Coon, W W
This review of the epidemiology of venous thromboembolism includes estimates of incidence and prevalence of venous thrombosis and its sequelae, a discussion geographical, annual and seasonal variations and data concerning possible risk factors. Selection of patients at increased risk for development of deep venous thrombosis or pulmonary embolism for specific diagnostic screening or for prophylactic therapy with low-dose heparin may be a more effective approach to lowering morbidity and mortality from this disease. PMID:329779
Hallundbæk Mikkelsen, Kristian; Knudsen, Stine Ulrik; Nannestad Jørgensen, Lars
A literature study on the association between travel and venous thromboembolism (VTE) is conducted. Studies examining the risk of travel-associated VTE, predisposing factors and prophylactic measures are presented. It is concluded that the absolute risk of travel-associated VTE is low and holds a 2-4 fold increase after travel. The risk increases with duration, presence of other risk factors for VTE and extremes of height. Stockings reduces the risk of asymptomatic VTE. Heparin is presumed to constitute protection whereas there is no evidence of a prophylactic effect of acetylsalicylic acid.
Heit, John A.
Thrombosis can affect any venous circulation. Venous thromboembolism (VTE) includes deep-vein thrombosis of the leg or pelvis, and its complication, pulmonary embolism. VTE is a fairly common disease, particularly in older age, and is associated with reduced survival, substantial health-care costs, and a high rate of recurrence. VTE is a complex (multifactorial) disease, involving interactions between acquired or inherited predispositions to thrombosis and various risk factors. Major risk factors for incident VTE include hospitalization for surgery or acute illness, active cancer, neurological disease with leg paresis, nursing-home confinement, trauma or fracture, superficial vein thrombosis, and—in women—pregnancy and puerperium, oral contraception, and hormone therapy. Although independent risk factors for incident VTE and predictors of VTE recurrence have been identified, and effective primary and secondary prophylaxis is available, the occurrence of VTE seems to be fairly constant, or even increasing. PMID:26076949
Monnerat, C; Hayoz, D
Congenital homocysteinuria is a rare inherited metabolic disorder with early onset atherosclerosis and arterial and venous trombosis. Moderate hyperhomocysteinemia is more frequently encountered and is recognized as an independent cardiovascular risk factor. Several case-control studies demonstrate an association between venous thromboembolism and moderate hyperhomocysteinemia. A patient with moderate hyperhomocysteinemia has a 2-3 relative risk of developing an episode of venous thromboembolism. The occurrence of mild hyperhomocysteinemia in heterozygotes for the mutation of Leiden factor V involves a 10-fold increase in the risk of venous thromboembolism. The biochemical mechanism by which homocysteine may promote thrombosis is not fully recognized. Homocysteine inhibits the expression of thrombomodulin, the thrombin cofactor responsible for protein C activation, and inhibits antithrombin-III binding. Treatment with folic acid reduces the plasma level of homocysteinemia, but no study has demonstrated its efficacy in reducing the incidence of venous thromboembolism or atherosclerosis. Hyperhomocysteinemia should be included in the screening of abnormalities of hemostasis and thrombosis in patients with idiopathic thromboembolism, and mild hyperhomocysteinemia may justify a trial of folic acid.
Laryea, Jonathan; Champagne, Bradley
Venous thromboembolism (VTE) can occur after major general surgery. Pulmonary embolism is recognized as the most common identifiable cause of death in hospitalized patients in the United States. The risk of deep venous thrombosis (DVT) and pulmonary embolism (PE) is higher in colorectal surgical procedures compared with general surgical procedures. The incidence of venous thromboembolism in this population is estimated to be 0.2 to 0.3%. Prevention of VTE is considered a patient-safety measure in most mandated quality initiatives. The measures for prevention of VTE include mechanical methods (graduated compression stockings and intermittent pneumatic compression devices) and pharmacologic agents. A combination of mechanical and pharmacologic methods produces the best results. Patients undergoing surgery should be stratified according to their risk of VTE based on patient risk factors, disease-related risk factors, and procedure-related risk factors. The type of prophylaxis should be commensurate with the risk of VTE based on the composite risk profile.
Laryea, Jonathan; Champagne, Bradley
Venous thromboembolism (VTE) can occur after major general surgery. Pulmonary embolism is recognized as the most common identifiable cause of death in hospitalized patients in the United States. The risk of deep venous thrombosis (DVT) and pulmonary embolism (PE) is higher in colorectal surgical procedures compared with general surgical procedures. The incidence of venous thromboembolism in this population is estimated to be 0.2 to 0.3%. Prevention of VTE is considered a patient-safety measure in most mandated quality initiatives. The measures for prevention of VTE include mechanical methods (graduated compression stockings and intermittent pneumatic compression devices) and pharmacologic agents. A combination of mechanical and pharmacologic methods produces the best results. Patients undergoing surgery should be stratified according to their risk of VTE based on patient risk factors, disease-related risk factors, and procedure-related risk factors. The type of prophylaxis should be commensurate with the risk of VTE based on the composite risk profile. PMID:24436666
D’Uva, Maristella; Di Micco, Pierpaolo; Strina, Ida; De Placido, Giuseppe
In recent decades, the association between a hypercoagulable state and its causes and adverse pregnancy outcome, in particular recurrent pregnancy loss (RPL) has been studied extensively. Although the first studies were focused only on the association between thrombophilia and RPL, subsequent studies underlined also a potential role of antithrombotic treatment to prevent vascular complication such as venous thromboembolism (VTE) during pregnancy. Thromboprophylaxis should be considered also for pregnant subjects carriers of molecular thrombophilia or that previously experienced VTE, in order to prevent VTE during pregnancy, while antithrombotic treatment for VTE should be performed during all pregnant periods. PMID:22282678
Yang, Genyan; De Staercke, Christine; Hooper, W Craig
Obesity has emerged as a global health issue that is associated with wide spectrum of disorders, including coronary artery disease, diabetes mellitus, hypertension, stroke, and venous thromboembolism (VTE). VTE is one of the most common vascular disorders in the United States and Europe and is associated with significant mortality. Although the association between obesity and VTE appears to be moderate, obesity can interact with other environmental or genetic factors and pose a significantly greater risk of VTE among individuals who are obese and who are exposed simultaneously to several other risk factors for VTE. Therefore, identification of potential interactions between obesity and certain VTE risk factors might offer some critical points for VTE interventions and thus minimize VTE morbidity and mortality among patients who are obese. However, current obesity measurements have limitations and can introduce contradictory results in the outcome of obesity. To overcome these limitations, this review proposes several future directions and suggests some avenues for prevention of VTE associated with obesity as well.
Wells, Philip S; Forgie, Melissa A; Rodger, Marc A
Venous thromboembolism (VTE), comprising deep vein thrombosis (DVT) and pulmonary embolism (PE), is a common, potentially lethal condition with acute morbidity. To review the etiology of VTE and the 3 phases of VTE treatment: acute (first 5-10 days), long-term (from end of acute treatment to 3-6 months), and extended (beyond 3-6 months). Cochrane reviews, meta-analyses, and randomized controlled trials, as well as other clinical trials for topics not covered by the former, were reviewed. Literature searches using broad terms were used to find meta-analyses published in the last 15 years. The ninth edition of the American College of Chest Physicians Antithrombotic Therapy Guidelines was used to supplement the literature search. Guidelines from specialty organizations were consulted when relevant. The Canadian Agency for Drugs and Technologies in Health was searched for relevant cost-effectiveness studies. We also searched our own literature database of 8386 articles for relevant research. Low-molecular-weight heparin (LMWH) along with with vitamin K antagonists and the benefits and proven safety of ambulation have allowed for outpatient management of most cases of DVT in the acute phase. Development of new oral anticoagulants further simplifies acute-phase treatment and 2 oral agents can be used as monotherapy, avoiding the need for LMWH. Patients with PE can also be treated in the acute phase as outpatients, a decision dependent on prognosis and severity of PE. Thrombolysis is best reserved for severe VTE; inferior vena cava filters, ideally the retrievable variety, should be used when anticoagulation is contraindicated. In general, DVT and PE patients require 3 months of treatment with anticoagulants, with options including LMWH, vitamin K antagonists, or direct factor Xa or direct factor IIa inhibitors. After this time, decisions for further treatment are based on balancing the risk of VTE recurrence, determined by etiology of the VTE (transient risk factors
Finks, Shannon W.; Trujillo, Toby C.; Dobesh, Paul P.
Objective: To review clinical data on direct oral anticoagulants (DOACs) used in the acute treatment of venous thromboembolism (VTE) as well as practical considerations when using these products. Data Sources: Searches of PubMed and Google Scholar for VTE, deep vein thrombosis, pulmonary embolism, and relevant drug international nonproprietary names were conducted. Additional online searches were conducted for prescribing information. Study Selection and Data Extraction: Relevant articles on dabigatran, rivaroxaban, apixaban, and edoxaban for the management of VTE compared with oral vitamin K antagonists (VKAs; published between 1966 and December 2015) were reviewed and summarized, together with information on dosing, pharmacokinetics/pharmacodynamics, and drug-drug interactions. Data Synthesis: The DOACs have the potential to circumvent many of the disadvantages of VKAs. At a minimum, they greatly increase the available therapeutic options, thus providing a greater opportunity for clinicians to select a management option that best fits the needs of individual patients. Despite the significant advance that DOACs represent, they are not without risk and require careful consideration of a number of clinical issues to optimize safety and efficacy. Conclusions: The emergence of DOACs for the management of thromboembolic disorders represents a paradigm shift from oral VKAs. The DOACs provide similar efficacy and improved safety in selected patients as compared with VKAs. Clinicians treating VTE need to be familiar with the intricacies involved in using these agents, including the appropriate dose selection for the relevant indication, avoidance of drug-drug and drug-disease interactions, and consideration of dose adjustments in specific clinical situations, such as organ dysfunction. PMID:26917821
Haley, Kristina M
Neonates are the pediatric population at highest risk for development of venous thromboembolism (VTE), and the incidence of VTE in the neonatal population is increasing. This is especially true in the critically ill population. Several large studies indicate that the incidence of neonatal VTE is up almost threefold in the last two decades. Central lines, fluid fluctuations, sepsis, liver dysfunction, and inflammation contribute to the risk profile for VTE development in ill neonates. In addition, the neonatal hemostatic system is different from that of older children and adults. Platelet function, pro- and anticoagulant proteins concentrations, and fibrinolytic pathway protein concentrations are developmentally regulated and generate a hemostatic homeostasis that is unique to the neonatal time period. The clinical picture of a critically ill neonate combined with the physiologically distinct neonatal hemostatic system easily fulfills the criteria for Virchow's triad with venous stasis, hypercoagulability, and endothelial injury and puts the neonatal patient at risk for VTE development. The presentation of a VTE in a neonate is similar to that of older children or adults and is dependent upon location of the VTE. Ultrasound is the most common diagnostic tool employed in identifying neonatal VTE, but relatively small vessels of the neonate as well as frequent low pulse pressure can make ultrasound less reliable. The diagnosis of a thrombophilic disorder in the neonatal population is unlikely to change management or outcome, and the role of thrombophilia testing in this population requires further study. Treatment of neonatal VTE is aimed at reducing VTE-associated morbidity and mortality. Recommendations for treating, though, cannot be extrapolated from guidelines for older children or adults. Neonates are at risk for bleeding complications, particularly younger neonates with more fragile intracranial vessels. Developmental alterations in the coagulation proteins as
Gran, Olga V.; Smith, Erin N.; Brækkan, Sigrid K.; Jensvoll, Hilde; Solomon, Terry; Hindberg, Kristian; Wilsgaard, Tom; Rosendaal, Frits R.; Frazer, Kelly A.; Hansen, John-Bjarne
Venous thromboembolism occurs frequently in cancer patients. Two variants in the factor 5 gene (F5), rs6025 encoding for the factor V Leiden mutation R506Q, and rs4524 encoding K858R, have been found to be associated with venous thromboembolism. We assessed the joint effect of active cancer and these two F5 variants on venous thromboembolism risk in a case-cohort study. Cases with a first venous thromboembolism (n=609) and a randomly selected age-weighted cohort (n=1,691) were sampled from the general population in Tromsø, Norway. Venous thromboembolism was classified as cancer-related if it occurred in the period 6 months before to 2 years after a diagnosis of cancer. Active cancer was associated with an 8.9-fold higher risk of venous thromboembolism (95% CI 7.2–10.9). The risk of cancer-related venous thromboembolism was 16.7-fold (95% CI 9.9–28.0) higher in subjects heterozygous for rs6025 compared with non-carriers of this variant without active cancer. In subjects with active cancer the risk of venous thromboembolism was 15.9-fold higher (95% CI 9.1–27.9) in those with one risk allele at rs4524, and 21.1-fold (95% CI 12.4–35.8) higher in those with two risk alleles compared with non-carriers without active cancer. A synergistic interaction was observed between active cancer and factor V Leiden (relative excess risk due to interaction 7.0; 95% CI 0.5–14.4) and rs4524 (relative excess risk due to interaction 15.0; 95% CI 7.5–29.2). The incidence of venous thromboembolism during the initial 6 months following a diagnosis of cancer was particularly high in subjects with risk alleles at these loci. This implies that the combination of cancer and F5 variants synergistically increases venous thromboembolism risk. PMID:27479824
Gran, Olga V; Smith, Erin N; Brækkan, Sigrid K; Jensvoll, Hilde; Solomon, Terry; Hindberg, Kristian; Wilsgaard, Tom; Rosendaal, Frits R; Frazer, Kelly A; Hansen, John-Bjarne
Venous thromboembolism occurs frequently in cancer patients. Two variants in the factor 5 gene (F5), rs6025 encoding for the factor V Leiden mutation R506Q, and rs4524 encoding K858R, have been found to be associated with venous thromboembolism. We assessed the joint effect of active cancer and these two F5 variants on venous thromboembolism risk in a case-cohort study. Cases with a first venous thromboembolism (n=609) and a randomly selected age-weighted cohort (n=1,691) were sampled from the general population in Tromsø, Norway. Venous thromboembolism was classified as cancer-related if it occurred in the period 6 months before to 2 years after a diagnosis of cancer. Active cancer was associated with an 8.9-fold higher risk of venous thromboembolism (95% CI 7.2-10.9). The risk of cancer-related venous thromboembolism was 16.7-fold (95% CI 9.9-28.0) higher in subjects heterozygous for rs6025 compared with non-carriers of this variant without active cancer. In subjects with active cancer the risk of venous thromboembolism was 15.9-fold higher (95% CI 9.1-27.9) in those with one risk allele at rs4524, and 21.1-fold (95% CI 12.4-35.8) higher in those with two risk alleles compared with non-carriers without active cancer. A synergistic interaction was observed between active cancer and factor V Leiden (relative excess risk due to interaction 7.0; 95% CI 0.5-14.4) and rs4524 (relative excess risk due to interaction 15.0; 95% CI 7.5-29.2). The incidence of venous thromboembolism during the initial 6 months following a diagnosis of cancer was particularly high in subjects with risk alleles at these loci. This implies that the combination of cancer and F5 variants synergistically increases venous thromboembolism risk. Copyright© Ferrata Storti Foundation.
Venous thromboembolic disease is a common cause of mortality and morbidity in patients with cancer. Patients have a 5–6‐fold increase in the risk for a venous thromboembolism (VTE) compared with the general population, increasing to 6–7‐fold for some cancers. Prophylaxis for VTE should be considered whenever additional risk factors intervene. About 10% of patients with an idiopathic VTE will harbour an occult cancer. Half of these can probably be detected after a focused history, examination, routine blood tests and a chest x ray. The remaining cases may be diagnosed with an intensive screening protocol. About 60% of patients diagnosed on screening will have early disease, but we do not know whether screening improves the outcome. Evidence suggests that patients with cancer and a VTE should be treated with low‐molecular‐weight heparin, and treatment continued until the cancer is cured. PMID:17068274
Otero Candelera, Remedios; Grau Segura, Enric; Jiménez Castro, David; Uresandi Romero, Fernando; López Villalobos, José Luis; Calderón Sandubete, Enrique; Medrano Ortega, Francisco Javier; Cayuela Domínguez, Aurelio
The recommendations on venous thromboprophylaxis have been updated on the basis of current evidence reviewed by a multidisciplinary team. The problem has been approached with regard to its relevance in both surgical and nonsurgical patients. It should be noted that these recommendations were drawn up for use in Spain and, therefore, should be implemented with the drugs and therapeutic practices authorized and generally accepted in this country.
Mendis, Shanthi; Yach, Derek; Alwan, Ala
There has recently been increased publicity on the risk of venous thrombosis after long-haul flights. This paper reviews the evidence base related to the association between air travel and venous thromboembolism. The evidence consists only of case reports, clinical case-control studies and observational studies involving the use of intermediate end-points, or expert opinion. Some studies have suggested that there is no clear association, whereas others have indicated a strong relationship. On the whole it appears that there is probably a link between air travel and venous thrombosis. However, the link is likely to be weak, mainly affecting passengers with additional risk factors for venous thromboembolism. The available evidence is not adequate to allow quantification of the risk. There are insufficient scientific data on which to base specific recommendations for prevention, other than that leg exercise should be taken during travel. Further studies are urgently needed in order to identify prospectively the incidence of the condition and those at risk. PMID:12077617
McNally, Michael P; Burns, Christopher J
Venous thromboembolic disease, which includes deep vein thromboses as well as pulmonary emboli, can be a significant complication in the postoperative patient. In particular, colorectal patients often carry a higher risk for venous thromboembolism when compared with patients undergoing other operative procedures. Features unique to colorectal patients are the high incidence of inflammatory bowel disease or malignancy. Typically, these patients will undergo lengthy pelvic procedures, which also contribute to a cumulative risk of venous thrombosis. It is critical that all patients and the proposed operative procedure are appropriately risk stratified. Risk stratification allows for easier implementation of an appropriate prophylactic strategy. There are a wide range of safe and effective mechanical and pharmacologic measures available. The authors provide very specific recommendations, but note that clinical judgment plays a significant role.
Mirpuri-Mirpuri, P G; Álvarez-Cordovés, M M; Pérez-Monje, A
Venous thromboembolic disease in its clinical spectrum includes both deep vein thrombosis and pulmonary thromboembolism, which is usually a complication of deep vein thrombosis. It is a relatively common disease with significant morbidity and requires an accurate diagnosis. They are numerous risk factors for venous thromboembolism, and there is evidence that the risk of thromboembolic disease increases proportionally to the number of predisposing risk factors present. The primary care physician should know the risk factors and suspect the presence of venous thromboembolic disease when there is a compatible clnical picture. The treatment for this pathology is anticoagulation. We report a patient with cardiovascular risk factors who was seen with pain in the right leg and shortness of breath and referred to the hospital with suspected venous thromboembolism, atrial fibrillation and pleural effusion. Copyright © 2012 Sociedad Española de Médicos de Atención Primaria (SEMERGEN). Publicado por Elsevier España. All rights reserved.
Rendon, Patrick; Burnett, Allison E; Zimmerberg-Helms, Jessica; Goot, Taylor; Streiff, Michael B
Diagnostic algorithms for venous thromboembolism exist, but most do not provide detailed guidance as to which patients, if any, may benefit from screening for thrombophilia. This article provides an overview of the optimized diagnosis of venous thromboembolism, with a focus on the appropriate use of thrombophilia screening. Copyright © 2017 Cleveland Clinic.
Recent comparison (SAFE study) of a mobile, synchronized compression device and low-molecular-weight heparin for prophylaxis of venous thromboembolism showed similar efficacy but significant differences in major bleeding. A model was constructed to evaluate any difference in cost-effectiveness between the 2 therapies incorporating rates and probabilities of major bleeding from the SAFE study with published costs for treating those adverse events. Evaluation of the cost-effectiveness of each therapy was performed and applied to hypothetical patient populations representative of annual health system volume. The model showed a cost-effectiveness advantage of the compression device resulting in a savings of more than $3.69 million in a 10 000-patient cohort. The result was primarily driven by a decrease in the amount of major bleeding, which requires significant health care resources to treat.
Mingo, Rebecca E; Gosling, Matthew G; Farrell, Sally L; Drake, Brent E; Loader, Robert J; Riordan, Richard D
Objective: We report the imaging outcomes of all pregnant patients referred for suspected thromboembolism over a 43-month period. Methods: We identified 168 patients who underwent ventilation/perfusion (VQ) single-photon emission CT (SPECT), CT pulmonary angiography (CTPA) or a Doppler ultrasound scan of the lower legs, as well as a control group of 89 non-pregnant age- and sex-matched patients who underwent VQ SPECT during the same period. Imaging outcomes were recorded, and radiation doses were calculated for individual patients. Results: VQ SPECT and CTPA were equally likely to diagnose pulmonary embolism (PE) in about one patient out of every seven patients investigated. One in three CTPA scans was of suboptimal quality. A Doppler ultrasound examination of the legs will find deep venous thrombosis much less often, in about 1 patient out of every 15 patients investigated. The prevalence of PE in pregnant patients (as diagnosed by VQ SPECT) was similar to that in the non-pregnant, age- and sex-matched control group. The effective dose and the absorbed radiation dose to the maternal breast were lower with VQ SPECT. The foetal dose is comparable for both VQ SPECT and CTPA. Conclusion: VQ SPECT and CTPA provide a similar diagnostic yield for diagnosing PE during pregnancy, but VQ SPECT does so with a lower radiation dose to the mother (effective dose and breast dose). Advances in knowledge: Ours is the first report of the diagnostic performance of VQ SPECT, rather than planar VQ scans, in pregnancy in a routine clinical setting. PMID:27055494
Blanco-Molina, Angeles; Monreal, Manuel
Hormonal contraceptives are a popular method of contraception, but their use has been associated with an increased risk for venous thromboembolism. In order to reduce such risk, these compounds have been changed in their dosage, chemical composition and route of administration. The absolute risk of death from pulmonary embolism in contraceptive users has been estimated to be 10.5 (95% CI: 6.2-16.6) per million woman-years. The safest option is an oral contraceptive containing levonorgestrel combined with a low dose of estrogen. Identifying women at increased risk for venous thromboembolism is difficult, and greater use of thromboprophylaxis during immobility or minor surgery should be warranted. Several authors have called for all women to be screened for thrombophilia before prescription of hormonal contraceptives, but its cost-effectiveness remains uncertain.
Diamantopoulos, Alexander; Lees, Michael; Wells, Philip S; Forster, Fiona; Ananthapavan, Jaithri; McDonald, Heather
This study aimed to evaluate the cost-effectiveness of prophylaxis with rivaroxaban vs. enoxaparin in the prevention of venous thromboembolism (VTE) after total hip replacement (THR) and total knee replacement (TKR) from the perspective of the Canadian healthcare system. A model was developed that included both acute VTE (represented as a decision tree) and long-term complications (represented as a Markov process with one-year cycles). Transition probabilities were derived from phase III clinical trials comparing rivaroxaban with enoxaparin and published literature. Costs were derived from the Ontario Case Costing Initiative and publicly available sources. Utilities were derived from published literature. The model reported VTE event rates, quality-adjusted life expectancy and direct medical costs over a five-year horizon. Costs are reported in 2007 Canadian Dollars (C$). When rivaroxaban and enoxaparin are compared in patients undergoing THR, rivaroxaban dominates enoxaparin. That is, rivaroxaban is associated with improved health outcomes as measured by increased quality-adjusted life years (QALYs; 0.0006) and fewer symptomatic VTE events (0.0061), and also with lower cost (savings of C$300) per patient. Similarly, rivaroxaban dominates enoxaparin in patients undergoing TKR, achieving a gain of 0.0018 QALYs, a reduction of 0.0192 symptomatic venous thromboembolic events and savings of C$129 per patient. Rivaroxaban is a cost-effective alternative to enoxaparin for VTE prophylaxis in patients undergoing THR and TKR. Over a five-year horizon, rivaroxaban dominated enoxaparin in the prevention of VTE events in patients undergoing THR and TKR, providing more quality-of-life benefit at a lower cost.
Kulik, Alexander; Rassen, Jeremy A; Myers, Jessica; Schneeweiss, Sebastian; Gagne, Joshua; Polinski, Jennifer M; Liu, Jun; Fischer, Michael A; Choudhry, Niteesh K
Controversy exists regarding the optimal preventative therapy for venous thromboembolism (VTE) after coronary artery bypass graft (CABG) surgery. We sought to compare the effectiveness and safety of the most commonly used regimens. We assembled a cohort of 92 699 patients who underwent CABG between 2004 and 2008, using the Premier database. Patients were categorized by method of VTE prevention initiated within 48 hours of surgery, including no preventative therapy (n=55 400), mechanical preventative therapy (n=21 162), subcutaneous unfractio--nated or low-molecular-weight heparin (n=10 718), subcutaneous fondaparinux (n=88), and concurrent mechanical-chemical therapy (n=5331). The incidence of VTE and major bleeding events within 6 weeks of CABG were compared, using multivariable and propensity score adjustment. The overall incidence of VTE for the entire cohort was 0.74%, and the incidence of major bleeding was 1.43%. VTE and bleeding events occurred with similar incidence in each of the patient categories (VTE: 0.70%, 0.79%, 0.81%, 1.14%, and 0.73%; major bleeding: 1.36%, 1.45%, 1.69%, 3.41%, 1.50%; no prevention, mechanical prevention, subcutaneous heparin, subcutaneous fondaparinux, concurrent mechanical-chemical prevention, respectively). Compared with receiving no prevention, the use of mechanical prevention or subcutaneous heparin did not significantly reduce the risk of VTE or change the risk of major bleeding (P=NS). Venous thromboembolism occurs infrequently after CABG. Compared with the use of no prevention, the administration of chemical or mechanical preventative therapies to CABG patients does not appreciably lower the risk of VTE. These data provide support for the common practice of administering no VTE preventative therapy after CABG, used for nearly 60% of patients within this cohort.
Gaertner, Sébastien; Cordeanu, Eléna-Mihaela; Nouri, Salah; Mirea, Corina; Stephan, Dominique
The pleiotropic effects of statins, beyond their cholesterol-lowering properties, are much debated. In primary prevention, several observational cohort and case-control studies appear to show that statins reduce the incidence of venous thromboembolism by about 30%. In a single randomized placebo-controlled clinical trial (JUPITER), which included 17,000 patients, rosuvastatin 20mg/day reduced the risk of venous thromboembolism by 43%. However, these patients were at low risk of venous thromboembolism, and the frequency of the event was, in principle, low. In secondary prevention, several observational studies and post-hoc analyses of randomized clinical trials have suggested that statins may prevent recurrence of venous thromboembolism. However, none of these studies had enough scientific weight to form the basis of a recommendation to use statins for secondary prevention. The putative preventive effect of statins appears to be independent of plasma cholesterol concentration and could be a pharmacological property of the statin class, although a dose-effect relationship has not been demonstrated. The mechanism through which statins might prevent venous thrombosis is thought to involve their anti-inflammatory and antioxidant effects or perhaps a more specific action, by blocking the degradation of antithrombotic proteins. A mechanism involving the action of statins on interactions between risk factors for atherosclerosis and venous thromboembolism is supported by some studies, but not all. In the absence of firm evidence, statins cannot currently be recommended for primary or secondary prevention of venous thromboembolism.
Murphy, Robert X; Alderman, Amy; Gutowski, Karol; Kerrigan, Carolyn; Rosolowski, Karie; Schechter, Loren; Schmitz, Delaine; Wilkins, Edwin
In July of 2011, the American Society of Plastic Surgeons Executive Committee approved the Venous Thromboembolism Task Force Report. The report includes a summary of the scientific literature relevant to venous thromboembolism and plastic surgery along with five evidence-based recommendations. The recommendations are divided into two sections: risk stratification and prevention. The risk stratification recommendations are based on the 2005 Caprini Risk Assessment Module, which has been validated in the scientific literature as an effective tool for risk-stratifying plastic and reconstructive surgery patients based on individual risk factors for 60-day venous thromboembolism. The three prophylaxis recommendations are dependent on an individual patient's 2005 Caprini Risk Assessment Module score.
Storti, S; Crucitti, P; Cina, G
In the last 20 years within the clinical research on venous thromboembolism a major objective was to identify and develop increasingly effective and safe methods of prevention. This trend is justified by the high incidence of thromboembolism as well as by the relevant mortality for acute pulmonary embolism and postphlebitic sequels of difficult treatment. A significant contribution to the rational application of methods of prevention was given by the knowledge of risk factors. Together with acquired risks, as surgery, age, malignant tumors, in the last 30 years some conditions of thrombophilia were identified. They are caused by deficiencies in coagulation inhibitors (antithrombin III, protein C, protein S) or other alteration of the anticoagulation system as resistance to activated protein C or antiphospholipid antibodies. The primary prophylaxis of venous thromboembolism is aimed at the prevention of thrombosis by pharmacologic methods able to oppose the procoagulant alterations while avoiding hemorrhagic complications. The physical methods tend to reduce the stasis in the veins of the lower extremities. Subcutaneous calcium heparin at the dose of 5000 U twice or three times a day is the most common pharmacologic method used. It was shown to be safe and effective especially in postoperative prophylaxis of venous thromboembolism in general surgery. More recently, low molecular weight heparin fractions have been introduced. As compared to standard heparin they have the advantage of a single daily dose and a better efficacy in some groups of patients, as those undergoing hip replacement. Among the substances under clinical experimentation, dermatan sulfate seems promising. Most common physical prevention methods consist in the use of elastic graduated compression stockings and systems of intermittent pneumatic calf compression. The former can be used also in presence of a hemorrhagic risk as in neurosurgery. The latter have shown a good efficacy in increasing flow
Teasell, R.W.; Hsieh, T.J.; Aubut, JA. L.; Eng, J.J.; Krassioukov, A.; Tu, L.
Objective To systematically review the published literature on the treatment of deep venous thromboembolism post-spinal cord injury (SCI). Data Sources MEDLINE/Pubmed, CINAHL, EMBASE, and PsycINFO databases were searched for articles addressing the treatment of deep venous thromboembolism post-SCI. Randomized controlled trials (RCTs) were assessed for methodologic quality using the Physiotherapy Evidence Database Scale, while non-RCTs were assessed using the Downs and Black evaluation tool. Study Selection Studies included RCTs, non-RCTS, cohort, case-control, case series, pre-post, and postinterventional studies. Case studies were included only when no other studies were available. Data Extraction Data extracted included demographics, the nature of the study intervention, and study results. Data Synthesis Levels of evidence were assigned to the interventions using a modified Sackett scale. Conclusions Twenty-three studies met inclusion criteria. Thirteen studies examined various pharmacologic interventions for the treatment or prevention of deep venous thrombosis in SCI patients. There was strong evidence to support the use of low molecular weight heparin in reducing venous thrombosis events, and a higher adjusted dose of unfractionated heparin was found to be more effective than 5000 units administered every 12 hours, although bleeding complication was more common. Nonpharmacologic treatments were also reviewed, but again limited evidence was found to support these treatments. PMID:19236977
Cundiff, David K
Context On the basis of theoretical rationale, heparoids and vitamin K antagonists are prescribed to prevent complications of venous thromboembolism (VTE, including pulmonary emboli [PE] and deep vein thrombosis [DVT]). They have been employed as the standard of care for treatment of VTE for over 40 years. Objective Critique the evidence supporting the efficacy of anticoagulants for the treatment of VTE in reducing morbidity and/or mortality. Data Sources This includes a search of reference lists and Medline. Study Selection This includes studies concerning the diagnosis and incidence of PE and DVT, efficacy of anticoagulants in preventing complications, risks of anticoagulant therapy, and the costs of diagnosis and the treatment of VTE. Data Extraction I analyzed references cited in reviews and meta-analyses of VTE, and from Medline searches concerning diagnosis and treatment. The data quality and validity of studies depended on the consistency of findings and statistical significance of the data. Data Synthesis No placebo-controlled trials of anticoagulants as treatment of PE with objective criteria for diagnosis have been published. Three randomized trials of anticoagulants vs no anticoagulants in DVT showed no benefit with heparin and vitamin K antagonists (combined all-cause mortality: anticoagulants = 6/66, un-anticoagulated controls = 1/60, P = .07). No placebo-controlled trials of low-molecular-weight heparins or thrombolytic drugs have been done; therefore, their efficacy in VTE depends entirely on randomized comparisons with unfractionated heparin. They have not been proven safer or more efficacious than unfractionated heparin. Thrombolysis causes more major and fatal bleeds than heparin and is no more effective in preventing PE. Diagnosing and treating VTE patients in the United States with anticoagulants costs $3.2 to $15.5 billion per year (1992 dollars). Bleeding and complications of angiography cause 1017-3525 deaths annually. Conclusion
Montoro-García, Silvia; Schindewolf, Marc; Stanford, Sophia; Larsen, Ole Halfdan; Thiele, Thomas
Multiple factors contribute to the risk of venous thromboembolism (VTE). Platelets have attracted much interest in arterial cardiovascular disease, whereas their role in VTE has received much less attention. Recent evidence suggests that platelets may play a more important role in VTE than previously anticipated. This review discusses the mechanisms that link platelets with venous thrombotic disease and their potential applications as novel risk factors for VTE. In addition, animal studies and randomized clinical trials that highlight the potential effect of antiplatelet therapy in venous thrombosis are evaluated to assess the role of platelets in VTE. The clinical significance of platelets for VTE risk assessment in specific patient cohorts and their role as a suitable therapeutic target for VTE prevention is acknowledged. The role of platelets in VTE is a promising field for future research.
Rahimi, Kazem; Bhala, Neeraj; Kamphuisen, Pieter; Emberson, Jonathan; Biere-Rafi, Sara; Krane, Vera; Robertson, Michele; Wikstrand, John; McMurray, John
Background It has been suggested that statins substantially reduce the risk of venous thromboembolic events. We sought to test this hypothesis by performing a meta-analysis of both published and unpublished results from randomised trials of statins. Methods and Findings We searched MEDLINE, EMBASE, and Cochrane CENTRAL up to March 2012 for randomised controlled trials comparing statin with no statin, or comparing high dose versus standard dose statin, with 100 or more randomised participants and at least 6 months' follow-up. Investigators were contacted for unpublished information about venous thromboembolic events during follow-up. Twenty-two trials of statin versus control (105,759 participants) and seven trials of an intensive versus a standard dose statin regimen (40,594 participants) were included. In trials of statin versus control, allocation to statin therapy did not significantly reduce the risk of venous thromboembolic events (465 [0.9%] statin versus 521 [1.0%] control, odds ratio [OR] = 0.89, 95% CI 0.78–1.01, p = 0.08) with no evidence of heterogeneity between effects on deep vein thrombosis (266 versus 311, OR 0.85, 95% CI 0.72–1.01) and effects on pulmonary embolism (205 versus 222, OR 0.92, 95% CI 0.76–1.12). Exclusion of the trial result that provided the motivation for our meta-analysis (JUPITER) had little impact on the findings for venous thromboembolic events (431 [0.9%] versus 461 [1.0%], OR = 0.93 [95% CI 0.82–1.07], p = 0.32 among the other 21 trials). There was no evidence that higher dose statin therapy reduced the risk of venous thromboembolic events compared with standard dose statin therapy (198 [1.0%] versus 202 [1.0%], OR = 0.98, 95% CI 0.80–1.20, p = 0.87). Risk of bias overall was small but a certain degree of effect underestimation due to random error cannot be ruled out. Please see later in the article for the Editors' Summary. Conclusions The findings from this meta-analysis do not support the
Takemoto, Clifford M
The incidence of venous thromboembolism (VTE) is increasing in the pediatric population. Individuals with cystic fibrosis (CF) have an increased risk of thrombosis due to central venous catheters (CVCs), as well as acquired thrombophilia secondary to inflammation, or deficiencies of anticoagulant proteins due to vitamin K deficiency and/or liver dysfunction. CVC-associated thrombosis commonly results in line occlusion, but may develop into serious life-threatening conditions such as deep venous thrombosis (DVT), superior vena cava syndrome or pulmonary embolism (PE). Post-thrombotic syndrome (PTS) may be a long complication. Local occlusion of the catheter tip may be managed with instillation of thrombolytics (such as tPA) within the lumen of the catheter; however, CVC-associated thrombosis involving the proximal veins is most often is treated with systemic anticoagulation. Initial treatment with heparin is a standard approach, but thrombolytic therapy, which may carry higher bleeding risks, should be considered for life and limb threatening episodes of VTE. Recommended duration of anticoagulation with low molecular weight heparin (LMWH) or warfarin ranges from 3 to 6 months for major removable thrombotic risks; longer anticoagulation is considered for recurrent thrombosis, major persistent thrombophilia, or the continued presence of a major risk factor such as a CVC. While CVCs are the most common risk for development of VTE in children, studies have not demonstrated a clear benefit with routine use of systemic thromboprophylaxis. The incidence and risk factors of VTE in CF patients will be reviewed and principles of diagnosis and management will be summarized.
Salmerón Febres, Luis Miguel; Cuenca Manteca, Jorge
Anticoagulation is the treatment of choice in the management of venous thromboembolic disease. This approach is applied to reduce mortality and the risk of recurrences and associated complications. Standard therapy for non-oncologic patients has traditionally been based on parenteral anticoagulation followed by vitamin K antagonists. However, this approach has many limitations. The aim of this manuscript was to critically review current evidence on the use of direct oral anticoagulants in the treatment of venous thromboembolic disease by analyzing the specific characteristics of each drug. Direct oral anticoagulants have many advantages over standard therapy. While they are equally effective as standard therapy for reducing the possibility of recurrence of venous thromboembolic disease, they carry a lower risk of major bleeding. Direct oral anticoagulants are an attractive alternative to standard therapy for the treatment of venous thromboembolism. Copyright © 2017 Elsevier Inc. All rights reserved.
Gandhi, Viral; Hewston, Matthew; Yadam, Suman; Ma, Kiet; Singh, Anil C; Cheema, Tariq
Venous thromboembolism includes both deep vein thrombosis and pulmonary embolism. They pose a significant risk for morbidity and mortality. In an appropriate clinical setting, invasive interventions, including administration of thrombolytics, anticoagulation, and placement of vena cava filter, are warranted. Bleeding, postthrombotic syndrome, recurrence, and filter-associated complications are few of the complications of this disease. More recently, chronic thromboembolic pulmonary hypertension has gained clinical interest in patients with pulmonary embolism and has warranted close follow-up.
Proietti, Marco; Lip, Gregory YH
Oral anticoagulation is the therapeutic cornerstone in preventing thromboembolic risk in both atrial fibrillation (AF) and venous thromboembolism (VTE). After decades of the sole therapeutic oral anticoagulation option being warfarin, the introduction of non-vitamin K antagonist oral anticoagulants has heralded a new era. Edoxaban is the latest addition to these available for clinical use. Edoxaban was as effective and safer than warfarin in preventing thromboembolic risk in AF patients. Similarly, edoxaban effectiveness and safety was evident when treating VTE patients to prevent recurrent VTE or VTE-related death. Therefore, edoxaban represents a valuable alternative in treating thromboembolic risk for AF and VTE patients. PMID:27013883
Liew, N C; Chang, Y H; Choi, G; Chu, P H; Gao, X; Gibbs, H; Ho, C O; Ibrahim, H; Kim, T K; Kritpracha, B; Lee, L H; Lee, L; Lee, W Y; Li, Y J; Nicolaides, A N; Oh, D; Pratama, D; Ramakrishnan, N; Robless, P A; Villarama-Alemany, G; Wong, R
Venous thromboembolism (VTE) prophylaxis is under-utilized in Asia because of the misconception that its incidence is lower in Asians as compared to the Caucasians. The available data on VTE in Asia is limited due to the lack of well-designed multicenter randomized controlled trials as well as non-standardized research designs, making data comparison difficult. Emerging data indicates that the VTE incidence is not low in Asia, and is comparable to that reported in the Western literature in some instances. There is also a trend towards increasing incidence of VTE, as demonstrated by a number of hospital-based studies in Asia. This could be attributed to lifestyle changes, ageing population, increasing awareness of VTE and wider availability of Duplex ultrasound. The risk of VTE in hospitalized patients remain the same in Asians and Caucasians, even though there may be factors that are inherent to patients in Asia that influence the slight variation in incidence. The utilization rate of VTE prophylaxis remains suboptimal in Asia. The Asian Venous Thrombosis Forum (AVTF) comprises participants from various countries such as China, Hong Kong, India, Indonesia, Korea, Malaysia, Philippines, Singapore, Taiwan, Thailand and experts from Australia and Europe. The forum evaluated the available data on VTE from the Asian region and formulated guidelines tailored to meet the needs of the region. We recommend that serious considerations are given to VTE prophylaxis especially in the at-risk group and a formal hospital policy be established to facilitate the implementation. On admission to the hospital, we recommend assessing the patients for both VTE and bleeding risk. We recommend mechanical prophylaxis for patients at increased risk of bleeding and utilizing it as an adjunctive measure in combination with pharmacological prophylaxis in patients with high risk of VTE. For patients undergoing general or gynecological surgery and with moderate risk for VTE, we recommend
Kapoor, Alok; Chuang, Warren; Radhakrishnan, Nila; Smith, Kenneth J; Berlowitz, Dan; Segal, Jodi B; Katz, Jeffrey N; Losina, Elena
Total hip and knee replacements (THR and TKR) are high-risk settings for venous thromboembolism (VTE). This review summarizes the cost effectiveness of VTE prophylaxis regimens for THR and TKR. We searched MEDLINE (January 1997 to October 2009), EMBASE (January 1997 to June 2009) and the UK NHS Economic Evaluation Database (1997 to October 2009). We analysed recent cost-effectiveness studies examining five categories of comparisons: (i) anticoagulants (warfarin, low-molecular-weight heparin [LMWH] or fondaparinux) versus acetylsalicylic acid (aspirin); (ii) LMWH versus warfarin; (iii) fondaparinux versus LMWH; (iv) comparisons with new oral anticoagulants; and (v) extended-duration (> or =3 weeks) versus short-duration (<3 weeks) prophylaxis. We abstracted information on cost and effectiveness for each prophylaxis regimen in order to calculate an incremental cost-effectiveness ratio. Because of variations in effectiveness units reported and horizon length analysed, we calculated two cost-effectiveness ratios, one for the number of symptomatic VTE events avoided at 90 days and the other for QALYs at the 1-year mark or beyond. Our search identified 33 studies with 67 comparisons. After standardization, comparisons between LMWH and warfarin were inconclusive, whereas fondaparinux dominated LMWH in nearly every comparison. The latter results were derived from radiographic VTE rates. Extended-duration prophylaxis after THR was generally cost effective. Small numbers prohibit conclusions about aspirin, new oral anticoagulants or extended-duration prophylaxis after TKR. Fondaparinux after both THR and TKR and extended-duration LMWH after THR appear to be cost-effective prophylaxis regimens. Small numbers for other comparisons and absence of trials reporting symptomatic endpoints prohibit comprehensive conclusions.
