  PMID: 24202053
VASCULAR MEDICINE; EPIDEMIOLOGY
4.  The incidence of venous thromboembolism and practice of deep venous thrombosis prophylaxis in hospitalized cirrhotic patients 
Thrombosis Journal  2011;9:1.
Background
Cirrhotic patients are characterized by a decreased synthesis of coagulation and anticoagulation factors. The coagulopathy of cirrhotic patients is considered to be auto-anticoagulation. Our aim was to determine the incidence and predictors of venous thromboembolism (VTE) and examine the practice of deep venous thrombosis (DVT) prophylaxis among hospitalized cirrhotic patients.
Methods
A retrospective cohort study was performed in a tertiary teaching hospital. We included all adult patients admitted to the hospital with a diagnosis of liver cirrhosis from January 1, 2009 to December 31, 2009. We grouped our cohort patients in two groups, cirrhotic patients without VTE and cirrhotic with VTE.
Results
Over one year, we included 226 cirrhotic patients, and the characteristics of both groups were similar regarding their clinical and laboratory parameters and their outcomes. Six patients (2.7%) developed VTE, and all of the VTEs were DVT. Hepatitis C was the most common (51%) underlying cause of liver cirrhosis, followed by hepatitis B (22%); 76% of the cirrhotic patients received neither pharmacological nor mechanical DVT prophylaxis.
Conclusion
Cirrhotic patients are at risk for developing VTE. The utilization of DVT prophylaxis was suboptimal.
doi:10.1186/1477-9560-9-1
PMCID: PMC3033790  PMID: 21244669
5.  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.
Methods:
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.
Results:
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
6.  Venous Thromboembolism and Bleeding in a Community Setting: The Worcester Venous Thromboembolism Study 
Thrombosis and haemostasis  2009;101(5):878-885.
Background
Bleeding is the most frequent complication of antithrombotic therapy for venous thromboembolism (VTE). However, little attention has been paid to the impact of bleeding after VTE in the community setting. The purpose of this investigation was to describe the incidence rate of bleeding after VTE, to characterize patients most at risk for bleeding, and to assess the impact of bleeding on rates of recurrent VTE and all-cause mortality.
Methods
The medical records of residents of the Worcester (MA) metropolitan area diagnosed with ICD-9 codes consistent with potential VTE during 1999, 2001, and 2003 were individually validated and reviewed by trained data abstracters. Clinical characteristics, acute treatment, and outcomes (including VTE recurrence rates, bleeding rates, and mortality) over follow-up (up to 3 years maximum) were evaluated.
Results
Bleeding occurred in 228 (12%) of 1,897 patients with VTE during our follow-up. Of these, 115 (58.8%) had evidence of early bleeding occurring within 30 days of VTE diagnosis. Patient characteristics associated with bleeding included impaired renal function and recent trauma. Other than a history of prior VTE, the occurrence of bleeding was the strongest predictor of recurrent VTE (HR 2.18; 95% CI 1.54-3.09) and was also a predictor of total mortality (HR 1.97 1.57-2.47).
Conclusions
The occurrence of bleeding following VTE is associated with an increased risk of recurrent VTE and mortality. Future study of antithrombotic strategies for VTE should be informed by this finding. Advances that result in decreased bleeding rates may paradoxically decrease the risk of VTE recurrence.
PMCID: PMC2827872  PMID: 19404541
venous thromboembolism; bleeding; hemorrhage; epidemiology
7.  The Impact of Venous Thromboembolism on Risk of Death or Hemorrhage in Older Cancer Patients 
Background
Among older cancer patients, there is uncertainty about the degree to which venous thromboembolism (VTE) and its treatment increase the risk of death or major hemorrhage.
Objective
To determine the prevalence of VTE in a cohort of older cancer patients, as well as the degree to which VTE increased the risk of death or major hemorrhage.