Anticoagulation therapy is essential for the effective treatment and secondary prevention of venous thromboembolism (VTE). For many years, anticoagulation for acute VTE was limited to the use of initial parenteral heparin, overlapping with and followed by a vitamin K antagonist. Although highly effective, this regimen has several limitations and is particularly challenging when given in an ambulatory setting. Current treatment pathways for most patients with deep-vein thrombosis typically involve initial hospital or community-based ambulatory care with subsequent follow-up in a secondary care setting. With the introduction of non-vitamin K antagonist oral anticoagulants (NOACs) into routine clinical practice, it is now possible for the initial acute management of patients with deep-vein thrombosis to be undertaken by primary care. As hospital admissions associated with VTE become shorter, primary care will play an increasingly important role in the long-term management of these patients. Although the NOACs can potentially simplify patient management and improve clinical outcomes, primary care physicians may be less familiar with these new treatments compared with traditional therapy. To assist primary care physicians in further understanding the role of the NOACs, this article outlines the main differences between NOACs and traditional anticoagulation therapy and discusses the benefit–risk profile of the different NOACs in the treatment and secondary prevention of recurrent VTE. Key considerations for the use of NOACs in the primary care setting are highlighted, including dose transition, risk assessment and follow-up, duration of anticoagulant therapy, how to minimize bleeding risks, and the importance of patient education and counseling. PMID:27217793
Lecumberri, Ramón; Marqués, Margarita; Díaz-Navarlaz, María Teresa; Panizo, Elena; Toledo, Jon; García-Mouriz, Alberto; Páramo, José A
Despite current guidelines, venous thromboembolism (VTE) prophylaxis is underused. Computerized programs to encourage physicians to apply thromboprophylaxis have been shown to be effective in selected populations. Our aim was to analyze the impact of the implementation of a computer-alert system for VTE risk in all hospitalized patients of a teaching hospital. A computer program linked to the clinical record database was developed to assess all hospitalized patients' VTE risk daily. The physician responsible for patients at high risk was alerted, but remained free to order or withhold prophylaxis. Over 19,000 hospitalized, medical and surgical, adult patients between January to June 2005 (pre-intervention phase), January to June 2006 and January to June 2007 (post-intervention phase), were included. During the first semesters of 2006 and 2007, an electronic alert was sent to 32.8% and 32.2% of all hospitalized patients, respectively. Appropriate prophylaxis among alerted patients was ordered in 89.7% (2006) and 88.5% (2007) of surgical patients, and in 49.2% (2006) and 64.4% (2007) of medical patients. A sustained reduction of VTE during hospitalization was achieved, Odds ratio (OR): 0.53, 95% confidence interval (CI) (0.25-1.10) and OR: 0.51, 95%CI (0.24-1.05) during the first semesters of 2006 and 2007 respectively, the impact being significant (p < 0.05) among medical patients in 2007, OR: 0.36, 95%CI (0.12-0.98). The implementation of a computer-alert program helps physicians to assess each patient's thrombotic risk, leading to a better use of thromboprophylaxis, and a reduction in the incidence of VTE among hospitalized patients. For the first time, an intervention aimed to improve VTE prophylaxis shows maintained effectiveness over time.
Adomaityte, Jurga; Farooq, Maria; Qayyum, Rehan
Raloxifene, a selective estrogen receptor modulator, is indicated for the prevention of osteoporosis in postmenopausal women. However, its effect on the risk of deep venous thrombosis (DVT) and pulmonary embolism (PE) is unclear. Therefore, we conducted a meta-analysis to evaluate the effect of raloxifene on these outcomes. To identify randomized controlled trials of raloxifene, a systematic search of PubMed, EMBASE, and Cochrane Collaboration databases was performed from the date of inception of these databases to October 2007. Search was limited to trials that were published in peer-reviewed English-language medical journals. Articles were included in the meta-analysis if they had reported on DVT, PE, or thromboembolic events. Nine trials, including 24,523 postmenopausal women, (median age 59.4 years, range 55 to 67 years; median follow-up 24 months, range 3 to 67 months) met inclusion criteria. Therapy with raloxifene was associated with a 62% increase in odds of either DVT or PE (odds ratio = 1.62; 95% confidence interval = 1.25 to 2.09; p-value < 0.001). Similarly, raloxifene therapy was associated with 54% increase in odds of DVT (odds ratio = 1.54; 95% confidence interval = 1.13 to 2.11; p-value = 0.006) and 91% increase in odds of PE alone (odds ratio = 1.91;95% confidence interval = 1.05 to 3.47; p-value = 0.03). Raloxifene increases the risk of DVT and PE in postmenopausal women.
Coleman, Craig I; Bunz, Thomas J; Turpie, Alexander G G
The efficacy and safety or rivaroxaban versus enoxaparin/vitamin K antagonist for treatment and prevention recurrence of venous thromboembolism (VTE) was demonstrated in the randomised EINSTEIN trials. We assessed the effectiveness and safety of rivaroxaban versus warfarin in VTE patients managed in routine practice. Using US MarketScan claims from 1/2012-6/2015, we included adults with a primary diagnosis of deep vein thrombosis (DVT) or pulmonary embolism (PE) during a hospitalisation/emergency department visit, newly-initiated on rivaroxaban or warfarin within 30-days after the VTE and with ≥180-days of continuous medical/prescription benefits prior to the VTE (baseline). Patients with a claim for anticoagulation at baseline were excluded. Recurrent VTE, major bleeding, intracranial haemorrhage (ICH) and gastrointestinal bleeding (GIB) were assessed. Differences in baseline characteristics between cohorts were adjusted for using inverse probability of treatment weights based on propensity-scores. Patients had a maximum of 12-months period of follow-up post-VTE or until endpoint occurrence, switch/discontinuation of index anticoagulation, insurance disenrollment or end-of-follow-up. Cox regression was performed and reported as hazard ratios (HRs) with 95 % confidence intervals (CIs). In total, 13,609 rivaroxaban and 32,244 warfarin users experiencing VTE were included. Rivaroxaban was associated with an 19 % (95 %CI=10-27 %) reduction in recurrent VTE and a 21 % (95 %CI=4-35 %) reduction in major bleeding hazard versus warfarin. Rivaroxaban was also associated with significantly decreased hazards of ICH (HR=0.40) and GIB (HR=0.72). Rivaroxaban appears to reduce patients' hazard of both recurrent VTE and major bleeding in routine practice. These results appear consistent with EINSTEIN and post-marketing registry studies.
Brighton, Timothy A; Eikelboom, John W; Mann, Kristy; Mister, Rebecca; Gallus, Alexander; Ockelford, Paul; Gibbs, Harry; Hague, Wendy; Xavier, Denis; Diaz, Rafael; Kirby, Adrienne; Simes, John
Patients who have had a first episode of unprovoked venous thromboembolism have a high risk of recurrence after anticoagulants are discontinued. Aspirin may be effective in preventing a recurrence of venous thromboembolism. We randomly assigned 822 patients who had completed initial anticoagulant therapy after a first episode of unprovoked venous thromboembolism to receive aspirin, at a dose of 100 mg daily, or placebo for up to 4 years. The primary outcome was a recurrence of venous thromboembolism. During a median follow-up period of 37.2 months, venous thromboembolism recurred in 73 of 411 patients assigned to placebo and in 57 of 411 assigned to aspirin (a rate of 6.5% per year vs. 4.8% per year; hazard ratio with aspirin, 0.74; 95% confidence interval [CI], 0.52 to 1.05; P=0.09). Aspirin reduced the rate of the two prespecified secondary composite outcomes: the rate of venous thromboembolism, myocardial infarction, stroke, or cardiovascular death was reduced by 34% (a rate of 8.0% per year with placebo vs. 5.2% per year with aspirin; hazard ratio with aspirin, 0.66; 95% CI, 0.48 to 0.92; P=0.01), and the rate of venous thromboembolism, myocardial infarction, stroke, major bleeding, or death from any cause was reduced by 33% (hazard ratio, 0.67; 95% CI, 0.49 to 0.91; P=0.01). There was no significant between-group difference in the rates of major or clinically relevant nonmajor bleeding episodes (rate of 0.6% per year with placebo vs. 1.1% per year with aspirin, P=0.22) or serious adverse events. In this study, aspirin, as compared with placebo, did not significantly reduce the rate of recurrence of venous thromboembolism but resulted in a significant reduction in the rate of major vascular events, with improved net clinical benefit. These results substantiate earlier evidence of a therapeutic benefit of aspirin when it is given to patients after initial anticoagulant therapy for a first episode of unprovoked venous thromboembolism. (Funded by National Health
Gallus, Alexander S
Current evidence indicates that prolonged air travel predisposes to venous thrombosis and pulmonary embolism. An effect is seen once travel duration exceeds 6 to 9 hours and becomes obvious in long-haul passengers traveling for 12 or more hours. A recent records linkage study found that increase in thrombosis rate among arriving passengers peaked during the first week and was no longer apparent after 2 weeks. Medium- to long-distance travelers have a 2- to 4-fold increase in relative thrombosis risk compared with nontravelers, but the averaged absolute risk is small (approximately one symptomatic event per 2 million arrivals, with a case-fatality rate of approximately 2%) and there is no evidence that thrombosis is more likely in economy class than in business- or first-class passengers. It remains uncertain whether and to what extent thrombosis risk is increased by short-distance air travel or prolonged travel by motorcar, train, or other means. Most travelers who develop venous thrombosis or pulmonary embolism also have one or more other predisposing risk factors that may include older age, obesity, recent injury or surgery, previous thrombosis, venous insufficiency, malignancy, hormonal therapies, or pregnancy. Limited (though theoretically plausible) evidence suggests that factor V Leiden and the prothrombin gene mutation predispose to thrombosis in otherwise healthy travelers. Given that very many passengers with such predispositions do not develop thrombosis, and a lack of prospective studies to link predisposition with disease, it is not now possible to allocate absolute thrombosis risk among intending passengers or to estimate benefit-to-risk ratios or benefit-to-cost ratios for prophylaxis. Randomized comparisons using ultrasound imaging indicate a measurable incidence of subclinical leg vein thrombosis after prolonged air travel, which appears to increase with travel duration and is reduced by graded pressure elastic support stockings. Whether this
Leme, Luiz Eugênio Garcez; Sguizzatto, Guilherme Turolla
The relevance of prophylaxis of venous thromboembolism and its complications in orthopedic surgery is increasingly significant. This review discusses the pathophysiology of thrombus formation in general and orthopedic surgery, its incidence, predisposing factors and complications. It also presents an updated presentation and critique of prophylaxis currently available in our environment. PMID:27047885
Venous thromboembolism (VTE) is a primary cause of preventable hospital death. The need for effective VTE prophylaxis has been recognized by the Surgical Care Improvement Program (SCIP) and the Joint Commission, which is offering VTE prevention as a core measure set, starting October 1, 2009. The adoption of SCIP VTE measures and mandate to publicly report these rates offers the opportunity to improve the use of prophylaxis in surgical patients and reduce VTE-related morbidity, mortality, and costs. Essential to this reduction is a team approach to implementing real-time interventions. Crucial to the success of the team is early identification of each patient's VTE risk and a mechanism to provide key information to ensure that the physician prescribes appropriate prophylaxis. In addition, it may be the nurse who is responsible for ensuring that a patient receives the appropriate prophylaxis, as well as being the first clinician to observe the clinical signs of a VTE event.
Le Gal, G; Righini, M
Over the last decades, important advances have been made in the diagnosis of venous thromboembolism (VTE). Current diagnostic strategies rely on the sequential use of non-invasive diagnostic tests, based on the pretest clinical probability of disease. Diagnostic tests include D-dimer measurement, leg vein compression ultrasonography, chest computed tomography pulmonary angiography, or ventilation perfusion (V/Q) lung scan. The safety and cost-effectiveness of these strategies have been extensively validated. They have been widely implemented in clinical practice and have replaced the historical gold standard diagnostic tests (venography and pulmonary angiography). However, new challenges arise, including a lower clinical suspicion threshold and concerns on potential over-diagnosis of VTE. Moreover, the diagnostic management remains suboptimal in many subgroups of patients with suspected VTE: patients with prior VTE, pregnant women, or elderly patients.
Overgaard, K; Hauch, O; Lidegaard, O
Ever since 1961, there has been discussion on possible thromboembolic effects from the use of oral contraceptives. The purpose of this Danish study was to determine if birth-control pill users did have an increased risk of venous thromboembolic disease (VTD), including deep venous thrombosis and pulmonary embolism. In previous research, morbidity from VTD has been found to show a great variance, as high as 1/330 woman years in 1 study to as low as 1/5,000 woman years in another. In these studies no significant difference was found between users and non-users of oral contraceptives. Only in 1 study was there found to be increased morbidity from VTD among pill users: 1/5,200 woman years, compared with 1/35,000 woman years for non-pill users. As a possible explanation of the pill's effect, several studies have demonstrated a rise in certain coagulation factors, increased fibrinogen and lowered antithrombin III. In the present study, medical records of all women aged 34 or under who had been referred to a Copenhagen hospital between 1981 and 1983 for treatment of phlebographic-or lungescintographic-confirmed VTD were investigated. After controlling for exclusion factors, there remained 35 test subjects between the ages of 16 and 34 (median age 22). Of the 22 cases of known etiology, 16 suffered from iatrogenic VTD. Of 13 women who suffered from VTD of unknown etiology, 69% were pill users, compared with only 29% (a significant difference) in a background-population interview study conducted in Denmark during 1983. With a known disposition to VTD, oral-contraceptive usage meant a relative risk of 0.9 for developing the disease, which figure conforms well with other cited research (in which the risk factor varied from 0.4 to 3.8).
Summary: Chemoprophylaxis has been recommended for plastic surgery patients judged to be at increased risk for venous thromboembolism. Several investigators have encountered this complication in patients despite anticoagulation therapy. An increased rate of complications related to postoperative bleeding has been reported. This article examines the efficacy and safety of this intervention, along with ethical considerations, in an attempt to determine whether any benefits of chemoprophylaxis justify the additional risks. The statistical methods and conclusion of the Venous Thromboembolism Prevention Study are challenged. Other preventative measures that do not cause negative side effects are discussed as safer alternatives. PMID:25289217
Developments in the understanding, prevention, and treatment of thromboembolism are reviewed in the light of the author's own experience and that of others. Particular attention is paid to the role of antithrombotic drugs in prophylaxis and to the place of pulmonary embolectomy in the treatment of massive pulmonary embolism. Images FIG. 3 FIG. 4 FIG. 6 FIG. 7 FIG. 8 PMID:7081914
Lee, Agnes Y Y; Levine, Mark N
Cancer and its treatments are well-recognized risk factors for venous thromboembolism (VTE). Evidence suggests that the absolute risk depends on the tumor type, the stage or extent of the cancer, and treatment with antineoplastic agents. Furthermore, age, surgery, immobilization, and other comorbid features will also influence the overall likelihood of thrombotic complications, as they do in patients without cancer. The role of hereditary thrombophilia in patients with cancer and thrombosis is still unclear, and screening for this condition in cancer patients is not indicated. The most common malignancies associated with thrombosis are those of the breast, colon, and lung, reflecting the prevalence of these malignancies in the general population. When adjusted for disease prevalence, the cancers most strongly associated with thrombotic complications are those of the pancreas, ovary, and brain. Idiopathic thrombosis can be the first manifestation of an occult malignancy. However, intensive screening for cancer in patients with VTE often does not improve survival and is not generally warranted. Independently of the timing of cancer diagnosis (before or after the VTE), the life expectancy of cancer patients with VTE is relatively short, because of both deaths from recurrent VTE and the cancer itself. Patients with cancer and acute VTE who take anticoagulants for an extended period are at increased risk of recurrent VTE and bleeding. A recent randomized trial, the Randomized Comparison of Low Molecular Weight Heparin versus Oral Anticoagulant Therapy for Long-Term Anticoagulation in Cancer Patients with Venous Thromboembolism (CLOT) study, showed that low molecular weight heparin may be a better treatment option for this group of patients. The antineoplastic effects of anticoagulants are being actively investigated with promising preliminary results.
Pérez R, Diego; Maldonado J, Daniela; Andresen H, Max
We report two cases of paradoxical cerebral embolism associated with acute venous thromboembolic disease. The first case corresponds to a 49-year-old woman with sudden onset of dyspnea and syncope, followed by right upper extremity paresis, aphasia and dysarthria. The admission brain computed tomography (CT) was unremarkable, but lung CT showed multilobar and multisegmentary pulmonary embolism. Echocardiography showed dilated right ventricle with impaired systolic function, moderate tricuspid regurgitation, moderate pulmonary hypertension and positive bubble test, suggestive of a patent foramen ovale (PFO) which was successfully closed by endovascular Amplatzer device placement. The patient was discharged with anticoagulation therapy and permanent antiplatelet aggregation therapy. The second case is a 60-year-old woman found unconscious. Neurological examination revealed expressive aphasia, right hemianopsia, right central facial paralysis and right-sided paresis with a National institute of Health Stroke Scale of 19. Brain CT showed signs of acute left middle cerebral artery infarction. Later, she developed greater impairment of consciousness. A new brain CT showed significant edema with mass effect requiring a decompressive craniotomy. Echocardiography showed PFO and lower extremities' Doppler ultrasound showed a left infrapopliteal posterior tibial right deep venous thrombosis. An inferior vena cava filter was placed and two days after surgery, anticoagulation was started.
Pabinger-Fasching, Ingrid; Eichinger-Hasenauer, Sabine; Grohs, Josef; Hochreiter, Josef; Kastner, Norbert; Korninger, Hans Christian; Kozek-Langenecker, Sibylle; Marlovits, Stefan; Niessner, Herwig; Rachbauer, Franz; Ritschl, Peter; Wurnig, Christian; Windhager, Reinhard
Musculoskeletal surgery is associated with a high risk of venous thrombosis and pulmonary embolism. The introduction of direct oral anticoagulants (DOAK) has broadened the possibilities for prevention of venous thromboembolism in the course of orthopedic and trauma surgery. Addressing this recent development, the Austrian Societies of Orthopedics and Orthopedic Surgery (ÖGO), Trauma Surgery (ÖGU), Hematology and Oncology (OeGHO) and of Anaesthesiology, Reanimation und Intensive Care Medicine (ÖGARI) have taken the initiative to create Austrian guidelines for the prevention of thromboembolism after total hip and knee replacement, hip fracture surgery, interventions at the spine and cases of minor orthopedic and traumatic surgery. Furthermore, the pharmacology of the DOAK and the pivotal trial data for each of the three currently available substances - apixaban, dabigatran, and rivaroxaban - are briefly presented. Separate chapters are dedicated to "anticoagulation and neuroaxial anesthesia" and "bridging".
Chan, Wee-Shian; Rey, Evelyne; Kent, Nancy E; Chan, Wee-Shian; Kent, Nancy E; Rey, Evelyne; Corbett, Thomas; David, Michèle; Douglas, M Joanne; Gibson, Paul S; Magee, Laura; Rodger, Marc; Smith, Reginald E
To present an approach, based on current evidence, for the diagnosis, treatment, and thromboprophylaxis of venous thromboembolism in pregnancy and postpartum. Published literature was retrieved through searches of PubMed, Medline, CINAHL, and The Cochrane Library from November 2011 to July 2013 using appropriate controlled vocabulary (e.g. pregnancy, venous thromboembolism, deep vein thrombosis, pulmonary embolism, pulmonary thrombosis) and key words (e.g., maternal morbidity, pregnancy complications, thromboprophylaxis, antithrombotic therapy). Results were restricted to systematic reviews, randomized control trials/controlled clinical trials, and observational studies published in English or French. There were no date restrictions. Grey (unpublished) literature was identified through searching the websites of clinical practice guideline collections, clinical trial registries, and national and international medical specialty societies. The quality of evidence in this document was rated using the criteria described in the Report of the Canadian Task Force on Preventative Health Care (Table 1).
Bellen, Bonno van; Godoy, Ivan de Barros; Reis, Andrea Almeida; Bertevello, Pedro
Morbid obesity is associated with various co-morbidities, including chronic venous insufficiency. Bariatric surgery is the only effective treatment for morbid obesity, but with potential risks and possible complications, including venous thromboembolism. To determine the prevalence of clinical and ultrasonographic signs of chronic venous insufficiency in morbid obese patients in preparation for bariatric surgery and the incidence of post-operative venous thromboembolic disease. Patients on work-up for bariatric surgery of Centro Terapêutico Especializado em Fígado (CETEFI) and Pro-Gastro surgical teams of the Hospital Beneficência Portuguesa de São Paulo were included. The analysed data were pre-operative findings for venous insufficiency (CEAP - clinical, etiological, anatomical, physiopathologic - classification and venous ultrasonographic findings), type of surgery (open or laparoscopic), abdominal circumference, body mass index (BMI) and post-operative ultrasonography search for venous insufficiency and deep venous thrombosis. Between March 2007 and December 2009, 95 patient candidates for bariatric surgery had clinical and duplex scan evaluation of the lower limbs venous system. Of the 95 patients, 53 were submitted to the surgical procedure. There was a predominance of women (77.9%), the average age was 38.5 years, average preoperative weight 124.6 kg and average BMI of 45.5 kg/m2. Regarding obesity, 16.8% were obese, and 83.1% were morbidly obese. In relation to the venous findings, 86.3% of the patients did fit CEAP classification less than 3 and 13.7% greater than or equal to 3. Among the post-operative complications, there were four cases of wound infection. Three patients developed post-operative distal venous thrombosis (7.5%), but no one had clinically manifested pulmonary embolism. No relation between BMI, CEAP classification and venous ultrasonographic findings were found. Although prophylaxis was used in all patients, the incidence of post
Malec, Lynn; Young, Guy
Given the increased incidence of venous thromboembolism (VTE) in pediatric patients, which has been associated with increased survival of medically complex patients and increased use of invasive supportive measures, it is important to understand treatment options and unique aspects of anticoagulant use in children. The objective of this mini-review is to outline the goals of treatment, treatment options, and adverse events associated with the use of anticoagulants in pediatric patients with VTE. PMID:28293549
Zhou, Lin; Qi, Xiao-long; Xu, Ming-xin; Mao, Yu; Liu, Ming-lin; Song, Hao-ming
Microparticles are small membrane fragments shed primarily from blood and endothelial cells during either activation or apoptosis. There is mounting evidence suggesting that microparticles perform a large array of biological functions and contribute to various diseases. Of these disease processes, a significant link has been established between microparticles and venous thromboembolism. Advances in research on the role of microparticles in thrombosis have yielded crucial insights into possible mechanisms, diagnoses and therapeutic targets of venous thromboembolism. In this review, we discuss the definition and properties of microparticles and venous thromboembolism, provide a synopsis of the evidence detailing the contributions of microparticles to venous thromboembolism, and propose potential mechanisms, by which venous thromboembolism occurs. Moreover, we illustrate a possible role of microparticles in cancer-related venous thromboembolism. PMID:25152025
Quan, Reagan W; Gillespie, David L; Stuart, Rory P; Chang, Audrey S; Whittaker, David R; Fox, Charles J
The management of venous trauma remains controversial. Critics of venous repair have cited an increased incidence of associated venous thromboembolic events with this management. We analyzed the current treatment of wartime venous injuries in United States military personnel in an effort to answer this question. From December 1, 2001, to October 31, 2005, all United States casualties with named venous injuries were evaluated. A retrospective review of a clinical database was performed on demographics, mechanism of injury, associated injuries, treatment, outcomes, and venous thromboembolic events. Data were analyzed using the Fisher exact test, analysis of variance, and logarithmic transformation. During this 5-year period, 82 patients sustained 103 named venous injuries due to combat operations. All patients were male, with an average age of 27.9 years (range, 20.3-58.3 years). Blast injuries accounted for 54 venous injuries (65.9%), gunshot wounds for 25 (30.5%), and motor vehicle accidents for 3 (3.6%). The venous injury was isolated in 28 patients (34.1%), and 16 (19.5%) had multiple venous injuries. The venous injury in two patients was associated with acute phlegmasia, with fractures in 33 (40.2%), and 22 (28.1%) sustained neurologic deficits. Venous injuries were treated by ligation in 65 patients (63.1%) and by open surgical repair in 38 (36.9%). Postoperative extremity edema occurred in all patients irrespective of method of management. Thrombosis after venous repair occurred in six of the 38 cases (15.8%). Pulmonary emboli developed in three patients, one after open repair and two after ligation (P > .99). In the largest review of military venous trauma in more than three decades, we found no difference in the incidence of venous thromboembolic complications between venous injuries managed by open repair vs ligation. Blast injuries of the extremities have caused most of the venous injuries. Ligation is the most common modality of treatment in combat zones
Agnelli, Giancarlo; Buller, Harry R; Cohen, Alexander; Curto, Madelyn; Gallus, Alexander S; Johnson, Margot; Porcari, Anthony; Raskob, Gary E; Weitz, Jeffrey I
Apixaban, an oral factor Xa inhibitor that can be administered in a simple, fixed-dose regimen, may be an option for the extended treatment of venous thromboembolism. In this randomized, double-blind study, we compared two doses of apixaban (2.5 mg and 5 mg, twice daily) with placebo in patients with venous thromboembolism who had completed 6 to 12 months of anticoagulation therapy and for whom there was clinical equipoise regarding the continuation or cessation of anticoagulation therapy. The study drugs were administered for 12 months. A total of 2486 patients underwent randomization, of whom 2482 were included in the intention-to-treat analyses. Symptomatic recurrent venous thromboembolism or death from venous thromboembolism occurred in 73 of the 829 patients (8.8%) who were receiving placebo, as compared with 14 of the 840 patients (1.7%) who were receiving 2.5 mg of apixaban (a difference of 7.2 percentage points; 95% confidence interval [CI], 5.0 to 9.3) and 14 of the 813 patients (1.7%) who were receiving 5 mg of apixaban (a difference of 7.0 percentage points; 95% CI, 4.9 to 9.1) (P<0.001 for both comparisons). The rates of major bleeding were 0.5% in the placebo group, 0.2% in the 2.5-mg apixaban group, and 0.1% in the 5-mg apixaban group. The rates of clinically relevant nonmajor bleeding were 2.3% in the placebo group, 3.0% in the 2.5-mg apixaban group, and 4.2% in the 5-mg apixaban group. The rate of death from any cause was 1.7% in the placebo group, as compared with 0.8% in the 2.5-mg apixaban group and 0.5% in the 5-mg apixaban group. Extended anticoagulation with apixaban at either a treatment dose (5 mg) or a thromboprophylactic dose (2.5 mg) reduced the risk of recurrent venous thromboembolism without increasing the rate of major bleeding. (Funded by Bristol-Myers Squibb and Pfizer; AMPLIFY-EXT ClinicalTrials.gov number, NCT00633893.).
Hass, Bastian; Pooley, Jayne; Harrington, Adrian E; Clemens, Andreas; Feuring, Martin
Effective treatment of venous thromboembolism (VTE) strikes a balance between prevention of recurrence and bleeding complications. The current standard of care is heparin followed by a vitamin K antagonist such as warfarin. However, this option is not without its limitations, as the anticoagulant effect of warfarin is associated with high inter- and intra-patient variability and patients must be regularly monitored to ensure that anticoagulation is within the narrow target therapeutic range. Several novel oral anticoagulant agents are in the advanced stages of development for VTE treatment, some of which are given after an initial period of heparin treatment, in line with current practice, while others switch from high to low doses after the initial phase of treatment. In this review we assess the critical considerations for treating VTE in light of emerging clinical data for new oral agents and discuss the merits of novel treatment regimens for patients who have experienced an episode of deep vein thrombosis or pulmonary embolism.
Klai, Sarra; Fekih-Mrissa, Najiba; Sassi, Raja B; Mrissa, Ridha; Rachdi, Radhouen; Gritli, Nasredine
Our aim was to assess thrombophilic risk factors and the non-O blood group as contributors to the development of venous thromboembolism during pregnancy and the postpartum period. A total of 199 women underwent blood typing and an extensive thombophilia screening. Factor V Leiden, FII G20210A, protein C deficiency and non-O blood group were significantly associated with venous thromboembolism during pregnancy and postpartum period. A known thrombophilic factor may have consequences for future pregnancies and could have implications for clinical practice. For this reason, women with a history of thromboembolism should be screened for thrombophilia. The non-O blood group could also have an important influence, especially when concomitant with another prothrombotic risk factor mainly pregnancy and thrombophilia.
Chang, Wei-Ting; Chang, Chia-Li; Ho, Chung-Han; Hong, Chon-Seng; Wang, Jhi-Joung; Chen, Zhih-Cherng
Patients with unprovoked venous thromboembolism (VTE) are at an increased risk of mortality, but whether their cardiovascular risks also increase remains to be determined. We aimed to investigate the factors associated with overall mortality and major adverse cardiovascular events in patients with unprovoked VTE. We identified 2154 patients newly diagnosed with unprovoked VTE from Taiwan's National Health Insurance Database between 2000 and 2013, excluding those with reversible etiologies, underlying cancer, or autoimmune diseases. These patients with VTE were compared with an age-, sex-, and cardiovascular risk-matched cohort of 4308 controls. The risk of mortality and major adverse cardiovascular events in patients with VTE was 2.23 (CI, 1.93-2.57; P<0.0001) and 1.86 (CI, 1.65-2.09; P<0.0001) times, respectively, higher than that of the conditions in controls. These events mostly occurred during the first year after the diagnosis of unprovoked VTE. Among patients with VTE, advanced age, male sex, and comorbid diabetes mellitus indicated a higher incidence of mortality and major adverse cardiovascular events. Conversely, comorbid hyperlipidemia attenuated these risks. This nation-wide cohort study revealed that patients with unprovoked VTE, particularly older males with diabetes mellitus, had an elevated risk of both mortality and cardiovascular events. Risk of mortality and major adverse cardiovascular events were highest within the first year after diagnosis and persisted during the 10 years of follow-up. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.
Muñoz-Figueroa, Gloria Patricia; Ojo, Omorogieva
This article aims to review the use of graduated compression stockings in the prevention of venous thromboembolism (VTE). This is particularly important owing to the increasing number of people who die from hospital-acquired VTE and deep vein thrombosis. In addition, there is the need to raise awareness among nurses and other health professionals on the overall impact of VTE, and the number of patients with a range of conditions including cancer who may be at risk of developing VTE. Graduated compression stockings, when used alone, have been found to be effective in preventing VTE in a number of patients in hospital and community settings. However, there is evidence that when used together with other preventative measures such as pharmacological prophylaxis are more effective than graduated compression stockings alone. It is also important that the correct size of graduated compression stocking is used and how they are applied as these may have a significant impact on VTE. The role of the nurse in thromboprophylaxis and implications for practice are discussed.
Khorana, Alok A.
Venous thromboembolism (VTE) is a frequent complication of malignancy, and its incidence has increased markedly in recent years. VTE itself can directly lead to patient mortality, and is the second leading cause of death in patients with cancer. Furthermore, emerging data suggest that activation of coagulation in malignancy is integrally linked with tumor biology, particularly with angiogenesis. The development of the clinical hypercoagulable state is also linked with adverse prognosis in patients with cancer, including patients receiving systemic chemotherapy. This review focuses on the clinical evidence documenting a link between VTE and adverse short-term and long-term prognosis in patients with cancer. PMID:20097409
Lecumberri, Ramón; Feliu, Jesús; Rocha, Eduardo
The association between neoplastic diseases and venous thromboembolism (VTE) is known since long time ago. The nature of this association is bidirectional. On one hand, cancer increases the incidence of venous thrombosis and, on the other hand, the hemostatic system does play a key role in the tumorigenesis process. However, despite recent advances in the field, prophylaxis and treatment of VTE in cancer patients is still a challenge, due to the complexity of this type of patients. This review is focused on some important points regarding management of VTE in cancer patients such as physiopathology, epidemiology, search for hidden malignancy, prognostic impact, prophylaxis in the medical and surgical setting, or initial and long-term treatment.
Franco-Moreno, A I; de Ancos-Aracil, C L; García-Navarro, M J
For patients with idiopathic venous thromboembolism (unprovoked), the risk of recurrence is high. Secondary prophylaxis with anticoagulant therapy reduces the thrombotic risk but at the expense of an increased risk of haemorrhage. A number of factors, such as the male sex and an increase in dimer-D concentrations after completing the anticoagulation therapy, are associated with an increased risk of recurrence. Other factors such as residual venous thrombosis have a more controversial and sometimes contradictory relationship. A number of models have been proposed for predicting thrombotic recurrence risk after anticoagulation therapy in unprovoked TVD. However, these models need external validation to determine their current usefulness in clinical practice. In this article, we analyse the risk factors for thrombotic recurrence and the existing prediction models.
Schousboe, John T; Brown, Gregory A
There is controversy regarding the most appropriate strategy to prevent venous thromboembolism following total joint arthroplasty. Our objective was to estimate the lifetime costs, quality-adjusted life-years (QALYs), and costs per QALY gained using low-molecular-weight heparin compared with low-dose aspirin for two weeks after total knee or total hip arthroplasty in patients with no history of venous thromboembolism. We used a Markov cohort model with health states of healthy after surgery, no postphlebitic syndrome after venous thromboembolism, postphlebitic syndrome after venous thromboembolism, and survival after intracranial hemorrhage to compare treatment with low-molecular-weight heparin or aspirin (160 mg) for fourteen days after total knee arthroplasty or total hip arthroplasty in patients with an age of fifty-five, sixty, sixty-five, seventy, seventy-five, eighty, or eighty-five years. We estimated lifetime costs, QALYs gained, and costs per QALY gained for both strategies, and applied a cost-effectiveness threshold of $100,000 (2010 U.S. dollars) per QALY gained. For patients undergoing total hip arthroplasty at the ages of fifty-five and seventy years, costs per QALY gained for low-molecular-weight heparin compared with aspirin were $315,000 and $1.4 million, respectively. For those undergoing total hip arthroplasty at the age of eighty or eighty-five years, aspirin cost less and saved more QALYs than low-molecular-weight heparin. For patients undergoing total knee arthroplasty at the ages of fifty-five, seventy, and eighty-five years, costs per QALY gained with low-molecular-weight heparin were $36,000, $112,000, and $448,000, respectively. Probabilistic sensitivity analyses confirmed a low probability of low-molecular-weight heparin being cost-effective for patients undergoing total hip arthroplasty and for those with an age of eighty years or older undergoing total knee arthroplasty. For individuals younger than eighty years of age undergoing total
Larsen, Torben Bjerregaard; Skjøth, Flemming; Grove, Erik Lerkevang; Nielsen, Peter Brønnum; Christensen, Thomas Decker
Patient-self-management (PSM) of oral anticoagulant therapy (OAT) with vitamin K antagonists for venous thromboembolism (VTE) has demonstrated efficacy in randomised, controlled trials. The aim of this study was to evaluate the effectiveness of PSM of OAT in everyday clinical practice. Prospectively registered patient data were obtained from databases at two hospitals, and cross-linkage with national patient registries provided detailed information on comorbidities and events. Patients with VTE performing PSM affiliated to major PSM centres were included as cases (N=444). A control group of patients on conventional treatment was propensity score selected in a ratio of 1:5 (N=2220) within matched groups. The effectiveness and safety was estimated using recurrent VTE, major bleeding events and all-cause death as outcomes. We found a lower rate of recurrent VTE among PSM patients compared to the control group with a hazard ratio (HR) of 0.63; 95 % confidence interval (CI) 0.42-0.95, whereas no difference was seen with bleeding (HR: 0.95; 95 % CI 0.44-2.02). The risk of all-cause death was lower for PSM patients (HR: 0.41; 95 % CI 0.21-0.81). A net clinical benefit analysis sums the effect on recurrent VTE and bleeding up to a weighted rate difference of 0.86 (95 % CI 0.00-1.72) in favour of PSM. In conclusion, PSM of anticoagulant treatment was associated with a statistically significant lower rate of recurrent VTE and all-cause death compared to patients on conventionally managed anticoagulant treatment. All major thromboembolic outcomes were less frequent among self-managed patients, whereas bleedings were observed with similar frequency.
Kapoor, Alok; Shaffer, Nicholas; Hanchate, Amresh; Roberts, Mark; Smith, Kenneth
Patients with venous thromboembolism (VTE) require access to comprehensive physician and pharmacy benefits to prevent recurrence and hemorrhage. Before 2006, Massachusetts provided these benefits through a program restricted to safety net hospitals called Free Care. Providing portable health insurance through Massachusetts health reform could improve outcomes for uninsured with VTE but its cost-effectiveness is unknown. We constructed a Markov decision analysis model comparing our conceptualization of the Massachusetts health reform (health reform strategy) to no health reform strategy for a patient beginning warfarin for new episode of VTE. In the model, a patient may develop recurrent VTE or develop hemorrhage or stop warfarin after 6 months if no event occurs. To measure effectiveness, we analyzed laboratory data from Boston Medical Center, the largest safety net hospital in Massachusetts. Specifically, we measured the probability of having a subtherapeutic warfarin level for patients newly insured compared with those on Free Care prereform adjusting for secular trends. To calculate inpatient costs, we used the Health Care Utilization Project. We then calculated the incremental cost-effectiveness ratio for the health reform strategy adjusted to 2014 USD per quality-adjusted life-year (QALY) and performed sensitivity analyses. The health reform strategy cost less and gained more QALYs than the no health reform strategy. Our result was most sensitive to the odds that Health Reform protected against a subtherapeutic warfarin level, the cost of Health Reform, and the percentage of total health care costs attributable to VTE in Massachusetts. The health reform strategy cost less and was more effective than the no health reform strategy for patients with VTE.
Marini, Bernard L; Funk, Kylee; Kraft, Michael D; Fong, Jessica M; Naanos, Roxanne; Stout, Stephen M; Wagner, Deborah
Venous thromboembolism (VTE) is the leading cause of preventable death in hospitalized patients. Educational videos have been effectively used to increase patient satisfaction and knowledge. This study examined possible benefits of an educational video about VTE. Medical patients receiving VTE prophylaxis were screened within 48 h of admission. Upon enrollment, patients were randomly assigned to either watch a 5 min educational video on VTE or not, in addition to standard VTE education. Within 24-48 h after randomization, all patients completed a survey assessing VTE prophylaxis knowledge and satisfaction. Patients who watched the video averaged 83% correct responses to knowledge-based questions (regarding VTE risk, symptoms, and preventative measures) versus an average score of 62% for patients in the no video group (p<0.001). Patients who watched the video were more satisfied with their VTE education (4.8 vs. 3.4 out of 5, p<0.001). This educational video effectively provided baseline information to patients about VTE and improved patient satisfaction. A VTE educational video can be an effective tool for improving patient knowledge of the condition. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.
Faustino, E. Vincent S.; Raffini, Leslie J.
Venous thromboembolism, which includes deep venous thrombosis and pulmonary embolism, is a potentially preventable condition in children. In adults, pharmacologic prophylaxis has been shown to significantly reduce the incidence of venous thromboembolism in distinct patient cohorts. However, pediatric randomized controlled trials have failed to demonstrate the efficacy of pharmacologic prophylaxis against thrombosis associated with central venous catheters, the most important risk factor for venous thromboembolism in children. Despite the lack of supporting evidence, hospital-based initiatives are being undertaken to try to prevent venous thromboembolism in children. In this study, we sought to review the published guidelines on the prevention of venous thromboembolism in hospitalized children. We identified five guidelines, all of which were mainly targeted at adolescents and used various risk-stratification approaches. In low-risk children, ambulation was the recommended prevention strategy, while mechanical prophylaxis was recommended for children at moderate risk and pharmacologic and mechanical prophylaxis were recommended for the high-risk group. The effectiveness of these strategies has not been proven. In order to determine whether venous thromboembolism can be prevented in children, innovative clinical trial designs are needed. In the absence of these trials, guidelines can be a source of valuable information to inform our practice. PMID:28184368
O'Brien, Sarah H
Venous thromboembolism (VTE) is a rare but serious complication of combined hormonal contraception. While the absolute risk of VTE is low in adolescents, thrombotic events in contraception users younger than the age of 20 years account for 5 to 10% of total contraception-related VTE events in population studies, because of the high frequency of contraception use in adolescents. An increased risk of VTE exists not only with oral contraceptives, but also the contraceptive patch and vaginal ring. Most adolescents who experience contraception-related VTE have additional transient or inherited thrombotic risk factors at the time of VTE. Although the presence of inherited thrombophilia impacts the risk of contraception-related VTE, thrombophilia screening before contraception prescribing should be targeted only to high-risk populations. Pediatric institutions, caregivers, and young women need to be aware of the risk of VTE with estrogen-containing contraception, and maintain a high index of suspicion for this complication in women using these agents.
Hospitalization for surgery has a high risk of developing venous thromboembolism, a condition that encompasses both deep-vein thrombosis and its potentially fatal complication, pulmonary embolism. Colorectal surgery implies a specific high risk for postoperative thromboembolic complications relative to other general surgery. This may be a result of pelvic dissection, the perioperative positioning of these patients, or the presence of additional risk factors common to this patient group, such as cancer, advanced age, or inflammatory bowel disease. The potential impact of venous thromboembolism and the need for effective thromboprophylaxis often are underestimated in these patients. Recommendations for thromboprophylaxis in colorectal surgery patients are based on the American College of Chest Physicians guidelines for thrombosis prevention in general surgery patients, with treatment stratified according to the type of surgery and additional venous thromboembolism risk factors present. Prophylaxis with low-molecular-weight heparin or unfractionated heparin is recommended for colorectal surgery patients classified as moderate to high risk. The small number of studies focusing specifically on colorectal patients, or on cancer or abdominal surgery patients with a colorectal subgroup, has shown that both low-molecular-weight heparin and unfractionated heparin can effectively reduce the incidence of venous thromboembolism. Low-molecular-weight heparin has the practical advantage of once-daily administration and shows a lower risk of heparin-induced thrombocytopenia. This review will assess the risk of venous thromboembolism in colorectal surgery patients and discuss current evidence-based guidelines and recommendations for prevention of venous thromboembolism.
Saghazadeh, Amene; Rezaei, Nima
Inflammatory markers are highly amenable to appraise and adjust and could already serve as a diagnostic indicator and also as a predictor of prognosis over the management of many health problems. Inflammation is implicated in venous thromboembolism (VTE). However there is still an intense curiosity about whether it is a cause or only a consequence of the thromboembolic process. The more likely scenario is that some inflammatory mediators contribute to the development of VTE, which per se induces an inflammatory reaction. Here we will review evidences supporting the role of inflammation as a cause of VTE. Genetic association studies have provided possible links between inflammation-related genetic variants, especially cytokines (e.g. IL-1, IL-4, IL-6, IL-10, and IL-13), and VTE, leading to establish the fundamental role of genetic background in predisposition to VTE and variable inflammatory processes in individuals. Additionally, several inflammation-related conditions including aging, autoimmune disease, cancer, cardiovascular diseases, hormone replacement therapy, infectious diseases, metabolic diseases, overweight or obesity, pregnancy or postpartum, respiratory diseases, and trauma have been associated with an increased risk of VTE. At this moment, despite their theoretical potential, to achieve the implementation of the inflammation-related laboratory tests in practice is a long task and future studies with larger sample sizes are required to address whether the properties of the inflammatory process, particularly intensity and duration, are useful in determining the risk of VTE and following outcomes.
Fowler, Robert A; Mittmann, Nicole; Geerts, William; Heels-Ansdell, Diane; Gould, Michael K; Guyatt, Gordon; Krahn, Murray; Finfer, Simon; Pinto, Ruxandra; Chan, Brian; Ormanidhi, Orges; Arabi, Yaseen; Qushmaq, Ismael; Rocha, Marcelo G; Dodek, Peter; McIntyre, Lauralyn; Hall, Richard; Ferguson, Niall D; Mehta, Sangeeta; Marshall, John C; Doig, Christopher James; Muscedere, John; Jacka, Michael J; Klinger, James R; Vlahakis, Nicholas; Orford, Neil; Seppelt, Ian; Skrobik, Yoanna K; Sud, Sachin; Cade, John F; Cooper, Jamie; Cook, Deborah
Venous thromboembolism (VTE) is a common complication of acute illness, and its prevention is a ubiquitous aspect of inpatient care. A multicenter blinded, randomized trial compared the effectiveness of the most common pharmocoprevention strategies, unfractionated heparin (UFH) and the low-molecular-weight heparin (LMWH) dalteparin, finding no difference in the primary end point of leg deep-vein thrombosis but a reduced rate of pulmonary embolus and heparin-induced thrombocytopenia among critically ill medical-surgical patients who received dalteparin. To evaluate the comparative cost-effectiveness of LMWH vs UFH for prophylaxis against VTE in critically ill patients. Prospective economic evaluation concurrent with the Prophylaxis for Thromboembolism in Critical Care Randomized Trial (May 2006 to June 2010). The economic evaluation adopted a health care payer perspective and in-hospital time horizon; derived baseline characteristics and probabilities of intensive care unit and in-hospital events; and measured costs among 2344 patients in 23 centers in 5 countries and applied these costs to measured resource use and effects of all enrolled patients. Costs, effects, incremental cost-effectiveness of LMWH vs UFH during the period of hospitalization, and sensitivity analyses across cost ranges. Hospital costs per patient were $39,508 (interquartile range [IQR], $24,676 to $71,431) for 1862 patients who received LMWH compared with $40,805 (IQR, $24,393 to $76,139) for 1862 patients who received UFH (incremental cost, -$1297 [IQR, -$4398 to $1404]; P = .41). In 78% of simulations, a strategy using LMWH was most effective and least costly. In sensitivity analyses, a strategy using LMWH remained least costly unless the drug acquisition cost of dalteparin increased from $8 to $179 per dose and was consistent among higher- and lower-spending health care systems. There was no threshold at which lowering the acquisition cost of UFH favored prophylaxis with UFH. From a
Bauersachs, Rupert; Berkowitz, Scott D; Brenner, Benjamin; Buller, Harry R; Decousus, Hervé; Gallus, Alex S; Lensing, Anthonie W; Misselwitz, Frank; Prins, Martin H; Raskob, Gary E; Segers, Annelise; Verhamme, Peter; Wells, Phil; Agnelli, Giancarlo; Bounameaux, Henri; Cohen, Alexander; Davidson, Bruce L; Piovella, Franco; Schellong, Sebastian
Rivaroxaban, an oral factor Xa inhibitor, may provide a simple, fixed-dose regimen for treating acute deep-vein thrombosis (DVT) and for continued treatment, without the need for laboratory monitoring. We conducted an open-label, randomized, event-driven, noninferiority study that compared oral rivaroxaban alone (15 mg twice daily for 3 weeks, followed by 20 mg once daily) with subcutaneous enoxaparin followed by a vitamin K antagonist (either warfarin or acenocoumarol) for 3, 6, or 12 months in patients with acute, symptomatic DVT. In parallel, we carried out a double-blind, randomized, event-driven superiority study that compared rivaroxaban alone (20 mg once daily) with placebo for an additional 6 or 12 months in patients who had completed 6 to 12 months of treatment for venous thromboembolism. The primary efficacy outcome for both studies was recurrent venous thromboembolism. The principal safety outcome was major bleeding or clinically relevant nonmajor bleeding in the initial-treatment study and major bleeding in the continued-treatment study. The study of rivaroxaban for acute DVT included 3449 patients: 1731 given rivaroxaban and 1718 given enoxaparin plus a vitamin K antagonist. Rivaroxaban had noninferior efficacy with respect to the primary outcome (36 events [2.1%], vs. 51 events with enoxaparin-vitamin K antagonist [3.0%]; hazard ratio, 0.68; 95% confidence interval [CI], 0.44 to 1.04; P<0.001). The principal safety outcome occurred in 8.1% of the patients in each group. In the continued-treatment study, which included 602 patients in the rivaroxaban group and 594 in the placebo group, rivaroxaban had superior efficacy (8 events [1.3%], vs. 42 with placebo [7.1%]; hazard ratio, 0.18; 95% CI, 0.09 to 0.39; P<0.001). Four patients in the rivaroxaban group had nonfatal major bleeding (0.7%), versus none in the placebo group (P=0.11). Rivaroxaban offers a simple, single-drug approach to the short-term and continued treatment of venous thrombosis that may
Kittelson, John M.; Spyropoulos, Alex C.; Halperin, Jonathan L.; Kessler, Craig M.; Schulman, Sam; Steg, Gabriel; Turpie, Alexander G. G.; Cutler, Neal R.; Hiatt, William R.
Antithrombotic trials in venous thromboembolism treatment and prevention, including those evaluating the new oral anticoagulants, have typically evaluated thromboembolism risk as an efficacy endpoint and bleeding risk as a separate safety endpoint. Findings often occur in opposition (i.e., decreased thromboembolism accompanied by increased bleeding, or vice-versa), leading to variable interpretation of the results, which may ultimately be judged as equivocal. In this paper, we offer an alternative to traditional designs based on the concept of a bivariate primary endpoint that accounts for simultaneous effects on antithrombotic efficacy and bleeding harm. We suggest a bivariate endpoint as a general approach to the assessment of “net clinical benefit” in recently published trials and to the design of future trials. Lastly, we illustrate the bivariate endpoint design using two examples: a recently published superiority trial of rivaroxaban (RECORD1), and an ongoing non-inferiority trial of the duration of anticoagulant therapy in children with venous thrombosis (Kids-DOTT). PMID:23773172
Pedrajas, J M; Garmendia, C; Portillo, J; Gabriel, F; Mainez, C; Yera, C; Monreal, M
The Computerized Registry of Patients with Venous Thromboembolism (RIETE) is a prospective registry that consecutively includes patients diagnosed with venous thromboembolism. We compared the clinical presentation and response to anticoagulant treatment in patients with idiopathic venous thromboembolism (IVT) versus secondary venous thromboembolism (SVT, associated with a risk factor). We analyzed the differences in clinical characteristics, comorbidity, treatment and events during the first 3months after the diagnosis of venous thromboembolism in patients with IVT or SVT and according to their initial clinical presentation. A total of 39,921 patients with IVT (n=18,029; 45.1%) or SVT (n=21,892; 54.9%) were enrolled. The patients with IVT had a greater history of venous thromboembolism than those diagnosed with SVT (p<.001). The initial treatment was similar for the 2 groups, but more inferior vena cava filters were placed in the SVT group (p<.001). In the long term, low-molecular-weight heparin was used more often in the SVT group than in the IVT group. At 90days, bleeding, death and the recurrence of venous thromboembolism were significantly more frequent in the SVT group. The multivariate analysis confirmed that IVT was associated with fewer major (OR, 0.60; 95%CI, 0.50-0.61; p<.001) and fatal (OR, 0.41; 95%CI, 0.29-0.62; p<.001) bleedings, fewer relapses (OR, 0.58; 95%CI, 0.39-0.78; p<.001) and fewer fatal pulmonary embolisms (OR, 0.29; 95%CI, 0.12-0.52; p<.001). These differences were maintained in patients whose venous thromboembolism started with a pulmonary embolism or with deep vein thrombosis. IVT has a better prognosis than SVT at 90days of the diagnosis. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.
Chakrabarti, Anob M
There have been a number of developments in the management of venous thromboembolism over the past few years. Old questions, such as thrombolysis, have been revisited in recent trials. New initiatives, such as ambulatory care pathways, are being established across the country. This conference brought together doctors from the UK, USA, Spain and Australia to review the up-to-date management of venous thromboembolism.
Stevanović, J; de Jong, L A; Kappelhoff, B S; Dvortsin, E P; Voorhaar, M; Postma, M J
Dabigatran was proven to have similar effect on the prevention of recurrence of venous thromboembolism (VTE) and a lower risk of bleeding compared to vitamin K antagonists (VKA). The aim of this study is to assess the cost-effectiveness (CE) of dabigatran for the treatment and secondary prevention in patients with VTE compared to VKAs in the Dutch setting. Previously published Markov model was modified and updated to assess the CE of dabigatran and VKAs for the treatment and secondary prevention in patients with VTE from a societal perspective in the base-case analysis. The model was populated with efficacy and safety data from major dabigatran trials (i.e. RE-COVER, RECOVER II, RE-MEDY and RE-SONATE), Dutch specific costs, and utilities derived from dabigatran trials or other published literature. Univariate, probabilistic sensitivity and a number of scenario analyses evaluating various decision-analytic settings (e.g. the perspective of analysis, use of anticoagulants only for treatment or only for secondary prevention, or comparison to no treatment) were tested on the incremental cost-effectiveness ratio (ICER). In the base-case scenario, patients on dabigatran gained an additional 0.034 quality adjusted life year (QALY) while saving €1,598. Results of univariate sensitivity analysis were quite robust. The probability that dabigatran is cost-effective at a willingness-to-pay threshold of €20,000/QALY was 98.1%. From the perspective of healthcare provider, extended anticoagulation with dabigatran compared to VKAs was estimated at €2,158 per QALY gained. The ICER for anticoagulation versus no treatment in patients with equipoise risk of recurrent VTE was estimated at €33,379 per QALY gained. Other scenarios showed dabigatran was cost-saving. From a societal perspective, dabigatran is likely to be a cost-effective or even cost-saving strategy for treatment and secondary prevention of VTE compared to VKAs in the Netherlands.
Capri, Stefano; Ageno, Walter; Imberti, Davide; Palareti, Gualtiero; Piovella, Franco; Scannapieco, Gianluigi; Moia, Marco
Enoxaparin is the most frequently used low-molecular weight heparin in the world, given in order to prevent venous thromboembolism (VTE) in patients undergoing major orthopaedic surgery (MOS). Fondaparinux is an effective and safe alternative. The aim of our study was to compare the cost-effectiveness of enoxaparin and fondaparinux in the extended thromboprophylaxis of patients undergoing MOS in Italy. A decision-tree model was developed: probabilities of symptomatic events were derived from the published trials; use of resources in Italy was evaluated by means of a questionnaire administered to a panel of experts. Only the direct costs of VTE (acute treatment of events and of complications) were considered. Cost units were derived from the current cost of drugs, and from the Italian National Healthcare tariffs in 2007. Incremental cost-effectiveness ratios were analysed at three time points: 30 days, 1 year and 5 years. The higher cost of fondaparinux was counterbalanced by reduced rates of early DVT, early PE and prophylaxis-related major bleeding. If compared with enoxaparin, after 30 days of extended prophylaxis, fondaparinux is associated with a savings of
Viejo Moreno, R; Sánchez-Izquierdo Riera, J Á; Molano Álvarez, E; Barea Mendoza, J A; Temprano Vázquez, S; Díaz Castellano, L; Montejo González, J C
To improve critical patient safety in the prevention of venous thromboembolic disease, using failure mode and effects analysis as safety tool. A contemporaneous cohort study covering the period January 2014-March 2015 was made in 4 phases: phase 1) prior to failure mode and effects analysis; phase 2) conduction of mode analysis and implementation of the detected improvements; phase 3) evaluation of outcomes, and phase 4) (post-checklist introduction impact. Patients admitted to the adult polyvalent ICU of a third-level hospital center. A total of 196 patients, older than 18 years, without thromboembolic disease upon admission to the ICU and with no prior anticoagulant treatment. A series of interventions were implemented following mode analysis: training, and introduction of a protocol and checklist to increase preventive measures in relation to thromboembolic disease. Indication and prescription of venous thrombosis prevention measures before and after introduction of the measures derived from the failure mode and effects analysis. A total of 59, 97 and 40 patients were included in phase 1, 3 and 4, respectively, with an analysis of the percentage of subjects who received thromboprophylaxis. The failure mode and effects analysis was used to detect potential errors associated to a lack of training and protocols referred to thromboembolic disease. An awareness-enhancing campaign was developed, with staff training and the adoption of a protocol for the prevention of venous thromboembolic disease. The prescription of preventive measures increased in the phase 3 group (91.7 vs. 71.2%, P=.001). In the post-checklist group, prophylaxis was prescribed in 97.5% of the patients, with an increase in the indication of dual prophylactic measures (4.7, 6.7 and 41%; P<.05). There were no differences in complications rate associated to the increase in prophylactic measures. The failure mode and effects analysis allowed us to identify improvements in the prevention of
Pavon, Juliessa M; Adam, Soheir S; Razouki, Zayd A; McDuffie, Jennifer R; Lachiewicz, Paul F; Kosinski, Andrzej S; Beadles, Christopher A; Ortel, Thomas L; Nagi, Avishek; Williams, John W
Thromboprophylaxis regimens include pharmacologic and mechanical options such as intermittent pneumatic compression devices (IPCDs). There are a wide variety of IPCDs available, but it is uncertain if they vary in effectiveness or ease of use. This is a systematic review of the comparative effectiveness of IPCDs for selected outcomes (mortality, venous thromboembolism [VTE], symptomatic or asymptomatic deep vein thrombosis, major bleeding, ease of use, and adherence) in postoperative surgical patients. We searched MEDLINE (via PubMed), Embase, CINAHL, and Cochrane CENTRAL from January 1, 1995, to October 30, 2014, for randomized controlled trials, as well as relevant observational studies on ease of use and adherence. We identified 14 eligible randomized controlled trials (2633 subjects) and 3 eligible observational studies (1724 subjects); most were conducted in joint arthroplasty patients. Intermittent pneumatic compression devices were comparable to anticoagulation for major clinical outcomes (VTE: risk ratio, 1.39; 95% confidence interval, 0.73-2.64). Limited data suggest that concurrent use of anticoagulation with IPCD may lower VTE risk compared with anticoagulation alone, and that IPCD compared with anticoagulation may lower major bleeding risk. Subgroup analyses did not show significant differences by device location, mode of inflation, or risk of bias elements. There were no consistent associations between IPCDs and ease of use or adherence. Intermittent pneumatic compression devices are appropriate for VTE thromboprophylaxis when used in accordance with current clinical guidelines. The current evidence base to guide selection of a specific device or type of device is limited. Copyright © 2016 Elsevier Inc. All rights reserved.
Borch, Knut H; Nyegaard, Cecilie; Hansen, John-Bjarne; Mathiesen, Ellisiv B; Njølstad, Inger; Wilsgaard, Tom; Brækkan, Sigrid K
The goal of this study was to investigate the combined effect of obesity and body height on the risk of venous thromboembolism (VTE) in a prospective population-based study. Personal characteristics, including measures of obesity and body height, were collected in 26 714 men and women, aged 25 to 97 years, who participated in the Tromsø Study in 1994 to 1995. Incident VTE events were registered through September 1, 2007. There were 461 incident VTE events during a median of 12.5 years of follow-up. A tall stature was associated with increased risk of VTE in normal-weight (body mass index <25 kg/m(2)) and obese (body mass index ≥30 kg/m(2)) men, but not in women. The combination of obesity and tall stature synergistically increased the risk of VTE in both sexes. Tall (≥182 cm), obese men had a 5-fold (multivariable hazard ratio 5.16; 95% CI 2.39 to 11.14) increased risk of VTE compared with normal-weight men with short (≤172 cm) stature. Tall (≥168 cm), obese women had an almost 3-fold (multivariable hazard ratio 2.89; 95% CI 1.31 to 6.35) increased risk of VTE compared with normal-weight, short (≤159 cm) women. The combination of obesity and a tall stature was associated with a substantially increased risk of VTE, especially in men, suggesting synergistic effects of obesity and height on risk of VTE in both sexes.
Jaffray, Julie; Bauman, Mary; Massicotte, Patti
The use of central venous catheters (CVCs) in children is escalating, which is likely linked to the increased incidence of pediatric venous thromboembolism (VTE). In order to better understand the specific risk factors associated with CVC-VTE in children, as well as available prevention methods, a literature review was performed. The overall incidence of CVC-VTE was found to range from 0 to 74%, depending on the patient population, CVC type, imaging modality, and study design. Throughout the available literature, there was not a consistent determination regarding whether a particular type of central line (tunneled vs. non-tunneled vs. peripherally inserted vs. implanted), catheter material, insertion technique, or insertion location lead to an increased VTE risk. The patient populations who were found to be most at risk for CVC-VTE were those with cancer, congenital heart disease, gastrointestinal failure, systemic infection, intensive care unit admission, or involved in a trauma. Both mechanical and pharmacological prophylactic techniques have been shown to be successful in preventing VTE in adult patients, but studies in children have yet to be performed or are underpowered. In order to better determine true CVC-VTE risk factors and best preventative techniques, an increase in large, prospective pediatric trials needs to be performed.
Jaffray, Julie; Bauman, Mary; Massicotte, Patti
The use of central venous catheters (CVCs) in children is escalating, which is likely linked to the increased incidence of pediatric venous thromboembolism (VTE). In order to better understand the specific risk factors associated with CVC-VTE in children, as well as available prevention methods, a literature review was performed. The overall incidence of CVC-VTE was found to range from 0 to 74%, depending on the patient population, CVC type, imaging modality, and study design. Throughout the available literature, there was not a consistent determination regarding whether a particular type of central line (tunneled vs. non-tunneled vs. peripherally inserted vs. implanted), catheter material, insertion technique, or insertion location lead to an increased VTE risk. The patient populations who were found to be most at risk for CVC-VTE were those with cancer, congenital heart disease, gastrointestinal failure, systemic infection, intensive care unit admission, or involved in a trauma. Both mechanical and pharmacological prophylactic techniques have been shown to be successful in preventing VTE in adult patients, but studies in children have yet to be performed or are underpowered. In order to better determine true CVC-VTE risk factors and best preventative techniques, an increase in large, prospective pediatric trials needs to be performed. PMID:28168186
Czeyda-Pommersheim, Ferenc; Magee, Shantel T.; Cooper, Cirrelda; Hahn, Winnie Y.; Spies, James B.
Thromboembolic complications after uterine fibroid embolization (UFE) are infrequent. The incidence and predisposing factors of thromboembolism after UFE are unknown. We present eight cases of nonfatal thromboembolic complications after UFE and estimate the frequency of such events as 0.4%.
Borch, Knut H; Hansen-Krone, Ida; Braekkan, Sigrid K; Mathiesen, Ellisiv B; Njolstad, Inger; Wilsgaard, Tom; Hansen, John-Bjarne
Previous studies have shown differences in the impact of regular physical exercise on the risk of venous thromboembolism. The inconsistent findings may have depended on differences in study design and specific population cohorts (men only, women only and elderly). We conducted a prospective, population-based cohort to investigate the impact of regular physical exercise on the risk of venous thromboembolism. Risk factors, including self-reported moderate intensity physical exercise during leisure time, were recorded for 26,490 people aged 25-97 years old, who participated in a population health survey, the Tromsø study, in 1994-95. Incident venous thromboembolic events were registered during the follow-up until September 1, 2007. There were 460 validated incident venous thromboembolic events (1.61 per 1000 person-years) during a median of 12.5 years of follow-up. Age, body mass index, the proportion of daily smokers, total cholesterol, and serum triglycerides decreased (P<0.001), whereas high density cholesterol increased (P<0.001) across categories of more physical exercise. Regular physical exercise of moderate to high intensity during leisure time did not significantly affect the risk of venous thromboembolism in the general population. However, compared to inactivity, high amounts of physical exercise (≥ 3 hours/week) tended to increase the risk of provoked venous thromboembolism (multivariable hazard ratio, 1.30; 95% confidence interval, 0.84-2.0), and total venous thromboembolism in the elderly (multivariable hazard ratio, 1.33; 95% confidence interval, 0.80-2.21) and in the obese (multivariable hazard ratio, 1.49; 95% confidence interval, 0.63-3.50). Contrariwise, compared to inactivity, moderate physical activity (1.0-2.9 hours/week) was associated with a border-line significant decreased risk of venous thromboembolism among subjects under 60 years old (multivariable hazard ratio, 0.72; 95% confidence interval, 0.48-1.08) and subjects with a body mass
Kwong, Louis M; Kimball, Jon A
Elective total hip or knee arthroplasty places patients at risk for venous thromboembolism (VTE). As our understanding of the pathophysiology of VTE after joint arthroplasty has increased, pharmacologic strategies have been developed to target different aspects of the coagulation cascade. Various approaches have been used as risk reduction strategies. In 2011 and 2014 the Food and Drug Administration approved rivaroxaban and apixaban as new oral antithrombotic agents. Although controversies remain with regard to the ideal VTE pharmacoprophylactic agent, this class of novel oral anticoagulants has been demonstrated to be safe and to be more effective than enoxaparin. Copyright © 2016 Elsevier Inc. All rights reserved.
This paper reviews the literature on the association between venous thromboembolism and travel. There are plausible physiological reasons why sitting still for long periods (particularly in the cramped conditions of most aircraft) might predispose to venous thromboembolism. This may have been the explanation for the apparent excess of deaths from pulmonary embolism seen during the first months of the London blitz. No published controlled studies of thromboembolism and travel were identified, but eight case reports were analysed. They covered 25 people aged from 19 to 84 years with deep vein thrombosis or pulmonary embolism following travel. The reports suggest that long journeys are a particular risk and that there are often no symptoms until many hours after leaving the plane (so conventional methods of assessing the hazards of air travel may underestimate the problem). It is concluded that the literature tends to support the hypothesis that venous thromboembolism is associated with travel, but that carefully controlled studies are needed to test this properly.
Stevanović, J.; de Jong, L. A.; Kappelhoff, B. S.; Dvortsin, E. P.; Voorhaar, M.; Postma, M. J.
Background Dabigatran was proven to have similar effect on the prevention of recurrence of venous thromboembolism (VTE) and a lower risk of bleeding compared to vitamin K antagonists (VKA). The aim of this study is to assess the cost-effectiveness (CE) of dabigatran for the treatment and secondary prevention in patients with VTE compared to VKAs in the Dutch setting. Methods Previously published Markov model was modified and updated to assess the CE of dabigatran and VKAs for the treatment and secondary prevention in patients with VTE from a societal perspective in the base-case analysis. The model was populated with efficacy and safety data from major dabigatran trials (i.e. RE-COVER, RECOVER II, RE-MEDY and RE-SONATE), Dutch specific costs, and utilities derived from dabigatran trials or other published literature. Univariate, probabilistic sensitivity and a number of scenario analyses evaluating various decision-analytic settings (e.g. the perspective of analysis, use of anticoagulants only for treatment or only for secondary prevention, or comparison to no treatment) were tested on the incremental cost-effectiveness ratio (ICER). Results In the base-case scenario, patients on dabigatran gained an additional 0.034 quality adjusted life year (QALY) while saving €1,598. Results of univariate sensitivity analysis were quite robust. The probability that dabigatran is cost-effective at a willingness-to-pay threshold of €20,000/QALY was 98.1%. From the perspective of healthcare provider, extended anticoagulation with dabigatran compared to VKAs was estimated at €2,158 per QALY gained. The ICER for anticoagulation versus no treatment in patients with equipoise risk of recurrent VTE was estimated at €33,379 per QALY gained. Other scenarios showed dabigatran was cost-saving. Conclusion From a societal perspective, dabigatran is likely to be a cost-effective or even cost-saving strategy for treatment and secondary prevention of VTE compared to VKAs in the
Revankar, Nikhil; Patterson, John; Kadambi, Ananth; Raymond, Vincent; El-Hadi, Wissam
Occurrence of a venous thromboembolism (VTE) in patients undergoing major orthopedic surgery who are not given thromboprophylactic therapy presents considerable danger to patient medical outcomes and a significant economic burden to the health care system at large. Apixaban is a direct factor Xa inhibitor that has been shown in clinical trial use to safely reduce the composite of VTE and mortality rates in patients undergoing total hip arthroplasty (THA) and total knee arthroplasty (TKA); however, the cost-effectiveness of apixaban treatment in Canadian settings has not been studied. Our study evaluated the cost-effectiveness of apixaban compared with enoxaparin as VTE preventive therapy in patients undergoing elective THA or TKA in Canada. An economic model, including both a decision-tree component and a Markov model, was created. The decision tree considered VTE, bleeding, and mortality incidence that occurred in patients within 90 days post-surgery using data from the Apixaban Versus Enoxaparin for Thromboprophylaxis After Knee or Hip Replacement (ADVANCE) trials, which compared apixaban therapy with 30-mg twice daily and 40-mg daily enoxaparin treatment. The Markov model provided the option to simulate events that may occur over the long term, such as recurrent VTE and post-thrombotic syndrome. Outcomes during the short-term phase directly impact the risk of events occurring during the long-term phase (5 years post-surgery). The results of our analysis indicated that apixaban is dominant (ie, more effective and less expensive) than enoxaparin in treating patients undergoing THA and TKA. There were fewer occurrences of VTEs, bleeding events, recurrent VTEs, and post-thrombotic syndrome events in the TKA population with apixaban therapy. Similar results were seen in patients undergoing THA, with the exception of bleeding events, which were more common with apixaban treatment. Savings of $180 to $270 per patient are expected with apixaban treatment compared with
Lefebvre, Patrick; Coleman, Craig I; Bookhart, Brahim K; Wang, Si-Tien; Mody, Samir H; Tran, Kevin N; Zhuo, Daisy Y; Huynh, Lynn; Nutescu, Edith A
Venous thromboembolism (VTE), comprised of deep vein thrombosis (DVT) and pulmonary embolism (PE), is commonly treated with a low-molecular-weight heparin such as enoxaparin plus a vitamin K antagonist (VKA) to prevent recurrence. Administration of enoxaparin + VKA is hampered by complexities of laboratory monitoring and frequent dose adjustments. Rivaroxaban, an orally administered anticoagulant, has been compared with enoxaparin + VKA in the EINSTEIN trials. The objective was to evaluate the cost-effectiveness of rivaroxaban compared with enoxaparin + VKA as anticoagulation treatment for acute, symptomatic, objectively-confirmed DVT or PE. A Markov model was built to evaluate the costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios associated with rivaroxaban compared to enoxaparin + VKA in adult patients treated for acute DVT or PE. All patients entered the model in the 'on-treatment' state upon commencement of oral rivaroxaban or enoxaparin + VKA for 3, 6, or 12 months. Transition probabilities were obtained from the EINSTEIN trials during treatment and published literature after treatment. A 3-month cycle length, US payer perspective ($2012), 5-year time horizon and a 3% annual discount rate were used. Treatment with rivaroxaban cost $2,448 per-patient less and was associated with 0.0058 more QALYs compared with enoxaparin + VKA, making it a dominant economic strategy. Upon one-way sensitivity analysis, the model's results were sensitive to the reduction in index VTE hospitalization length-of-stay associated with rivaroxaban compared with enoxaparin + VKA. At a willingness-to-pay threshold of $50,000/QALY, probabilistic sensitivity analysis showed rivaroxaban to be cost-effective compared with enoxaparin + VKA approximately 76% of the time. The model did not account for the benefits associated with an oral and minimally invasive administration of rivaroxaban. 'Real-world' applicability is limited
Di Minno, G; Tufano, A
Aging itself is a risk factor for venous thromboembolism, and the prevalence in the elderly of additional risk factors (e.g. cancer, orthopedic surgery, immobility) increase its intrinsic risk. Many in the medical community are reluctant to prescribe anticoagulation (for primary and secondary prevention of venous thromboembolism) to their geriatric patients for the fear that bleeding complications may outweigh the benefits. A thorough analysis of the data support the concept that the under-use of heparin in primary prevention in the elderly is more related to medical beliefs than to facts. The risk of bleeding due to oral anticoagulants (secondary prevention) is greatly reduced by keeping the International Normalized Ratio (INR) values within therapeutic ranges and carefully avoiding conditions/drugs that may interfere with such treatment. The oral direct thrombin inhibitor ximelagatran has been studied for primary (hip and knee replacement surgery) and for secondary prophylaxis of venous thromboembolism, and for acute venous thromboembolism treatment. The selective factor Xa inhibitor fondaparinux has been approved for primary prophylaxis of venous thromboembolism in hip and knee replacement surgery and in hip fracture surgery. Studies on the latter drugs, where most of the patients were > 65 years of age, further show that the fear of bleeding complications due to anticoagulation in the elderly is largely unjustified.
Wang, Tao; Yang, Si-Dong; Huang, Wen-Zheng; Liu, Feng-Yu; Wang, Hui; Ding, Wen-Yuan
Abstract Background: A meta-analysis was performed to explore predicted factors of venous thromboembolism (VTE) after surgery in the treatment for spine degeneration diseases. Summary of background data: Many scholars have focused on VTE after spine surgery, but as for the risk factors of VTE have not reached a consensus. Methods: An extensive search of literature, “spine or spinal,” “degeneration,” “after surgery or postoperation,” and “venous thromboembolism” as key words, was performed in PubMed/MEDLINE, Embase, the Cochrane library, CNKI, and WANFANG databases. The following variables were extracted: wearing elastic stocking, hypertension (HT), heart disease, diabetes, drinking, anticoagulant therapy, walking disability preoperation, smoking, sex, age, surgical duration, fusion versus nonfusion (lumbar fusion vs lumbar discectomy), surgical site (cervical vs lumbar), blood loss, and body mass index. Data analysis was conducted with RevMan 5.3 and STATA 12.0. Results: A total of 12 studies were identified, including 34,597 patients of whom 624 patients had VTE, and the incidence of VTE was 2% in all patients who underwent spine surgery. The incidence of VTE for Asian patients was 7.5%, compared with 1% VTE for Occidental patients; the difference was significant (P < 0.0001). The pooled analysis showed that there were significant differences regarding wearing elastic stocking (odds ratio [OR] = 11.71, 95% confidence interval [CI] [1.46, 94.00], P = 0.02), walking disability preoperation (OR = 4.80, 95% CI [2.53, 9.12], P < 0.00001), surgical site (lumbar surgery) (OR = 0.23, 95% CI [0.20, 0.27], P < 0.00001), HT (OR = 1.59, 95% CI [1.21, 2.10], P = 0.001), and diabetes (OR = 2.12, 95% CI [1.09, 4.10], P = 0.03). However, there were no significant differences in blood loss, heart disease, smoking, sex, surgical duration, body mass index, surgical duration, anticoagulant therapy, wearing elastic stocking
Streiff, Michael B; Holmstrom, Bjorn; Ashrani, Aneel; Bockenstedt, Paula L; Chesney, Carolyn; Eby, Charles; Fanikos, John; Fenninger, Randolph B; Fogerty, Annemarie E; Gao, Shuwei; Goldhaber, Samuel Z; Hendrie, Paul; Kuderer, Nicole; Lee, Alfred; Lee, Jason T; Lovrincevic, Mirjana; Millenson, Michael M; Neff, Anne T; Ortel, Thomas L; Paschal, Rita; Shattil, Sanford; Siddiqi, Tanya; Smock, Kristi J; Soff, Gerald; Wang, Tzu-Fei; Yee, Gary C; Zakarija, Anaadriana; McMillian, Nicole; Engh, Anita M
The NCCN Guidelines for Cancer-Associated Venous Thromboembolic Disease outline strategies for treatment and prevention of venous thromboembolism (VTE) in adult patients with a diagnosis of cancer or for whom cancer is clinically suspected. VTE is a common complication in patients with cancer, which places them at greater risk for morbidity and mortality. Therefore, risk-appropriate prophylaxis is an essential component for the optimal care of inpatients and outpatients with cancer. Critical to meeting this goal is ensuring that patients get the most effective medication in the correct dose. Body weight has a significant impact on blood volume and drug clearance. Because obesity is a common health problem in industrialized societies, cancer care providers are increasingly likely to treat obese patients in their practice. Obesity is a risk factor common to VTE and many cancers, and may also impact the anticoagulant dose needed for safe and effective prophylaxis. These NCCN Guidelines Insights summarize the data supporting new dosing recommendations for VTE prophylaxis in obese patients with cancer. Copyright © 2015 by the National Comprehensive Cancer Network.
Fernandez, Maria M; Hogue, Susan; Preblick, Ronald; Kwong, Winghan Jacqueline
Background Venous thromboembolism (VTE) is the second most common medical complication and a cause of excess length of hospital stay. Its incidence and economic burden are expected to increase as the population ages. We reviewed the recent literature to provide updated cost estimates on VTE management. Methods Literature search strategies were performed in PubMed, Embase, Cochrane Collaboration, Health Economic Evaluations Database, EconLit, and International Pharmaceutical Abstracts from 2003–2014. Additional studies were identified through searching bibliographies of related publications. Results Eighteen studies were identified and are summarized in this review; of these, 13 reported data from the USA, four from Europe, and one from Canada. Three main cost estimations were identified: cost per VTE hospitalization or per VTE readmission; cost for VTE management, usually reported annually or during a specific period; and annual all-cause costs in patients with VTE, which included the treatment of complications and comorbidities. Cost estimates per VTE hospitalization were generally similar across the US studies, with a trend toward an increase over time. Cost per pulmonary embolism hospitalization increased from $5,198–$6,928 in 2000 to $8,764 in 2010. Readmission for recurrent VTE was generally more costly than the initial index event admission. Annual health plan payments for services related to VTE also increased from $10,804–$16,644 during the 1998–2004 period to an estimated average of $15,123 for a VTE event from 2008 to 2011. Lower costs for VTE hospitalizations and annualized all-cause costs were estimated in European countries and Canada. Conclusion Costs for VTE treatment are considerable and increasing faster than general inflation for medical care services, with hospitalization costs being the primary cost driver. Readmissions for VTE are generally more costly than the initial VTE admission. Further studies evaluating the economic impact of new
Wendelboe, A M; McCumber, M; Hylek, E M; Buller, H; Weitz, J I; Raskob, G
Data on public awareness about thrombosis in general and venous thromboembolism (VTE) in particular are limited. We aimed to measure the global awareness of thrombosis to address this gap. With Ipsos-Reid, from 22 July to 5 August 2014, we surveyed 800 respondents in their native language from each of Argentina, Australia, Canada, Germany, Japan, Thailand, the Netherlands, the United Kingdom and the United States to measure general awareness about thrombosis, including deep vein thrombosis (DVT) and pulmonary embolism (PE). In each country, respondents were distributed among three age groups: 18-39 years, 40-64 years, and over 65 years of age. Proportions and 95% confidence intervals (CIs) were calculated. Overall, the proportion of respondents that were aware of thrombosis, DVT and PE (68%, 44% and 54%, respectively) was lower than the proportion that was aware of other thrombotic disorders, such as heart attack and stroke (88% and 85%, respectively), and health conditions such as hypertension, breast cancer, prostate cancer and AIDS (90%, 85%, 82% and 87%, respectively). Although there was variation across countries, lower awareness was associated with younger age and being male. Only 45% (95% CI, 43.9-46.5) of respondents were aware that blood clots were preventable, and awareness of cancer, hospitalization and surgery as risk factors was low (16%, 25%, and 36%, respectively). On a global level, public awareness about thrombosis overall, and VTE in particular, is low. Campaigns to increase public awareness about VTE are needed to reduce the burden from this largely preventable thrombotic disorder. © 2015 International Society on Thrombosis and Haemostasis.
Venous thromboembolism (VTE) prophylaxis is indicated while in the hospital after major surgery. There is evidence that the prevalence of asymptomatic deep-vein thrombosis, detected by routine venography after major orthopedic surgery, is lower at hospital discharge in patients who have received 10 days rather than 5 days of prophylaxis. This observation supports the current American College of Chest Physicians (ACCP) recommendation for a minimum of 7 to 10 days of prophylaxis after hip and knee replacement, even if patients are discharged from the hospital within 7 days of surgery. As risk of VTE persists for up to 3 months after surgery, patients at high risk for postoperative VTE may benefit from extended prophylaxis (eg, an additional 3 weeks after the first 7 to 10 days). Extended prophylaxis with low-molecular-weight heparin (LMWH) reduces the frequency of postdischarge VTE by approximately two thirds after hip replacement; however, the resultant absolute reduction in the frequency of fatal pulmonary embolism is small (ie, estimated at 1 per 2,500 patients). Indirect evidence suggests that, compared with LMWH, efficacy of extended prophylaxis after hip replacement is greater with fondaparinux, similar with warfarin, and less with aspirin. Extended prophylaxis is expected to be of less benefit after knee than after hip replacement. In keeping with current ACCP recommendations, at a minimum, extended prophylaxis should be used after major orthopedic surgery in patients who have additional risk factors for VTE (eg, previous VTE, cancer). If anticoagulant drug therapy is stopped after 7 to 10 days, an additional month of prophylaxis with aspirin should be considered.
Harenberg, Job; Jörg, Ingrid; Vukojevic, Yvonne; Mikus, Gerd; Weiss, Christel
To gather information on anticoagulant effects after the termination of long-term therapy with idraparinux. The anticoagulant effects of idraparinux, a synthetic polymethylated analogue of its pentasaccharide, were analysed in 23 patients after termination of a 6- or 12-month therapy period for the prevention of recurrent venous thromboembolism (VTE). Plasma samples of patients initially randomized to 2.5 mg idraparinux (normal creatinine clearance) or 1.5 mg idraparinux (creatinine clearance < 30 ml/min) were investigated in the van Gogh trials. At 3-month intervals for up to 15 months following the termination of the therapy, the factor Xa-specific S2222 chromogenic substrate (aXa) assay and Heptest were used to determine various pharmacokinetic parameters and prothrombin-induced clotting time (PiCT), activated partial thromboplastin time (aPTT) and prothrombin time (PT) were determined. Based on the aXa assay and Heptest, the half lives (t1/2) were 60.2 days and 107.7 days (p < 0.0001), maximum drug concentrations (Cmax) were 0.30 and 0.39 microg/l (p = 0.0016), areas under the activity time curve (AUC) were 33.7 and 38.0 microg/l per day (p = 0.0002), plasma clearances were 0.09 and 0.06 ml/min (p < 0.0001), mean residence times (MRT) were 75.4 and 121.9 (p < 0.0001) and volumes of distribution (Vdiss) were 7.4 and 8.61 (p = 0.1336), respectively. After 12 months of treatment (n = 18), the S2222 and Heptest results showed significantly higher Cmax and AUC, lower Vdiss and clearance and unchanged t1/2 and MRT values compared to 6 months of treatment (n = 5). The PiCT was prolonged for a period of 9 months. Coagulation times of aPTT and PT were not influenced. The results of these parameters did not differ between 12 and 6 months of treatment. The data support reports on a non-ionic binding of idraparinux to antithrombin and other proteins. We suggest that these findings may explain some of the findings of the van Gogh Extension trial.
Jetty, Vybhav; Glueck, Charles J; Freiberg, Richard A; Wang, Ping
Venous thromboembolism is uncommon after knee arthroscopy, and there are no guidelines for thromboprophylaxis in elective routine knee arthroscopy. Preoperative evaluation of common thrombophilias should provide guidance for postarthroscopy thromboprophylaxis in otherwise healthy patients who are at high risk for venous thromboembolism. This study assessed 10 patients with venous thromboembolism after total hip or knee arthroplasty. Patients were assessed if venous thromboembolism occurred within 6 months after knee arthroscopy (n=10) or total hip or knee arthroplasty (n=21). This study assessed gene mutations (factor V Leiden, prothrombin G20210A, plasminogen activator inhibitor, methylenetetrahydrofolate reductase) and serologic thrombophilias (high levels of factors VIII and XI, homocysteine, anticardiolipin immunoglobulin G and immunoglobulin M antibodies, and lupus anticoagulant; low antigenic protein C, S, and free S; and antithrombin III deficiency). The same coagulation data were obtained for normal subjects (n=110). The major thrombophilias in the arthroscopy group were factor V Leiden heterozygosity (40%), high factor VIII level (50%), and high homocysteine (30%). The respective values in control subjects were 2% (P=.0004), 7% (P=.0011), and 5% (P=.02). When the arthroscopy group was compared with the 21 patients who had venous thromboembolism after total hip or knee arthroplasty, the sole difference was factor V Leiden heterozygosity, which was 40% vs 0%, respectively (P=.007). Although venous thromboembolism after knee arthroscopy is uncommon, to identify high-risk patients and guide postoperative thromboprophylaxis, the authors suggest routine preoperative measurement of 3 common familial thrombophilias: factor V Leiden, factor VIII, and homocysteine. [Orthopedics. 2016; 39(6):e1052-e1057.].
Bignamini, Angelo A.; Davì, Giovanni; Palareti, Gualtiero; Matuška, Jiří; Holý, Martin; Pawlaczyk-Gabriel, Katarzyna; Džupina, Andrej; Sokurenko, German Y.; Didenko, Yury P.; Andrei, Laurentia D.; Lessiani, Gianfranco; Visonà, Adriana
Background— Patients with a first episode of unprovoked venous thromboembolism have a high risk of recurrence after discontinuation of anticoagulant therapy. Extending anticoagulation reduces the risk of recurrence but is associated with increased bleeding. Sulodexide, a glycosaminoglycan, exerts antithrombotic and profibrinolytic actions with a low bleeding risk when administered orally, but its benefit for preventing recurrent venous thromboembolism is not well known. Methods and Results— In this multicenter, double-blind study, 615 patients with first-ever unprovoked venous thromboembolism who had completed 3 to 12 months of oral anticoagulant treatment were randomly assigned to sulodexide 500 lipasemic units twice daily or placebo for 2 years, in addition to elastic stockings. The primary efficacy outcome was recurrence of venous thromboembolism. Major or clinically relevant bleeding was the primary safety outcome. Venous thromboembolism recurred in 15 of the 307 patients who received sulodexide and in 30 of the 308 patients who received placebo (hazard ratio, 0.49; 95% confidence interval [CI], 0.27–0.92; P=0.02). The analysis in which lost to follow-up was assigned to failure yielded a risk ratio among treated versus control subjects of 0.54 (95% confidence interval, 0.35–0.85; P=0.009). No major bleeding episodes occurred; 2 patients in each treatment group had a clinically relevant bleeding episode. Adverse events were similar in the 2 groups. Conclusion— Sulodexide given after discontinuation of anticoagulant treatment reduced the risk of recurrence in patients with unprovoked venous thromboembolism, with no apparent increase of bleeding risk. Clinical Trial Registration— URL: https://www.clinicaltrialsregister.eu/. Identifier: EudraCT number 2009-016923-77. PMID:26408273
O'Brien, Sarah H; Candrilli, Sean D
To describe the incidence and risk factors of venous thromboembolism in a large sample of critical care pediatric, adolescent, and young adult trauma patients. The National Trauma Data Bank-the largest and most complete aggregation of trauma registry data in the United States. Seven hundred eighty-four level I to level IV trauma centers. Patients ≤ 21 yrs of age who spent at least 1 day in a critical care unit during a trauma admission between 2001 and 2005. To characterize differences between patients with and without venous thromboembolism, we extracted variables regarding patient demographics, injury pattern and severity, procedures, total length of stay, and intensive care unit and ventilator days. Odds ratios for predictors of venous thromboembolism were estimated with a logistic regression model. Among the 135,032 critical care patients analyzed, venous thromboembolism was uncommon (6 per 1,000 discharges). Placement of a central venous catheter was a significant predictor of venous thromboembolism (odds ratio = 2.24; p < .0001) when populations were analyzed collectively. When we narrowed our focus to injuries associated with venous thromboembolism, such as lower-extremity fractures, the effects of central venous catheter were of even greater magnitude, particularly in adolescents and young adults. The risk of venous thromboembolism in critical care patients without a central venous catheter was <1% even in adolescents/young adults. Venous thromboembolism is rare in young critical care trauma patients, even older adolescents. The absence of published data on both the baseline risk of venous thromboembolism in pediatric critical care patients and the efficacy and safety of venous thromboembolism prophylaxis preclude the ability to make definitive recommendations for the use of venous thromboembolism prophylaxis in this setting. Our results, however, suggest that venous thromboembolism prophylaxis may need to be considered only in critically injured
Walker, A M
Research on the relationship between venous thromboembolism and the progestagen content of combined oral contraceptives has pointed to an increase in risk associated with products containing desogestrel and gestodene. Although many biases must have been at play in these nonexperimental studies, the errors that have been suggested and examined are not of a sufficient magnitude to account for the observed results. The most plausible explanation of the available data is that combined oral contraceptives containing desogestrel and gestodene carry a very small risk of venous thromboembolism, which exceeds the even smaller risk carried by products containing levonorgestrel. The position of norgestimate is uncertain.