Methods
We conducted a retrospective cohort study of linked Surveillance, Epidemiology, and End Results cancer registry and Medicare administrative claims data. Patients with any of ten invasive cancers diagnosed during 1995 through 1999 were included; the independent variable was VTE diagnosed concomitantly with cancer diagnosis. Outcomes included major hemorrhage during the first year after cancer diagnosis and all-cause mortality;
Results
Overall, about 1% of patients who were diagnosed with cancer also had a VTE diagnosed concomitantly. After adjusting for sociodemographic factors and cancer stage and grade, concomitant VTE was associated with a relative increase in the risk of death for 8 of the 10 cancer types; the increase in risk tended to range 20–40% across most cancer types. Approximately 16.8% (95% confidence interval [CI] 14.9–18.8%) of patients with a concomitant VTE and 7.9% (95% CI 7.7–8.0%) of patients without a VTE experienced a major hemorrhage during the year after cancer diagnosis (P value <.001). The excess risk of hemorrhage associated with VTE varied substantially across cancer types, ranging from no significant excess (kidney and uterine cancer) to 11.5% (lymphoma).
Conclusion
Concomitant VTE is not only a marker and potential mediator of increased risk of death among older cancer patients, but patients with a VTE have a marked increased risk of major hemorrhage.
doi:10.1007/s11606-006-0019-x
PMCID: PMC1824718  PMID: 17356962
thrombosis; cancer; hemorrhage; epidemiology
8.  The Impact of Venous Thromboembolism on Risk of Death or Hemorrhage in Older Cancer Patients 
Background
Among older cancer patients, there is uncertainty about the degree to which venous thromboembolism (VTE) and its treatment increase the risk of death or major hemorrhage.
Objective
To determine the prevalence of VTE in a cohort of older cancer patients, as well as the degree to which VTE increased the risk of death or major hemorrhage.
Methods
We conducted a retrospective cohort study of linked Surveillance, Epidemiology, and End Results cancer registry and Medicare administrative claims data. Patients with any of ten invasive cancers diagnosed during 1995 through 1999 were included; the independent variable was VTE diagnosed concomitantly with cancer diagnosis. Outcomes included major hemorrhage during the first year after cancer diagnosis and all-cause mortality;
Results
Overall, about 1% of patients who were diagnosed with cancer also had a VTE diagnosed concomitantly. After adjusting for sociodemographic factors and cancer stage and grade, concomitant VTE was associated with a relative increase in the risk of death for 8 of the 10 cancer types; the increase in risk tended to range 20–40% across most cancer types. Approximately 16.8% (95% confidence interval [CI] 14.9–18.8%) of patients with a concomitant VTE and 7.9% (95% CI 7.7–8.0%) of patients without a VTE experienced a major hemorrhage during the year after cancer diagnosis (P value <.001). The excess risk of hemorrhage associated with VTE varied substantially across cancer types, ranging from no significant excess (kidney and uterine cancer) to 11.5% (lymphoma).
Conclusion
Concomitant VTE is not only a marker and potential mediator of increased risk of death among older cancer patients, but patients with a VTE have a marked increased risk of major hemorrhage.
doi:10.1007/s11606-006-0019-x
PMCID: PMC1824718  PMID: 17356962
thrombosis; cancer; hemorrhage; epidemiology
9.  Are There Any Differences in the Clinical and Economic Outcomes Between US Cancer Patients Receiving Appropriate or Inappropriate Venous Thromboembolism Prophylaxis? 
Journal of Oncology Practice  2009;5(4):159-164.
Prophylaxis is often underused and inappropriately prescribed. This study compares the efficacy and cost of appropriate and partial prophylaxis in cancer patients at risk for VTE.
Purpose:
Despite evidence-based recommendations existing for the prevention of venous thromboembolism (VTE) in cancer patients, prophylaxis is often underused and inappropriately prescribed. This study compared the efficacy and cost of appropriate and partial prophylaxis in cancer patients at risk of VTE.
Methods:
Discharge records for inpatients age ≥ 40 years, with a primary cancer diagnosis, and receiving some form of American College of Chest Physicians (ACCP) –recommended therapy in the Premier Perspective database (Premier Inc, Charlotte, NC; January 2002 to December 2006) were categorized into appropriate (in accordance with ACCP recommendations) or partial prophylaxis (inappropriate type, insufficient dose, or insufficient duration of prophylaxis) groups. VTE events, death, 30-day readmission, major and minor bleeds, and hospital costs were compared between groups using univariate and multivariate regression analysis.
Results:
Of the 83,794 discharges included, only 16% received appropriate prophylaxis. Partial prophylaxis conferred a significantly increased risk in hospital-acquired VTE (odds ratio [OR], 3.09; 95% CI, 2.51 to 3.80; P < .001), in-hospital death (OR, 1.48; 95% CI, 1.29 to 1.69; P < .001), and 30-day VTE readmission (OR, 3.11; 95% CI, 1.54 to 6.26; P = .002) compared with appropriate prophylaxis. No major bleeds were recorded in the database and no difference was observed in the rates of minor bleeding. The total cost per discharge was higher for partial prophylaxis ($17,128) than appropriate prophylaxis ($15,384), with an adjusted mean difference of $1,275 in favor of appropriate prophylaxis.