Seddighzadeh, Ali; Shetty, Ranjith; Goldhaber, Samuel Z
Patients with cancer have an increased risk of venous thromboembolism (VTE). To further define the demographics, comorbidities, and risk factors of VTE in these patients, we analyzed a prospective registry of 5,451 patients with ultrasound confirmed deep vein thrombosis (DVT) from 183 hospitals in the United States. Cancer was reported in 1,768 (39%), of whom 1,096 (62.0%) had active cancer. Of these, 599 (54.7%) were receiving chemotherapy, and 226 (20.6%) had metastases. Lung (18.5%), colorectal (11.8%), and breast cancer (9.0%) were among the most common cancer types. Cancer patients were younger (median age 66 years vs. 70 years; p < 0.0001), were more likely to be male (50.4% vs. 44.5%; p = 0.0005), and had a lower average body mass index (26.6 kg/m(2) vs. 28.9 kg/m(2); p < 0.0001). Cancer patients less often received VTE prophylaxis prior to development of DVT compared to those with no cancer (308 of 1,096, 28.2% vs. 1,196 of 3,444, 34.6%; p < 0.0001). For DVT therapy, low-molecular-weight heparin (LMWH) as monotherapy without warfarin (142 of 1,086, 13.1% vs. 300 of 3,429, 8.7%; p < 0.0001) and inferior vena caval filters (234 of 1,086, 21.5% vs. 473 of 3,429, 13.8%; p < 0.0001) were utilized more often in cancer patients than in DVT patients without cancer. Cancer patients with DVT and neurological disease were twice as likely to receive inferior vena caval filters than those with no cancer (odds ratio 2.17, p = 0.005). In conclusion, cancer patients who develop DVT receive prophylaxis less often and more often receive filters than patients with no cancer who develop DVT. Future studies should focus on ways to improve implementation of prophylaxis in cancer patients and to further define the indications, efficacy, and safety of inferior vena caval filters in this population.
Flute, P T
The pathogenesis of venous thrombosis is briefly discussed as a basis for the understanding of preventive measures used in this condition. Prophylaxis in venous thrombosis is then reviewed with emphasis on pharmacological treatment, and more particularly on heparin.
Beuhler, K O; D'Lima, D D; Colwell, C W; Otis, S M; Walker, R H
Postoperative duplex ultrasonography screening after total hip arthroplasty has been shown to identify patients who may require treatment or additional monitoring for venous thromboembolic disease. The potential for manifestation of venous thromboembolic disease subsequent to screening remains a concern. The objective of this study was to determine the prevalence of symptomatic venous thromboembolic disease after total hip arthroplasty and after inhospital prophylaxis, inhospital screening with negative results for proximal deep venous thrombosis, and no posthospitalization venous thromboembolic disease prophylaxis. One hundred fifty patients undergoing primary hybrid total hip arthroplasty and using pneumatic compression stockings and aspirin as prophylaxis against venous thromboembolic disease were screened for deep venous thrombosis with duplex ultrasonography on the fourth day after surgery. Duplex ultrasonography screening revealed 17 (11.3%) patients with asymptomatic proximal deep venous thrombosis. In response to duplex ultrasonography screening, these patients with proximal deep venous thrombosis received therapeutic anticoagulation. Of 133 patients with a duplex screen with negative results for proximal deep venous thrombosis, 131 (98.5%) continued to have no symptoms of venous thromboembolic disease and two (1.5%) began to have symptoms for venous thromboembolic disease (one with proximal deep venous thrombosis, one with nonfatal pulmonary embolism) during 12 months of clinical followup after total hip arthroplasty. The overall prevalence of venous thromboembolic disease requiring anticoagulation was 19 of 150 (12.6%) patients. The remaining 131 (87.4%) were not exposed to the risks of postoperative anticoagulation and did not have subsequent symptomatic venous thromboembolic disease.
Dahl, Ola E; Gudmundsen, Tor E; Pripp, Are H; Aanesen, Joakim J
We describe annual incidences and 6-month postoperative patterns of clinical venous thromboembolism (VTE) in 9078 patients undergoing major joint surgery in a Scandinavian hospital. In cohort I (1989-1999), low-molecular-weight heparin thromboprophylaxis for 7 to 10 days was uniformly introduced, 5-week thromboprophylaxis becoming routine after total hip replacement (THR), partially applied after hip fracture surgery (HFS), but not used after total knee replacement (TKR) thereafter (2003-2011; cohort II). Mean annual VTE incidence was lower in cohort II than in cohort I after THR and HFS but not after TKR. In cohort I, the cumulative VTE incidence increased sharply during the first 5 postoperative weeks in all groups, subsequently plateauing up to 6 months postsurgery. In cohort II, this incidence remained low and stable during 5 weeks post-THR, rising gradually up to 6 months, with a comparable but less pronounced pattern following HFS but not TKR. In conclusion, the VTE risk after major joint surgery seems to persist after 5- and 1-week prophylaxis in patients undergoing hip surgery and TKR, respectively.
Iorio, Matthew L; Venturi, Mark L; Davison, Steven P
Venous thromboembolism is a complication that results in a wide range of patient morbidity and potential mortality. Awareness of this risk has led to recent advances in both the perioperative planning of chemoprophylaxis and the stratification of risk factors. Together, these modifications have helped reduce the incidence and severity of venous thromboembolism. Major hospital-based initiatives to decrease the overall rate of venous thromboembolism and halt the progression of severe complications, including pulmonary embolism, are one such change. However, surgeon reluctance based on the potential for bleeding complications continues to decrease the use of these algorithms, despite several reports that fail to demonstrate an increase in postoperative bleeding or hematoma formation with chemoprophylaxis administered at appropriate dosages. This review summarizes the current recommendations and procedure-specific strategies for venous thromboembolism prophylaxis with a focus on elective or aesthetic surgery-based procedures. The authors will recommend which patients are appropriate, what doses are appropriate, and when the doses should be administered for aesthetic and elective surgery.
Wawrzyńska, L; Hajduk, B; Vertun-Baranowska, B; Kober, J; Filipecki, S
The analysis of 49 fatal cases of venous thromboembolism--VTE (15% of total ambulatory patients number during long observation was performed. The advanced age of patients, multiple risk factors, underlying circulatory and respiratory tract diseases, malignancies, previous episodes of VTE especially with secondary pulmonary hypertension were the most important factors determining fatal prognoses in those patients.
Arcelus, Juan Ignacio; Lozano, Francisco S; Ramos, José L; Alós, Rafael; Espín, Eloy; Rico, Pedro; Ros, Eduardo
Postoperative venous thromboembolic disease (VTED) affects approximately one in four general surgery patients who do not receive preventive measures. In addition to the risk of pulmonary embolism, which is often fatal, patients with VTED may develop long-term complications such as post-thrombotic syndrome or chronic pulmonary hypertension. In addition, postoperative VTED is usually asymptomatic or produces clinical manifestations that are attributed to other processes and consequently this complication is often unnoticed by the surgeon who performed the procedure. Thus, the most effective strategy consists of effective prevention of VTED using the most appropriate prophylactic measures against the patient's thromboembolic risk. There is sufficient evidence that VTED can be prevented by pharmacological methods, especially heparin and its derivatives and with mechanical methods such as support tights or intermittent pneumatic compression of the lower extremities. To reduce the incidence of VTED as far as possible, strategies have been proposed that include a combination of drugs and mechanical methods, new antithrombotic drugs, or prolonging the duration of prophylaxis in patients at very high risk, such as those who have undergone surgery for cancer. Another important aspect is the optimal moment to initiate prophylaxis with anticoagulant drugs with the aim of achieving an adequate equilibrium between antithrombotic efficacy and the risk of hemorrhagic complications. The present article reviews the available evidence to attempt to optimize prevention of VTED in general surgery and in some special groups, such as laparoscopic surgery, short-stay surgery and obesity.
Petty, John K
Although venous thromboembolism (VTE) occurs in less than 1% of hospitalized pediatric trauma patients, care providers must make decisions about VTE prophylaxis on a daily basis. The consequences of VTE are significant; the risks of developing VTE are variable; and the effectiveness of prophylaxis against VTE is not conclusive in children. While the value of VTE prophylaxis is well defined in adult trauma care, it is unclear how this translates to the care of injured children. This review evaluates the incidence and risks of VTE in pediatric trauma and assesses the merits of prophylaxis in children. Pharmacologic prophylaxis against VTE is a reasonable strategy in critically injured adolescent trauma patients. Further study is needed to establish the risks and benefits of VTE prophylaxis across the spectrum of injured children. Copyright © 2017 Elsevier Inc. All rights reserved.
Lecumberri, Ramón; Feliu, Jesús; Rocha, Eduardo
Treatment of venous thromboembolism includes an acute phase treatment, followed by a secondary prophylaxis period. Oral anticoagulants have been the usual treatment for secondary prophylaxis of VTE. However, some issues regarding oral anticoagulant treatment (OAT), such as length or intensity are controversial. The appropriate duration of OAT depends on the individual risk of both, thrombotic recurrence and hemorrhagic complications. Recent studies suggest that full-dose OAT is more effective and as safe as low-dose OAT. On the other hand, low-molecular-weight heparins are an alternative for the secondary prophylaxis of VTE, being the treatment of choice in patients with cancer or during pregnancy. Probably, new antithrombotic drugs such as idraparinux or ximelagatran, will be considered as another therapeutic alternative in a near future.
Sanderson, Brenton; Hitos, Kerry; Fletcher, John P
Surgery for colorectal cancer conveys a high risk of venous thromboembolism (VTE). The effect of thromboprophylactic regimens of varying duration on the incidence of VTE was assessed in 417 patients undergoing surgery between 2005 and 2009 for colorectal cancer. Low-dose unfractionated heparin (LDUH) was used in 52.7% of patients, low-molecular-weight heparin (LMWH) in 35.3%, and 10.7% received LDUH followed by LMWH. Pharmacological prophylaxis was continued after hospitalisation in 31.6%. Major bleeding occurred in 4% of patients. The 30-day mortality rate was 1.9%. The incidence of symptomatic VTE from hospital admission for surgery to 12 months after was 2.4%. There were no in-hospital VTE events. The majority of events occurred in the three-month period after discharge, but there were VTE events up to 12 months, especially in patients with more advanced cancer and multiple comorbidities.
Boey, Jir Ping; Gallus, Alexander
Half of all patients with acute venous thromboembolism are aged over 70 years; they then face the added hazard of an age-related increase in the incidence of major bleeding. This makes it even more important to weigh the balance of benefit and risk when considering anticoagulant treatment and treatment duration. Traditional treatment with a heparin (usually low molecular weight) followed by a vitamin K antagonist such as warfarin is effective but is often complicated, especially in the elderly. The direct-acting oral anticoagulants (DOACs), i.e. the thrombin inhibitor dabigatran and the factor Xa inhibitors rivaroxaban, apixaban and edoxaban, are given in fixed doses, do not need laboratory monitoring, have fewer drug-drug interactions and are therefore much easier to take. Randomised trials, their meta-analyses and 'real-world' data indicate the DOACs are no less effective than warfarin (are non-inferior) and probably cause less major bleeding (especially intracranial). It seems the relative safety of DOACs extends to age above 65 or 70 years, although bleeding becomes more likely regardless of the chosen anticoagulant. Renal impairment, comorbidities (especially cancer) and interventions are special hazards. Ways to minimise bleeding include patient selection and follow-up, education about venous thromboembolism, anticoagulants, drug interactions, regular checks on adherence and avoiding needlessly prolonged treatment. The relatively short circulating half-lives of DOACs mean that time, local measures and supportive care are the main response to major bleeding. They also simplify the management of invasive interventions. An antidote for dabigatran, idarucizumab, was recently approved by regulators, and a general antidote for factor Xa inhibitors is in advanced development.
Stansal, A; Perrier, E; Coste, S; Bisconte, S; Manen, O; Lazareth, I; Conard, J; Priollet, P
In France, approximately 3000 people are repatriated every year, either in a civil situation by insurers. Repatriation also concerns French army soldiers. The literature is scarce on the topic of venous thromboembolic risk and its prevention during repatriation for medical reasons, a common situation. Most studies have focused on the association between venous thrombosis and travel, a relationship recognized more than 60 years ago but still subject to debate. Examining the degree of venous thromboembolic risk during repatriation for medical reasons must take into account several parameters, related to the patient, to comorbid conditions and to repatriation modalities. Appropriate prevention must be determined on an individual basis. Copyright © 2015 Elsevier Masson SAS. All rights reserved.
Shuman, Andrew G.; Hu, Hsou Mei; Pannucci, Christopher J.; Jackson, Christopher R.; Bradford, Carol R.; Bahl, Vinita
Objective The consequences of perioperative venous thromboembolism (VTE) are devastating; identifying patients at risk is an essential step in reducing morbidity and mortality. The utility of perioperative VTE risk assessment in otolaryngology is unknown. This study was designed to risk-stratify a diverse population of otolaryngology patients for VTE events. Study Design Retrospective cohort study. Setting Single-institution academic tertiary care medical center. Subjects and Methods Adult patients presenting for otolaryngologic surgery requiring hospital admission from 2003 to 2010 who did not receive VTE chemoprophylaxis were included. The Caprini risk assessment was retrospectively scored via a validated method of electronic chart abstraction. Primary study variables were Caprini risk scores and the incidence of perioperative venous thromboembolic outcomes. Results A total of 2016 patients were identified. The overall 30-day rate of VTE was 1.3%. The incidence of VTE in patients with a Caprini risk score of 6 or less was 0.5%. For patients with scores of 7 or 8, the incidence was 2.4%. Patients with a Caprini risk score greater than 8 had an 18.3% incidence of VTE and were significantly more likely to develop a VTE when compared to patients with a Caprini risk score less than 8 (P <.001). The mean risk score for patients with VTE (7.4) was significantly higher than the risk score for patients without VTE (4.8) (P <.001). Conclusion The Caprini risk assessment model effectively risk-stratifies otolaryngology patients for 30-day VTE events and allows otolaryngologists to identify patient subgroups who have a higher risk of VTE in the absence of chemoprophylaxis. PMID:22261490
To provide current and emerging evidence on oral contraceptives and the risk of venous thromboembolism. Articles published in English from 2005 were retrieved through searches of PubMed and Medline, using the following terms: venous thromboembolism, VTE, contraception, oral contraceptives, hormonal contraception. Results were restricted to systematic reviews, randomized control trials/controlled clinical trials, and observational studies. Searches were updated on a regular basis and incorporated in the guideline to May 2010. Grey (unpublished) literature was identified through searching the websites of health technology assessment and health technology assessment-related agencies, clinical practice guideline collections, clinical trial registries, and national and international medical specialty societies. The quality of evidence was rated using the criteria described by the Canadian Task Force on Preventive Health Care (Table). SUMMARY STATEMENTS: 1. Modern oral contraceptives offer highly effective contraception and a range of non-contraceptive benefits. (I) 2. Venous thromboembolism, although rare, remains one of the serious adverse consequences of hormonal contraception. Best evidence indicates that venous thromboembolism rates in non-users of reproductive age approximate 4-5/10 000 women per year; rates in oral contraceptive users are in the range of 9-10/10 000 women per year. For comparison, venous thromboembolism rates in pregnancy approach 29/10 000 overall and may reach 300-400/10 000 in the immediate postpartum period. (II-1) 3. Research demonstrates that oral contraceptives with ≤ 35 µg of ethinyl estradiol carry a lower risk of venous thromboembolism than oral contraceptives with 50 µg. (II-2) Although preliminary data suggest a possible further reduction in venous thromboembolism with oral contraceptives with < 35 µg ethinyl estradiol, robust data to support this conclusion are presently lacking. 4. Recent contradictory evidence and the ensuing
Vallès, J A; Vallano, A; Torres, F; Arnau, J M; Laporte, J R
1. Thromboembolic disease (TED) is an important cause of in-hospital morbidity and mortality. Although different prophylactic approaches have been shown to be effective and cost-effective, surveys have suggested that they are underused. The aim of this study was to estimate the prevalence of use of TED prophylaxis in our hospitals. 2. All patients admitted on a specified day to the Internal Medicine and General Surgery wards of seven Spanish university hospitals were included in the study. They were identified cross-sectionally and followed up until discharge or for 15 days. Information about the following variables was collected: risk factors for venous thromboembolism, prophylactic measures used (if any), contraindications to the use of each specific drug or other prophylactic measure, and dosage schedule of the drug used, if any. 3. Nine hundred and thirty-nine patients (53% men) were studied. The most common risk factors for venous thromboembolism were: age > or = 40 years (802; 85%), major surgery (298; 32%), immobilization > or = 6 days (285; 30%), obesity (241; 26%), and cancer (202; 22%). 4. Prophylactic measures were used in 320 patients (34%). Of these, 297 (93%) received heparin, mainly as low molecular weight heparins (248, 78%); physical measures were rarely used. 5. Five hundred and eighty-three patients (62%) fulfilled criteria for moderate or high risk of venous thromboembolism; only 275 (47%) of them received any form of prophylaxis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8198934
França, Ana; De Sousa, Joaquim Abreu; Felicíssimo, Paulo; Ferreira, Daniel
Venous thromboembolism is a frequent clinical condition with high impact on both morbidity and mortality. Venous thromboembolism risk is particularly high in hospitalized patients as well as in oncologic patients, being a factor of poor prognosis for the oncologic disease. Several clinical studies have shown the need to develop effective hospital strategies using a systematic and individualized assessment of venous thromboembolism risk, and additionally to optimize the institution of prophylaxis treatment and its proper use in the context of in-hospital and outpatient management. The ARTE national study is a non-interventional, multicentre, prospective study which is divided in two phases. In the first phase patients are followed in the hospital; in the second phase patients are followed in ambulatory context for a period of 6 months after discharge. Four thousand patients will be included, equally distributed over medical, surgical, oncologic and orthopaedic patients. Data will be collected from the patient's clinical files and through direct clinical evaluation of risk factors for venous thromboembolism, in the departments of medicine, oncology, surgery, and orthopaedics of the participating centres. The main objectives of the study are to assess the risk profile of venous thromboembolism of the study population using a risk assessment model adapted from the Caprini and Khorana et al models, and the validation of the score for the Portuguese population. Simultaneously, the secondary objectives are as follows: to determine the proportion of patients with venous thromboembolism risk, according to the risk assessment model, that are doing prophylaxis; to determine the duration of prophylaxis during the hospitalization; to determine the proportion of patients doing long-term prophylaxis, at the moment of the discharge; to determine the incidence of thromboembolic events (deep venous thrombosis; stroke; pulmonary thromboembolism; transient ischemic attack
Glynn, Robert J; Ridker, Paul M; Goldhaber, Samuel Z; Zee, Robert Y L; Buring, Julie E
Supplementation with vitamin E may antagonize vitamin K in healthy adults, but it is unclear whether intake of vitamin E decreases the risk of venous thromboembolism (VTE). The Women's Health Study randomized 39,876 women > or = 45 years of age to receive 600 IU of natural source vitamin E or placebo on alternate days. Before randomization, 26,779 participants gave blood samples, which were used to determine factor V Leiden, G20210A prothrombin, and 677C>T MTHFR polymorphisms. Documented VTE (including deep vein thrombosis or pulmonary embolism) and unprovoked VTE (no recent surgery, trauma, or cancer diagnosis) were prospectively evaluated, secondary end points of the trial. During a median follow-up period of 10.2 years, VTE occurred in 482 women: 213 in the vitamin E group and 269 in the placebo group, a significant 21% hazard reduction (relative hazard, 0.79; 95% CI, 0.66 to 0.94; P=0.010). For unprovoked VTE, the hazard reduction was 27% (relative hazard, 0.73; 95% CI, 0.57 to 0.94; P=0.016). In subgroup analyses, the 3% of participants who reported VTE before randomization had a 44% hazard reduction (relative hazard, 0.56; 95% CI, 0.31 to 1.00; P=0.048), whereas women without prior VTE had an 18% hazard reduction (relative hazard 0.82; 95% CI, 0.68 to 0.99; P=0.040). Women with either factor V Leiden or the prothrombin mutation had a 49% hazard reduction associated with vitamin E treatment (relative hazard, 0.51; 95% CI, 0.30 to 0.87; P=0.014). These data suggest that supplementation with vitamin E may reduce the risk of VTE in women, and those with a prior history or genetic predisposition may particularly benefit.
Lecumberri, Ramón; Soler, Silvia; Del Toro, Jorge; Barba, Raquel; Rosa, Vladimir; Ciammaichella, Maurizio M; Monreal, Manuel
The influence of the day of diagnosis (weekends vs. weekdays) on outcome in patients with acute venous thromboembolism (VTE) has not been thoroughly studied. We used the RIETE database to compare the clinical characteristics, treatment details, and mortality rate at 7 and 30 days, of all patients diagnosed with acute VTE on weekends versus those diagnosed on weekdays. Up to January 2010, 30,394 patients were included in RIETE, of whom 5,479 (18%) were diagnosed on weekends. Most clinical characteristics were similar in both groups, but patients diagnosed on weekends had less often cancer (20% vs. 22%; p=0.004), and presented more likely with pulmonary embolism (PE) than those diagnosed on weekdays (52% vs. 47%; p <0.001). Most patients in both groups received initial therapy with low-molecular-weight heparin (90% and 91%, respectively; p=0.01), then switched to vitamin K antagonists (72% and 71%, respectively; p=0.007). The 7-day mortality rate in patients presenting with PE was 2.75% in those diagnosed on weekends versus 3.00% in those diagnosed on weekdays (p=0.49). At 30 days, the mortality rate was 6.51% versus 6.06%, respectively (p=0.38). In patients presenting with deep vein thrombosis alone, the 7-day mortality rate in those diagnosed on weekends was 1.04% versuss 0.66% in those diagnosed on weekdays (p=0.053). The mortality rate at 30 days was of 3.41% versus 2.88% (p=0.14), respectively. In RIETE, the clinical characteristics, treatment strategies, and 7- and 30-day mortality rates of patients diagnosed on weekends were similar to those in patients diagnosed on weekdays.
Li, Francesca; Walker, Kim; McInnes, Elizabeth; Duff, Jed
The aim of this study was to examine whether educational outreach visits improve nurses' compliance with applying best practice mechanical venous thromboembolism prophylaxis. The design was as a pretest/posttest study with a 7-week follow-up. It was conducted in a mixed medical/surgical unit in a 250-bed private hospital in Sydney, Australia. The target population was 25 medical/surgical nurses in educational outreach visits (EOVs). The main outcome measures included change in percentage between baseline and endpoint of eligible patients receiving mechanical VTE prophylaxis and all patients having VTE risk documented in their medication charts, as well as nurses' feedback on how supportive and useful they found EOVs. The results showed an overall, but not significant increase (p = 0.201) in the percentage of patients who received mechanical VTE prophylaxis (59.4% baseline to 75% endpoint). There was a significant increase in the percentage of patients having VTE risk status documented in the medication chart (0%-28%) (p = 0.002). Improvements in compliance were more likely for surgical than medical patients (95% and 35%, respectively) and risk documentation (47% and 6%, respectively). Most nurses reported that the EOVs supported them in implementing best practice VTE mechanical prophylaxis. Researchers conclude that improvements in compliance with best practice VTE prevention can be achieved using EOVs which were easily conducted and well-received in a busy unit setting. More work is needed to increase the compliance rate with medical patients. Copyright 2010 Society for Vascular Nursing, Inc. Published by Mosby, Inc. All rights reserved.
Liew, Ngoh C; Alemany, Gina V; Angchaisuksiri, Pantep; Bang, Soo M; Choi, Gordon; DE Silva, Deidre A; Hong, Ji M; Lee, Limi; Li, Yong J; Rajamoney, Ganesan N; Suviraj, John; Tan, Thiam C; Tse, Eric; Teo, Li T; Visperas, Julie; Wong, Raymond S; Lee, Lai H
The Asian venous thromboembolism (VTE) prophylaxis guidelines were first published in 2012. Since its first edition, the Asian Venous Thrombosis Forum (AVTF) working group have updated the Asian VTE epidemiology and reviewed issues that were not addressed in the previous guidelines. The authors noted that the rising incidence of VTE across Asia may be attributable to aging population, dietary changes, and increasing incidence of obesity and diabetes. The new additions in the guideline include role of thrombophilia in VTE, bleeding risk in Asians, individual risk assessment, updates in the prevention of VTE in medically ill, bariatric surgery, cancer, orthopedic and trauma patients. The influence of primary thrombophilia in perioperative VTE is still unclear. The secondary risk factors, however, are similar between Asians and Caucasians. The group found no evidence of increased risk of bleeding while using pharmacological agents, including the use of novel anti-coagulants. At present, Caprini risk assessment model is widely used for individual risk assessment. Further validation of this model is needed in Asia. In medically ill patients, pharmacological agents are preferred if there is no bleeding risk. Intermittent pneumatic compression device (IPC) is recommended in patients with bleeding risk but we do not recommend using graduated compressive stockings. In bariatric patients, data on VTE is lacking in Asia. We recommend following current international guidelines. A high index of suspicion should be maintained during postbariatric surgery to detect and promptly treat portomesenteric venous thrombosis. Different cancer types have different thrombotic risks and the types of surgery influence to a large extent the overall VTE risk. Cancer patients should receive further risk assessment. In patients with higher thrombotic risk, either due to predisposing risk or concomitant surgery, low molecular weight heparin is indicated. Different countries appear to have
Lundkvist, Jonas; Bergqvist, David; Jönsson, Bengt
A model was developed to estimate costs and clinical effectiveness of fondaparinux compared with enoxaparin after hip fracture surgery in Sweden. Outcomes and costs of venous thromboembolism (VTE)-related care from a health care perspective were incorporated, with symptomatic deep-vein thrombosis and pulmonary embolism, recurrent VTE, post-thrombotic syndrome, major haemorrhage and all-cause death being included. Event probabilities were derived from fondaparinux clinical trial data and published data. VTE-related resource use and associated costs as well as costs of prophylaxis were based on local Swedish data. Extended prophylaxis with fondaparinux could avoid an additional 28 symptomatic VTE per 1,000 patients compared with extended prophylaxis with enoxaparin in hip fracture surgery patients. Although the prophylaxis costs were higher in the fondaparinux group, these were offset by the lower costs associated with treating fewer VTE, which thus indicates that extended fondaparinux prophylaxis is the dominant alternative when compared with enoxaparin in hip fracture surgery.
Lippi, Giuseppe; Favaloro, Emmanuel J
Allergic diseases are very frequent conditions worldwide. The pathogenesis of allergic reactions and venous thromboembolism (VTE) shares several risk factors and predisposing conditions. In particular, the concentration of immunoglobulin E (IgE) is considerably increased in patients with allergic diseases, and this immunoglobulin exert many prothrombotic and antifibrinolytic activities, especially through interaction with mast cells. Therefore, this narrative review is aimed to provide an overview of the current scientific evidence supporting a potential relationship between allergy and the risk of VTE. Although no prospective studies have been published so far, the evidence provided by six large cross-sectional studies and several case reports support the existence of an unquestionable epidemiological association between different allergic diseases (especially atopy, asthma, and celiac disease) and venous thrombosis. Two additional investigations reported that the concentration of IgE might predict the onset of severe complications of pulmonary embolism such as pulmonary infarction and pleural fluid accumulation. Therefore, the existence of a convincing epidemiologic link between allergy and VTE paves the way to future investigations aimed to establish whether the prevention or treatment of allergic diseases might be regarded as an effective measure to lower the risk of VTE.
Greene, M Todd; Spyropoulos, Alex C; Chopra, Vineet; Grant, Paul J; Kaatz, Scott; Bernstein, Steven J; Flanders, Scott A
Patients hospitalized for acute medical illness are at increased risk for venous thromboembolism. Although risk assessment is recommended and several at-admission risk assessment models have been developed, these have not been adequately derived or externally validated. Therefore, an optimal approach to evaluate venous thromboembolism risk in medical patients is not known. We conducted an external validation study of existing venous thromboembolism risk assessment models using data collected on 63,548 hospitalized medical patients as part of the Michigan Hospital Medicine Safety (HMS) Consortium. For each patient, cumulative venous thromboembolism risk scores and risk categories were calculated. Cox regression models were used to quantify the association between venous thromboembolism events and assigned risk categories. Model discrimination was assessed using Harrell's C-index. Venous thromboembolism incidence in hospitalized medical patients is low (1%). Although existing risk assessment models demonstrate good calibration (hazard ratios for "at-risk" range 2.97-3.59), model discrimination is generally poor for all risk assessment models (C-index range 0.58-0.64). The performance of several existing risk assessment models for predicting venous thromboembolism among acutely ill, hospitalized medical patients at admission is limited. Given the low venous thromboembolism incidence in this nonsurgical patient population, careful consideration of how best to utilize existing venous thromboembolism risk assessment models is necessary, and further development and validation of novel venous thromboembolism risk assessment models for this patient population may be warranted. Published by Elsevier Inc.
Eades, Shannan; Turiy, Yuliya
OBJECTIVES: With the apparent increase in venous thromboembolism noted in the pediatric population, it is important to define which children are at risk for clots and to determine optimal preventative therapy. The purpose of this study was to determine the risk factors for venous thromboembolism in pediatric patients with central venous line placement. METHODS: This was an observational, retrospective, case-control study. Control subjects were patients aged 0 to 18 years who had a central venous line placed. Case subjects had a central line and a radiographically confirmed diagnosis of venous thromboembolism. RESULTS: A total of 150 patients were included in the study. Presence of multiple comorbidities, particularly the presence of a congenital heart defect (34.7% case vs. 14.7% control; p < 0.005), was found to put pediatric patients at increased risk for thrombosis. Additionally, the administration of parenteral nutrition through the central line (34.7% case vs. 18.7% control; p = 0.03) and location of the line increased the risk for clot formation. CONCLUSIONS: With increased awareness of central venous line–related thromboembolism, measures should be taken to reduce the number and duration of central line placements, and further studies addressing the need for thromboprophylaxis should be conducted. PMID:26472949
Pinède, Laurent; Ninet, Jacques
The curative anticoagulant treatment of venous thromboembolism is non fractionated heparin or low molecular weight heparin, secondly substituted by oral anticoagulant therapy. Early mobilisation and elastic contention should be systematically prescribed. Low molecular weight heparin once or twice a day and early substitution by vitamin K antagonist allow an ambulatory treatment for deep vein thrombosis. It is still recommended a hospital management for patients with symptomatic pulmonary embolism. It is necessary to tailor the duration of anticoagulation individually according to the extension of venous thromboembolism and the presence (or absence) of risk or triggering factors. Bleeding is the major risk of anticoagulant therapy, particularly the vitamin K antagonists, justifying patient's education, adapted and regular biological surveillance, co-ordinated care approach with practical recommendations, patient's self-monitoring.
Oduber, C E U; van Beers, E J; Bresser, P; van der Horst, C M A M; Meijers, J C M; Gerdes, V E A
In Klippel-Trenaunay syndrome (KTS), a congenital combined vascular (capillary, venous and lymphatic) malformation with localised disturbed growth, venous thromboembolisms (VTEs) are frequently reported in small cohorts. We quantified the frequency of VTE by screening a large KTS-patient cohort with duplex compression ultrasonography. Additionally, we performed a case-control study to evaluate whether coagulation alterations were related to VTE and magnitude of vascular malformations as quantified by magnetic resonance imaging (MRI). Twenty-nine (39%) of 75 patients had signs of current or previous VTE, including superficial venous thrombosis, six (8%) of whom had a deep venous thrombosis or a pulmonary embolism. Compared with 105 controls, 54 adult patients (both: median age 33 years) had higher plasma levels of D-dimer, medians 266 (IQR 195-366) versus 457 (IQR 270-3840) mg÷l (p.
Ko, Richard H.; Thornburg, Courtney D.
Venous thromboembolism (VTE) in children is multifactorial and most often related to a combination of inherited and acquired thrombophilias. Children with cancer and blood disorders are often at risk for VTE due to disease-related factors such as inflammation and abnormal blood flow and treatment-related factors such as central venous catheters and surgery. We will review risk factors for VTE in children with leukemia, lymphoma, and solid tumors. We will also review risk factors for VTE in children with blood disorders with specific focus on sickle cell anemia and hemophilia. We will present the available evidence and clinical guidelines for prevention and treatment of VTE in these populations. PMID:28220143
Madan, Shivanshu; Shah, Shenil; Dale, Patrick; Partovi, Sasan
New oral anticoagulants (NOAC) serve as alternatives for patients currently using warfarin for the prevention and treatment of venous thromboembolic (VTE) disease. This article provides a brief summary of the clinical use of these drugs as well as a review of the landmark clinical trials which evaluated described their safety and efficacy. As more data becomes available, a fundamental understanding of these medications will be vital to cardiovascular practitioners managing patients with VTE. PMID:28123977
Kaatz, Scott; Spyropoulos, Alex C
Deep vein thrombosis and pulmonary embolism, the common clinical manifestations of venous thromboembolism (VTE), are among the most preventable complications of hospitalized patients. However, survey data repeatedly show poor rates of compliance with guideline-based preventive strategies. This has led the Centers for Medicare and Medicaid Services to deny reimbursement for hospital readmission for thromboembolic complications in patients undergoing total hip or knee arthroplasty. Multiple strategies and national initiatives have been developed to improve rates of VTE prophylaxis during hospitalization; however, most VTE occurs in the outpatient setting. Epidemiologic data suggest that recent surgery or hospitalization is a strong risk factor for the development of VTE and that this risk may persist for up to 6 months. These observations call into question whether VTE prophylaxis should be administered only during hospitalization or if this preventive strategy should be continued after hospital discharge. Many of the randomized trials showing efficacy of VTE prophylaxis have used longer durations of prophylaxis than are typical for current length of hospital stay, highlighting the issue of how long the duration of prophylaxis should be. Several patient groups have undergone formal testing to evaluate the risks and benefits of extended-duration VTE prophylaxis, but this issue is less clear for other categories of patients. Although there is clear consensus that most hospitalized patients should receive VTE prophylaxis, there is uncertainty about whether to continue VTE prophylaxis in the immediate post-hospital period or for an extended duration. The transition from inpatient to outpatient care is a key event in the coordination of continuity of care, but VTE-specific care transition guidance is limited. In this article, we review the evidence for both standard- and extended-duration VTE prophylaxis and discuss the difficulties in effectively maintaining VTE
Reiner, M F; Stivala, S; Limacher, A; Bonetti, N R; Méan, M; Egloff, M; Rodondi, N; Aujesky, D; von Schacky, C; Lüscher, T F; Camici, G G; Beer, J H
Essentials The role of omega-3 fatty acids (n-3 FAs) in recurrent venous thromboembolism (VTE) is unknown. Association of n-3 FAs with recurrent VTE or total mortality was investigated in 826 patients. Whole blood n-3 FAs were inversely correlated with recurrent VTE or total mortality. Major and non-major bleeding was not increased in patients with higher levels of n-3 FAs.
Agnelli, Giancarlo; Buller, Harry R; Cohen, Alexander; Curto, Madelyn; Gallus, Alexander S; Johnson, Margot; Masiukiewicz, Urszula; Pak, Raphael; Thompson, John; Raskob, Gary E; Weitz, Jeffrey I
Apixaban, an oral factor Xa inhibitor administered in fixed doses, may simplify the treatment of venous thromboembolism. In this randomized, double-blind study, we compared apixaban (at a dose of 10 mg twice daily for 7 days, followed by 5 mg twice daily for 6 months) with conventional therapy (subcutaneous enoxaparin, followed by warfarin) in 5395 patients with acute venous thromboembolism. The primary efficacy outcome was recurrent symptomatic venous thromboembolism or death related to venous thromboembolism. The principal safety outcomes were major bleeding alone and major bleeding plus clinically relevant nonmajor bleeding. The primary efficacy outcome occurred in 59 of 2609 patients (2.3%) in the apixaban group, as compared with 71 of 2635 (2.7%) in the conventional-therapy group (relative risk, 0.84; 95% confidence interval [CI], 0.60 to 1.18; difference in risk [apixaban minus conventional therapy], -0.4 percentage points; 95% CI, -1.3 to 0.4). Apixaban was noninferior to conventional therapy (P<0.001) for predefined upper limits of the 95% confidence intervals for both relative risk (<1.80) and difference in risk (<3.5 percentage points). Major bleeding occurred in 0.6% of patients who received apixaban and in 1.8% of those who received conventional therapy (relative risk, 0.31; 95% CI, 0.17 to 0.55; P<0.001 for superiority). The composite outcome of major bleeding and clinically relevant nonmajor bleeding occurred in 4.3% of the patients in the apixaban group, as compared with 9.7% of those in the conventional-therapy group (relative risk, 0.44; 95% CI, 0.36 to 0.55; P<0.001). Rates of other adverse events were similar in the two groups. A fixed-dose regimen of apixaban alone was noninferior to conventional therapy for the treatment of acute venous thromboembolism and was associated with significantly less bleeding (Funded by Pfizer and Bristol-Myers Squibb; ClinicalTrials.gov number, NCT00643201).
Højen, Anette Arbjerg; Gorst-Rasmussen, Anders; Lip, Gregory Y H; Lane, Deirdre A; Rasmussen, Lars Hvilsted; Sørensen, Erik Elgaard; Larsen, Torben Bjerregaard
The mental health prognosis following a venous thromboembolism in youth has not been investigated comprehensively. Using psychotropic drug purchase as a proxy for mental health status, we investigated this issue in a large cohort of young incident venous thromboembolism patients. Using Danish nationwide administrative registries from the period 1997-2010, we identified 4,132 patients aged 13-33 years with a first-time venous thromboembolism diagnosis and no history of psychotropic drug usage. We sampled comparison cohort of random general population controls, matched individually in a 1:5 ratio based on sex and birth year. Participants were followed in prescription purchase registries for their first psychotropic drug purchase. Among young venous thromboembolism case cases, the 1-year risk of psychotropic drug purchase was 7.1% (95% confidence interval [CI] 6.3, 7.9) and the 5-year risk 22.1% (95% CI 20.7, 23.5). This was substantially higher than among population controls, with 1- and 5-year risk differences relative to the controls of 4.7% (95% CI 3.9, 5.5), and 10.8% (95% CI 9.4, 12.3), respectively. Adjustment for the effects of recent pregnancy or somatic provocations attenuated risk differences to 4.1% (95% CI 3.5, 5.1) after 1 year and 9.6% (95% CI 8.3, 11.2) after 5 years. A venous thromboembolism diagnosis in youth is associated with a poorer mental health prognosis: one in five patients are prescribed psychotropic medication within the first 5 year after diagnosis. Copyright © 2015 Elsevier Ltd. All rights reserved.
Chen, Po-Hao; Lane, Hsien-Yuan; Lin, Chieh-Hsin
Neuroleptic malignant syndrome (NMS) is one of the most severe iatrogenic emergencies in clinical service. The symptoms including sudden consciousness change, critical temperature elevation and electrolytes imbalance followed by mutli-organ system failure were common in NMS. In addition to aggressive interventions with intravenous fluid resuscitation and antipyretics, several antidotes have been suggested to prevent further progression of the muscle damage. Dantrolene has been reported to be one of the most effective treatments for NMS. However, the adverse effects of dantrolene treatment for NMS have not yet been evaluated thoroughly. Here we report a young male patient with bipolar I disorder who developed NMS after rapid tranquilization with haloperidol. Dantrolene was given intravenously for the treatment of NMS. However, fever accompanied with local tenderness, hardness with clear border and swelling with heat over the patient’s left forearm occurred on the sixth day of dantrolene treatment. Venous thromboembolism (VTE) over intravenous indwelling site at the patient’s forearm was noted and confirmed by Doppler ultrasound. The patient’s VTE recovered after heparin and warfarin thrombolytic therapy. To our knowledge, this is the first case report demonstrating the possible relationship between dantrolene use and VTE in a patient with antipsychotic treatment. Although the causal relationship and the underlying pathogenesis require further studies, dantrolene should be used with caution for patients with NMS. PMID:27776396
Bartlett, Matthew A; Mauck, Karen F; Daniels, Paul R
Bariatric surgical procedures are now a common method of obesity treatment with established effectiveness. Venous thromboembolism (VTE) events, which include deep vein thrombosis and pulmonary embolism, are an important source of postoperative morbidity and mortality among bariatric surgery patients. Due to an understanding of the frequency and seriousness of these complications, bariatric surgery patients typically receive some method of VTE prophylaxis with lower extremity compression, pharmacologic prophylaxis, or both. However, the optimal approach in these patients is unclear, with multiple open questions. In particular, strategies of adjusted-dose heparins, postdischarge anticoagulant prophylaxis, and the role of vena cava filters have been evaluated, but only to a limited extent. In contrast to other types of operations, the literature regarding VTE prophylaxis in bariatric surgery is notable for a dearth of prospective, randomized clinical trials, and current professional guidelines reflect the uncertainties in this literature. Herein, we summarize the available evidence after systematic review of the literature regarding approaches to VTE prevention in bariatric surgery. Identification of risk factors for VTE in the bariatric surgery population, analysis of the effectiveness of methods used for prophylaxis, and an overview of published guidelines are presented. PMID:26316771
Bartlett, Matthew A; Mauck, Karen F; Daniels, Paul R
Bariatric surgical procedures are now a common method of obesity treatment with established effectiveness. Venous thromboembolism (VTE) events, which include deep vein thrombosis and pulmonary embolism, are an important source of postoperative morbidity and mortality among bariatric surgery patients. Due to an understanding of the frequency and seriousness of these complications, bariatric surgery patients typically receive some method of VTE prophylaxis with lower extremity compression, pharmacologic prophylaxis, or both. However, the optimal approach in these patients is unclear, with multiple open questions. In particular, strategies of adjusted-dose heparins, postdischarge anticoagulant prophylaxis, and the role of vena cava filters have been evaluated, but only to a limited extent. In contrast to other types of operations, the literature regarding VTE prophylaxis in bariatric surgery is notable for a dearth of prospective, randomized clinical trials, and current professional guidelines reflect the uncertainties in this literature. Herein, we summarize the available evidence after systematic review of the literature regarding approaches to VTE prevention in bariatric surgery. Identification of risk factors for VTE in the bariatric surgery population, analysis of the effectiveness of methods used for prophylaxis, and an overview of published guidelines are presented.
Arnold, Justin D; Sarkodie, Eleanor P; Coleman, Megan E; Goldstein, Deborah A
One of the most serious known adverse effects of feminizing cross-sex hormone therapy (CSHT) is venous thromboembolism (VTE); however, no study has assessed the incidence of VTE from the hormone therapies used in the United States because previous publications on this topic have originated in Europe. CSHT in the United States typically includes estradiol with the antiandrogen spironolactone, whereas in Europe estradiol is prescribed with the progestin cyproterone acetate. To estimate the incidence of VTE from the standard feminizing CSHTs used in the United States. A retrospective chart review of transgender women who had been prescribed oral estradiol at a District of Columbia community health center was performed. The primary outcomes of interest were deep vein thrombosis or pulmonary emboli. From January 1, 2008 through March 31, 2016, 676 transgender women received oral estradiol-based CSHT for a total of 1,286 years of hormone treatment and a mean of 1.9 years of CSHT per patient. Only one individual, or 0.15% of the population, sustained a VTE, for an incidence of 7.8 events per 10,000 person-years. There was a low incidence of VTE in this population of transgender women receiving oral estradiol. Copyright © 2016 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.
Eskildsen, Scott M; Moll, Stephan; Lim, Moe R
Venous thromboembolic embolism (VTE) is a potentially serious and life-threatening complication in spine surgery. However, VTE incidence and prophylaxis in spine surgery remains controversial. Current recommendations for VTE prophylaxis address "spine surgery" as a single broad category and mainly consider patient factors when determining risk. We performed a literature review to determine the varying VTE and bleeding risks within spine surgery to develop an individualized prophylactic algorithm. Our review suggests that the current guidelines on VTE prophylaxis for spine surgery from NASS and ACCP are suboptimal. Consideration of (1) patient-related VTE risks, (2) procedure-related VTE risks, and (3) the risk of neurological compromise from bleeding complications will more appropriately balance safety and effectiveness when choosing a VTE prophylaxis method. To better individualize VTE prophylaxis, we have developed the VTE Prophylaxis Risk/Benefit Score that considers this currently available best evidence to arrive at a recommendation for the most appropriate form of VTE prophylaxis. This algorithm informs the surgeon to help make a more nuanced and individualized determination of prophylaxis.
Fernandes, Caio Julio Cesar dos Santos; Júnior, José Leonidas Alves; Gavilanes, Francisca; Prada, Luis Felipe; Morinaga, Luciana Kato; Souza, Rogerio
Worldwide, venous thromboembolism (VTE) is among the leading causes of death from cardiovascular disease, surpassed only by acute myocardial infarction and stroke. The spectrum of VTE presentations ranges, by degree of severity, from deep vein thrombosis to acute pulmonary thromboembolism. Treatment is based on full anticoagulation of the patients. For many decades, it has been known that anticoagulation directly affects the mortality associated with VTE. Until the beginning of this century, anticoagulant therapy was based on the use of unfractionated or low-molecular-weight heparin and vitamin K antagonists, warfarin in particular. Over the past decades, new classes of anticoagulants have been developed, such as factor Xa inhibitors and direct thrombin inhibitors, which significantly changed the therapeutic arsenal against VTE, due to their efficacy and safety when compared with the conventional treatment. The focus of this review was on evaluating the role of these new anticoagulants in this clinical context. PMID:27167437
Dede, Ruth J; Pruemer, Jane M
Patients with multiple myeloma have an increased incidence of venous thromboembolism. The risk for venous thromboembolism further increases when these patients are placed on immunomodulatory drug therapy. This study aims to determine the incidence of venous thromboembolism in patients with multiple myeloma receiving immunomodulatory drug therapy in the ambulatory setting at UC Health and to investigate adherence with guidelines developed by The National Comprehensive Cancer Network for venous thromboembolism prevention in this patient population. A retrospective chart review of patients with multiple myeloma initiated on immunomodulatory drug therapy between January 2000 and January 2014 was conducted. Sixty-two cases met inclusion criteria and were included for analysis. The National Comprehensive Cancer Network guidelines were followed in 33.9% of cases. The rate of venous thromboembolism was 4.8% in guideline adherent cases and 12.2% in guideline nonadherent cases (p = 0.65). The overall incidence of venous thromboembolism was 9.7%. No patients on a low-molecular-weight-heparin agent or warfarin developed a venous thromboembolism, 7.9% patients on aspirin therapy developed a venous thromboembolism, and 23.1% patients on no pharmacologic thromboprophylaxis developed a venous thromboembolism (p = 0.26). Ambulatory patients with multiple myeloma who are considered for immunomodulatory drug therapy should be placed on pharmacologic thromboprophylaxis based on individual venous thromboembolism and bleeding risk factors. This study identified the need for increased adherence to national guidelines for venous thromboembolism prevention in patients with multiple myeloma receiving immunomodulatory drug therapy so as to increase the quality of care provided at UC Health. © The Author(s) 2015.
Rey, Marie-Antoinette; Bron, Cédric; Haesler, Erik; Mazzolai, Lucia
Venous thromboembolic (VTE) disease is frequent and questions regarding its treatment or prevention are numerous. This review is aimed at summarizing and pointing out the novelties on VTE treatment and prevention recently published in the Chest journal earlier this year (8th edition of ACCP guidelines). Generally, the aim of guidelines and of this review as well, is to offer guidance to practictioners in making the most appropriate choice for treating or preventing VTE. They are not intended for strict application and doctors will always have to decide individually case by case taking into account patients preference and the risk-benefit balance.
It is necessary to spread the knowledge about the disease, however, venous thromboembolic guidelines published in this issue give little attention to prevention, minimize the evaluation of the risk factors, do not evaluate its impact on the non-surgical patient, and do not emphasize the benefits of non-pharmacological and extended thromboprophylaxis. Guidelines for clinical practice of the Instituto Mexicano del Seguro Social must suggest the way to attend patients at the lowest cost with quality. Because prevention is the best tool to fight VTD, these guidelines do not totally accomplish their institutional objectives.
Lozano, Francisco S; Arcelus, Juan I; Ramos, José L; Alós, Rafael; Espín, Eloy; Rico, Pedro; Ros, Eduardo
Despite preventive efforts, venous thromboembolic disease (VTED) is still a major problem for surgeons due to its frequency and the morbidity, mortality and enormous resource consumption caused by this entity. However, the most important feature of VTED is that it is one of the most easily preventable complications and causes of death. To take appropriate prophylactic decisions (indication, method, initiation, duration, etc.), familiarity with the epidemiology of VTED in general surgery and some of its most significant populations (oncologic, laparoscopic, bariatric, ambulatory and short-stay) is essential. These factors must also be known to determine the distinct risk factors in these settings with a view to stratifying preoperative risk.
Win, Lei Lei
Inferior vena cava (IVC) filters are used as an alternative to anticoagulants for prevention of fatal pulmonary embolism (PE) in venous thromboembolic disorders. Retrievable IVC filters have become an increasingly attractive option due to the long-term risks of permanent filter placement. These devices are shown to be technically feasible in insertion and retrieval percutaneously while providing protection from PE. Nevertheless, there are complications and failed retrievals with these retrievable filters. The aim of the paper is to review the retrievable filters and their efficacy, safety, and retrievability. PMID:24967292
Kutiyal, Aditya S.; Dharmshaktu, Pramila; Kataria, Babita; Garg, Abhilasha
The development of acute myeloid leukemia has been attributed to various factors, including hereditary, radiation, drugs, and certain occupational exposures. The association between malignancy and venous thromboembolism events is well established. Here, we present a case of a 70-year-old Indian man who had presented with arterial and venous thrombosis, and the patient was later diagnosed with acute promyelocytic leukemia (APL). In our case, the patient presented with right lower limb deep venous thrombosis and pulmonary thromboembolism four months prior to the diagnosis of APL. Although thromboembolic event subsequent to the diagnosis of malignancy, and especially during the chemotherapy has been widely reported, this prior presentation with simultaneous occurrence of both venous and arterial thromboembolism has rarely been reported. We take this opportunity to state the significance of a complete medical evaluation in cases of recurrent or unusual thrombotic events. PMID:26949347
Losonczy, Hajna; Nagy, Ágnes; Tar, Attila
Cancer patients have a 2-7 fold increased risk of venous thromboembolism compared with the general population and, since 1990, this is associated with significant morbidity and mortality. This review summarizes the current knowledge on venous thromboembolism and cancer. Notably, the risk of venous thromboembolism varies depending on the type and stage of cancer. For instance, pancreatic and brain cancer patients have a higher risk of venous thromboembolism than breast and prostate cancer patients. Moreover, patients with metastatic disease have a higher risk than those with localized tumors. Tumor-derived procoagulant factors, cytokines and growth factors may directly and indirectly enhance venous thromboembolism. Chemotherapy produces ~6,5 fold increase in venous thromboembolism incidence in cancer patients compared to the general population. Prevention of this complication is challenging. The authors review the development of guidelines concerning venous thromboembolism prevention in hospitalized and also in ambulatory cancer patients treated with chemotherapy. Current guidelines recommend the use of low-molecular-weight heparin. Understanding the underlying mechanisms may allow the development of new therapies to safely prevent venous thromboembolism in cancer patients.
Lopes, Maria-Cecilia; da Silva, Henrique Salmazo; Bittencourt, Lia Rita A; Chervin, Ronald D; Tufik, Sergio
Commercial passenger flights have been increasing around the world. The effect of these flights on health is unclear. Venous thromboembolism has been noted after recent long-distance airplane flight, even in the absence of other risk factors. Hypoxia caused by the low ambient pressure during flights could contribute, and individuals with obstructive sleep apnea may be particularly vulnerable. The association between the effects of long airplane travel and sleep-disordered breathing deserves further study.
Bosevski, Marijan; Srbinovska-Kostovska, Elizabeta
BACKGROUND: Pulmonary embolism and deep venous thrombosis, known as venous thromboembolism (VTE), are associated with a high proportion of morbidity and mortality. AIM: Aim of this review is to emphasise current diagnostic and therapeutic modalities for VTE. RESULTS: No differences have been noticed in European and American guidelines in diagnostic approach of this disorder. Today there is enough clinical information for the use of heparin (either, unfractionated or low molecular) and vitamin K antagonists in the treatment of acute and chronic phases of VTE. Novel oral anticoagulants seem to have some advantages in the treatment of this disorder. Rivaroxaban has been approved widespread, for use as a single-drug approach of VTE. CONCLUSION: Both guidelines are almost similar and good basis for evidence-based treatment of this disorder. PMID:27703586
Fahrni, Jennifer; Husmann, Marc; Gretener, Silvia B; Keo, Hong H
Recurrent venous thromboembolism (VTE) is associated with increased morbidity and mortality. This risk is lowered by anticoagulation, with a large effect in the initial phase following the venous thromboembolic event, and with a smaller effect in terms of secondary prevention of recurrence when extended anticoagulation is performed. On the other hand, extended anticoagulation is associated with an increased risk of major bleeding and thus leads to morbidity and mortality. Therefore, it is necessary to assess the risk of recurrence for VTE on an individual basis, and a recommendation for secondary prophylaxis should be specifically based on risk calculation of recurrence of VTE and bleeding. In this review, we provide a comprehensive summary of relevant risk factors for recurrent VTE and a practical approach for assessing the risk of recurrence in daily practice. PMID:26316770
Fahrni, Jennifer; Husmann, Marc; Gretener, Silvia B; Keo, Hong H
Recurrent venous thromboembolism (VTE) is associated with increased morbidity and mortality. This risk is lowered by anticoagulation, with a large effect in the initial phase following the venous thromboembolic event, and with a smaller effect in terms of secondary prevention of recurrence when extended anticoagulation is performed. On the other hand, extended anticoagulation is associated with an increased risk of major bleeding and thus leads to morbidity and mortality. Therefore, it is necessary to assess the risk of recurrence for VTE on an individual basis, and a recommendation for secondary prophylaxis should be specifically based on risk calculation of recurrence of VTE and bleeding. In this review, we provide a comprehensive summary of relevant risk factors for recurrent VTE and a practical approach for assessing the risk of recurrence in daily practice.
Philbrick, John T; Shumate, Rebecca; Siadaty, Mir S; Becker, Daniel M
Despite multiple attempts to document and quantify the danger of venous thromboembolism (VTE) following prolonged travel, there is still uncertainty about the magnitude of risk and what can be done to lower it. To review the methodologic strength of the literature, estimate the risk of travel-related VTE, evaluate the efficacy of preventive treatments, and develop evidence-based recommendations for practice. Studies identified from MEDLINE from 1966 through December 2005, supplemented by a review of the Cochrane Central Registry of Controlled Trials, the Database of Abstracts of Reviews of Effects, and relevant bibliographies. We included all clinical studies that either reported primary data concerning travel as a risk factor for VTE or tested preventive measures for travel-related VTE. Two reviewers reviewed each study independently to assess inclusion criteria, classify research design, and rate methodologic features. The effect of methodologic differences, VTE risk, and travel duration on VTE rate was evaluated using a logistic regression model. Twenty-four published reports, totaling 25 studies, met inclusion criteria (6 case-control studies, 10 cohort studies, and 9 randomized controlled trials). Method of screening for VTE [screening ultrasound compared to usual clinical care, odds ratio (OR) 390], outcome measure [all VTE compared to pulmonary embolism (PE) only, OR 21], duration of travel (<6 hours compared to 6-8 hours, OR 0.011), and clinical risk ("higher" risk travelers compared to "lower," OR 3.6) were significantly related to VTE rate. Clinical VTE after prolonged travel is rare [27 PE per million flights diagnosed through usual clinical care, 0.05% symptomatic deep venous thrombosis (DVT) diagnosed through screening ultrasounds], but asymptomatic thrombi of uncertain clinical significance are more common. Graduated compression stockings prevented travel-related VTE (P < 0.05 in 4 of 6 studies), aspirin did not, and low-molecular-weight heparin (LMWH
Ceresetto, Jose Manuel
There are various region-specific challenges to the diagnosis and effective treatment of venous thromboembolism in Latin America. Clear guidance for physicians and patient education could improve adherence to existing guidelines. This review examines available information on the burden of pulmonary embolism and deep vein thrombosis in Latin America and the regional issues surrounding the diagnosis and treatment of pulmonary embolism and deep vein thrombosis. Potential barriers to appropriate care, as well as treatment options and limitations on their use, are discussed. Finally, an algorithmic approach to the diagnosis and treatment of venous thromboembolism in ambulatory patients is proposed and care pathways for patients with pulmonary embolism and deep vein thrombosis are outlined for primary care providers in Latin America.
Choi, Myunghan; Hector, Melvin
To provide information on current evidence-based clinical management of venous thromboembolism (VTE) for nurse practitioners working for older adults in long-term care facilities. METHODS AND DATA RESOURCES: A systematic review and summary using current clinical guidelines and reliable clinical research studies: American Medical Directors Association, American College of Chest Physicians, Medline, PubMed, Refworks, and CINAHL. The management of VTE focuses on a comprehensive approach including acute and long-term pharmacologic approach, surgical and mechanical approach, prophylaxis of recurrent VTE, maintaining INR, and monitoring lab values. Recommendations based on the most current clinical research studies and guidelines will facilitate a cost-effective management of venous thromboembolism for older adults in long-term care facilities. ©2012 The Author(s) Journal compilation ©2012 American Academy of Nurse Practitioners.
Ceresetto, Jose Manuel
There are various region-specific challenges to the diagnosis and effective treatment of venous thromboembolism in Latin America. Clear guidance for physicians and patient education could improve adherence to existing guidelines. This review examines available information on the burden of pulmonary embolism and deep vein thrombosis in Latin America and the regional issues surrounding the diagnosis and treatment of pulmonary embolism and deep vein thrombosis. Potential barriers to appropriate care, as well as treatment options and limitations on their use, are discussed. Finally, an algorithmic approach to the diagnosis and treatment of venous thromboembolism in ambulatory patients is proposed and care pathways for patients with pulmonary embolism and deep vein thrombosis are outlined for primary care providers in Latin America. PMID:26872082
Páramo, José A; Lecumberri, Ramón
Thousands of individuals suffer from deep vein thrombosis (DVT) all over the world, and many will die from its main complication, pulmonary embolism (PE). An important problem is that the diagnose is easy to overlook because the signs and symptoms are often difficult to recognize. Why do DVT and PE remain such a serious problem, particularly given the availability of effective strategies for preventing and treating them? The answer lays primarily in the failure to consistently use evidence-based interventions in high-risk individuals and in the lack of adherence to the different prophylactic interventions. In order to impact the incidence and burden of DVT/PE and increase public awareness, implementation of electronic alerts and evidence-based approaches, and scientific translational research are required. The commitment of all levels of governments as well as public and private institutions will be crucial to reduce the incidence of DVT, a leading cause of death.
Sud, Sachin; Mittmann, Nicole; Cook, Deborah J; Geerts, William; Chan, Brian; Dodek, Peter; Gould, Michael K; Guyatt, Gordon; Arabi, Yaseen; Fowler, Robert A
Venous thromboembolism is difficult to diagnose in critically ill patients and may increase morbidity and mortality. To evaluate the cost-effectiveness of strategies to reduce morbidity from venous thromboembolism in critically ill patients. A Markov decision analytic model to compare weekly compression ultrasound screening (screening) plus investigation for clinically suspected deep vein thrombosis (DVT) (case finding) versus case finding alone; and a hypothetical program to increase adherence to DVT prevention. Probabilities were derived from a systematic review of venous thromboembolism in medical-surgical intensive care unit patients. Costs (in 2010 $US) were obtained from hospitals in Canada, Australia, and the United States, and the medical literature. Analyses were conducted from a societal perspective over a lifetime horizon. Outcomes included costs, quality-adjusted life-years (QALY), and incremental cost-effectiveness ratios. In the base case, the rate of proximal DVT was 85 per 1,000 patients. Screening resulted in three fewer pulmonary emboli than case-finding alone but also two additional bleeding episodes, and cost $223,801 per QALY gained. In sensitivity analyses, screening cost less than $50,000 per QALY only if the probability of proximal DVT increased from a baseline of 8.5-16%. By comparison, increasing adherence to appropriate pharmacologic thromboprophylaxis by 10% resulted in 16 fewer DVTs, one fewer pulmonary emboli, and one additional heparin-induced thrombocytopenia and bleeding event, and cost $27,953 per QALY gained. Programs achieving increased adherence to best-practice venous thromboembolism prevention were cost-effective over a wide range of program costs and were robust in probabilistic sensitivity analyses. Appropriate prophylaxis provides better value in terms of costs and health gains than routine screening for DVT. Resources should be targeted at optimizing thromboprophylaxis.
Alizadeh, Kayvon; Hyman, Neil
Patients who undergo colorectal surgery are at a substantially higher risk for deep vein thrombosis (DVT) than their general surgery counterparts. The incidence of DVT in colorectal surgery patients who do not receive prophylaxis is approximately 30%; a four-fold increase exists in the incidence of pulmonary embolism. The precise reasons for the increased risk are uncertain; likely, contributing factors are the need for pelvic dissection, patient positioning (eg, use of stirrups), and indications for surgery (eg, inflammatory bowel disease, cancer). Despite the clear evidence that supports the safety and efficacy of DVT prophylaxis, appropriate preventive measures are frequently not used. Heparin preparations and mechanical compression in combination likely represents the most appropriate prophylactic regimen in these high-risk patients. Standard heparin appears to be as effective as low-molecular-weight heparin and considerably less costly. In the presence of relatively poor adherence to consensus guidelines for prophylaxis, critical pathways or electronic alerts may be useful to facilitate compliance with appropriate preventive measures.
BACKGROUND Venous thromboembolism (VTE) is a specific reproductive health risk for women. METHODS Searches were performed in Medline and other databases. The selection criteria were high-quality studies and studies relevant to clinical reproductive medicine. Summaries were presented and discussed by the European Society of Human Reproduction and Embryology Workshop Group. RESULTS VTE is a multifactorial disease with a baseline annual incidence around 50 per 100 000 at 25 years and 120 per 100 000 at age 50. Its major complication is pulmonary embolism, causing death in 1-2% of patients. Higher VTE risk is associated with an inherited thrombophilia in men and women. Changes in the coagulation system and in the risk of clinical VTE in women also occur during pregnancy, with the use of reproductive hormones and as a consequence of ovarian stimulation when hyperstimulation syndrome and conception occur together. In pregnancy, the risk of VTE is increased ~5-fold, while the use of combined hormonal contraception (CHC) doubles the risk and this relative risk is higher with the more recent pills containing desogestrel, gestodene and drospirenone when compared with those with levonorgestrel. Similarly, hormone replacement therapy (HRT) increases the VTE risk 2- to 4-fold. There is a synergistic effect between thrombophilia and the various reproductive risks. Prevention of VTE during pregnancy should be offered to women with specific risk factors. In women who are at high risk, CHC and HRT should be avoided. CONCLUSIONS Clinicians managing pregnancy or treating women for infertility or prescribing CHC and HRT should be aware of the increased risks of VTE and the need to take a careful medical history to identify additional co-existing risks, and should be able to diagnose VTE and know how to approach its prevention.
Horvei, Lars D; Brækkan, Sigrid K; Mathiesen, Ellisiv B; Njølstad, Inger; Wilsgaard, Tom; Hansen, John-Bjarne
Obesity is a risk factor for arterial and venous thromboembolism. However, it is not known whether obesity mediates risk through shared mechanisms. In a population-based cohort, we aimed to compare the impact of obesity measures on risk of venous thromboembolism (VTE) and myocardial infarction (MI), and explore how obesity-related atherosclerotic risk factors influenced these relationships. Measures of body composition including body mass index , waist circumference (WC), hip circumference (HC), waist-hip ratio (WHR) and waist-to-height ratio (WHtR) were registered in 6,708 subjects aged 25-84 years, who participated in the Tromsø Study (1994-1995). Incident VTE- and MI-events were registered until January 1, 2011. There were 288 VTEs and 925 MIs during a median of 15.7 years of follow-up. All obesity measures were related to risk of VTE. In linear models, WC showed the highest risk estimates in both genders. In categorized models (highest versus lowest quintile), WC showed highest risk in men (HR 3.59; 95 % CI 1.82-7.06) and HC in women (HR 2.27; 95 % CI 1.54-4.92). Contrary, WHR and WHtR yielded the highest risk estimates for MI. The HR of MI (highest vs. lowest quintile) for WHR was 2.11 (95 % CI 1.59-2.81) in men and 1.62 (95 % CI 1.13-2.31) in women. The risk estimates for MI were substantially attenuated after adjustment for atherosclerotic risk factors, whereas the estimates for VTE remained unchanged. Our findings suggest that the impact of body fat distribution, and the causal pathway, differs for the association between obesity and arterial and venous thrombosis.
Virkus, Rie Adser; Løkkegaard, Ellen; Lidegaard, Øjvind; Langhoff-Roos, Jens; Nielsen, Anne Kristine; Rothman, Kenneth J.; Bergholt, Thomas
Objective To quantify risk factors for venous thromboembolism during pregnancy and the puerperal period. Design In a nationwide prospective cohort study we followed pregnant and puerperal women in Denmark from 1995 to 2009 for venous thromboembolism. Information on risk factors and confounders was retrieved from national registries. The diagnosis of venous thromboembolism was confirmed through medical charts. We calculated adjusted incidence rates per 10,000 women years and used Poisson regression to estimate effects during pregnancy and the puerperal period. Results We studied 1,297,037 pregnancies and related puerperal periods, during which there were 748 venous thromboembolisms. The incidence rate for venous thromboembolism during a pregnancy with and without hospitalization for hyperemesis was 15.2/10,000 yr and 6.3/10,000 yr, respectively, (adjusted rate ratio: 2.5 (95%-confidence interval; 1.4–4.5)). The incidence rate among women with multiple pregnancies was 18.2/10,000 yr and 6.3/10,000 yr in singletons (adjusted rate ratio: 2.8 (1.9–4.2)). Increased risk was found with hospitalization during pregnancy or the puerperal period with incidence rates of 42.1/10.000 and 54.7/10.000, respectively, (rate ratios: 12.2 (8.7–17) and 5.9 (4.0–8.8)). Women hospitalized with infections during pregnancy had incidence rates of 25.9/10,000 yr and 29.3/10,000 yr during pregnancy and the puerperal period, respectively, and of 62.7/10,000 yr if hospitalized with infection in the puerperal period. Puerperal venous thromboembolism was associated with hospitalization for preeclampsia and intrauterine growth restriction/fetal death with incidence rates of 45.8/10,000 yr and 18.3/10,000 yr, respectively (rate ratio: 5.0 (3.1–7.8) and 1.9 (0.9–4.4)). Additionally puerperal venous thromboembolism was associated with obesity, elective and acute caesarean sections and major postpartum bleeding with incidence rates of 25.5/10,000 yr, 23.2/10,000 yr, 34.0/10,000 yr and 20
Greig, Sarah L; McKeage, Kate
Dabigatran etexilate (Pradaxa(®), Prazaxa(®)) has recently been approved for the treatment of acute venous thromboembolism (VTE) and prevention of VTE recurrence. Dabigatran etexilate is an oral prodrug of dabigatran, a selective, reversible, competitive, direct thrombin inhibitor. Dabigatran etexilate has a wide therapeutic range that allows for fixed-dose administration without the need for routine monitoring, a requirement of standard vitamin K antagonist (VKA) therapy. In randomized phase III trials in patients with acute VTE (RE-COVER and RE-COVER II), long-term treatment with oral dabigatran etexilate 150 mg twice daily for 6 months after initial parenteral anticoagulation was noninferior to dose-adjusted warfarin with regard to the incidence of recurrent symptomatic VTE or related death. In randomized trials of patients with previously treated VTE, extended dabigatran etexilate treatment was noninferior to warfarin (RE-MEDY) and significantly more effective than placebo (RE-SONATE) with regard to the incidence of recurrent VTE or related death. Dabigatran etexilate was generally well tolerated, with a similar incidence of major bleeding to that with warfarin in individual studies (although pooled data showed a significantly lower incidence in patients with acute VTE), and significantly lower incidences of the combined endpoint of major or clinically relevant nonmajor bleeding and of any bleeding than with warfarin. However, in the RE-SONATE trial, dabigatran etexilate was associated with a higher risk of bleeding than placebo. In conclusion, dabigatran etexilate is a valuable treatment option for acute VTE and prevention of VTE recurrence, providing an effective and convenient alternative to standard VKA therapy with the potential for a lower overall rate of bleeding.
Brækkan, Sigrid K.; Mathiesen, Ellisiv B.; Njølstad, Inger; Wilsgaard, Tom; Hansen, John-Bjarne
Background Hematocrit above the normal range for the population, such as in primary or secondary erythrocytosis, predisposes to both arterial and venous thrombosis. However, little is known about the association between hematocrit and risk of venous thromboembolism in a general population. Design and Methods Hematocrit and related hematologic variables such as hemoglobin, red blood cell count, mean corpuscular volume, and baseline characteristics were measured in 26,108 subjects, who participated in the Tromsø Study in 1994–1995. Incident venous thromboembolic events during follow-up were registered up to September 1st, 2007. Results There were 447 venous thromboembolic events during a median of 12.5 years of follow-up. Multivariable hazard ratios per 5% increment of hematocrit for the total population, adjusted for age, body mass index and smoking, were 1.25 (95% CI: 1.08–1.44) for total venous thromboembolism and 1.37 (95% CI: 1.10–1.71) for unprovoked venous thromboembolism. In category-based analyses, men with a hematocrit in the upper 20th percentile (≥46% in men) had a 1.5-fold increased risk of total venous thromboembolism (95% CI: 1.08–2.21) and a 2.4-fold increased risk of unprovoked venous thromboembolism (95% CI: 1.36–4.15) compared to men whose hematocrit was in the lower 40th percentile. The risk estimates were higher for men than for women both in continuous and category-based analyses. The findings for hemoglobin and red blood cell count were similar to those for hematocrit, whereas mean corpuscular volume was not associated with venous thromboembolism. Conclusions Our findings suggest that hematocrit and related hematologic variables such as hemoglobin and red blood cell count are risk factors for venous thromboembolism in a general population. PMID:19833630
Braekkan, Sigrid K; Mathiesen, Ellisiv B; Njølstad, Inger; Wilsgaard, Tom; Hansen, John-Bjarne
Hematocrit above the normal range for the population, such as in primary or secondary erythrocytosis, predisposes to both arterial and venous thrombosis. However, little is known about the association between hematocrit and risk of venous thromboembolism in a general population. Hematocrit and related hematologic variables such as hemoglobin, red blood cell count, mean corpuscular volume, and baseline characteristics were measured in 26,108 subjects, who participated in the Tromsø Study in 1994-1995. Incident venous thromboembolic events during follow-up were registered up to September 1(st), 2007. There were 447 venous thromboembolic events during a median of 12.5 years of follow-up. Multivariable hazard ratios per 5% increment of hematocrit for the total population, adjusted for age, body mass index and smoking, were 1.25 (95% CI: 1.08-1.44) for total venous thromboembolism and 1.37 (95% CI: 1.10-1.71) for unprovoked venous thromboembolism. In category-based analyses, men with a hematocrit in the upper 20(th) percentile (>or=46% in men) had a 1.5-fold increased risk of total venous thromboembolism (95% CI: 1.08-2.21) and a 2.4-fold increased risk of unprovoked venous thromboembolism (95% CI: 1.36-4.15) compared to men whose hematocrit was in the lower 40(th) percentile. The risk estimates were higher for men than for women both in continuous and category-based analyses. The findings for hemoglobin and red blood cell count were similar to those for hematocrit, whereas mean corpuscular volume was not associated with venous thromboembolism. Conclusions Our findings suggest that hematocrit and related hematologic variables such as hemoglobin and red blood cell count are risk factors for venous thromboembolism in a general population.
Farge-Bancel, D; Florea, L; Bosquet, L; Debourdeau, P
Venous thromboembolism (VTE) disease, as defined by the occurrence of deep venous thrombosis or pulmonary embolism, occurs among 4 to 20% of patients with cancer and is a leading cause of death among these patients. Use of classical anticoagulation to treat VTE in a cancer patient is associated with a higher risk of major bleeding and of VTE recurrence as compared to noncancer patients. Updated comprehensive and systematic review of current data from the medical literature allows to reconsider the classical approach used for anticoagulant treatment in cancer patients and to implement adapted recommendations. In 2008, the use of daily subcutaneous low-molecular-weight heparin (LMWH) for at least three to six months is recommended as first line therapy to treat VTE disease in cancer patients. If LMWH are contra-indicated (renal insufficiency), other therapeutic approaches are warranted, such as use of unfractionated heparin (UFH) with early introduction of anti-vitamin K for at least three months or venous cava filter in case of absolute contra-indications to anticoagulation. VTE prophylaxis in cancer patients relies on the same therapeutic approaches as currently used for noncancer patients at high risk of VTE. The definition of more specific prophylactic approaches for patients with cancer considered at higher risks of VTE, will be the subject of many clinical trials in the forthcoming years.
Pergantou, Helen; Avgeri, Maria; Komitopoulou, Anna; Xafaki, Panagiota; Kapsimali, Zoey; Mazarakis, Michail; Adamtziki, Eftychia; Platokouki, Helen
We retrospectively analyzed the data of 24 children (whereof 11 neonates), with non-central venous line-related and nonmalignancy-related venous thromboembolism (VTE) at uncommon sites, referred to our Unit from January 1999 to January 2012. Thirty patients who also suffered deep vein thrombosis, but in upper/low extremities, were not included in the analysis. The location of rare site VTE was: portal (n=7), mesenteric (n=2) and left facial vein (n=1), spleen (n=3), lung (n=3), whereas 10 neonates developed renal venous thrombosis. The majority of patients (91.7%) had at least 1 risk factor for thrombosis. Identified thrombophilic factors were: antiphospholipid antibodies (n=2), FV Leiden heterozygosity (n=6), MTHFR C677T homozygosity (n=4), protein S deficiency (n=2), whereas all neonates had age-related low levels of protein C and protein S. All but 6 patients received low-molecular-weight heparin, followed by warfarin in 55% of cases, for 3 to 6 months. Prolonged anticoagulation was applied in selected cases. During a median follow-up period of 6 years, the clinical outcome was: full recovery in 15 patients, evolution to both chronic portal hypertension and esophageal varices in 2 children, and progression to renal failure in 7 of 10 neonates. Neonates are greatly vulnerable to complications after VTE at uncommon sites, particularly renal. Future multicentre long-term studies on neonatal and pediatric VTE at unusual sites are considered worthwhile.
Mattiuzzi, Camilla; Franchini, Massimo
Background Among the various risk factors of venous thromboembolism (VTE), nutrients seem to play a significant role in the pathogenesis of this condition. This study aimed to clarify the relationship between coffee intake and venous thrombosis, and we performed a critical review of clinical studies that have been published so far. Methods An electronic search was carried out in Medline, Scopus and ISI Web of Science with the keywords “coffee” AND “venous thromboembolism” OR “deep vein thrombosis” OR “pulmonary embolism” in “Title/Abstract/Keywords”, with no language and date restriction. Results According to our criteria, three studies (two prospective and one case-control) were finally selected (inter-study heterogeneity: 78%; P<0.001). Cumulative data suggests that a modest intake of coffee (i.e., 1-4 cups/day) may be associated with an 11% increased risk of VTE compared to abstainers, whereas a larger intake (i.e., ≥5 coffee/day) may be associated with a 25% decreased risk. Conclusions Our analysis of published data seemingly confirm the existence of a U-shape relationship between coffee intake and VTE, thus exhibiting a trend that overlaps with that previously reported for cardiovascular disease (CVD). PMID:26244139
Boef, Anna G C; Souverein, Patrick C; Vandenbroucke, Jan P; van Hylckama Vlieg, Astrid; de Boer, Anthonius; le Cessie, Saskia; Dekkers, Olaf M
A potentially useful role for instrumental variable (IV) analysis may be as a complementary analysis to assess the presence of confounding when studying adverse drug effects. There has been discussion on whether the observed increased risk of venous thromboembolism (VTE) for third-generation oral contraceptives versus second-generation oral contraceptives could be (partially) attributed to confounding. We investigated how prescribing preference IV estimates compare with conventional estimates. Women in the Clinical Practice Research Database who started a second-generation or third-generation oral contraceptive from 1989 to 2013 were included. Ordinary least squares and two-stage least squares regression were used to estimate risk differences in VTE. Cox regression and IV for Cox proportional hazards regression were used to calculate hazard ratios (HR). The instrument used was the proportion of prescriptions for third-generation oral contraceptives by the general practitioner in the year preceding the current prescription. All analyses pointed in the direction of an increased VTE risk for third-generation oral contraceptives. The adjusted HR from the conventional Cox regression was 1.62 (95% confidence interval 1.16-2.27) and the fully adjusted HR from the IV Cox regression was 3.45 (95% confidence interval; 0.97-11.7), showing a larger risk and wider confidence intervals in the IV analysis. The similarity in direction of results from the IV analyses and conventional analyses suggests that major confounding is unlikely. IV analysis can be a useful complementary analysis to assess the presence of confounding in studies of adverse drug effects in very large databases. Copyright © 2016 John Wiley & Sons, Ltd.
Lau, Brandyn D; Shaffer, Dauryne L; Hobson, Deborah B; Yenokyan, Gayane; Wang, Jiangxia; Sugar, Elizabeth A; Canner, Joseph K; Bongiovanni, David; Kraus, Peggy S; Popoola, Victor O; Shihab, Hasan M; Farrow, Norma E; Aboagye, Jonathan K; Pronovost, Peter J; Streiff, Michael B; Haut, Elliott R
Venous thromboembolism (VTE) is a common cause of preventable harm in hospitalized patients. While numerous successful interventions have been implemented to improve prescription of VTE prophylaxis, a substantial proportion of doses of prescribed preventive medications are not administered to hospitalized patients. The purpose of this trial was to evaluate the effectiveness of nurse education on medication administration practice. This was a double-blinded, cluster randomized trial in 21 medical or surgical floors of 933 nurses at The Johns Hopkins Hospital, an academic medical center, from April 1, 2014 -March 31, 2015. Nurses were cluster-randomized by hospital floor to receive either a linear static education (Static) module with voiceover or an interactive learner-centric dynamic scenario-based education (Dynamic) module. The primary and secondary outcomes were non-administration of prescribed VTE prophylaxis medication and nurse-reported satisfaction with education modules, respectively. Overall, non-administration improved significantly following education (12.4% vs. 11.1%, conditional OR: 0.87, 95% CI: 0.80-0.95, p = 0.002) achieving our primary objective. The reduction in non-administration was greater for those randomized to the Dynamic arm (10.8% vs. 9.2%, conditional OR: 0.83, 95% CI: 0.72-0.95) versus the Static arm (14.5% vs. 13.5%, conditional OR: 0.92, 95% CI: 0.81-1.03), although the difference between arms was not statistically significant (p = 0.26). Satisfaction scores were significantly higher (p<0.05) for all survey items for nurses in the Dynamic arm. Education for nurses significantly improves medication administration practice. Dynamic learner-centered education is more effective at engaging nurses. These findings suggest that education should be tailored to the learner. ClinicalTrials.gov NCT02301793.
Sisante, Jason-Flor V; Abraham, Michael G; Phadnis, Milind A; Billinger, Sandra A; Mittal, Manoj K
Ischemic stroke patients are at high risk (up to 18%) for venous thromboembolism. We conducted a retrospective cross-sectional study to understand the predictors of acute postmild ischemic stroke patient's ambulatory status and its relationship with venous thromboembolism, hospital length of stay, and in-hospital mortality. We identified 522 patients between February 2006 and May 2014 and collected data about patient demographics, admission NIHSS (National Institutes of Health Stroke Scale), venous thromboembolism prophylaxis, ambulatory status, diagnosis of venous thromboembolism, and hospital outcomes (length of stay, mortality). Chi-square test, t-test and Wilcoxon rank-sum test, and binary logistic regression were used for statistical analysis as appropriate. A total of 61 (11.7%), 48 (9.2%), and 23 (4.4%) mild ischemic stroke patients developed venous thromboembolism, deep venous thrombosis, and pulmonary embolism, respectively. During hospitalization, 281 (53.8%) patients were ambulatory. Independent predictors of in-hospital ambulation were being married (OR 1.64, 95% CI 1.10-2.49), being nonreligious (OR 2.19, 95% CI 1.34-3.62), admission NIHSS (per unit decrease in NIHSS; OR 1.62, 95% CI 1.39-1.91), and nonuse of mechanical venous thromboembolism prophylaxis (OR 1.62, 95% CI 1.02-2.61). After adjusting for confounders, ambulatory patients had lower rates of venous thromboembolism (OR .47, 95% CI .25-.89), deep venous thrombosis (OR .36, 95% CI .17-.73), prolonged length of hospital stay (OR .24, 95% CI .16-.37), and mortality (OR .43, 95% CI .21-.84). Our findings suggest that for hospitalized acute mild ischemic stroke patients, ambulatory status is an independent predictor of venous thromboembolism (specifically deep venous thrombosis), hospital length of stay, and in-hospital mortality. Copyright © 2016 National Stroke Association. Published by Elsevier Inc. All rights reserved.
Young, V Leroy; Watson, Marla E
The reader is presumed to have a broad understanding of plastic surgical procedures and concepts. After studying this article, the participant should be able to: Physicians may earn 1 AMA PRA Category 1 credit credit by successfully completing the examination based on material covered in this article. The examination begins on page 176. ASAPS members can also complete this CME examination online by logging onto the ASAPS Members-Only Web site (http://www.surgery.org/members) and clicking on "Clinical Education" in the menu bar. Little has been published about venous thromboembolism (VTE) complications in plastic surgery. The authors investigated the recent literature, particularly literature reviews and meta-analyses of clinical studies, in order to outline strategies for prevention of deep vein thrombosis (DVT) and pulmonary embolism (PE) applicable to plastic surgery patients. Major risk factors for VTE include trauma, a prior history of VTE, older age, use of oral contraceptives or hormone replacement therapy, and prolonged travel. Although the frequency of VTE among plastic surgery patients is estimated to be from less than 1% to 2% of cases, in fact many of our patients are at moderate to high risk of VTE. Moreover, the actual frequency of VTE among plastic surgery patients is probably higher than we know, because up to two thirds of cases are asymptomatic. Mechanical methods of VTE prophylaxis include graduated compression stockings (GCSs), intermittent pneumatic compression (IPC) devices, and venous foot pumps (VFPs). They are recommended primarily for patients with a high risk of bleeding or as an adjunct to chemoprophylaxis. Intermittent pneumatic compression devices were found to be more effective than passive compression using GCSs. For plastic surgery patients, IPC devices or VFPs are recommended for any procedure that lasts more than 1 hour, and for all patients receiving general anesthesia. Use should begin 30 to 60 minutes before surgery. Low
Khalil, Jihane; Bensaid, Badr; Elkacemi, Hanan; Afif, Mohamed; Bensaid, Younes; Kebdani, Tayeb; Benjaafar, Noureddine
Venous thromboembolism (VTE) is a major health problem among patients with cancer, its incidence in this particular population is widely increasing. Although VTE is associated with high rates of mortality and morbidity in cancer patients, its severity is still underestimated by many oncologists. Thromboprophylaxis of VTE now considered as a standard of care is still not prescribed in many institutions; the appropriate treatment of an established VTE is not yet well known by many physicians and nurses in the cancer field. Patients are also not well informed about VTE and its consequences. Many studies and meta-analyses have addressed this question so have many guidelines that dedicated a whole chapter to clarify and expose different treatment strategies adapted to this particular population. There is a general belief that the prevention and treatment of VTE cannot be optimized without a complete awareness by oncologists and patients. The aim of this article is to make VTE a more clear and understood subject.
Goyal, Gaurav; Bhatt, Vijaya Raj
The occurrence of venous thromboembolism (VTE) in acute lymphocytic leukemia patients receiving L-asparaginase therapy may cause significant morbidity, neurological sequela and possibly worse outcomes. The prophylactic use of antithrombin infusion (to keep antithrombin activity >60%) or low molecular weight heparin (LMWH) may reduce the risk of VTE. The decision to continue L-asparaginase therapy after the development of VTE should be based on anticipated benefits, severity of VTE and the ability to continue therapeutic anticoagulation. In patients receiving asparaginase rechallenge, the use of therapeutic LMWH, monitoring of anti-Xa level and antithrombin level are important. Novel oral anticoagulants are not dependent on antithrombin level, hence offer theoretical advantages over LMWH for the prevention and therapy of asparaginase-related VTE.
Clinical manifestations of venous thromboembolism are often subtle or misleading. Yet it is a potentially fatal condition. Although the symptoms and signs at presentation have a poor sensitivity and specificity when considered singly, the physician can accurately assess a clinical probability based on the history, the risk factors, the physical examination and some simple laboratory exams. This essential step allows us to identify a low risk group of patients which will benefit of a non invasive diagnostic strategy. More recently explicit prediction rules were proposed to offset the lack of standardization of this clinical assessment. These new didactic tools can simplify clinical evaluation. Nevertheless, their comparison to implicit evaluation reveals that they should be complemented by the physician's judgement.
Nadeem, Omar; Gui, Jiang; Ornstein, Deborah L.