Conclusion:
In cancer patients at risk of VTE, appropriate prophylaxis reduced the hospital costs and incidence of VTE, mortality, and VTE readmission compared with partial prophylaxis. Increased appropriate use of ACCP recommendations may reduce the clinical and economic burden of VTE.
doi:10.1200/JOP.0942002
PMCID: PMC2795419  PMID: 20856628
10.  Clinical use of parnaparin in major and minor orthopedic sugery: a review 
Patients undergoing arthroplasty or other orthopedic surgery show a high risk of venous thromboembolism (VTE), involving mortality, morbidity, and social costs; however, the risk for VTE in minor orthopedic surgery should not be underestimated and antithrombotic prophylaxis may be required. According to the literature, low-molecular-weight heparins (LMWHs) are more effective in preventing VTE than unfractionated heparins (UFHs) or vitamin K antagonists, and have a lower hemorrhagic risk. By comparing different prophylactic regimens, it has been shown that starting the prophylaxis near the time of the operation is the most critical point for efficacy, whether or not the first dose is administered pre- or post-operatively. Moreover, most thromboembolic complications are observed after discharge and, therefore, many clinicians advocate continuing prophylaxis for longer times (6–8 weeks) in order to further reduce the rate for VTE. The literature on parnaparin, a new LMWH, in VTE prophylaxis was reviewed. Parnaparin is equally effective as UFH, but it offers the advantages of a once-daily administration and improved tolerability, thus allowing the home management of patients with no need for laboratory coagulation tests.
PMCID: PMC2605328  PMID: 19183746
orthopedic surgery; low molecular weight heparins; antithromboembolic prophylaxis; parnaparin
11.  Venous thromboembolic events in isolated severe traumatic brain injury 
Objective:
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.
Results:
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.
Conclusion:
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.
doi:10.4103/0974-2700.93102
PMCID: PMC3299146  PMID: 22416148
Anticoagulation; isolated severe head injury; mortality; traumatic brain injury; venous thromboembolic event
12.  Use of anticoagulants in elderly patients: practical recommendations 
Elderly people represent a patient population at high thromboembolic risk, but also at high hemorrhagic risk. There is a general tendency among physicians to underuse anticoagulants in the elderly, probably both because of underestimation of thromboembolic risk and overestimation of bleeding risk. The main indications for anticoagulation are venous thromboembolism (VTE) prophylaxis in medical and surgical settings, VTE treatment, atrial fibrillation (AF) and valvular heart disease. Available anticoagulants for VTE prophylaxis and initial treatment of VTE are low molecular weight heparins (LMWH), unfractionated heparin (UFH) or synthetic anti-factor Xa pentasaccharide fondaparinux. For long-term anticoagulation vitamin K antagonists (VKA) are the first choice and only available oral anticoagulants nowadays. Assessing the benefit-risk ratio of anticoagulation is one of the most challenging issues in the individual elderly patient, patients at highest hemorrhagic risk often being those who would have the greatest benefit from anticoagulants. Some specific considerations are of utmost importance when using anticoagulants in the elderly to maximize safety of these treatments, including decreased renal function, co-morbidities and risk of falls, altered pharmacodynamics of anticoagulants especially VKAs, association with antiplatelet agents, patient education. Newer anticoagulants that are currently under study could simplify the management and increase the safety of anticoagulation in the future.
PMCID: PMC2685237  PMID: 19503778
anticoagulation; elderly patients; venous thromboembolism; hemorrhagic risk; atrial fibrillation; thrombin inhibitors; factor Xa inhibitor
13.  Potential role of new anticoagulants for prevention and treatment of venous thromboembolism in cancer patients 
Venous thromboembolism (VTE), encompassing deep vein thrombosis and pulmonary embolism, represents a major cause of morbidity and mortality in patients with cancer. Low molecular weight heparins are the preferred option for anticoagulation in cancer patients according to current clinical practice guidelines. Fondaparinux may also have a place in prevention of VTE in hospitalized cancer patients with additional risk factors and for initial treatment of VTE. Although low molecular weight heparins and fondaparinux are effective and safe, they require daily subcutaneous administration, which may be problematic for many patients, particularly if long-term treatment is needed. Studying anticoagulant therapy in oncology patients is challenging because this patient group has an increased risk of VTE and bleeding during anticoagulant therapy compared with the population without cancer. Risk factors for increased VTE and bleeding risk in these patients include concomitant treatments (surgery, chemotherapy, placement of central venous catheters, radiotherapy, hormonal therapy, angiogenesis inhibitors, antiplatelet drugs), supportive therapies (ie, steroids, blood transfusion, white blood cell growth factors, and erythropoiesis-stimulating agents), and tumor-related factors (local vessel damage and invasion, abnormalities in platelet function, and number). New anticoagulants in development for prophylaxis and treatment of VTE include parenteral compounds for once-daily administration (ie, semuloparin) or once-weekly dosing (ie, idraparinux and idrabiotaparinux), as well as orally active compounds (ie, dabigatran, rivaroxaban, apixaban, edoxaban, betrixaban). In the present review, we discuss the pharmacology of the new anticoagulants, the results of clinical trials testing these new compounds in VTE, with special emphasis on studies that included cancer patients, and their potential advantages and drawbacks compared with existing therapies.
doi:10.2147/VHRM.S35843
PMCID: PMC3652561  PMID: 23674896
anticoagulants; venous thromboembolism; cancer; dabigatran; apixaban; rivaroxaban
14.  Venous thromboembolism risk and prophylaxis in the acute hospital care setting: report from the ENDORSE study in Egypt 
Thrombosis Journal  2012;10:20.
Background
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.
Methods
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.
Results
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.
Conclusions
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.
doi:10.1186/1477-9560-10-20
PMCID: PMC3502290  PMID: 22950681
Venous thromboembolism; Egypt; Thromboprophylaxis; Risk factors
15.  Normal levels of protein C and protein S tested in the acute phase of a venous thromboembolic event are not falsely elevated 
Thrombosis Journal  2010;8:10.
Background
Protein C (PC) and protein S (PS) determination is part of the thrombophilia investigation in patients with idiopathic venous thromboembolism (VTE). Based on scarce evidence it is a common notion that PC and PS levels decrease during the acute phase of VTE, necessitating delay of testing and temporary transition from warfarin to low molecular weight heparin. We have previously demonstrated that an abnormal PC or PS result determined within 24 hours of VTE diagnosis and before the initiation of warfarin needs to be repeated for confirmation ≥3 months after starting treatment and ≥14 days after stopping anticoagulation therapy. In the current study, we sought to show that normal PC and PS values determined during the acute phase of VTE are not false negatives.
Methods
99 patients with acute idiopathic VTE who had normal PC and PS determination within the first 24 hours of presentation and who subsequently had their oral anticoagulation discontinued after six months of therapy. PC and PS determinations were repeated ≥6 months after starting treatment and ≥ 14 days after stopping warfarin. Proportions of patients who tested abnormal on the second test were calculated and 95% confidence intervals obtained using the Wilson's score method. Data from a previously published study on patients with abnormal initial tests was included for comparison.
Results
None of the 99 patients who had normal PC and PS initially had an abnormal result on repeated testing (0%; 95% CI 0 - 3.7%). Data from the previous study showed that, among patients who initially had abnormal results, 40% (95%CI 35.4-84.8%) were confirmed to have low PC and 63.6% (95%CI 16.8-68.7%) low PS on repeated testing. The difference between proportions was statistically significant (χ2 p-value < 0.001).
Conclusion
Our results suggest that PC and PS can be determined during the acute phase of VTE and whereas abnormal results need to be confirmed with repeat testing at a later date, a normal result effectively rules out deficiency with only one test.