To investigate an association between secondary polycythemia and venous thromboembolism (VTE) risk, we performed a case–control study to compare the prevalence of VTE in participants with secondary polycythemia due to chronic obstructive pulmonary disease (COPD; N = 86) to that in age- and sex-matched controls with COPD without secondary polycythemia (N = 86). Although there was a significant difference in mean hematocrit between cases and controls (53.5% vs 43.6%, respectively; P < .005), we identified no difference in the number of total or idiopathic VTE events in the 2 groups. Patients with VTE, however, had a significantly higher body mass index than patients without VTE. Our findings suggest that secondary polycythemia alone may not be a significant risk factor for VTE but that VTE risk in this population may be related to known risk factors such as obesity. The role of phlebotomy for VTE risk reduction secondary polycythemia is therefore questionable. PMID:23007895
Nadeem, Omar; Gui, Jiang; Ornstein, Deborah L
To investigate an association between secondary polycythemia and venous thromboembolism (VTE) risk, we performed a case-control study to compare the prevalence of VTE in participants with secondary polycythemia due to chronic obstructive pulmonary disease (COPD; N = 86) to that in age- and sex-matched controls with COPD without secondary polycythemia (N = 86). Although there was a significant difference in mean hematocrit between cases and controls (53.5% vs 43.6%, respectively; P < .005), we identified no difference in the number of total or idiopathic VTE events in the 2 groups. Patients with VTE, however, had a significantly higher body mass index than patients without VTE. Our findings suggest that secondary polycythemia alone may not be a significant risk factor for VTE but that VTE risk in this population may be related to known risk factors such as obesity. The role of phlebotomy for VTE risk reduction secondary polycythemia is therefore questionable.
Gabriel Botella, F; Labiós Gómez, M; Brasó Aznar, J V; Llavador Ros, G; Bort Martí, J
Thromboembolic disease (TD), which includes deep venous thrombosis (DVT) and pulmonary embolism (PE), is the most common acute cardiovascular condition after ischemic cardiopathy and stroke. It is often difficult to diagnose, as it is well-known that half of PE episodes appear are recognized while the patient is still alive and which appear in 30-40% of symptomatic patients. Nonetheless, there are two well-differentiated phases in the diagnosis of TD: the suspicion, and the diagnosis. The first is very important, and is within the competence of any physician. The second can be ratified when carrying out specific tests. We have developed successive steps in the two phases of diagnosis, we critically review the distinct parts currently implicated in the strategic diagnosis of TD. Finally, we analyze the new diagnostic techniques to substitute, possibly, angiography in many cases, and perhaps to include ventilation/perfusion (V/Q) pulmonary gammagraphy, once become generally available.
Muslimani, Alaa A; Spiro, Timothy P; Chaudhry, Asif A; Taylor, Harris C; Jaiyesimi, Ishmael; Daw, Hamed A
Monoclonal gammopathy of undetermined significance (MGUS) is defined by the presence of a serum M-protein at a concentration of 3 g/dL or less, with less than 10% plasma cells in the bone marrow, and the absence of lytic bone lesions, anemia, hypercalcemia, and renal insufficiency related to the plasma cell proliferative process. The annual risk of MGUS progressing to a symptomatic plasma cell proliferation or other related malignancy is approximately 1%. The association between malignancy and venous thromboembolism (VTE) is well recognized. In this retrospective study of MGUS patients, VTE was seen in 8% (9/112) of patients, a rate that is 22.8-fold higher than that in the general population (P is less than .001). Although many studies have identified VTE as a marker for subsequent malignancy, we did not find a significant difference in the incidence of VTE as a function of the risk factor group.
Jacobsen, Anne Flem; Sandset, Per Morten
Venous thromboembolism (VTE) is a major cause of maternal morbidity and mortality during or early after pregnancy and in women taking hormonal therapy for contraception or for replacement therapy. Post-thrombotic syndrome, including leg oedema and leg pain, is an unrecognized burden after pregnancy-related VTE, which will affect more than two of five women. Women with a prior VTE, a family history of VTE, certain clinical risk factors and thrombophilia are at considerably increased risk both for pregnancy-related VTE and for VTE on hormonal therapy. This review critically assesses the epidemiology and risk factors for pregnancy-related VTE and current guidelines for prophylaxis and treatment. We also provide information on the risk of VTE related to hormonal contraception and replacement therapy.
Spyropoulos, Alex C; Brotman, Daniel J; Amin, Alpesh N; Deitelzweig, Steven B; Jaffer, Amir K; McKean, Sylvia C
Cancer patients, especially those undergoing surgery for cancer, are at extremely high risk for developing venous thromboembolism (VTE), even with appropriate thromboprophylaxis. Anticoagulant prophylaxis in cancer surgery patients has reduced the incidence of VTE events by approximately one-half in placebo-controlled trials, and extended prophylaxis (for up to 1 month) has also significantly reduced out-of-hospital VTE events in clinical trials in this population. Clinical trials show no difference between low-molecular-weight heparin (LMWH) and unfractionated heparin in VTE prophylaxis efficacy or bleeding risk in this population, although the incidence of heparin-induced thrombocytopenia is lower with LMWH. The risk-benefit profile of low-dose anticoagulant prophylaxis appears to be favorable even in many cancer patients undergoing neurosurgery, for whom pharmacologic VTE prophylaxis has been controversial because of bleeding risks.
Jaffer, Amir K; Amin, Alpesh N; Brotman, Daniel J; Deitelzweig, Steven B; McKean, Sylvia C; Spyropoulos, Alex C
Hospitalized acutely ill medical patients are at high risk for venous thromboembolism (VTE), and clinical trials clearly demonstrate that pharmacologic prophylaxis of VTE for up to 14 days significantly reduces the incidence of VTE in this population. Guidelines recommend use of low-molecular-weight heparin (LMWH) or unfractionated heparin (5,000 U three times daily) for VTE prophylaxis in hospitalized medical patients with risk factors for VTE; in patients with contraindications to anticoagulants, mechanical prophylaxis is recommended. All hospitalized medical patients should be assessed for their risk of VTE at admission and daily thereafter, and those with reduced mobility and one or more other VTE risk factors are candidates for aggressive VTE prophylaxis. Based on results from the recently reported EXCLAIM trial, extended postdischarge prophylaxis with LMWH for 28 days should be considered for hospitalized medical patients with reduced mobility who are older than age 75 or have a cancer diagnosis or a history of VTE.
Murray, Katie M.; Parker, William; Stephany, Heidi; Redger, Kirk; Mirza, Moben; Lopez-Corona, Ernesto; Holzbeierlein, Jeffrey M.; Lee, Eugene K.
Objectives To detect the incidence of immediate postoperative deep vein thrombosis (DVT) using screening lower extremity ultrasonography (US) in patients undergoing radical cystectomy (RC) and to determine the rate of symptomatic pulmonary embolism (PE) after RC and identify risk factors for venous thromboembolic (VTE) events in a RC population. Patients and methods We performed a retrospective review of prospective data collected on patients who underwent RC between July 2008 and January 2012. These patients underwent screening US at 2/3 days after RC to determine the rate of asymptomatic DVT. A chart review was completed to identify those who had a symptomatic PE. Univariate and multivariable analysis was used to identify risk factors associated with DVT, PE and total VTE events. Results In all, 221 patients underwent RC and asymptomatic DVT was identified in 21 (9.5%) on screening US. Nine (4.5%) developed symptomatic PE at a median of 9 days, of which no patients had positive lower extremity US postoperatively. Increased length of hospital stay, increased estimated blood loss, and lower body mass index were linked to risk of PE, and only a previous history of DVT was associated with postoperative DVT. Conclusion Patients who undergo RC are at high-risk for thromboembolic events and multimodal prophylaxis should be administered. Clinicians should be especially vigilant in those who demonstrate factors associated with higher risk for VTE events. PMID:26966592
Siniarski, Aleksander; Wypasek, Ewa; Fijorek, Kamil; Gajos, Grzegorz; Undas, Anetta
Prolonged work and recreation-related seated immobility increases the risk of venous thromboembolism (VTE). Little is known about links of thrombophilia and prolonged immobility. We sought to determine factors associated with the occurrence of seated immobility venous thromboembolism (SIT). Four hundred and ninety-three consecutive outpatients with a history of first-ever VTE, aged up to 65 years were referred for evaluation of suspected thrombophilia. Exclusion criteria were provoked VTE unless family history of VTE was positive, arterial thrombosis, cancer, infection and chronic inflammatory diseases. The prolonged immobility group was defined as being seated at least 8 h daily and at least 3 h daily without getting up, or 10 h daily and 2 h daily without getting up, or 12 h daily and 1 h daily without getting up during 12 weeks prior to VTE onset. SIT was observed in 115 patients (24.5%). Inherited thrombophilia was more common among SIT patients than in the remainder [Odds ratio (OR) 3.98, 95% confidence interval (CI) 2.55-6.25], with a major impact of factor V Leiden mutation (FVL) (OR 4.86, 95% CI 2.95-8.05). In multivariate analysis, FVL (OR 5.43, 95% CI 3.23-9.15), trauma (OR 2.55, 95% CI 1.30-4.99), current smoking (OR 1.68, 95% CI 1.06-2.67) and varices (OR 2.08, 95% CI 1.27-3.40) were independent predictors of SIT. Moreover, FVL (OR 4.05, 95% CI 2.12-7.76), prothrombin G20210A variant (OR 3.84, 95% CI 1.47-10.05) and computer use (OR 2.84, 95% CI 1.43-5.63) were independent predictors of unprovoked VTE in the SIT group. Inherited thrombophilia, current smoking and varices characterize patients with SIT.
Introduction Despite evidence-based guidelines for venous thromboembolism prevention, substantial variability is found in practice. Many economic evaluations of new drugs for thromboembolism prevention do not occur prospectively with efficacy studies and are sponsored by the manufacturers, raising the possibility of bias. We performed a systematic review of economic analyses of venous thromboembolism prevention in hospitalized patients to inform clinicians and policy makers about cost-effectiveness and the potential influence of sponsorship. Methods We searched MEDLINE, EMBASE, Cochrane Databases, ACP Journal Club, and Database of Abstracts of Reviews of Effects, from 1946 to September 2011. We extracted data on study characteristics, quality, costs, and efficacy. Results From 5,180 identified studies, 39 met eligibility and quality criteria. Each addressed pharmacologic prevention: low-molecular-weight heparins versus placebo (five), unfractionated heparin (12), warfarin (eight), one or another agents (five); fondaparinux versus enoxaparin (11); and rivaroxaban and dabigatran versus enoxaparin (two). Low-molecular-weight heparins were most economically attractive among most medical and surgical patients, whereas fondaparinux was favored for orthopedic patients. Fondaparinux was associated with increased bleeding events. Newer agents rivaroxaban and dabigatran may offer additional value. Of all economic evaluations, 64% were supported by manufacturers of a "new" agent. The new agent had a favorable outcome in 38 (97.4%) of 39 evaluations [95% confidence interval [CI] (86.5 to 99.9)]. Among studies supported by a pharmaceutical company, the sponsored medication was economically attractive in 24 (96.0%) of 25 [95% CI, 80.0 to 99.9)]. We could not detect a consistent bias in outcome based on sponsorship; however, only a minority of studies were unsponsored. Conclusion Low-molecular-weight heparins and fondaparinux are the most economically attractive drugs for venous
Ferraris, Augusto; Szmulewicz, Alejandro G; Vazquez, Fernando J; Vollmer, William M; Angriman, Federico
Treatment with antipsychotic (AP) agents is associated with incident thromboembolic events. However, the underpinnings of this association remain unknown. We sought to evaluate the effect of AP agents-categorized by their metabolic/sedative and hyperprolactinemia adverse effect profile-on the risk of venous thromboembolic disease during long-term follow-up. A retrospective cohort study of adult patients initiating AP treatment for the first time was conducted. Primary outcome was defined as the time to venous thromboembolism (VTE) (either deep venous thrombosis or acute pulmonary embolism). Antipsychotic agents were categorized by their risk (high vs low) of either drug-induced (a) sedation/metabolic adverse event or (b) hyperprolactinemia. We used a propensity score-adjusted Cox proportional hazards model to control for confounding. One thousand eight patients (mean age, 72.4 y) were followed for a median of 36 months. Incident VTE occurred in 6.25% of patients, corresponding to an incidence rate of 184 cases per 10,000 person-years. We found no difference in the hazard of VTE during follow-up between high- and low-risk groups (hazard ratio, 1.23 [95% confidence interval, 0.74-2.04] for drug-induced sedation/metabolic adverse event risk categories, and hazard ratio 0.81 [95% confidence interval, 0.50-1.35] for high versus low hyperprolactinemia risk). These results suggest that the risk of thromboembolic events in older adults who started AP treatment for the first time does not seem to be related to these drugs' risk of either sedation/metabolic adverse events or hyperprolactinemia. However, VTE remains a common problem in this subgroup of patients.
Semchuk, William M.; Sperlich, Catherine
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
Ferrari, E; Schiano, N; Benhamou, M; Baudouy, M
The necessity of anticoagulant treatment after a pulmonary embolus or a deep venous thrombosis has been demonstrated. The modalities of this treatment have been well established, especially the usefulness of initial heparin therapy followed by a period of antivitamin K treatment with an "ideal target INR" between 2 and 3. One of the last questions in this therapeutic protocol is the duration of antivitamin K treatment. The choice of duration of treatment must be made on numerous criteria. It is necessary to distinguish the circumstances of the occurrence of the DVT or the PE and the context. It is thus possible for less than 3 months treatment in secondary venous thrombo-embolic disease, which occurs in precise, recognised circumstances for which the cause will have been controlled. Otherwise, in so-called idiopathic venous thrombo-embolic disease, which is distinguished by a higher prevalence of recurrences, it is known that long-term antivitamin K treatment is effective for the thrombo-embolic recurrences but at the price of a risk of haemorrhage. Finally thrombo-embolic recurrences also benefit from a long treatment. These circumstances of occurrence are thus important in order to decide the choice of treatment duration. But, in our opinion, the compliance to antivitamin K treatment remains the primary criterion to consider. The dilemma facing the prescriber is to evaluate the risk-benefit ratio of each patient, asking especially if the antivitamin K treatment surveillance of a particular patient will be done as well as in the randomised studies. For the future, long-term antivitamin K does not perhaps represent the only therapeutic option. The results of studies evaluating the durations of long-term treatment with less intense levels of anticoagulation (INR < 2) as well as therapeutic alternatives to antivitamin K (antiaggregants or other antithrombins) are awaited.
Jang, Moon Ju; Kim, Hee-Jin; Bang, Soo-Mee; Lee, Jeong-Ok; Yhim, Ho-Young; Kim, Yeo-Kyeoung; Kim, Yang-Ki; Choi, Won-Il; Lee, Eun-Young; Kim, In-Ho; Park, Seonyang; Sohn, Hee-Jung; Kim, Duk-Kyung; Kim, Minji; Oh, Doyeun
There have been conflicting results on seasonal variation in the occurrence of venous thromboembolism (VTE). It also has never been studied in Asian population. To address these issues, we investigated seasonal changes of the incidence of VTE in Korean population using 1,495 patients with VTE between January 2001 and December 2010. VTE occurred most frequently in the winter and least frequently in the summer (χ2=11.83, P=0.008). In the subset analyses, the same trend was shown in the PE±DVT group, the unprovoked VTE group, and the VTE without malignancy group. The monthly occurrence rate peaked in December and was at its lowest in July (P=0.004). In conclusion, our study provides evidence that there is an increased risk for VTE in Korean population in the winter season.
Steinhubl, Steven R; Eikelboom, John W; Hylek, Elaine M; Dauerman, Harold L; Smyth, Susan S; Becker, Richard C
The contribution of platelets in the pathophysiology of low-shear thrombosis-specifically, in atrial fibrillation (AF) and venous thromboembolic events (VTE)-remains less clear than for arterial thrombosis. AF itself appears to lead to platelet activation, offering a potential target for aspirin and other antiplatelet agents. Randomized trial results suggest a small benefit of aspirin over placebo, and of dual antiplatelet therapy (aspirin plus clopidogrel) over aspirin alone, for prevention of cardioembolic events in AF. Antiplatelet therapy thus can represent an option for patients with AF who are unsuitable for therapy with warfarin or novel oral anticoagulant agents. For VTE, the rationale for antiplatelet therapy reflects the venous response to disrupted blood flow-interactions among monocytes, neutrophil extracellular traps, and platelets. Early randomized trials generally showed poorer performance of aspirin relative to heparins and danaparoid sodium in prevention of VTE. However, results from large placebo- and dalteparin-controlled randomized trials have spurred changes in the most recent practice guidelines-aspirin is now recommended after major orthopedic surgery for patients who cannot receive other antithrombotic therapies.
Chima, Ranjit S.; Hanson, Sheila J.
Critically ill children and those sustaining severe traumatic injuries are at higher risk for developing venous thromboembolism (VTE) than other hospitalized children. Multiple factors including the need for central venous catheters, immobility, surgical procedures, malignancy, and dysregulated inflammatory state confer this increased risk. As well as being at higher risk of VTE, this population is frequently at an increased risk of bleeding, making the decision of prophylactic anticoagulation even more nuanced. The use of pharmacologic and mechanical prophylaxis remains variable in this high-risk cohort. VTE pharmacologic prophylaxis is an accepted practice in adult trauma and intensive care to prevent VTE development and associated morbidity, but it is not standardized in critically ill or injured children. Given the lack of pediatric specific guidelines, prevention strategies are variably extrapolated from the successful use of mechanical and pharmacologic prophylaxis in adults, despite the differences in developmental hemostasis and thrombosis risk between children and adults. Whether the burden of VTE can be reduced in the pediatric critically ill or injured population is not known given the lack of robust data. There are no trials in children showing efficacy of mechanical compression devices or prophylactic anticoagulation in reducing the rate of VTE. Risk stratification using clinical factors has been shown to identify those at highest risk for VTE and allows targeted prophylaxis. It remains unproven if such a strategy will mitigate the risk of VTE and its potential sequelae. PMID:28349046
Bertoletti, L; Quenet, S; Mismetti, P; Hernández, L; Martín-Villasclaras, J J; Tolosa, C; Valdés, M; Barrón, M; Todolí, J A; Monreal, M
Chronic obstructive pulmonary disease (COPD) is a moderate risk factor for venous thromboembolism (VTE), but neither the clinical presentation nor the outcome of VTE in COPD patients is well known. The clinical presentation of VTE, namely pulmonary embolism (PE) or deep venous thrombosis (DVT), and the outcome at 3 months (death, recurrent VTE or bleeding) were compared between 2,984 COPD patients and 25,936 non-COPD patients included in the RIETE (Registro Informatizado de la Enfermedad TromboEmbólica) registry. This ongoing international, multi-centre registry includes patients with proven symptomatic PE or DVT. PE was the more frequent VTE presentation in COPD patients (n = 1,761, 59%). PE presentation was more significantly associated with COPD patients than non-COPD patients (OR 1.64, 95% CI 1.49-1.80). During the 3-month follow-up, mortality (10.8% versus 7.6%), minor bleeding (4.5% versus 2.3%) or first VTE recurrences as PE (1.5% versus 1.1%) were significantly higher in COPD patients than in non-COPD patients. PE was the most common cause of death. COPD patients presented more frequently with PE than DVT. It may explain the worse prognosis of COPD patients, with a higher risk of death, bleeding or VTE recurrences as PE compared with non-COPD patients. Further therapeutic options are needed.
Ademi, Zanfina; Sutherland, C Simone; Van Stiphout, Joris; Michaud, Jöelle; Tanackovic, Goranka; Schwenkglenks, Matthias
Use of combined oral contraceptives (COCs) by women increases the risk of venous thromboembolism (VTE), which can have a major impact on an individuals' quality of life. VTE is also associated with an increase in healthcare costs. Our aim was to systematically review cost-effectiveness analyses (CEAs) considering any screening for risk of VTE in women using COCs. The quality of reporting in each study was assessed, a summary of results was prepared, and the key drivers of cost effectiveness in each of the eligible CEAs were identified. A search strategy using MeSH terms was performed in MEDLINE, Embase, the Centre for Review and Dissemination (CRD) database including the Economic Evaluation Database from the UK National Health Service, and Cochrane reviews. Two reviewers independently screened and determined the final articles, and a third reviewer resolved any discrepancies. Consolidated Health Economic Evaluation Reporting Standards was used to assess the quality of reporting in terms of perspective, effectiveness measures, model structure, cost, time-horizon and discounting. Four publications (three from Europe, one from the United States) were eligible for inclusion in the review. According to current criteria, relevant elements were sometimes not captured and the sources of epidemiological and effectiveness data used in the CEAs were of limited quality. The studies varied in terms of type of costs assessed, country settings, model assumptions and uncertainty around input parameters. Key drivers of CEAs were sensitivity and specificity of the test, incidence rate of VTE, relative risk of prophylaxis, and costs of the test. The reviewed studies were too dissimilar to draw a firm conclusion on cost-effectiveness analysis about universal and selective screening in high-risk groups. The new emerging diagnostic tools for identifying women at risk of developing VTE, that are more predictive and less costly, highlight the need for more studies that apply the latest
Cerebral Vein Thrombosis; Deep Vein Thrombosis; Gonadal Thrombosis; Hepatic Thrombosis; Malignant Neoplasm; Mesenteric Thrombosis; Metastatic Malignant Neoplasm; Portal Vein Thrombosis; Pulmonary Embolism; Renal Vein Thrombosis; Splenic Thrombosis; Venous Thromboembolism
Monn, M. Francesca; Hui, Xuan; Lau, Brandyn D.; Streiff, Michael; Haut, Elliott R.; Wick, Elizabeth C.; Efron, Jonathan E.; Gearhart, Susan L.
BACKGROUND There is evidence demonstrating an association between infection and venous thromboembolism. We recently identified this association in the postoperative setting; however, the temporal relationship between infection and venous thromboembolism is not well defined OBJECTIVE We sought to determine the temporal relationship between venous thromboembolism and postoperative infectious complications in patients undergoing colorectal surgery. DESIGN, SETTING, AND PATIENTS A retrospective cohort analysis was performed using data for patients undergoing colorectal surgery in the National Surgical Quality Improvement Project 2010 database. MAIN OUTCOME MEASURES The primary outcome measures were the rate and timing of venous thromboembolism and postoperative infection among patients undergoing colorectal surgery during 30 postoperative days. RESULTS Of 39,831 patients who underwent colorectal surgery, the overall rate of venous thromboembolism was 2.4% (n = 948); 729 (1.8%) patients were diagnosed with deep vein thrombosis, and 307 (0.77%) patients were diagnosed with pulmonary embolism. Eighty-eight (0.22%) patients were reported as developing both deep vein thrombosis and pulmonary embolism. Following colorectal surgery, the development of a urinary tract infection, pneumonia, organ space surgical site infection, or deep surgical site infection was associated with a significantly increased risk for venous thromboembolism. The majority (52%–85%) of venous thromboembolisms in this population occurred the same day or a median of 3.5 to 8 days following the diagnosis of infection. The approximate relative risk for developing any venous thromboembolism increased each day following the development of each type of infection (range, 0.40%–1.0%) in comparison with patients not developing an infection. LIMITATIONS We are unable to account for differences in data collection, prophylaxis, and venous thromboembolism surveillance between hospitals in the database
Schädlich, Peter K; Kentsch, Michael; Weber, Manfred; Kämmerer, Wolfgang; Brecht, Josef Georg; Nadipelli, Vijay; Huppertz, Eduard
To estimate, from the hospital perspective in Germany, the cost effectiveness of the low-molecular-weight heparin (LMWH) subcutaneous enoxaparin sodium 40 mg once daily (ENOX) relative to no pharmacological prophylaxis (NPP) and relative to subcutaneous unfractionated heparin (UFH) 5,000 IU three times daily (low-dose UFH [LDUFH]). Each is used in addition to elastic bandages/compression stockings and physiotherapy in the prevention of venous thromboembolic events (VTE) in immobilised acutely ill medical inpatients without impaired renal function or extremes of body weight. The incremental cost-effectiveness ratios (ICERs) of the 'additional cost for ENOX per clinical VTE avoided versus NPP' and 'additional cost for ENOX per episode of major bleeding avoided versus LDUFH' were chosen as target variables. The target variables were quantified using a modelling approach based on the decision-tree technique. Resource use during thromboprophylaxis, diagnosis and treatment of VTEs, episode of major bleeding and secondary pneumonia after pulmonary embolism (PE) was collected from a hospital survey. Costs were exclusively those to hospitals incurred by staff expenses, drugs, devices, disposables, laboratory tests and equipment for diagnostic procedures. These costs were determined by multiplying utilised resource items by the price or tariff of each item as of the first quarter of 2003. Safety and efficacy values of the comparators were taken from the MEDENOX (prophylaxis in MEDical patients with ENOXaparin) and the THE-PRINCE (THromboEmbolism-PRevention IN Cardiac or respiratory disease with Enoxaparin) trials and from a meta-analysis. The evaluation encompassed 8 (6-14) days of thromboprophylaxis plus time to treat VTE and episode of major bleeding in hospital. Point estimates of all model parameters were applied exclusively in the base-case analysis. There were incremental costs of euro 1,106 for ENOX per clinical VTE avoided versus NPP (1 euro approximately equals 1
Vora, Pareen; Soriano-Gabarró, Montse; Suzart, Kiliana; Persson Brobert, Gunnar
Purpose The risk of venous thromboembolism (VTE) recurrence is high following an initial VTE event, and it persists over time. This recurrence risk decreases rapidly after starting with anticoagulation treatment and reduces by ~80%–90% with prolonged anticoagulation. Nonpersistence with anticoagulants could lead to increased risk of VTE recurrence. This systematic review aimed to estimate persistence at 3, 6, and 12 months with anticoagulants in patients with VTE, and to evaluate the risk of VTE recurrence in nonpersistent patients. Methods PubMed and Embase® were searched up to May 3, 2014 and the search results updated to May 31, 2015. Studies involving patients with VTE aged ≥18 years, treatment with anticoagulants intended for at least 3 months or more, and reporting data for persistence were included. Proportions were transformed using Freeman–Tukey double arcsine transformation and pooled using the DerSimonian–Laird random-effects approach. Results In total, 12 observational studies (7/12 conference abstracts) were included in the review. All 12 studies either reported or provided data for persistence. The total number of patients meta-analyzed to estimate persistence at 3, 6, and 12 months was 71,969 patients, 58,940 patients, and 68,235 patients, respectively. The estimated persistence for 3, 6, and 12 months of therapy was 83% (95% confidence interval [CI], 78–87; I2=99.3%), 62% (95% CI, 58–66; I2=98.1%), and 31% (95% CI, 22–40; I2=99.8%), respectively. Only two studies reported the risk of VTE recurrence based on nonpersistence – one at 3 months and the other at 12 months. Conclusion Limited evidence showed that persistence was suboptimal with an estimated 17% patients being nonpersistent with anticoagulants in the crucial first 3 months. Persistence declined over 6 and 12 months. Observational data on persistence with anticoagulation treatment, especially direct oral anticoagulants, in patients with VTE and its effect on risk of VTE
Vora, Pareen; Soriano-Gabarró, Montse; Suzart, Kiliana; Persson Brobert, Gunnar
The risk of venous thromboembolism (VTE) recurrence is high following an initial VTE event, and it persists over time. This recurrence risk decreases rapidly after starting with anticoagulation treatment and reduces by ~80%-90% with prolonged anticoagulation. Nonpersistence with anticoagulants could lead to increased risk of VTE recurrence. This systematic review aimed to estimate persistence at 3, 6, and 12 months with anticoagulants in patients with VTE, and to evaluate the risk of VTE recurrence in nonpersistent patients. PubMed and Embase(®) were searched up to May 3, 2014 and the search results updated to May 31, 2015. Studies involving patients with VTE aged ≥18 years, treatment with anticoagulants intended for at least 3 months or more, and reporting data for persistence were included. Proportions were transformed using Freeman-Tukey double arcsine transformation and pooled using the DerSimonian-Laird random-effects approach. In total, 12 observational studies (7/12 conference abstracts) were included in the review. All 12 studies either reported or provided data for persistence. The total number of patients meta-analyzed to estimate persistence at 3, 6, and 12 months was 71,969 patients, 58,940 patients, and 68,235 patients, respectively. The estimated persistence for 3, 6, and 12 months of therapy was 83% (95% confidence interval [CI], 78-87; I (2)=99.3%), 62% (95% CI, 58-66; I (2)=98.1%), and 31% (95% CI, 22-40; I (2)=99.8%), respectively. Only two studies reported the risk of VTE recurrence based on nonpersistence - one at 3 months and the other at 12 months. Limited evidence showed that persistence was suboptimal with an estimated 17% patients being nonpersistent with anticoagulants in the crucial first 3 months. Persistence declined over 6 and 12 months. Observational data on persistence with anticoagulation treatment, especially direct oral anticoagulants, in patients with VTE and its effect on risk of VTE recurrence were scarce and further
Barnes, Geoffrey D; Izzo, Brett; Conte, Marisa L; Chopra, Vineet; Holbrook, Anne; Fagerlin, Angela
Optimal care of patients with venous thromboembolism requires the input of patient preferences into clinical decision-making. However, the availability and impact of decision aids to facilitate shared decision making in care of venous thromboembolism is not well known. To assess the availability, clinical impact and outcomes associated with the use of decision aids in patients with or at risk for venous thromboembolism. A systematic review of the literature was performed exploring the use of decision aids in patients with venous thromboembolism. Criteria for primary inclusion required use of patient values clarification in the decision aid. A secondary review without the requirement of a patient values clarification was performed to be more inclusive. The data was summarized such that knowledge gaps and opportunities for enquiry were identified. The primary review identified one study that explored the decision to extend anticoagulation in patients with a recent venous thromboembolism beyond the stipulated 3-month duration. The secondary review identified an additional study exploring the decision to undergo computer tomography testing in patients at low risk for pulmonary embolism in an emergency department setting. Both studies were of modest quality given a lack of control group for comparison analysis. Despite numerous calls to increase use of shared decision-making, a paucity of data exists to help patients engage in the treatment decisions for venous thromboembolism. Future studies of additional VTE clinical decisions with longer-term clinical outcomes appear necessary. Copyright © 2016 Elsevier Ltd. All rights reserved.
Hald, Erin M; Brækkan, Sigrid K; Vik, Anders; Brodin, Ellen E; Hansen, John-Bjarne
Patients with arterial cardiovascular disease have increased postprandial lipemia, and plasma levels of postprandial remnants are related to the progression of atherosclerosis. Studies have shown that patients with unprovoked venous thromboembolism have increased risk of arterial cardiovascular disease. To investigate whether patients with a history of unprovoked venous thromboembolism have increased postprandial lipemia. A population-based case-control study was performed in 20 patients with a history of unprovoked venous thromboembolism and 20 age- and gender-matched healthy controls. Participants were subjected to a standard fat tolerance test (1 g/kilo body weight) with subsequent blood sampling every second hour for 8 hours. Lipids were measured by traditional methods and lipoprotein subclasses by proton nuclear magnetic resonance. Fasting lipids and lipoprotein subclasses did not differ between groups. The postprandial lipemia, assessed by the incremental area under the triglyceride curve, was not different in venous thromboembolism patients and healthy controls (5.0 ± 3.6 mmol/L∗h vs 5.3 ± 4.4 mmol/L∗h, P = .81). Similarly, the distribution and size of the lipoprotein subclasses obtained 4 hours postprandially did not differ between groups. Patients with a history of unprovoked venous thromboembolism had similar lipoprotein subclasses size, distribution, and postprandial lipemia as healthy controls. Our findings indicate that postprandial lipemia is not a link between unprovoked venous thromboembolism and arterial cardiovascular disease. Copyright © 2013 National Lipid Association. Published by Elsevier Inc. All rights reserved.
Sode, Birgitte F; Allin, Kristine H; Dahl, Morten; Gyntelberg, Finn; Nordestgaard, Børge G
ABO blood type locus has been reported to be an important genetic determinant of venous and arterial thrombosis in genome-wide association studies. We tested the hypothesis that ABO blood type alone and in combination with mutations in factor V Leiden R506Q and prothrombin G20210A is associated with the risk of venous thromboembolism and myocardial infarction in the general population. We used data from 2 Danish studies that followed members of the general public from 1977 through 2010. We obtained the genotype of 66 001 white participants for ABO blood type, factor V Leiden R506Q and prothrombin G20210A. We calculated hazard ratios (HRs) and population attributable risk. Our main outcome measures were venous thromboembolism and myocardial infarction. The multivariable adjusted HR for venous thromboembolism was 1.4 (95% confidence interval [CI] 1.3-1.5) for non-O blood type (v. O blood type). For the factor V Leiden R506Q mutation, the adjusted HR was 2.2 (95% CI 2.0-2.5) for heterozygous participants and 7.0 (95%CI 4.8-10) for homozygous participants (v. participants without the mutation). For prothrombin G20210A, the adjusted HR was 1.5 (95%CI 1.2-1.9) for heterozygous participants and 11 (95% CI 2.8-44) for homozygous participants (v. participants without the mutation). When we combined ABO blood type and factor V Leiden R506Q or prothrombin G20210A genotype, there was a stepwise increase in the risk of venous thromboembolism (trend, p<0.001). The population attributable risk of venous thromboembolism was 20% for ABO blood type, 10% for factor V Leiden R506Q and 1% for prothrombin G20210A. Multivariable adjusted HRs for myocardial infarction by genotypes did not differ from 1.0. ABO blood type had an additive effect on the risk of venous thromboembolism when combined with factor V Leiden R506Q and prothrombin G20210A mutations; blood type was the most important risk factor for venous thromboembolism in the general population.
Sode, Birgitte F.; Allin, Kristine H.; Dahl, Morten; Gyntelberg, Finn; Nordestgaard, Børge G.
Background: ABO blood type locus has been reported to be an important genetic determinant of venous and arterial thrombosis in genome-wide association studies. We tested the hypothesis that ABO blood type alone and in combination with mutations in factor V Leiden R506Q and prothrombin G20210A is associated with the risk of venous thromboembolism and myocardial infarction in the general population. Methods: We used data from 2 Danish studies that followed members of the general public from 1977 through 2010. We obtained the genotype of 66 001 white participants for ABO blood type, factor V Leiden R506Q and prothrombin G20210A. We calculated hazard ratios (HRs) and population attributable risk. Our main outcome measures were venous thromboembolism and myocardial infarction. Results: The multivariable adjusted HR for venous thromboembolism was 1.4 (95% confidence interval [CI] 1.3–1.5) for non-O blood type (v. O blood type). For the factor V Leiden R506Q mutation, the adjusted HR was 2.2 (95% CI 2.0–2.5) for heterozygous participants and 7.0 (95%CI 4.8–10) for homozygous participants (v. participants without the mutation). For prothrombin G20210A, the adjusted HR was 1.5 (95%CI 1.2–1.9) for heterozygous participants and 11 (95% CI 2.8–44) for homozygous participants (v. participants without the mutation). When we combined ABO blood type and factor V Leiden R506Q or prothrombin G20210A genotype, there was a stepwise increase in the risk of venous thromboembolism (trend, p < 0.001). The population attributable risk of venous thromboembolism was 20% for ABO blood type, 10% for factor V Leiden R506Q and 1% for prothrombin G20210A. Multivariable adjusted HRs for myocardial infarction by genotypes did not differ from 1.0. Interpretation: ABO blood type had an additive effect on the risk of venous thromboembolism when combined with factor V Leiden R506Q and prothrombin G20210A mutations; blood type was the most important risk factor for venous thromboembolism in
Venous Thromboembolism Prophylaxis in Meningioma Surgery: A Population-Based Comparative Effectiveness Study of Routine Mechanical Prophylaxis with or without Preoperative Low-Molecular-Weight Heparin.
Sjåvik, Kristin; Bartek, Jiri; Solheim, Ole; Ingebrigtsen, Tor; Gulati, Sasha; Sagberg, Lisa Millgård; Förander, Petter; Jakola, Asgeir Store
Venous thromboembolism (VTE) is a serious complication after intracranial meningioma surgery. To what extent systemic prophylaxis with pharmacotherapy is beneficial with respect to VTE risk, or associated with increased risk of bleeding and postoperative hemorrhage, remains debated. The current study aimed to clarify the risk/benefit ratio of prophylactic pharmacotherapy initiated the evening before craniotomy for meningioma. In a Scandinavian population-based cohort, we conducted a retrospective review of 979 operations for intracranial meningioma between 2007 and 2013 at 3 neurosurgical centers with population-based referral. We compared 2 different treatment strategies analyzing frequencies of VTE and proportions of postoperative intracranial hematomas requiring surgery or intensified subsequent observation or care (intensive care unit or other intensified observation or treatment). One neurosurgical center favored preoperative prophylaxis with low-molecular-weight heparin (LMWH) (LMWH routine group) in addition to mechanical prophylaxis, and 2 centers favored mechanical prophylaxis with LMWH only given as needed in cases of delayed mobilization (LMWH as needed group). In the LMWH routine group, VTE was diagnosed after 24/626 operations (3.9%), and VTE was diagnosed after 11/353 (3.1%) operations in the LMWH as needed group (P = 0.56). Clinically relevant postoperative hematomas occurred after 57/626 operations (9.1%) in the LMWH routine group compared with 23/353 (6.5%) in the LMWH as needed group (P = 0.16). Surgically evacuated postoperative hematomas occurred after 19/626 operations (3.0%) in the LMWH routine group compared with 8/353 operations (2.3%) in the LMWH as needed group (P = 0.26). There is no benefit of routine preoperative LMWH starting before intracranial meningioma surgery. Neither could we for primary outcomes detect a significant increase in clinically relevant postoperative hematomas secondary to this regimen. We suggest that as needed
Dobesh, Paul P; Stacy, Zachary A
The American College of Chest Physicians (ACCP) recommends unfractionated heparin (UFH) or low-molecular-weight heparin (LMWH) for prevention of venous thromboembolism (VTE) in medically ill patients. Despite these recommendations, a previous analysis at our institution revealed a low utilization of VTE prophylaxis in medically ill patients. Our objective was to evaluate the effects of a pharmacy-driven education program on the quantity and quality of VTE prophylaxis in medically ill patients. An educational program focusing on the importance of VTE prophylaxis in medically ill patients was developed by clinical pharmacists and presented to nurses, pharmacists, and physicians in a 493-bed community teaching hospital. The educational program was conducted between June 2002 and June 2003 and consisted of in-service presentations, newsletters, and quality assurance presentations on VTE prophylaxis. The educational program focused on 4 main points: (1) hospitalized medically ill patients are at risk for developing VTE, (2) how to identify medically ill patients who require VTE prophylaxis, (3) the fact that VTE prophylaxis is currently underutilized in medically ill patients, and (4) appropriate VTE prophylaxis strategies for medically ill patients. A posteducation retrospective chart review was performed in medically ill patients with discharge dates between October 2003 and March 2004, and these posteducation medical chart data were compared with the results from a preeducation analysis of patents with discharge dates from January 2001 to March 2002. Data collection included patient demographics, VTE risk factors, and use and type of VTE prophylaxis. The posteducation retrospective chart review was performed for 297 medically ill patients with discharge dates between October 2003 and March 2004 and for 344 preeducation patients discharged between January 2001 and March 2002. Patient demographics and primary diagnoses were similar between the preeducation and
Braekkan, S K; Grosse, S D; Okoroh, E M; Tsai, J; Cannegieter, S C; Naess, I A; Krokstad, S; Hansen, J-B; Skjeldestad, F E
Essentials The burden of venous thromboembolism (VTE) related to permanent work-related disability is unknown. In a cohort of 66 005 individuals, the risk of work-related disability after a VTE was assessed. Unprovoked VTE was associated with 52% increased risk of work-related disability. This suggests that indirect costs due to loss of work time may add to the economic burden of VTE. Background The burden of venous thromboembolism (VTE) related to permanent work-related disability has never been assessed among a general population. Therefore, we aimed to estimate the risk of work-related disability in subjects with incident VTE compared with those without VTE in a population-based cohort. Methods From the Tromsø Study and the Nord-Trøndelag Health Study (HUNT), Norway, 66 005 individuals aged 20-65 years were enrolled in 1994-1997 and followed to 31 December 2008. Incident VTE events among the study participants were identified and validated, and information on work-related disability was obtained from the Norwegian National Insurance Administration database. Cox-regression models using age as time-scale and VTE as time-varying exposure were used to estimate hazard ratios (HRs) with 95% confidence intervals (CIs) adjusted for sex, body mass index, smoking, education level, marital status, history of cancer, diabetes, cardiovascular disease and self-rated general health. Results During follow-up, 384 subjects had a first VTE and 9862 participants were granted disability pension. The crude incidence rate of work-related disability after VTE was 37.5 (95% CI, 29.7-47.3) per 1000 person-years, vs. 13.5 (13.2-13.7) per 1000 person-years among those without VTE. Subjects with unprovoked VTE had a 52% higher risk of work-related disability than those without VTE (HR, 1.52; 95% CI, 1.09-2.14) after multivariable adjustment, and the association appeared to be driven by deep vein thrombosis. Conclusion VTE was associated with subsequent work-related disability in a cohort
Bjøri, E; Arshad, N; Johnsen, H S; Hansen, J-B; Braekkan, S K
Essentials Recurrence risk after a hospital-related venous thromboembolism (VTE) is underinvestigated. We explored this association in a cohort of patients with a first VTE from the Tromsø study. Stratification on hospital-related factors revealed considerable differences in recurrence risk. The recurrence risk was high in cases with a VTE related to hospitalization for medical illness. Background Hospitalization is a well-established risk factor for first venous thromboembolism (VTE), but the risk of recurrence, particularly in patients hospitalized for conditions other than cancer or surgery, has scarcely been investigated. The cumulative incidence of recurrence in hospital-related VTE may be influenced by the competing risk of death. Objectives To investigate the risk of recurrence and mortality among patients with a first hospital-related VTE in models with and without death as a competing event. Methods Information on hospital-related risk factors was collected in 822 patients with a first-lifetime VTE derived from the Tromsø study. Recurrent VTEs and deaths were recorded during follow-up (1994-2012). Results During a median of 2.79 years of follow-up, 132 patients experienced a recurrent VTE. Stratification on hospital-related factors revealed considerable differences in recurrence risk. The 5-year cumulative incidence of recurrence was 27.4%, 11.0% and 20.1% in patients with incident VTEs related to cancer, surgery or other medical illness, respectively, and 18.4% in patients with a non-hospital-related first VTE. The mortality rates were high for all subgroups of hospital-related VTE, except for surgery-related events. Consequently, the cumulative incidence of recurrence dropped in the competing risk analyses, showing a 5-year cumulative incidence of 14.4%, 11.7% and 9.7% in patients with a first VTE related to hospitalization for other medical illness, cancer or surgery, respectively. Conclusions Our findings suggest that patients with incident VTEs
Mannucci, Pier Mannuccio; Franchini, Massimo
Thrombophilia is defined as a condition predisposing to the development of venous thromboembolic complications. Over the past decades, there have been great advances in the understanding of the pathogenesis of venous thromboembolism (VTE) through the identification of several inherited and acquired risk factors. However, in spite of such progress, a number of questions remain unanswered. In particular, it is well known that some subjects carrying several risk factors for VTE will never experience a thrombotic episode while other individuals developed recurrent thromboembolic events with no known risk factor. In this review, we summarize the current knowledge on the various thrombophilia markers, and also discuss their role in the development of thrombotic complications.