doi:10.1186/1477-9560-8-10
PMCID: PMC2887791  PMID: 20482785
16.  Optional Inferior Vena Cava Filters in the Trauma Patient 
ABSTRACT
Trauma patients are at exceedingly high risk of development of venous thromboembolism (VTE) including deep venous thrombosis and pulmonary embolism (PE). The epidemiology of VTE in trauma patients is reviewed. PE is thought to be the third major cause of death after trauma in those patients who survive longer than 24 hours after onset of injury. In fact, patients recovering from trauma have the highest rate of VTE among all subgroups of hospitalized patients. Various prophylactic and surveillance methods have been evaluated and found helpful in certain situations, but VTE complications can occur despite such measures. Therapeutic and prophylactic uses of inferior vena cava (IVC) filters in trauma patients are reviewed. Prophylactic IVC filter use is revealed to be a controversial subject with valid arguments on both sides of the issue. With the lack of prospective randomized trials of IVC filter use in trauma, it is impossible to make evidence-based recommendations. Unfortunately, two sets of guidelines are available for insertion of filters in trauma patients, with conflicting recommendations. The introduction of retrievable IVC filters seems to offer a unique solution for VTE protection in the trauma patient population, which often consists of younger members of our population. Lastly, current generations of FDA-approved retrieval filters are discussed.
doi:10.1055/s-0030-1247890
PMCID: PMC3036500  PMID: 21359016
Venous thromboembolism; inferior vena cava filter; trauma
17.  Novel Biomarkers Associated with Deep Venous Thrombosis: A Comprehensive Review 
Biomarker Insights  2008;3:93-100.
Primary and recurrent venous thromboembolic disease (VTE, deep venous thrombosis and pulmonary embolism) remain a significant source of morbidity and mortality in the hospitalized patient. Non-specific subjective complaints and lack of specific objective findings related to acute deep venous thrombosis (DVT) and pulmonary embolism (PE) complicate the diagnosis. There remains no single serum marker available to exclusively confirm the diagnosis of VTE. While D-dimer is highly sensitive and useful for diagnostic exclusion, it lacks the specificity necessary for diagnostic confirmation resulting in the need for a variety of additional studies (i.e.: duplex ultrasound, venography, V/Q scanning, helical thoracic and pelvic CT scans and pulmoary angiography). There is evolving research supporting the utility of various plasma markers as novel “biomarkers” for VTE including selectins, microparticles, interleukin-10 and other cytokines. This review attempts to examine recent literature assessing the utility of P-selectin, microparticles, D-dimer, E-selectin, thrombin, interleukins and fibrin monomers in the diagnosis and guidance of therapy for VTE.
PMCID: PMC2699262  PMID: 19578498
deep venous thrombosis; microparticles; D-dimer; P-selectin
18.  Computer Surveillance of Patients at High Risk for and with Venous Thromboembolism 
Venous thromboembolism (VTE), including deep vein thrombosis (DVT) and pulmonary embolism (PE), may be the number one preventable cause of death associated with hospitalization. Numerous evidence-based guidelines for effective VTE prophylaxis therapy exist. However, underuse is common due to the difficulty in integrating VTE risk assessment into routine patient care. Previous studies utilizing computer decision support to identify high-risk patients report improved use of prophylaxis therapy and reduced VTE. However, those studies did not report the sensitivity, specificity or positive predictive value of their methods to identify patients at high risk. We report an evaluation of a computerized tool to identify patients at high risk for VTE that found a sensitivity of 98% and positive predictive value of 99%. Another computer program used to detect VTE had a sensitivity of 92%, specificity of 99% and a positive predictive value of 97% to identify DVT and a sensitivity of 100%, specificity of 98% and positive predictive value of 89% to identify PE. These tools were found to provide a dependable method to identify patients at high risk for and with VTE.
PMCID: PMC3041332  PMID: 21346972
19.  Clustering Patterns of Comorbidities Associated with In-Hospital Death in Hospitalizations of US Adults with Venous Thromboembolism 
Background: Venous thromboembolism (VTE) is a significant source of mortality, morbidity, disability, and impaired health-related quality of life in the world.
Objective: We aimed to evaluate the clustering patterns and associations of 29 comorbidities with in-hospital death among adult hospitalizations with a diagnosis of VTE in the United States by analyzing data from the 2009 Nationwide Inpatient Sample.
Methods: This cross-sectional study included 153,124 adult hospitalizations with a diagnosis of VTE. Adjusted rate ratios and 95% confidence intervals (CI) for in-hospital death were generated by using multivariable log-linear regression models to measure independent associations between comorbidities and in-hospital death.
Results: We estimated that 44,200 in-hospital deaths occurred in 2009 among 773,273 US adult hospitalizations with a diagnosis of VTE. Subgroups of hospitalizations with comorbidities of “congestive heart failure,” “chronic pulmonary disease,” “coagulopathy,” “liver disease,” “lymphoma,” “fluid and electrolyte disorders,” “metastatic cancer,” “peripheral vascular disorders,” “pulmonary circulation disorders,” “renal failure,” “solid tumor without metastasis,” or “weight loss” were positively and independently associated with 1.07 (95% CI: 1.02-1.12 ) to 2.06 (95% CI: 1.97-2.16) times increased likelihoods of in-hospital death, when compared to those without the corresponding comorbidities. The clustering patterns of these comorbidities by 4 disease categories (i.e., “cancer,” “cardiovascular/respiratory/blood,” “gastrointestinal/urologic,” and “nutritional/bodyweight”) were associated with 2.74 to 10.28 times increased likelihoods of in-hospital death, as compared to hospitalizations without any of these comorbidities. The overall increase in the cumulative number of comorbidities corresponded to significantly elevated risks (P-trend<0.01) for in-hospital death among hospitalizations with a diagnosis of VTE.
Conclusion: The presence of multiple comorbidities is ubiquitous among hospitalizations of adults with VTE and among in-hospital deaths with VTE in the United States. The findings of our study further suggest that, among hospitalizations of adults with VTE, the presence of certain comorbidities or clustering of these comorbidities significantly elevates the risk of in-hospital death.
doi:10.7150/ijms.6714
PMCID: PMC3753416  PMID: 23983596
Comorbidity; Clustering pattern; Elixhauser comorbidity index; Venous thromboembolism; Hospitalization; Death; Mortality.
20.  Prevention of venous thromboembolism in obesity 
Venous thromboembolism (VTE) is a significant cause of morbidity and mortality in hospitalized patients. Where appropriate, evidence-based methods of prophylaxis are implemented and the burden of VTE can be reduced substantially. Obesity, including morbid obesity, is associated with a high risk of VTE and, unfortunately, fixed doses of US FDA-approved anticoagulant regimens, including unfractionated heparins, low-molecular-weight heparins and factor Xa inhibitors, may not provide optimal VTE prophylaxis in these patients. Although the data are still limited, a rapidly growing body of literature and cumulative evidence suggests that anticoagulant dose adjustments in morbidly obese patients may optimize pharmacodynamic activity and reduce VTE risk. With the prevalence of morbid obesity continuing to rise, more high-quality clinical data are needed to better understand the pathobiology of VTE in obesity and provide effective, yet safe, prevention strategies.
doi:10.1586/erc.10.160
PMCID: PMC3245959  PMID: 21108553
deep vein thrombosis; fondaparinux; low-molecular-weight heparin; morbid obesity; pulmonary embolism; special populations; venous thromboembolism prophylaxis
21.  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.
doi:10.1002/cncr.24665
PMCID: PMC3714853  PMID: 19827150
venous thromboembolism; cancer; anticoagulation; low-molecular-weight heparin; prophylaxis
22.  Impact of Venous Thromboembolism and Anticoagulation on Cancer and Cancer Survival 
Journal of Clinical Oncology  2009;27(29):4902-4911.
Changes in the hemostatic system and chronic hemostatic activation are frequently observed in patients with cancer, even in the absence of venous thromboembolism (VTE). VTE is a leading cause of death among patients with cancer and contributes to long-term mortality in patients with early as well as advanced-stage cancer. Mounting evidence suggests that components of the clotting cascade and associated vascular factors play an integral part in tumor progression, invasion, angiogenesis, and metastasis formation. Furthermore, there are intriguing in vitro and animal findings that anticoagulants, in particular the low molecular weight heparins (LMWHs), exert an antineoplastic effect through multiple mechanisms, including interference with tumor cell adhesion, invasion, metastasis formation, angiogenesis, and the immune system. Several relatively small randomized controlled clinical trials of anticoagulation as cancer therapy in patients without a VTE diagnosis have been completed. These comprise studies with LMWH, unfractionated heparin, and vitamin K antagonists, with overall encouraging but nonconclusive results and some limitations. Meta-analyses performed for the American Society of Clinical Oncology VTE Guidelines Committee and the Cochrane Collaboration suggest overall favorable effects of anticoagulation on survival of patients with cancer, mainly with LMWH. However, definitive clinical trials have been elusive and questions remain regarding the importance of tumor type and stage on treatment efficacy, the impact of fatal thromboembolic events, optimal anticoagulation therapy, and safety with differing chemotherapy regimens. Although the LMWHs and related agents hold promise for improving outcomes in patients with cancer, additional studies of their efficacy and safety in this setting are needed.
doi:10.1200/JCO.2009.22.4584
PMCID: PMC2799059  PMID: 19738120
23.  Current and future management of pediatric venous thromboembolism 
American journal of hematology  2012;87(0 1):S68-S74.