Borch, Knut H.; Hansen-Krone, Ida; Braekkan, Sigrid K.; Mathiesen, Ellisiv B.; Njolstad, Inger; Wilsgaard, Tom; Hansen, John-Bjarne
Background Previous studies have shown differences in the impact of regular physical exercise on the risk of venous thromboembolism. The inconsistent findings may have depended on differences in study design and specific population cohorts (men only, women only and elderly). We conducted a prospective, population-based cohort to investigate the impact of regular physical exercise on the risk of venous thromboembolism. Design and Methods Risk factors, including self-reported moderate intensity physical exercise during leisure time, were recorded for 26,490 people aged 25–97 years old, who participated in a population health survey, the Tromsø study, in 1994–95. Incident venous thromboembolic events were registered during the follow-up until September 1, 2007. Results There were 460 validated incident venous thromboembolic events (1.61 per 1000 person-years) during a median of 12.5 years of follow-up. Age, body mass index, the proportion of daily smokers, total cholesterol, and serum triglycerides decreased (P<0.001), whereas high density cholesterol increased (P<0.001) across categories of more physical exercise. Regular physical exercise of moderate to high intensity during leisure time did not significantly affect the risk of venous thromboembolism in the general population. However, compared to inactivity, high amounts of physical exercise (≥3 hours/week) tended to increase the risk of provoked venous thromboembolism (multivariable hazard ratio, 1.30; 95% confidence interval, 0.84–2.0), and total venous thromboembolism in the elderly (multivariable hazard ratio, 1.33; 95% confidence interval, 0.80–2.21) and in the obese (multivariable hazard ratio, 1.49; 95% confidence interval, 0.63–3.50). Contrariwise, compared to inactivity, moderate physical activity (1.0–2.9 hours/week) was associated with a border-line significant decreased risk of venous thromboembolism among subjects under 60 years old (multivariable hazard ratio, 0.72; 95% confidence
Suenaga, Mitsukuni; Mizunuma, Nobuyuki; Kobayashi, Kokoro; Shinozaki, Eiji; Matsusaka, Satoshi; Chin, Keisho; Kuboki, Yasutoshi; Ichimura, Takashi; Ozaka, Masato; Ogura, Mariko; Fujiwara, Yoshimasa; Matsueda, Kiyoshi; Konishi, Fumio; Hatake, Kiyohiko
Venous thromboembolism associated with use of a central venous access system is an urgent problem in patients treated with bevacizumab (bev). We investigated the effectiveness of Doppler ultrasound imaging (DUS) in the early detection of catheter-related thrombosis for avoidance of severe venous thromboembolism. Patients with metastatic colorectal cancer received either FOLFOX-4 + bev or FOLFIRI + bev. DUS was performed on the deep venous system for detection of thrombus formation during the initial cycle of treatment, followed by re-evaluation after the third cycle in patients with asymptomatic thrombus formation. All patients were followed up until treatment was interrupted. Median duration of follow-up was 484 days (range 72-574). Among 41 enrolled patients, curable symptomatic thrombosis occurred in one, and asymptomatic thrombosis in 21 (51.2%). Of 21 patients undergoing re-evaluation, thrombi remained without progression in 17 patients, and enlargement in 4 patients. In two of the patients in whom there was progression, pulmonary embolism occurred after the sixth cycle. In the asymptomatic group, no thrombi developed as far as the superior vena cava in any patient. In the cases of progression, thrombotic enlargement was observed in all the 4 patients, with decreased vascular flow in 2. Using DUS, we were able to detect asymptomatic thrombosis in the early cycles of treatment, indicating its potential in the monitoring of venous thrombi. In the event of an enlarging asymptomatic thrombosis developing into the superior vena cava along with decreased vascular flow, careful follow-up and appropriate anticoagulant therapy may be recommended without increased risk of bleeding.
Weitz, Jeffrey I; Jaffer, Iqbal H; Fredenburgh, James C
The direct oral anticoagulants (DOACs) have now supplanted vitamin K antagonists (VKAs) for the treatment of venous thromboembolism (VTE). The DOACs include dabigatran, which inhibits thrombin, and rivaroxaban, apixaban, and edoxaban, which inhibit factor Xa. The DOACs are as effective for the prevention of recurrence as conventional VTE treatment, consisting of a parenteral anticoagulant followed by a VKA, and are associated with less bleeding. Because of these properties and the convenience of fixed dosing without the need for routine coagulation monitoring, guidelines now recommend DOACs over VKAs for VTE treatment in patients without active cancer. This paper examines the increasing role of the DOACs for VTE treatment.
Martín-Martos, Francisco; Trujillo-Santos, Javier; Barrón, Manuel; Vela, Jerónimo; Javier Marchena, Pablo; Braester, Andrei; Hij, Adrian; Hernández-Blasco, Luis; Verhamme, Peter; Manuel, Monreal
The outcome of cancer patients with acute venous thromboembolism (VTE) may differ according to gender. We used the RIETE database to compare the rate of VTE (pulmonary embolism [PE] or deep vein thrombosis [DVT]) recurrences), major bleeding and mortality during the course of anticoagulation, according to gender. As of August 2014, 11,055 patients with active cancer were enrolled in RIETE, of whom 5,104 (46%) were women. During the course of anticoagulation (mean: 142 days), 505 patients developed recurrent VTE, 429 bled and 2730 died. Compared with men, women had a significantly lower rate of fatal bleeding (risk ratio [RR]: 0.69; 95% CI: 0.47-0.99) and death (RR: 0.90; 95% CI: 0.83-0.97), and a non-significantly lower rate of PE recurrences (RR 0.83; 95% CI: 0.65-1.06) and major bleeding (RR: 0.89; 95% CI: 0.74-1.08). During the course of anticoagulation, cancer women with VTE had a better outcome than men. © 2015 Elsevier Ltd. All rights reserved.
Masopust, Jiří; Malý, Radovan; Vališ, Martin
The evidence to date on the relation between the risk of venous thromboembolic disease (VTE) and antipsychotic agents derives primarily from observational and case history studies. While an increased risk of VTE has been associated with first-generation low-potency antipsychotic agents, particularly clozapine, there appears to be a growing number of reports on the occurrence of this adverse reaction during the use of second-generation antipsychotics, such as risperidone and olanzapine. The highest risk of pathological blood clotting emerges during the first 3 months after initiation of treatment with the product. Potential etiopathogenetic factors leading to VTE during treatment with antipsychotic agents include sedation, obesity, elevation of antiphospholipid antibodies, increased platelet activation and aggregation, hyperhomocysteinemia, and hyperprolactinemia. Diagnoses of schizophrenia and/or bipolar affective disorder, as well as hospitalization or stress with sympathetic activation and elevation of catecholamine levels, have been reported as known prothrombogenic factors. The present article contains the new version of the guideline for the prevention of VTE in psychiatric patients with limited mobility. Further prospective studies are necessary to elucidate the biological mechanisms of the relations between antipsychotic agents and VTE. © 2012 The Authors. Psychiatry and Clinical Neurosciences © 2012 Japanese Society of Psychiatry and Neurology.
Kim, Victor; Goel, Nishant; Gangar, Jinal; Zhao, Huaqing; Ciccolella, David E.; Silverman, Edwin K.; Crapo, James D.; Criner, Gerard J.
Background: COPD patients are at increased risk for venous thromboembolism (VTE). VTE however remains under-diagnosed in this population and the clinical profile of VTE in COPD is unclear. Methods: Global initiative for chronic Obstructive Lung Disease (GOLD) stages II-IV participants in the COPD Genetic Epidemiology (COPDGene) study were divided into 2 groups: VTE+, those who reported a history of VTE by questionnaire, and VTE-, those who did not. We compared variables in these 2 groups with either t-test or chi-squared test for continuous and categorical variables, respectively. We performed a univariate logistic regression for VTE, and then a multivariate logistic regression using the significant predictors of interest in the univariate analysis to ascertain the determinants of VTE. Results: The VTE+ group was older, more likely to be Caucasian, had a higher body mass index (BMI), smoking history, used oxygen, had a lower 6-minute walk distance, worse quality of life scores, and more dyspnea and respiratory exacerbations than the VTE- group. Lung function was not different between groups. A greater percentage of the VTE+ group described multiple medical comorbidities. On multivariate analysis, BMI, 6-minute walk distance, pneumothorax, peripheral vascular disease, and congestive heart failure significantly increased the odds for VTE by history. Conclusions: BMI, exercise capacity, and medical comorbidities were significantly associated with VTE in moderate to severe COPD. Clinicians should suspect VTE in patients who present with dyspnea and should consider possibilities other than infection as causes of COPD exacerbation. PMID:25844397
Meyer, Melissa R.; Witt, Daniel M.; Delate, Thomas; Johnson, Samuel G.; Fang, Margaret; Go, Alan; Clark, Nathan P.
Background Thrombophilia testing has limited value in determining the selection and duration of anticoagulation therapy for venous thromboembolism (VTE), yet is commonly performed. This study describes the patterns and appropriateness of thrombophilia testing in a large cohort of patients with acute VTE. Materials and methods This was a retrospective study of a random sample of patients with a validated diagnosis of acute VTE diagnosed between January 1, 2004 and December 31, 2010. Events were identified from administrative data and verified via manual review. Patients were grouped by thrombophilia testing status and compared on patient characteristics and thrombophilia testing results and appropriateness. Results Of 1,314 patients with validated VTE, 315 (24%) underwent thrombophilia testing, 62 (20%) of whom had ≥ 1 positive test. Tested patients were younger and more likely to have had a family history of VTE. Factor V Leiden (17%) and prothrombin G20210A mutation (4%) were the most commonly detected thrombophilias. Only 31 (10%) of tested patients met eligibility criteria for thrombophilia testing (i.e., at least one strong thrombophilic risk factor present) and were tested at least 90 days following unprovoked index VTE. Conclusions Thrombophilia is commonly evaluated in patients without a clear indication for testing and during times where results may be unreliable. Future studies are needed to assess interventions aimed at reducing inappropriate thrombophilia testing without adversely affecting patient outcomes. PMID:26477821
Barnes, Geoffrey D; Kanthi, Yogendra; Froehlich, James B
Initial treatment for venous thromboembolism (VTE) includes the acute and intermediate phases, usually lasting for 3 months. The choice to extend therapy beyond the initial 3-month window involves assessing a combination of risk factors for VTE recurrence and bleeding, along with weighing patient preferences. In some cases, such as VTE provoked by a reversible surgical risk factor, the recurrence risk is sufficiently low that most patients should not receive extended therapy. In other cases, such as VTE associated with malignancy, the recurrence risk is sufficiently high that treatment should be extended beyond the initial 3 months. However, a large number of patients fall into a grey zone where the decision on extended therapy is less clear-cut. In this review, we summarize the evidence for VTE recurrence risk and the role for extended anticoagulation given a variety of patient-specific factors and laboratory results. We also review the role of VTE risk prediction tools and provide a recommended algorithm for approaching the decision of extended anticoagulation therapy. Various agents available for extended VTE therapy, including warfarin, aspirin and the direct oral anticoagulant agents, are discussed. PMID:25832602
Akpinar, Evrim Eylem; Hosgün, Derya; Akan, Burak; Ates, Can; Gülhan, Meral
OBJECTIVE: Pulmonary embolism (PE) is an important complication of major orthopedic surgery. The aim of this study was to evaluate the incidence of venous thromboembolism (VTE) and factors influencing the development of VTE in patients undergoing major orthopedic surgery in a university hospital. METHODS: Patients who underwent major orthopedic surgery (hip arthroplasty, knee arthroplasty, or femur fracture repair) between February of 2006 and June of 2012 were retrospectively included in the study. The incidences of PE and deep vein thrombosis (DVT) were evaluated, as were the factors influencing their development, such as type of operation, age, and comorbidities. RESULTS: We reviewed the medical records of 1,306 patients. The proportions of knee arthroplasty, hip arthroplasty, and femur fracture repair were 63.4%, 29.9%, and 6.7%, respectively. The cumulative incidence of PE and DVT in patients undergoing major orthopedic surgery was 1.99% and 2.22%, respectively. Most of the patients presented with PE and DVT (61.5% and 72.4%, respectively) within the first 72 h after surgery. Patients undergoing femur fracture repair, those aged ≥ 65 years, and bedridden patients were at a higher risk for developing VTE. CONCLUSIONS: Our results show that VTE was a significant complication of major orthopedic surgery, despite the use of thromboprophylaxis. Clinicians should be aware of VTE, especially during the perioperative period and in bedridden, elderly patients (≥ 65 years of age). PMID:23857692
Pabinger, Ingrid; Thaler, Johannes; Ay, Cihan
Cancer patients are at increased risk of deep vein thrombosis and pulmonary embolism. The incidence among different groups of cancer patients varies considerably depending on clinical factors, the most important being tumor entity and stage. Biomarkers have been specifically investigated for their capacity of predicting venous thromboembolism (VTE) during the course of disease. Parameters of blood count analysis (elevated leukocyte and platelet count and decreased hemoglobin) have turned out to be useful in risk prediction. Associations between elevated levels and future VTE have been found for d-dimer, prothrombin fragment 1+2, and soluble P-selectin and also for clotting factor VIII and the thrombin generation potential. The results for tissue factor-bearing microparticles are heterogeneous: an association with occurrence of VTE in pancreatic cancer might be present, whereas in other cancer entities, such as glioblastoma, colorectal, or gastric carcinoma, this could not be confirmed. Risk assessment models were developed that include clinical and laboratory markers. In the high-risk categories, patient groups with up to a >20% VTE rate within 6 months can be identified. A further improvement in risk stratification would allow better identification of patients for primary VTE prevention using indirect or novel direct anticoagulants.
Isoda, Atsushi; Sato, Naru; Miyazawa, Yuri; Matsumoto, Yoshinobu; Koumoto, Mina; Ookawa, Masahito; Sawamura, Morio; Matsumoto, Morio
Lenalidomide treatment in combination with dexamethasone and/or chemotherapy is associated with a significant risk of venous thromboembolism (VTE) in patients with multiple myeloma (MM). However, the incidence of asymptomatic VTE in lenalidomide-treated MM patients remains unclear. A total of 80 relapsed and refractory MM patients treated with lenalidomide-containing regimens in a single institution between July 2010 and July 2014 were retrospectively analyzed. Of these, eight patients had asymptomatic VTE before starting lenalidomide. The remaining 72 patients received thromboprophylaxis with low-dose aspirin (100 mg daily) and monitoring of plasma D-dimer levels on each visit. During the median follow-up time of 7.3 months (range 1.0-43.5 months), 29 patients (40.3 %) showed an elevation of D-dimer (≥2.5 μg/mL), and 13 (18.1 %) showed asymptomatic VTE in a lower extremity. Median time to asymptomatic VTE events from initiation of lenalidomide treatment was 3.0 months (range 1.0-13.1 months). All patients having an asymptomatic VTE continued lenalidomide treatment on warfarinization (target international normalized ratio 1.5-2.5), and none of them developed symptomatic VTE. In conclusion, an asymptomatic VTE event occurred in 18 % of Japanese MM patients receiving lenalidomide-containing therapy despite aspirin prophylaxis. Serial monitoring of plasma D-dimer levels and early intervention may help to prevent symptomatic or lethal VTE events.
Reid, Robert L
Post-marketing surveillance of combined oral contraceptives (COCs) for rare complications such as venous thromboembolism (VTE) presents unique challenges. Prospective studies, which are costly and time consuming, have to date been undertaken by only a few contraceptive manufacturers willing to commit to full evaluation of product safety. Often such studies are conducted with the approval of regulatory authorities as a precondition for marketing. Alternatively, independent investigators with access to large databases have conducted retrospective studies to compare the incidence of VTE between new and older products. Such studies, however, run the risk of erroneous conclusions if they cannot ensure comparable risk profiles for users of these different products. Often database studies are unable to access information on important confounders, and medical records may not be available to validate the actual diagnosis of VTE. "Pill scares" generated following publication and media dissemination of worrisome findings, when the conclusions are in doubt and not corroborated by stronger prospective study designs, are frequently damaging to public health. From a review of recent publications on the VTE risk with drospirenone-containing COCs, it can be concluded that the best quality evidence does not support a difference in risk between users of COCs containing drospirenone and those of COCs containing levonorgestrel.
Bohler, Iain; George Mackenzie Jardine, Alan
Efficacy of clinical guidelines to improve patient care is highly dependent on the ability of hospital teams to interpret and implement advised standards of care. Trimester and bi-annual rotation changes often see transference and loss of acquired experience and knowledge from wards with ensuing shortfalls in patient safety and care quality. Such shortfalls were noticed in the ability of our unit to adhere to national venous thromboembolism (VTE) prophylaxis measures. A prospective quality improvement audit was embarked upon to address this. An initial audit of VTE prophylaxis in 112 patients demonstrated just 71% compliance with suggested measures. Errors were predominantly medical in origin and secondary to poor understanding, interpretation, and knowledge of VTE guidelines. Errors were also noted in nursing and patient compliance to measures. Repeated re-auditing demonstrated increased error (following initial improvement post audit) after periods of medical staff rotation. Through education of junior medical and nursing staff, and of patients, the unit was able to achieve 100% compliance. Rota changes often induce conflict of interest between maintaining adequate services and high levels of patient care or providing suitable and informed induction programmes for new medical staff. Emphasised education of VTE prophylaxis guidelines has now become part of induction of junior medical staff, whilst ward based measures ensure daily compliance. The success of the audit strategy has led to its use throughout other surgical units within the hospital.
Kwok, Amy M; Davis, James W; Dirks, Rachel C; Wolfe, Mary M; Kaups, Krista L
The safety and timing of venous thromboembolism (VTE) prophylaxis in patients with blunt splenic injuries is not well known. We hypothesized that early initiation of VTE prophylaxis does not increase failure of nonoperative management or transfusion requirements in these patients. A retrospective review of trauma patients with blunt splenic injury was performed. Patients were compared based on initiation and timing of VTE prophylaxis (<24 hours, 24 to 48 hours, 48 to 72 hours, and >72 hours). Patients who received VTE prophylaxis were matched with those who did not. Primary outcomes included were operation or angioembolization. A total of 497 patients (256 received VTE prophylaxis and 241 did not) were included. There was no difference in the number of interventions based on presence of or time to VTE prophylaxis initiation. Early initiation (<48 hours) of VTE prophylaxis is safe in patients with blunt splenic injuries treated nonoperatively, and may be safe as early as 24 hours. Copyright Â© 2016 Elsevier Inc. All rights reserved.
Conway, Susan E; Marcy, Todd R
Clinical practice guidelines currently suggest extended anticoagulation therapy for primary and secondary prevention of venous thromboembolism (VTE). The optimal duration of anticoagulation has been an active area of clinical investigation for patients undergoing orthopedic surgeries and those diagnosed with a first episode of unprovoked VTE. Practice guidelines, VTE incidence, clinical predictors/mediators, and clinical trial evidence is reviewed to help pharmacists and other health care providers make an informed, patient-specific decision on the optimal duration of anticoagulation therapy. Extended anticoagulation up to 5 weeks following orthopedic surgery for primary VTE prevention and indefinitely following a first episode of unprovoked VTE for secondary VTE prevention should be considered only if the risk of bleeding is not high and the cost and burden of anticoagulation is acceptable to the patient. The optimal duration of anticoagulation therapy for primary or secondary prevention of VTE should include the health care provider and patient making a decision based on evaluation of individual benefits, risks, and preferences.
Blanco-Molina, A; Rota, L L; Di Micco, P; Brenner, B; Trujillo-Santos, J; Ruiz-Gamietea, A; Monreal, M
Venous thromboembolism (VTE) is a leading cause of maternal death during pregnancy or postpartum, and in women using hormonal contraceptives. However, important issues concerning its natural history and therapy remain unsolved, and most of the protocols for treatment of VTE in this patient population are based on data extrapolated from other populations. RIETE is an ongoing registry of consecutive patients with objectively confirmed, symptomatic, acute VTE. We examined the clinical characteristics and three-month outcome of all enrolled women with pregnancy, postpartum or using hormonal contraceptives. As of December 2008, 173 pregnant women, 135 postpartum, and 798 contraceptive users were enrolled. Of these, 438 (40%) presented with pulmonary embolism (PE) and 668 with deep-vein thrombosis (DVT). Most women with acute PE had dyspnea (72%) or chest pain (75%), but only 2.0% had hypoxaemia. During the three-month study period, five women (0.45%; 95% CI: 0.17-1.00) died (3 had fatal PE), 13 (1.18%; 95% CI: 0.66-1.95) had VTE recurrences, and seven (0.63%; 95% CI: 0.28-1.25) major bleeding. Two of the three women with fatal PE died during the first few hours after arriving at the emergency ward, with no time to start any therapy. The outcome of pregnant or postpartum women with VTE is similar to that in contraceptive users, even though the treatment is different. The non-specific nature of PE signs may have caused some delay in PE diagnosis.
Villani, Michela; Ageno, Walter; Grandone, Elvira; Dentali, Francesco
Venous thromboembolism (VTE) in pregnancy represents an important cause of maternal morbidity and mortality in developed countries, with an incidence of 0.5-2.2 per 1000 pregnancies. In addition to hemostatic changes occurring during normal pregnancy, several risk factors have been identified. Thus, a variety of clinical conditions as well as fetal and maternal risks linked to a possible anticoagulant therapy should be considered for the management of VTE during pregnancy. Unfortunately, there is a paucity of high-quality evidence from randomized trials in this field, and current recommendations are based on observational studies or evidence gathered from studies in the non-pregnant population. Areas covered: The purpose of this review is to summarize available evidence on the prevention and treatment of pregnancy-related VTE. Expert commentary: Although the optimal prophylactic and therapeutic dosage has not yet been established, low-molecular-weight heparin (LMWH) represents the most efficacious and safe anticoagulant during pregnancy. Thus, after an accurate risk stratification of women during pregnancy and puerperium, LMWH should be recommended to women at risk for VTE and to those ones suffering from an acute event.
Marcucci, Maura; Iorio, Alfonso; Nobili, Alessandro; Tettamanti, Mauro; Pasina, Luca; Djade, Codjo Djignefa; Marengoni, Alessandra; Salerno, Francesco; Corrao, Salvatore; Mannucci, Pier Mannuccio
Pharmacological thromboprophylaxis (TP) is known to reduce venous thromboembolism (VTE) in medical inpatients, but the criteria for risk-driven prescription, safety and impact on mortality are still debated. We analyze data on elderly patients with multimorbidities admitted in the year 2010 to the Italian internal medicine wards participating in the REPOSI registry to investigate the rate of TP during the hospital stay, and analyze the factors that are related to its prescription. Multivariate logistic regression, area under the ROC curve and CART analysis were performed to look for independent predictors of TP prescription. Association between TP and VTE, bleeding and death in hospital and during the 3-month post-discharge follow-up were explored by logistic regression and propensity score analysis. Among the 1,380 patients enrolled, 171 (15.2 %) were on TP during the hospital stay (162 on low molecular weight heparins, 9 on fondaparinux). The disability Barthel index was the main independent predictor of TP prescription. Rate of fatal and non-fatal VTE and bleeding during and after hospitalization did not differ between TP and non-TP patients. In-hospital and post-discharge mortality was significantly higher in patients on TP, that however was not an independent predictor of mortality. Among elderly medical patients there was a relatively low rate of TP, that was more frequently prescribed to patients with a higher degree of disability and who had an overall higher mortality.
Hilger, Hans; von Beckerath, Olga; Kröger, Knut
We analysed the rate of physical restraint in acute and chronic psychiatric patients and looked at the safety of waiving venous thromboembolic disease (VTE) prophylaxis in the case of restraining of less than 24 h. We did a retrospective analysis of all episodes of restraining in 2012 and 2013, diagnosis of restrained patients, time of restraining and use of low molecular weight heparin (LMWH) for prophylaxis of VTE associated with restraining. Overall, 12 734 patients were hospitalised. The number of episodes of restraining was 1035 and involved 469 (7.4%) patients. Only 79 episodes of restraining lasted more than 24 h and affected only 36 (0.3%) individual patients. The most frequent psychiatric diagnoses were unstable borderline personality in 41 (52%) and schizophrenic or schizoaffective psychosis in 26 (33%) episodes. None of these prolonged restraints and none of the 956 episodes of restraining for less than 24 h were associated with clinical symptoms or signs of VTE that would have required additional diagnostic consequences. The concept of waiving VTE prophylaxis within the first 24 h of restraining seems to be safe. On the other hand, LMWH sufficiently protected the small sample being restrained for more than 24 h.
Gran, O V; Braekkan, S K; Paulsen, B; Skille, H; Rosendaal, F R; Hansen, J-B
Essentials Recurrence risk after an occult cancer-related incident venous thromboembolism (VTE) is unknown. We compared the risk of VTE recurrence in occult-, overt- and non-cancer related first VTE. Patients with occult-cancer related first VTE had the highest risk of VTE recurrence. The high recurrence risk in occult cancer is likely due to the advanced cancers. Background Although venous thromboembolism (VTE) is associated with a high recurrence rate, the absolute recurrence rates for cancer-related VTE, particularly occult cancer, are not well known. Objectives To investigate the risk of VTE recurrence in patients with occult and overt cancer-related VTE. Methods Incident VTE events among participants of the first to sixth Tromsø surveys occurring in the period 1994-2012 were included. Occult cancer was defined as cancer diagnosed within a year following a VTE, and overt cancer was defined as cancer diagnosed within the 2 years before a VTE. Results Among 733 patients with incident VTE, 110 had overt cancer and 40 had occult cancer. There were 95 recurrent VTE events during a median of 3.2 years of follow-up. The 1-year cumulative incidence of VTE recurrence was 38.6% in subjects with occult cancer, 15.5% in subjects with overt cancer, and 3.8% in non-cancer subjects. The 1-year risk of recurrence was 12-fold (hazard ratio [HR] 12.4, 95% confidence interval [CI] 5.9-26.3) higher in subjects with occult cancer and four-fold (HR 4.3, 95% CI 2.0-9.2) higher in subjects with overt cancer than in non-cancer subjects. The occult cancers associated with VTE recurrence were typically located at prothrombotic sites (i.e. lung and gastrointestinal) and presented at advanced stages. The majority (69%) of recurrences in subjects with occult cancer occurred before or shortly after cancer diagnosis, and were therefore not treatment-related. Conclusion Our findings suggest that the increased risk of recurrence in patients with occult cancer is mainly attributable to the
Mi, Yuhong; Yan, Shufeng; Lu, Yanhui; Liang, Ying; Li, Chunsheng
Abstract Background: Previous studies have shown that idiopathic pulmonary embolism is positively associated with other cardiovascular events, such as myocardial infarction and stroke, suggesting a potentially important association between atherosclerosis risk factors and venous thromboembolism (VTE). We performed a meta-analysis to evaluate the correlation between risk factors for atherosclerosis and VTE. Methods: In December 2014, we searched MEDLINE and EMBASE for studies evaluating the associations between VTE and risk factors for atherosclerosis and pooled outcome data using random-effects meta-analysis. In addition, we analyzed publication bias. Results: Thirty-three case-control and cohort studies with a total of 185,124 patients met the inclusion criteria. We found that participants with body mass index (BMI) ≥30 kg/m2 had a significantly higher prevalence of VTE than those with BMI <30 kg/m2 in both case-control studies (odds ratio [OR] = 2.45, 95% confidence interval [CI]: 1.78–3.35) and cohort studies (relative risk [RR] = 2.39, 95% CI: 1.79–3.17). VTE was more prevalent in patients with hypertension than without hypertension (OR = 1.40, 95% CI: 1.06–1.84; RR = 1.36, 95% CI: 1.11–1.67). The findings were similar for VTE prevalence between patients with and without diabetes (OR = 1.78, 95% CI: 1.17–2.69; RR = 1.41, 95% CI: 1.20–1.66). Current smoking was significantly associated with VTE prevalence in case-control studies (OR = 1.34, 95% CI: 1.01–1.77), but not in cohort studies (RR = 1.29, 95% CI: 0.96–1.72). In addition, we found that total cholesterol and triglyceride concentrations were significantly higher in patients with VTE than without VTE (weighted mean differences [WMD] = 8.94 mg/dL, 95% CI: 3.52–14.35 mg/dL, and WMD = 14.00 mg/dL, 95% CI: 8.85–19.16 mg/dL, respectively). High-density lipoprotein cholesterol concentrations were significantly lower in patients with VTE
Schouten, Henrike J.; Koek, Huiberdina L.; Kruisman-Ebbers, Marije; Geersing, Geert-Jan; Oudega, Ruud; Kars, Marijke C.; Moons, Karel G. M.; van Delden, Johannes J. M.
Background This study aimed to gather insights in physicians' considerations for decisions to either refer for- or to withhold additional diagnostic investigations in nursing home patients with a suspicion of venous thromboembolism. Methods Our study was nested in an observational study on diagnostic strategies for suspected venous thromboembolism in nursing home patients. Patient characteristics, bleeding-complications and mortality were related to the decision to withhold investigations. For a better understanding of the physicians' decisions, 21 individual face-to-face in-depth interviews were performed and analysed using the grounded theory approach. Results Referal for additional diagnostic investigations was forgone in 126/322 (39.1%) patients with an indication for diagnostic work-up. ‘Blind’ anticoagulant treatment was initiated in 95 (75.4%) of these patients. The 3month mortality rates were higher for patients in whom investigations were withheld than in the referred patients, irrespective of anticoagulant treatment (odds ratio 2.45; 95% confidence interval 1.40 to 4.29) but when adjusted for the probability of being referred (i.e. the propensity score), there was no relation of non-diagnosis decisions to mortality (odds ratio 1.75; 0.98 to 3.11). In their decisions to forgo diagnostic investigations, physicians incorporated the estimated relative impact of the potential disease; the potential net-benefits of diagnostic investigations and whether performing investigations agreed with established management goals in advance care planning. Conclusion Referral for additional diagnostic investigations is withheld in almost 40% of Dutch nursing home patients with suspected venous thromboembolism and an indication for diagnostic work-up. We propose that, given the complexity of these decisions and the uncertainty regarding their indirect effects on patient outcome, more attention should be focused on the decision to either use or withhold additional
Patel, Markand; Harris, Mark; Tapply, Ian; Longman, Rob
Extended venous thromboembolism prophylaxis (EVTEP) with low-molecular weight heparin such as enoxaparin for 28 days following surgery for cancer significantly reduces venous thromboembolic events compared to a standard 6-10 day course. National Institute of Clinical Excellence (NICE) guidelines suggest EVTEP should be offered to patients undergoing colorectal cancer surgery. Local EVTEP prescribing and monitoring guidelines in a busy inner city teaching hospital colorectal surgery unit, were devised to ensure NICE guidelines are followed. Adherence to local EVTEP guidelines was recorded through a retrospective audit of patients undergoing elective colorectal cancer surgery during February 2011 (n=19). Prospective re-audit cycles were undertaken during April-May (n=17) and September-December 2012 (n=17). The first audit cycle revealed that overall standards were not being met with just 11% of ‘at risk’ patients being correctly identified in pre-operative assessment clinic and continued low adherence to guidelines on the ward with only 44% of patients being prescribed EVTEP at discharge. Following each audit cycle, educational interventions were directed towards the multi-disciplinary team involved in the care of patients undergoing colorectal cancer surgery. This involved education of the team members regarding EVTEP, presentation of the audit results with instruction for improvement. Results of the second and third audit cycles showed improvements in guideline adherence with 100% of patients in these cohorts having been prescribed EVTEP at discharge. Marked improvements were also seen in the correct identification of ‘at risk’ patients, patient education in pre-operative assessment clinic, and warning of potential side-effects. This project has shown a significant global improvement in EVTEP-related patient care and adherence to local guidelines following education of the multi-disciplinary team involved, which consequently reduced the risk of venous
Patel, Markand; Harris, Mark; Tapply, Ian; Longman, Rob
Extended venous thromboembolism prophylaxis (EVTEP) with low-molecular weight heparin such as enoxaparin for 28 days following surgery for cancer significantly reduces venous thromboembolic events compared to a standard 6-10 day course. National Institute of Clinical Excellence (NICE) guidelines suggest EVTEP should be offered to patients undergoing colorectal cancer surgery. Local EVTEP prescribing and monitoring guidelines in a busy inner city teaching hospital colorectal surgery unit, were devised to ensure NICE guidelines are followed. Adherence to local EVTEP guidelines was recorded through a retrospective audit of patients undergoing elective colorectal cancer surgery during February 2011 (n=19). Prospective re-audit cycles were undertaken during April-May (n=17) and September-December 2012 (n=17). The first audit cycle revealed that overall standards were not being met with just 11% of 'at risk' patients being correctly identified in pre-operative assessment clinic and continued low adherence to guidelines on the ward with only 44% of patients being prescribed EVTEP at discharge. Following each audit cycle, educational interventions were directed towards the multi-disciplinary team involved in the care of patients undergoing colorectal cancer surgery. This involved education of the team members regarding EVTEP, presentation of the audit results with instruction for improvement. Results of the second and third audit cycles showed improvements in guideline adherence with 100% of patients in these cohorts having been prescribed EVTEP at discharge. Marked improvements were also seen in the correct identification of 'at risk' patients, patient education in pre-operative assessment clinic, and warning of potential side-effects. This project has shown a significant global improvement in EVTEP-related patient care and adherence to local guidelines following education of the multi-disciplinary team involved, which consequently reduced the risk of venous
van der Hulle, Tom; Tan, Melanie; den Exter, Paul L.; van Roosmalen, Mark J.G.; van der Meer, Felix J.M.; Eikenboom, Jeroen; Huisman, Menno V.; Klok, Frederikus A.
Patients with a second venous thromboembolism generally receive anticoagulant treatment indefinitely, although it is known that the recurrence risk diminishes over time while the risk of hemorrhage persists with continued anticoagulation and increases with age. Based on these arguments and limited evidence for indefinitely prolonged treatment, the Dutch guidelines recommend considering treatment of a limited duration (i.e. 12 months) for a ‘late’ second venous thromboembolism, defined by a second venous thromboembolism diagnosed more than 1 year after discontinuing treatment for a first event. It is hypothesized that the risk of continued anticoagulation might outweigh the benefits in such circumstances. We evaluated this management in daily practice. Since 2003, limited duration of treatment was systematically considered at our hospital in consecutive patients, in whom we determined the recurrence risk. Of 131 patients with late second venous thromboembolism, 77 were treated for a limited duration, of whom 26 developed a symptomatic third venous thromboembolism thereafter during a cumulative follow-up of 277 years, resulting in an incidence rate of 9.4/100 patient-years (95% confidence interval: 6.1–14). The incidence rates in patients with unprovoked and provoked venous thromboembolism were 12/100 patient-years (95% confidence interval: 7.4–19) and 5.6/100 patient-years (95% confidence interval: 2.2–12), respectively [adjusted hazard ratio 2.8 (95% confidence interval: 1.1–7.2)]. The recurrence risk after treatment of limited duration for ‘late’ second venous thromboembolism exceeded the risk of hemorrhage associated with extended anticoagulation. Most patients may, therefore, be better served by treatment of indefinite duration, although the risk-benefit ratio of extended anticoagulation should be weighed for every patient. PMID:25261098
Yoshikawa, Reigetsu; Yanagi, Hidenori; Noda, Masafumi; Ikeuchi, Hiroki; Nakano, Hiroki; Gega, Makoto; Tsukamoto, Kiyoshi; Oshima, Tsutomu; Inoue, Takashi; Fujiwara, Yoshinori; Shoji, Yasutsugu; Sakaki, Takatoshi; Higasa, Satoshi; Hashimoto-Tamaoki, Tomoko; Yamamura, Takehira
Colorectal cancer patients with central venous catheters (CVC) for pharmacokinetic modulating chemotherapy (PMC) have a substantial risk of venous thromboembolism (VTE). PMC, designed as a hybrid of lower metronomic and higher shorter plasma 5-FU concentrations, has been clinically successful. To determine the effectiveness and safety of D-dimer tests and multidetector-row CT (MDCT) for diagnosis in cancer patients with suspected VTE, we carried out a clinical outcome study on PMC outpatients. Patients received a D-dimer test before and after commencing the PMC regimen. MDCT was performed additionally if the D-dimer test appeared positive or showed signs of VTE. When CT results were positive for thromboembolism, anticoagulation was started. The overall prevalence of VTE in PMC patients was 2.0% (7 of 350 patients). In this study, 34 out of 102 colorectal cancer patients gave a positive D-dimer test (33.3%). CT identified venous thrombi in 2 of the 102 patients (2.0%), mural thrombosis on catheterized veins in another 3 patients (2.9%), and endothelial hyperplasia on catheterized veins in 8 patients (7.8%). The catheters of these patients did not show any significant abnormalities. Patients with negative D-dimer tests showed no signs or symptoms of VTE. In colorectal cancer patients receiving continuous 5-FU infusion via CVC, a D-dimer test can be safely used as the primary diagnostic test for ruling out VTE. We suggest 7.0 microg/ml as the D-dimer cut-off value. Thromboprophylaxis should be considered in the patients showing values >7.0 microg/ml.
Gholami, Kheirollah; Talasaz, Azita Hajhossein; Entezari-Maleki, Taher; Salarifar, Mojtaba; Hadjibabaie, Molouk; Javadi, Mohammad Reza; Dousti, Samaneh; Hamishehkar, Hadi; Maleki, Saleh
High plasma level of P-selectin is associated with the development of venous thromboembolism (VTE). Furthermore, supplementation of vitamin D could decrease thrombotic events. Hence, this study was designed to examine whether the administration of vitamin D can influence the plasma level of P-selectin in patients with VTE. In the randomized controlled trial, 60 patients with confirmed acute deep vein thrombosis and/or pulmonary embolism (PE) were randomized into the intervention (n = 20) and control (n = 40) groups. The intervention arm was given an intramuscular single dose of 300 000 IU vitamin D3 Plasma level of 25-hydroxy vitamin D, P-selectin, and high-sensitive C-reactive protein (hs-CRP) was measured at baseline and 4 weeks after. The plasma level of P-selectin (95% confidence interval = -5.99 to -1.63, P = .022) and hs-CRP (P = .024) significantly declined in vitamin D-treated group, while only hs-CRP was significantly decreased in the control group (P = .011). However, the magnitude of these reductions was not statistically significant. This study could not support the potential benefit of the high-dose vitamin D on plasma level of P-selectin and hs-CRP in patients with VTE.
Horton, Amanda L; Momirova, Valerija; Dizon-Townson, Donna; Wenstrom, Katharine; Wendel, George; Samuels, Philip; Sibai, Baha; Spong, Catherine Y; Cotroneo, Margaret; Sorokin, Yoram; Miodovnik, Menachem; O'Sullivan, Mary J; Conway, Deborah; Wapner, Ronald J
To estimate whether there is a correlation between family history of venous thromboembolism and factor V Leiden mutation carriage in gravid women without a personal history of venous thromboembolism. This is a secondary analysis of a prospective observational study of the frequency of pregnancy-related thromboembolic events among carriers of the factor V Leiden mutation. Family history of venous thromboembolism in either first- or second-degree relatives was self-reported. Sensitivity, specificity, and positive and negative predictive values of family history to predict factor V Leiden mutation carrier status were calculated. Women without a personal venous thromboembolism history and with available DNA were included (n=5,168). One hundred forty women (2.7% [95% confidence interval (CI) 2.3-3.2%]) were factor V Leiden mutation-positive. Four hundred twelve women (8.0% [95% CI 7.3-8.7%]) reported a family history of venous thromboembolism. Women with a positive family history were twofold more likely to be factor V Leiden mutation carriers than those with a negative family history (23 of 412 [5.6%] compared with 117 of 4,756 [2.5%], P<.001). The sensitivity, specificity, and positive predictive value of a family history of a first- or second-degree relative for identifying factor V Leiden carriers were 16.4% (95% CI 10.7-23.6%), 92.3% (95% CI 91.5-93.0%), and 5.6% (95% CI 3.6-8.3%), respectively. Although a family history of venous thromboembolism is associated with factor V Leiden mutation in thrombosis-free gravid women, the sensitivity and positive predictive values are too low to recommend screening women for the factor V Leiden mutation based solely on a family history.
Hald, Erin M; Lijfering, Willem M; Mathiesen, Ellisiv B; Johnsen, Stein Harald; Løchen, Maja-Lisa; Njølstad, Inger; Wilsgaard, Tom; Rosendaal, Frits R; Brækkan, Sigrid K; Hansen, John-Bjarne
Recent studies have suggested that arterial and venous thrombosis share common risk factors. Although carotid atherosclerosis is associated with arterial cardiovascular events, its role in venous thromboembolic disease is unclear. We wanted to investigate and compare the effect of carotid atherosclerosis on the risk of myocardial infarction (MI) and venous thromboembolism (VTE) in a general population, taking into account competing risks. Mean intima-media thickness and total plaque area in the right carotid artery were measured with ultrasound in 6257 people aged 25 to 84 years who participated in a population-based health study, the Tromsø Study, from 1994 to 1995. Incident MI and VTE events were registered from date of enrollment to end of follow-up on December 31, 2010. Cox proportional hazards regression models using age as time scale were used to estimate cause-specific hazard ratios with 95% confidence intervals for MI and VTE by increasing levels of intima-media thickness and total plaque area. There were 894 incident MI cases and 256 VTE events during a median of 15.4 years of follow-up. The risk of MI increased significantly across quartiles of mean intima-media thickness (P for trend <0.001) and with increasing total plaque area (P for trend <0.001), but neither intima-media thickness (P for trend=0.94) nor total plaque area (P for trend=0.45) was associated with VTE risk in multivariable-adjusted analysis. In this study, carotid atherosclerosis was strongly associated with future MI but not with VTE. Our findings suggest that carotid atherosclerosis does not represent a link between arterial and venous thrombosis.
Background 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
Wang, Isaac; Davenport, Matthew S; Kazerooni, Ella A
To measure diffusion of new knowledge and correlate imaging utilization for suspected acute venous thromboembolism (VTE) with d-dimer utilization, landmark publications, and institutional guidelines. Between 2000 and 2015, the number of CT pulmonary angiograms (CTPAs), CTPA combined with indirect CT venography (CTV), ventilation-perfusion (VQ) scans, and lower extremity venous Doppler ultrasound (US) examinations were obtained for inpatients and emergency department (ED) patients and correlated with d-dimer utilization, landmark publications regarding radiation and VTE imaging, and an institutional inpatient best-practice alert requiring VTE prophylaxis assessment (2008). Volume data were normalized per 1,000 patients. CTPA and d-dimer utilization were correlated (ED: r = 0.94, inpatient: r = 0.87; P < .001). VQ volume peaked in 2004 to 2005 (20 of 1,000 ED patients; 14 of 1,000 inpatients) and decreased since to a low of 1 of 1,000 and 3 of 1,000, respectively. US volume increased since 2002 and was higher than CT volume for inpatients (annual mean 149 of 1,000 patients [US], 46 of 1,000 patients [CT]), but not ED patients (annual mean 18 of 1,000 patients [US], 35 of 1,000 patients [CT]). For ED patients, CTPA volume peaked in 2008 at 57 of 1,000 patients, declined through 2012 to 30 of 1,000 patients, and rose annually since to 37 of 1,000 patients (2015). For inpatients, CTPA volume also peaked in 2008 at 70 of 1,000, but continued to decline through 2015 to 27 of 1,000 patients. After the Prospective Investigation of Pulmonary Embolism II and Brenner and Hall publications, there was a transient 4-year decline in ED CTPA utilization. The decline was sustained in inpatients, where a best-practice VTE prophylaxis alert was implemented. Best-practice alerts may sustain the impact of new knowledge. Copyright © 2017 American College of Radiology. Published by Elsevier Inc. All rights reserved.