Venous thromboembolism (VTE) is an increasingly common complication encountered in tertiary care pediatric settings. The purpose of this review is to summarize the epidemiology, current and emerging pharmacotherapeutic options, and management of this disease. Over 70% of VTE occur in children with chronic diseases. Although they are seen in children of all ages, adolescents are at greatest risk. Pediatric VTE is associated with an increased risk of in-hospital mortality; recurrent VTE and post-thrombotic syndrome are commonly seen in survivors. In recent years, anticoagulation with low molecular weight heparin has emerged as the mainstay of therapy, but compliance is limited by its onerous subcutaneous administration route. New anticoagulants either already approved for use in adults or in the pipeline offer the possibility of improved dose stability and oral routes of administration. Current recommended anticoagulation course durations are derived from very limited case series and cohort data, or extrapolations from adult literature. However, the pathophysiologic underpinnings of pediatric VTE are dissimilar from those seen in adults and are often variable within groups of pediatric patients. Clinical studies and trials in pediatric VTE are underway which will hopefully improve the quality of evidence from which therapeutic guidelines are derived.
doi:10.1002/ajh.23131
PMCID: PMC3790464  PMID: 22367975
24.  Taller women are at greater risk of recurrent venous thromboembolism: The Iowa Women’s Health Study 
American Journal of Hematology  2012;87(7):716-717.
Summary
Venous thromboembolism (VTE) recurs frequently. Greater height is associated with increased risk of incident VTE, but it is unclear if height is related to risk of VTE recurrence. Recurrent VTE is associated with substantial morbidity and mortality, thus identifying individuals at greatest risk of experiencing a recurrent event, who may benefit from extended anticoagulant therapy, is vitally important. Using data from the Iowa Women’s Health Study we explored whether greater height was associated with increased risk of VTE recurrence. Among 1691 women who experienced an initial VTE event 286 (16.9%) experienced a recurrent event. Risk of recurrence was 76% (95% CI: 16%–186%) higher among women ≥66 inches [~168 centimeters] tall relative to those ≤62 inches [~158 centimeters] tall, after adjustment for age and waist circumference. Future research should evaluate whether body height improves clinical prediction of VTE recurrence risk.
doi:10.1002/ajh.23199
PMCID: PMC3375396  PMID: 22488550
25.  The Association of Active Cancer With Venous Thromboembolism Location: A Population-Based Study 
Mayo Clinic Proceedings  2011;86(1):25-30.
OBJECTIVE: To test active cancer for an association with venous thromboembolism (VTE) location.
PATIENTS AND METHODS: Using the resources of the Rochester Epidemiology Project, we identified all Olmsted County, MN, residents with incident VTE during the 35-year period 1966-2000 (N=3385). We restricted analyses to residents with objectively diagnosed VTE during the 17-year period from January 1, 1984, to December 31, 2000 (N=1599). For each patient, we reviewed the complete medical records in the community for patient age, gender, and most recent body mass index at VTE onset; VTE event type and location; and previously identified independent VTE risk factors (ie, surgery, hospitalization for acute medical illness, active cancer, leg paresis, superficial venous thrombosis, and varicose veins). Using logistic regression we tested active cancer for an association with each of 4 symptomatic VTE locations (arm or intra-abdominal deep venous thrombosis [DVT], intra-abdominal DVT, pulmonary embolism, and bilateral leg DVT), adjusted for age, gender, body mass index, and other VTE risk factors.
RESULTS: In multivariate analyses, active cancer was independently associated with arm or intra-abdominal DVT (odds ratio [OR], 1.76; P=.01), intra-abdominal DVT (OR, 2.22; P=.004), and bilateral leg DVT (OR, 2.09; P=.02), but not pulmonary embolism (OR, 0.93).
CONCLUSION: Active cancer is associated with VTE location. Location of VTE may be useful in decision making regarding cancer screening.
Because active cancer is associated with venous thromboembolism location, the location of the thromboembolism may be useful in decision making regarding cancer screening.
doi:10.4065/mcp.2010.0339
PMCID: PMC3012630  PMID: 21193652

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