Lee, Yun-Gyoo; Kim, Inho; Kwon, Ji-hyun; Yoon, Sung Soo; Park, Seongyang; Song, Leo; Yoon, Jae-Ho; Shin, Seung-Hwan; Min, Woo-Sung; Kim, Hee-Je
Due to the high risk of thrombocytopenia and haemorrhage, thrombotic complications have received little attention in patients with acute myeloid leukemia (AML). Furthermore, the predictive role of cytogenetics on venous thromboembolism (VTE) has largely been ignored. This study aimed to evaluate the incidence, risk factors, and prognostic aspects of VTE in AML. A total of 811 consecutive patients with AML were enrolled and analysed retrospectively. Cox time-dependent covariate regression analysis was used to identify the significant predictors of VTE development. To minimise potential confounding factors, we used propensity-score matching to compare overall survival between patients with and without VTE. The six-month and one-year cumulative incidences of VTE were 3.1 % (95 % confidence interval [CI], 2.0-4.7) and 3.9 % (95 % CI, 2.6-5.7), respectively. Of the 26 cases of VTE, 22 (85 %) developed within 6 months of leukemia diagnosis and 13 (50 %) were catheter-related. In multivariate analysis, advanced age (≥ 65 years) (hazard ratio [HR], 2.70; p = 0.03) and increasing cytogenetic risk (common HR, 1.84; p = 0.05) were independent predictors of VTE. There was no significant association between VTE development and decreased survival (p = 0.32 for matched analysis). Advanced age and increasing cytogenetic risk, well-known predictors for clinical outcome in AML, were also independent risk factors of VTE development. Our results suggest that VTE does not hold prognostic implications for AML.
Lacruz, Beatriz; Tiberio, Gregorio; Núñez, Manuel Jesús; López-Jiménez, Luciano; Riera-Mestre, Antoni; Tiraferri, Eros; Verhamme, Peter; Mazzolai, Lucia; González, José; Monreal, Manuel
The balance between the efficacy and safety of anticoagulant therapy in patients aged ≥100years receiving anticoagulant therapy for venous thromboembolism (VTE) is uncertain. We used data from the RIETE (Registro Informatizado Enfermedad TromboEmbólica) database to assess the rate of VTE recurrences, bleeding events, and mortality appearing during the course of anticoagulant therapy in VTE patients aged ≥100years. Of 61,173 patients enrolled in RIETE as of January 2016, 47 (0.08%) were aged ≥100years. Of these, 10 (21%) were men, 21 (45%) presented with pulmonary embolism (PE), and 26 with deep vein thrombosis alone. Overall, 35 patients (74%) had severe renal insufficiency, 14 (30%) chronic heart failure, 30 (64%) anemia, 16 (34%) were taking antiplatelets, and 6 (13%) corticosteroids or non-steroidal anti-inflammatory drugs. Most patients (95%) were treated initially with low-molecular-weight heparin (LMWH) (mean daily dose, 168±42IU/kg). Then, 14 (30%) switched to vitamin K antagonists and 29 (62%) kept receiving long-term LMWH therapy (mean, 148±51IU/kg/day). During the course of anticoagulant therapy (mean duration, 139days), mortality was high (15/47; 32%). Two patients died of PE (initial PE one, recurrent PE one) and 5 (11%) had minor bleeding, but no major bleeding was reported. Among patients with acute VTE aged ≥100years, the risk of VTE recurrences during the course of anticoagulation outweighed the risk of bleeding. Our data suggest the use of standard anticoagulant therapy in this patient population, even if they have severe renal insufficiency. Copyright © 2016 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.
Blanco-Molina, Angeles; Enea, Iolanda; Gadelha, Telma; Tufano, Antonella; Bura-Riviere, Alessandra; Di Micco, Pierpaolo; Bounameaux, Henri; González, José; Villalta, Jaume; Monreal, Manuel
Abstract In patients with venous thromboembolism (VTE), the outcome during the course of anticoagulant therapy may differ according to the patient’s sex. We used the RIETE (Registro Informatizado Enfermedad TromboEmbólica) database to compare the rate of VTE recurrences, major bleeding, and mortality due to these events according to sex. As of August 2013, 47,499 patients were enrolled in RIETE, of whom 24,280 (51%) were women. Women were older, more likely presented with pulmonary embolism (PE), and were more likely to have recent immobilization but less likely to have cancer than men. During the course of anticoagulation (mean duration: 253 d), 659 patients developed recurrent deep vein thrombosis (DVT), 576 recurrent PE, 1368 bled, and 4506 died. Compared with men, women had a lower rate of DVT recurrences (hazard ratio [HR]: 0.78; 95% confidence interval [CI]: 0.67–0.91), a similar rate of PE recurrences (HR: 0.98; 95% CI: 0.83–1.15), a higher rate of major bleeding (HR: 1.21; 95% CI: 1.09–1.35), and higher mortality due to PE (HR: 1.24; 95% CI: 1.04–1.47). On multivariable analysis, any influence of sex on the risk for recurrent DVT (HR: 0.88; 95% CI: 0.75–1.03), major bleeding (HR: 1.10; 95% CI: 0.98–1.24), or fatal PE (HR: 1.01; 95% CI: 0.84–1.22) was no longer statistically significant. In conclusion, women had fewer DVT recurrences and more bleeds than men during the course of anticoagulation. These differences were not due to sex, but very likely to other patient characteristics more common in female patients and differences in treatment choice. PMID:25398066
Cohoon, Kevin P; Leibson, Cynthia L; Ransom, Jeanine E; Ashrani, Aneel A; Petterson, Tanya M; Long, Kirsten Hall; Bailey, Kent R; Heit, Johm A
To determine population-based estimates of medical costs attributable to venous thromboembolism (VTE) among patients currently or recently hospitalized for acute medical illness. Population-based cohort study conducted in Olmsted County, Minnesota. Using Rochester Epidemiology Project (REP) resources, we identified all Olmsted County residents with objectively diagnosed incident VTE during or within 92 days of hospitalization for acute medical illness over the 18-year period of 1988 to 2005 (n=286). One Olmsted County resident hospitalized for medical illness without VTE was matched to each case for event date (±1 year), duration of prior medical history, and active cancer status. Subjects were followed forward in REP provider-linked billing data for standardized, inflation-adjusted direct medical costs (excluding outpatient pharmaceutical costs) from 1 year before their respective event or index date to the earliest of death, emigration from Olmsted County, or December 31, 2011 (study end date). We censored follow-up such that each case and matched control had similar periods of observation. We used generalized linear modeling (controlling for age, sex, preexisting conditions, and costs 1 year before index) to predict costs for cases and controls. Adjusted mean predicted costs were 2.5-fold higher for cases ($62,838) than for controls ($24,464) (P<.001) from index to up to 5 years post index. Cost differences between cases and controls were greatest within the first 3 months after the event date (mean difference=$16,897) but costs remained significantly higher for cases compared with controls for up to 3 years. VTE during or after recent hospitalization for medical illness contributes a substantial economic burden.
Brækkan, Sigrid K.; Grosse, Scott D.; Okoroh, Ekwutosi M.; Tsai, James; Cannegieter, Suzanne C.; Næss, Inger Anne; Krokstad, Steinar; Hansen, John-Bjarne; Skjeldestad, Finn Egil
Background The burden of venous thromboembolism (VTE) related to permanent work-related disability has never been assessed among a general population. Therefore, we aimed to estimate the risk of work-related disability in subjects with incident VTE compared with those without VTE in a population-based cohort. Methods From the Tromsø Study and the Nord-Trøndelag Health Study (HUNT), Norway, 66005 individuals aged 20–65 years were enrolled in 1994–1997 and followed to December 31, 2008. Incident VTE events among the study participants were identified and validated, and information on work-related disability was obtained from the Norwegian National Insurance Administration database. Cox-regression models using age as time-scale and VTE as time-varying exposure were used to estimate hazard ratios (HR) with 95% confidence intervals (CI) adjusted for sex, BMI, smoking, education level, marital status, history of cancer, diabetes, cardiovascular disease and self-rated general health. Results During follow-up, 384 subjects had a first VTE and 9862 participants were granted disability pension. The crude incidence rate of work-related disability after VTE was 37.5 (95%CI: 29.7–47.3) per 1000 person-years, versus 13.5 (13.2–13.7) per 1000 person-years among those without VTE. Subjects with unprovoked VTE had a 52% higher risk of work-related disability than those without VTE (HR 1.52, 95%CI 1.09–2.14) after multivariable adjustment, and the association appeared to be driven by deep vein thrombosis. Conclusion VTE was associated with subsequent work-related disability in a cohort recruited from the general working-age population. Our findings suggest that indirect costs due to loss of work time may add to the economic burden of VTE. PMID:27411161
Cohoon, Kevin P.; Leibson, Cynthia L.; Ransom, Jeanine E.; Ashrani, Aneel A.; Petterson, Tanya M.; Long, Kirsten Hall; Bailey, Kent R.; Heit, John A.
Objective To determine population-based estimates of medical costs attributable to venous thromboembolism (VTE) among patients currently or recently hospitalized for acute medical illness. Study Design Population-based cohort study conducted in Olmsted County, Minn. Methods Using Rochester Epidemiology Project (REP) resources, we identified all Olmsted County, MN residents with objectively-diagnosed incident VTE within 92 days of hospitalization for acute medical illness over the 18-year period, 1988–2005 (n=286). One Olmsted County resident hospitalized for medical illness without VTE was matched to each case on event date (± 1 year), duration of prior medical history and active cancer status. Subjects were followed forward in REP provider-linked billing data for standardized, inflation-adjusted direct medical costs (excluding outpatient pharmaceutical costs) from 1 year before their respective event or index date to the earliest of death, emigration from Olmsted County, or 12/31/2011 (study end date). We censored follow-up such that each case and match control had similar periods of observation. We also controlled for length of follow-up from index to up to 5-years post-index. We used generalized linear modeling (controlling for age, sex, pre-existing conditions and costs 1 year before index) to predict costs for cases and controls. Results Adjusted mean predicted costs were 2.5-fold higher for cases ($62,838) than for controls ($24,464) (P=<0.001) from index to up to 5-years post-index. Cost differences between cases and controls were greatest within the first 3 months after the event date (mean difference=$16,897) but costs remained significantly higher for cases compared to controls for up to 3 years. Conclusions VTE during or after recent hospitalization for medical illness contributes a substantial economic burden. PMID:26244788
Piazza, Gregory; Rosenbaum, Erin J.; Pendergast, William; Jacobson, Joseph O.; Pendleton, Robert C.; McLaren, Gordon D.; Elliott, C. Gregory; Stevens, Scott M.; Patton, William F.; Dabbagh, Ousama; Paterno, Marilyn D.; Catapane, Elaine; Li, Zhongzhen; Goldhaber, Samuel Z.
Background Venous thromboembolism (VTE) prophylaxis remains underutilized among hospitalized patients. We designed and carried out a large multicenter randomized controlled trial to test the hypothesis that an alert from a hospital staff member to the Attending Physician will reduce the rate of symptomatic VTE among high-risk patients not receiving prophylaxis. Methods and Results We enrolled patients using a validated point score system to detect hospitalized patients at high risk for symptomatic VTE who were not receiving prophylaxis. 2,493 patients (82% on Medical Services) from 25 study sites were randomized to the intervention group (n=1,238), in which the responsible physician was alerted by another hospital staff member, versus the control group (n=1,255), in which no alert was issued. The primary end point was symptomatic, objectively confirmed VTE within 90 days. Patients whose physicians were alerted were more than twice as likely to receive VTE prophylaxis as controls (46.0% versus 20.6%, p<0.0001). The symptomatic VTE rate was lower in the intervention group (2.7% versus 3.4%; hazard ratio, 0.79; 95% confidence interval, 0.50 to 1.25), but the difference did not achieve statistical significance. The rate of major bleeding at 30 days in the alert group was similar to the control group (2.1% versus 2.3%, p=0.68). Conclusions A strategy of direct staff member to physician notification increases prophylaxis utilization and leads toward reducing the rate of symptomatic VTE in hospitalized patients. However, VTE prophylaxis continues to be underutilized even after physician notification, especially among Medical Service patients. PMID:19364975
Sindet-Pedersen, Caroline; Bruun Oestergaard, Louise; Gundlund, Anna; Fosbøl, Emil Loldrup; Aasbjerg, Kristian; Langtved Pallisgaard, Jannik; Gislason, Gunnar; Torp-Pedersen, Christian; Bjerring Olesen, Jonas
Identification of risk factors for venous thromboembolism (VTE) is of utmost importance to improve current prophylactic regimes and treatment guidelines. The extent to which a family history contributes to the risk of VTE needs further exploration. To examine the relative rate of VTE in first-degree relatives compared with the general population. By crosslinking Danish nationwide registries we identified patients with VTE between 1978 and 2012, and their familial relations. The first member in a family to acquire VTE was defined as the proband. All first-degree relatives to probands were followed from the VTE date of the proband and until an event (VTE), death, emigration, 100 year birthday or end of study: 31st of December 2012, whichever came first. The relative rate of VTE was estimated by standardized incidence ratios (SIR) using time-dependent Poisson regression models, with the general population as a fixed reference. We identified 70,767 children of maternal probands, 66,065 children of paternal probands, and 29,183 siblings to sibling probands. Having a maternal proband or a paternal proband were associated with a significantly increased VTE rate of 2.15 (CI: 2.00-2.30) and 2.06 (CI: 1.92-2.21), respectively. The highest estimate of VTE was observed among siblings (adjusted SIR of 2.60 [CI: 2.38-2.83]). Noteworthy, the rate of VTE increased for all first-degree relatives when the proband was diagnosed with VTE in a young age (≤ 50 years). A family history of VTE was associated with a significantly increased rate of VTE among first-degree relatives compared with the general population.
Nimeri, Abdelrahman A; Bautista, Jejomar; Ibrahim, Maha; Philip, Ruby; Al Shaban, Talat; Maasher, Ahmed; Altinoz, Ajda
Bariatric surgery patients are at high risk for venous thromboembolism (VTE), and chemoprophylaxis is recommended. Sheikh Khalifa Medical City (SKMC) is an American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) member since 2009. We report the rates of VTE in bariatric surgery patients from 2010 to 2016 compared to ACS NSQIP bariatric surgery programs before and after switching from heparin to low molecular weight heparin (LMWH), initiating mandatory risk assessment using Caprini scoring for VTE and adopting an aggressive strategy for high-risk patients regarding dosage of LMWH and chemoprophylaxis after discharge. During the study period, there were 1152 cases (laparoscopic Roux-en-Y gastric bypass (LRYGB) 625 and laparoscopic sleeve gastrectomy (LSG) 527) at Bariatric & Metabolic Institute (BMI) Abu Dhabi compared to 65,693 cases (LRYGB 32,130 and LSG 33,563) at ACS NSQIP bariatric surgery programs. VTE rates remained stable at ACS NSQIP bariatric surgery programs from 2010 to 2016 (0.45, 0.45, 0.45, 0.25, 0.35, 0.3, and 0.3%). In contrast, VTE rates at BMI Abu Dhabi decreased from 2.2% in 2011 to 0.35% after we adopted an aggressive strategy to VTE without an increase in bleeding complications. LRYGB patients with VTE had higher OR time, leak, collection, and mortality at ACS NSQIP hospitals compared to those at BMI Abu Dhabi. In contrast, rates were similar in LSG patients with VTE. Changing our approach to VTE management led our VTE rates to decrease and become like those of ACS NSQIP bariatric surgery patients in LSG and LRYGB.
Hernandez, Wenndy; Gamazon, Eric R.; Smithberger, Erin; O’Brien, Travis J.; Harralson, Arthur F.; Tuck, Matthew; Barbour, April; Kittles, Rick A.; Cavallari, Larisa H.
Venous thromboembolism (VTE) is the third most common life-threatening cardiovascular condition in the United States, with African Americans (AAs) having a 30% to 60% higher incidence compared with other ethnicities. The mechanisms underlying population differences in the risk of VTE are poorly understood. We conducted the first genome-wide association study in AAs, comprising 578 subjects, followed by replication of highly significant findings in an independent cohort of 159 AA subjects. Logistic regression was used to estimate the association between genetic variants and VTE risk. Through bioinformatics analysis of the top signals, we identified expression quantitative trait loci (eQTLs) in whole blood and investigated the messenger RNA expression differences in VTE cases and controls. We identified and replicated single-nucleotide polymorphisms on chromosome 20 (rs2144940, rs2567617, and rs1998081) that increased risk of VTE by 2.3-fold (P < 6 × 10−7). These risk variants were found in higher frequency among populations of African descent (>20%) compared with other ethnic groups (<10%). We demonstrate that SNPs on chromosome 20 are cis-eQTLs for thrombomodulin (THBD), and the expression of THBD is lower among VTE cases compared with controls (P = 9.87 × 10−6). We have identified novel polymorphisms associated with increased risk of VTE in AAs. These polymorphisms are predominantly found among populations of African descent and are associated with THBD gene expression. Our findings provide new molecular insight into a mechanism regulating VTE susceptibility and identify common genetic variants that increase the risk of VTE in AAs, a population disproportionately affected by this disease. PMID:26888256
Cardoso, Luiz Francisco; Krokoscz, Daniella Vianna C; de Paiva, Edison Ferreira; Furtado, Ilka Spinola; Mattar, Jorge; de Souza e Sá, Marcia Martiniano; de Lira, Antonio Carlos Onofre
Introduction Venous thromboembolism (VTE) is the leading cause of preventable death in hospitalized patients. However, existing prophylaxis guidelines are rarely followed. Objective The aim of the study was to present and discuss implementation strategies and the results of a VTE prophylaxis program for medical and surgical patients admitted to a large general hospital. Patients and methods This prospective observational study was conducted to describe the strategy used to implement a VTE prophylaxis program in hospitalized medical and surgical patients and to analyze the results in terms of the risk assessment rate within the first 24 hours after admission, adequacy of the prophylaxis prescription, and prevalence of VTE in the discharge records before and after program implementation. We used the Mantel–Haenszel chi-square test for the linear trend of the data analysis and set the significance level to P<0.05. Results With the support of an institutional VTE prophylaxis committee, a multiple-strategy approach was used in the implementation of the protocol, which included continuing education, complete data recording using computerized systems, and continuous auditing of and feedback to the medical staff and multidisciplinary teams. Approximately 90% of patients were evaluated within the first 24 hours after admission, and no significant difference in this percentage was observed among the years analyzed. A progressive increase in adherence to protocol recommendations, from 63.8% in 2010 to 75.0% in 2014 (P<0.001), was noted. The prevalence of symptomatic VTE in the discharge records of patients decreased from 2.03% in 2009 to 1.69% in 2014 (P=0.033). Conclusion The implementation of a VTE prophylaxis program targeting adult patients admitted to a large hospital employing a multiple-strategy approach achieved high rates of risk assessment within 24 hours of admission, improved the adherence to prophylaxis recommendations in high-risk patients, and reduced the
Sammour, Tarik; Chandra, Raaj; Moore, James W
There is level one evidence to support combined mechanical and chemical thromboprophylaxis for 7-10 days after colorectal cancer surgery, but there remains a paucity of data to support extended prophylaxis after discharge. The aim of this clinical review is to summarise the currently available evidence for extended venous thromboprophylaxis after elective colorectal cancer surgery. Clinical review of the major clinical guidelines and published clinical data evaluating extended venous thromboprophylaxis after elective colorectal cancer surgery. Five major guideline recommendations are outlined, and the results of the five published randomised controlled trials are summarised and reviewed with a specific focus on the efficacy and cost-effectiveness of extended heparin prophylaxis to prevent clinically relevant post-operative venous thromboembolism (VTE) after colorectal cancer surgery. Extended VTE prophylaxis after colorectal cancer surgery reduces the incidence of asymptomatic screen detected deep venous thrombosis (DVT) only, with no demonstrable reduction in symptomatic DVT, symptomatic PE, or VTE related death. Evidence for cost-effectiveness is limited. As the incidence of clinical VTE is very low in this patient subgroup overall, future research should be focused on higher risk patient subgroups in whom a reduction in VTE may be both more demonstrable and clinically relevant.
Branchford, Brian R; Mourani, Peter; Bajaj, Lalit; Manco-Johnson, Marilyn; Wang, Michael; Goldenberg, Neil A
Studies evaluating risk factors for in-hospital venous thromboembolism in children are limited by quality assurance of case definition and/or lack of controlled comparison. The objective of this study is to determine risk factors for the development of in-hospital venous thromboembolism in children. In a case-control study at The Children's Hospital, Colorado, from 1(st) January 2003 to 31(st) December 2009 we employed diagnostic validation methods to determine pediatric in-hospital venous thromboembolism risk factors. Clinical data on putative risk factors were retrospectively collected from medical records of children with International Classification of Diseases, 9th edition codes of venous thromboembolism at discharge, in whom radiological reports confirmed venous thromboembolism and no signs/symptoms of venous thromboembolism were noted on admission. We verified 78 cases of in-hospital venous thromboembolism, yielding an average incidence of 5 per 10,000 hospitalized children per year. Logistical regression analyses revealed that mechanical ventilation, systemic infection, and hospitalization duration of five days or over were statistically significant, independent risk factors for in-hospital venous thromboembolism (OR=3.29, 95%CI=1.53-7.06, P=0.002; OR=3.05, 95%CI=1.57-5.94, P=0.001; and OR=1.03, 95%CI=1.01-1.04, P=0.001, respectively). Using these factors in a risk model, post-test probability of venous thromboembolism was 3.6%. These data indicate that risk of in-hospital venous thromboembolism in children with this risk factor combination may exceed that of hospitalized adults in whom prophylactic anticoagulation is indicated. Substantiation of these findings via multicenter studies could provide the basis for future risk-stratified randomized control trials of pediatric venous thromboembolism prevention.
Ihaddadene, Ryma; Corsi, Daniel J.; Lazo-Langner, Alejandro; Shivakumar, Sudeep; Zarychanski, Ryan; Tagalakis, Vicky; Solymoss, Susan; Routhier, Nathalie; Douketis, James; Le Gal, Gregoire
Risk factors predictive of occult cancer detection in patients with a first unprovoked symptomatic venous thromboembolism (VTE) are unknown. Cox proportional hazard models and multivariate analyses were performed to assess the effect of specific risk factors on occult cancer detection within 1 year of a diagnosis of unprovoked VTE in patients randomized in the Screening for Occult Malignancy in Patients with Idiopathic Venous Thromboembolism (SOME) trial. A total of 33 (3.9%; 95% CI, 2.8%-5.4%) out of the 854 included patients received a new diagnosis of cancer at 1-year follow-up. Age ≥ 60 years (hazard ratio [HR], 3.11; 95% CI, 1.41-6.89; P = .005), previous provoked VTE (HR, 3.20; 95% CI, 1.19-8.62; P = .022), and current smoker status (HR, 2.80; 95% CI, 1.24-6.33; P = .014) were associated with occult cancer detection. Age, prior provoked VTE, and smoking status may be important predictors of occult cancer detection in patients with first unprovoked VTE. This trial was registered at www.clinicaltrials.gov as #NCT00773448. PMID:26817957
Harrington, Dominic J; Malefora, Agata; Schmeleva, Veronika; Kapustin, Sergey; Papayan, Ludmila; Blinov, Mikhail; Harrington, Pip; Mitchell, Mike; Savidge, Geoffrey F
We undertook genetic and biochemical assays in patients with arterial (n = 146) and venous (n = 199) thromboembolism and survivors of pulmonary embolism (n = 58) to study causation and gene-life style interactions. In the clinical material from North Western Russia, factor V Leiden was found to be a risk factor in venous thrombosis (OR = 3.6), while the methylenetetrahydrofolate reductase (MTHFR) C677T mutation was a significant variable in both venous (p = 0.03) and arterial thrombosis (p = 0.004). Homocysteine levels were determined (n = 84) and hyperhomocysteinemia correlated with the T allele of the MTHFR gene, and with smoking and coffee consumption. Vitamin supplementation reduced homocysteine levels dependent on MTHFR genotype (36% TT, 25% CT, 22% CC). In pulmonary embolism patients, frequency of the -455G/A beta-fibrinogen dimorphism was studied. Carriers of this allele were significantly underrepresented (p < 0.02) among pulmonary embolism survivors (34.5%) compared to controls (56.7%). Additionally, -455AA homozygotes were found in 11.7% controls but only 1.7% of pulmonary embolism patients (p = 0.006). In venous and arterial thrombosis cases, MTHFR and homocysteine data led to effective dietary supplementation with a reduced risk of disease progression. Results from the pulmonary embolism study may indicate that screening tests for the -455G/A beta-fibrinogen genetic variation could be of prognostic value, and may point the way for novel anticoagulation strategies.
Suissa, Samy; Rietbrock, Stephan; Katholing, Anja; Freedman, Ben; Cohen, Alexander T; Handelsman, David J
Objective To determine the risk of venous thromboembolism associated with use of testosterone treatment in men, focusing particularly on the timing of the risk. Design Population based case-control study Setting 370 general practices in UK primary care with linked hospital discharge diagnoses and in-hospital procedures and information on all cause mortality. Participants 19 215 patients with confirmed venous thromboembolism (comprising deep venous thrombosis and pulmonary embolism) and 909 530 age matched controls from source population including more than 2.22 million men between January 2001 and May 2013. Exposure of interest Three mutually exclusive testosterone exposure groups were identified: current treatment, recent (but not current) treatment, and no treatment in the previous two years. Current treatment was subdivided into duration of more or less than six months. Main outcome measure Rate ratios of venous thromboembolism in association with current testosterone treatment compared with no treatment were estimated using conditional logistic regression and adjusted for comorbidities and all matching factors. Results The adjusted rate ratio of venous thromboembolism was 1.25 (95% confidence interval 0.94 to 1.66) for current versus no testosterone treatment. In the first six months of testosterone treatment, the rate ratio of venous thromboembolism was 1.63 (1.12 to 2.37), corresponding to 10.0 (1.9 to 21.6) additional venous thromboembolisms above the base rate of 15.8 per 10 000 person years. The rate ratio after more than six months’ treatment was 1.00 (0.68 to 1.47), and after treatment cessation it was 0.68 (0.43 to 1.07). Increased rate ratios within the first six months of treatment were observed in all strata: the rate ratio was 1.52 (0.94 to 2.46) for patients with pathological hypogonadism and 1.88 (1.02 to 3.45) for those without it, and 1.41 (0.82 to 2.41) for those with a known risk factor for venous thromboembolism and 1.91 (1
Martinez, Carlos; Suissa, Samy; Rietbrock, Stephan; Katholing, Anja; Freedman, Ben; Cohen, Alexander T; Handelsman, David J
To determine the risk of venous thromboembolism associated with use of testosterone treatment in men, focusing particularly on the timing of the risk. Population based case-control study SETTING: 370 general practices in UK primary care with linked hospital discharge diagnoses and in-hospital procedures and information on all cause mortality. 19 215 patients with confirmed venous thromboembolism (comprising deep venous thrombosis and pulmonary embolism) and 909 530 age matched controls from source population including more than 2.22 million men between January 2001 and May 2013. Three mutually exclusive testosterone exposure groups were identified: current treatment, recent (but not current) treatment, and no treatment in the previous two years. Current treatment was subdivided into duration of more or less than six months. Rate ratios of venous thromboembolism in association with current testosterone treatment compared with no treatment were estimated using conditional logistic regression and adjusted for comorbidities and all matching factors. The adjusted rate ratio of venous thromboembolism was 1.25 (95% confidence interval 0.94 to 1.66) for current versus no testosterone treatment. In the first six months of testosterone treatment, the rate ratio of venous thromboembolism was 1.63 (1.12 to 2.37), corresponding to 10.0 (1.9 to 21.6) additional venous thromboembolisms above the base rate of 15.8 per 10 000 person years. The rate ratio after more than six months' treatment was 1.00 (0.68 to 1.47), and after treatment cessation it was 0.68 (0.43 to 1.07). Increased rate ratios within the first six months of treatment were observed in all strata: the rate ratio was 1.52 (0.94 to 2.46) for patients with pathological hypogonadism and 1.88 (1.02 to 3.45) for those without it, and 1.41 (0.82 to 2.41) for those with a known risk factor for venous thromboembolism and 1.91 (1.13 to 3.23) for those without one. Starting testosterone treatment was
Mahé, Isabelle; Chidiac, Jean; Bertoletti, Laurent; Font, Carme; Trujillo-Santos, Javier; Peris, Marisa; Pérez Ductor, Cristina; Nieto, Santiago; Grandone, Elvira; Monreal, Manuel
We hypothesized that the clinical course of venous thromboembolism in patients with active cancer may differ according to the specificities of primary tumor site. We used data from RIETE (international registry of patients with venous thromboembolism) to compare the clinical venous thromboembolism-related outcomes during the course of anticoagulation in patients with one of the 4 more frequent cancers (breast, prostate, colorectal, or lung cancer). As of September 2014, 3947 cancer patients were recruited, of whom 938 had breast, 629 prostate, 1189 colorectal, and 1191 lung cancer. Overall, 55% had metastatic disease (42%, 36%, 53%, and 72%, respectively). During the course of anticoagulant therapy (mean duration, 139 days), the rate of thromboembolic recurrences was similar to the rate of major bleeding in patients with breast (5.6 [95% confidence interval (CI), 3.8-8.1] vs 4.1 [95% CI, 2.7-5.9] events per 100 patient-years) or colorectal cancer (10 [95% CI, 7.6-13] vs 12 [95% CI, 9.4-15] per 100 patient-years). In contrast, in patients with prostate cancer, the rate of venous thromboembolic recurrences was half the rate of major bleeding (6.9 [95% CI, 4.4-10] vs 13 [95% CI, 9.2-17] events per 100 patient-years), whereas in those with lung cancer, the rate of thromboembolic recurrences was twofold higher than the rate of major bleeding (27 [95% CI, 22-23] vs 11 [95% CI, 8.6-15] per 100 patient-years). Significant differences in the clinical profile of venous thromboembolic-related outcomes were observed according to the site of cancer. These findings suggest the development of cancer-specific anticoagulant strategies as an area for further research. Copyright © 2016 Elsevier Inc. All rights reserved.
Sultan, Alyshah Abdul; West, Joe; Grainge, Matthew J; Riley, Richard D; Tata, Laila J; Stephansson, Olof; Fleming, Kate M; Nelson-Piercy, Catherine; Ludvigsson, Jonas F
Objective To develop and validate a risk prediction model for venous thromboembolism in the first six weeks after delivery (early postpartum). Design Cohort study. Setting Records from England based Clinical Practice Research Datalink (CPRD) linked to Hospital Episode Statistics (HES) and data from Sweden based registry. Participants All pregnant women registered with CPRD-HES linked data between 1997 and 2014 and Swedish medical birth registry between 2005 and 2011 with postpartum follow-up. Main outcome measure Multivariable logistic regression analysis was used to develop a risk prediction model for postpartum venous thromboembolism based on the English data, which was externally validated in the Swedish data. Results 433 353 deliveries were identified in the English cohort and 662 387 in the Swedish cohort. The absolute rate of venous thromboembolism was 7.2 per 10 000 deliveries in the English cohort and 7.9 per 10 000 in the Swedish cohort. Emergency caesarean delivery, stillbirth, varicose veins, pre-eclampsia/eclampsia, postpartum infection, and comorbidities were the strongest predictors of venous thromboembolism in the final multivariable model. Discrimination of the model was similar in both cohorts, with a C statistic above 0.70, with excellent calibration of observed and predicted risks. The model identified more venous thromboembolism events than the existing national English (sensitivity 68% v 63%) and Swedish guidelines (30% v 21%) at similar thresholds. Conclusion A new prediction model that quantifies absolute risk of postpartum venous thromboembolism has been developed and externally validated. It is based on clinical variables that are available in many developed countries at the point of delivery and could serve as the basis for real time decisions on obstetric thromboprophylaxis. PMID:27919934
Godin, Richard; Marcoux, Violaine; Tagalakis, Vicky
Abnormal uterine bleeding (AUB) is a common complication of anticoagulant therapy in premenopausal women affected with acute venous thromboembolism. AUB impacts quality of life, and can lead to premature cessation of anticoagulation. There is increasing data to suggest that the direct oral anticoagulants when used for the treatment of venous thromboembolism differ in their menstrual bleeding profile. This article aims to review the existing literature regarding the association between AUB and the direct oral anticoagulants and make practical recommendations. Copyright © 2017 Elsevier Inc. All rights reserved.
Blondon, Marc; Rodabough, Rebecca J; Budrys, Nicole; Johnson, Karen C; Berger, Jeffrey S; Shikany, James M; Raiesdana, Azad; Heckbert, Susan R; Manson, JoAnn E; LaCroix, Andrea Z; Siscovick, David; Kestenbaum, Bryan; Smith, Nicholas L; de Boer, Ian H
Experimental and epidemiological studies suggest that vitamin D may be implicated in haemostatic regulations and influence the risk of venous thromboembolism (VTE). The aim of this study was to investigate whether oral supplementation of vitamin D3 combined with calcium reduces the risk of VTE. In the randomised, double-blind, placebo-controlled Women's Health Initiative Calcium Plus Vitamin D trial, 36,282 postmenopausal women aged 50-79 years were randomised to receive 1,000 mg of calcium carbonate and 400 IU of vitamin D3 per day (n=18,176) or a matching placebo (n=18,106) during an average of seven years. This secondary analysis of the trial compared the incidence of VTE by treatment group using an intention-to-treat Cox regression analysis. The incidence of VTE did not differ between women randomised to calcium plus vitamin D and women randomised to placebo (320 vs 348 VTE events, respectively; hazard ratio (HR) 0.92, 95 % confidence interval (CI) 0.79-1.07). Results were not modified in an analysis using inverse-probability weights to take non-adherence into account (HR 0.94, 95 %CI 0.73-1.22) or in multiple subgroups. Whereas the risk of a non-idiopathic VTE was similar between groups, the risk of idiopathic VTE was lower in women randomised to calcium plus vitamin D (40 vs 65 events; HR 0.62, 95 %CI 0.42-0.92). In conclusion, daily supplementation with 1,000 mg of calcium and 400 IU of vitamin D did not reduce the overall incidence of VTE in generally healthy postmenopausal women. However, the observed reduced risk of idiopathic VTE in women randomised to calcium and vitamin D warrants further investigations.
Metcalf, Robert L; Al-Hadithi, Eamon; Hopley, Nicholas; Henry, Thomas; Hodgson, Clare; McGurk, Antony; Mansoor, Wasat; Hasan, Jurjees
To characterise venous thromboembolism (VTE) in gastrointestinal cancer and assess the clinical utility of risk stratification scoring. We performed a retrospective analysis using electronic patient records of 910 gastro-oesophageal (GO) cancer and 1299 colorectal cancer (CRC) patients referred to a tertiary cancer centre to identify the incidence of VTE, its relationship to chemotherapy and impact on survival. VTE risk scores were calculated using the Khorana index. Patients were classified as low risk (0 points), intermediate risk (1 to 2 points) or high risk (3 points). Data was analysed to determine the sensitivity of the Khorana score to predict VTE. The incidence of VTE was 8.9% for CRC patients and 9.7% for GO cancer patients. Pulmonary emboli (PE) were more common in advanced than in localised CRC (50% vs 21% of events respectively) and lower limb deep vein thrombosis (DVT) were more common in localised than in advanced CRC (62% vs 39% of events respectively). The median time to VTE from cancer diagnosis was 8.3 mo for CRC patients compared to 6.7 mo in GO cancer. In localised CRC median time to VTE was 7.1 mo compared with 10.1 mo in advanced CRC. In contrast in GO cancer, the median time to VTE was 12.5 mo in localised disease and 6.8 mo in advanced disease. No survival difference was seen between patients with and without VTE in this cohort. The majority of patients with CRC in whom VTE was diagnosed had low or intermediate Khorana risk score (94% for localised and 97% in advanced CRC). In GO cancer, all patients scored either intermediate or high risk due to the primary site demonstrating a limitation of the risk assessment score in discriminating high and low risk patients with GO cancers. Additional risk factors were identified in this cohort including surgery, chemotherapy or hospital admission. Overall, 81% of patients with CRC and 77% of patients with GO cancer had one or more of these factors within 4 wk prior to diagnosis VTE. These should be
Di Micco, Pierpaolo; Ruiz-Giménez, Nuria; Nieto, José Antonio; Aujesky, Drahomir; del Molino, Fátima; Valle, Reina; Barrón, Manuel; Maestre, Ana; Monreal, Manuel
The relationship between platelet count and outcome in patients with acute venous thromboembolism (VTE) has not been consistently explored. RIETE is an ongoing registry of consecutive patients with acute VTE. We categorised patients as having very low- (<80,000/µl), low- (80,000/µl to 150,000/µl), normal- (150,000/µl to 300,000/µl), high- (300,000/µl to 450,000/µl), or very high (>450,000/µl) platelet count at baseline, and compared their three-month outcome. As of October 2012, 43,078 patients had been enrolled in RIETE: 21,319 presenting with pulmonary embolism and 21,759 with deep-vein thrombosis. In all, 502 patients (1.2%) had very low-; 5,472 (13%) low-; 28,386 (66%) normal-; 7,157 (17%) high-; and 1,561 (3.6%) very high platelet count. During the three-month study period, the recurrence rate was: 2.8%, 2.2%, 1.8%, 2.1% and 2.2%, respectively; the rate of major bleeding: 5.8%, 2.6%, 1.7%, 2.3% and 4.6%, respectively; the rate of fatal bleeding: 2.0%, 0.9%, 0.3%, 0.5% and 1.2%, respectively; and the mortality rate: 29%, 11%, 6.5%, 8.8% and 14%, respectively. On multivariate analysis, patients with very low-, low-, high- or very high platelet count had an increased risk for major bleeding (odds ratio [OR]: 2.70, 95% confidence interval [CI]: 1.85-3.95; 1.43 [1.18-1.72]; 1.23 [1.03-1.47]; and 2.13 [1.65-2.75]) and fatal bleeding (OR: 3.70 [1.92-7.16], 2.10 [1.48-2.97], 1.29 [0.88-1.90] and 2.49 [1.49-4.15]) compared with those with normal count. In conclusion, we found a U-shaped relationship between platelet count and the three-month rate of major bleeding and fatal bleeding in patients with VTE.
Soria, José Manuel; Morange, Pierre‐Emmanuel; Vila, Joan; Souto, Juan Carlos; Moyano, Manel; Trégouët, David‐Alexandre; Mateo, José; Saut, Noémi; Salas, Eduardo; Elosua, Roberto
Background Genetics plays an important role in venous thromboembolism (VTE). Factor V Leiden (FVL or rs6025) and prothrombin gene G20210A (PT or rs1799963) are the genetic variants currently tested for VTE risk assessment. We hypothesized that primary VTE risk assessment can be improved by using genetic risk scores with more genetic markers than just FVL‐rs6025 and prothrombin gene PT‐rs1799963. To this end, we have designed a new genetic risk score called Thrombo inCode (TiC). Methods and Results TiC was evaluated in terms of discrimination (Δ of the area under the receiver operating characteristic curve) and reclassification (integrated discrimination improvement and net reclassification improvement). This evaluation was performed using 2 age‐ and sex‐matched case–control populations: SANTPAU (248 cases, 249 controls) and the Marseille Thrombosis Association study (MARTHA; 477 cases, 477 controls). TiC was compared with other literature‐based genetic risk scores. TiC including F5 rs6025/rs118203906/rs118203905, F2 rs1799963, F12 rs1801020, F13 rs5985, SERPINC1 rs121909548, and SERPINA10 rs2232698 plus the A1 blood group (rs8176719, rs7853989, rs8176743, rs8176750) improved the area under the curve compared with a model based only on F5‐rs6025 and F2‐rs1799963 in SANTPAU (0.677 versus 0.575, P<0.001) and MARTHA (0.605 versus 0.576, P=0.008). TiC showed good integrated discrimination improvement of 5.49 (P<0.001) for SANTPAU and 0.96 (P=0.045) for MARTHA. Among the genetic risk scores evaluated, the proportion of VTE risk variance explained by TiC was the highest. Conclusions We conclude that TiC greatly improves prediction of VTE risk compared with other genetic risk scores. TiC should improve prevention, diagnosis, and treatment of VTE. PMID:25341889
Hald, Erin M; Brækkan, Sigrid K; Mathiesen, Ellisiv B; Njølstad, Inger; Wilsgaard, Tom; Brox, Jan; Hansen, John-Bjarne
High-sensitivity C-reactive protein is associated with risk of arterial cardiovascular disease but conflicting results have been reported on its role in venous thromboembolic disease. The objective of our study was to investigate the association between high-sensitivity C-reactive protein levels and risk of future venous thromboembolism in a prospective cohort recruited from a general population. High-sensitivity C-reactive protein was measured in serum samples from 6,426 men and women, aged 25-84 years, recruited from the Tromsø Study in the period 1994-1995. Incident venous thromboembolism events (n=209) were registered during a median of 12.5 years of follow up. Cox's proportional hazards regression models were used to estimate age- and gender-and multivariable-adjusted hazard ratios with 95% confidence intervals for total venous thromboembolism, and for provoked and unprovoked venous thromboembolism by increasing levels of high-sensitivity C-reactive protein. There was no increased risk of venous thromboembolism per 1 standard deviation increase in high-sensitivity C-reactive protein (hazard ratio 1.08; 95% confidence interval 0.95-1.23) or across quartiles of high-sensitivity C-reactive protein (P for trend 0.6) in analyses adjusted for age and gender. Further adjustment for body mass index, smoking and diabetes did not alter the risk estimates. Moreover, high-sensitivity C-reactive protein was not associated with venous thromboembolism in either gender specific analysis or in separate analyses of provoked and unprovoked venous thromboembolism events. In this prospective study, serum levels of high-sensitivity C-reactive protein were not associated with future development of venous thromboembolism. Our findings do not suggest a causal role for C-reactive protein in the pathogenesis of venous thromboembolism.
Becker, D M; Philbrick, J T; Bachhuber, T L; Humphries, J E
D-dimer fragments can be measured easily in plasma and whole blood, and the presence or absence of D-dimer could be useful in the diagnostic evaluation of venous thromboembolism. We systematically reviewed the English literature for articles that compared D-dimer results with those of other tests for deep venous thrombosis or pulmonary embolism. Twenty-nine studies were selected for detailed review, and we noted wide variability in assay performance, heterogeneity among subjects, and failure to define absence or presence of venous thromboembolism by a comprehensive criterion standard for diagnosis. These methodologic problems limit the generalizability of the published estimates of D-dimer accuracy for deep venous thrombosis or pulmonary embolism, and the clinical utility of this potentially important test remains unproved.
Lazo-Langner, A; Fleet, J L; McArthur, E; Garg, A X
Rivaroxaban is increasingly used to prevent venous thromboembolism after hip or knee arthroplasty. Studies evaluating the effectiveness of rivaroxaban compared to low molecular weight heparin after orthopedic surgery in routine practice are scarce. We conducted a retrospective cohort study in 121 hospitals in Ontario, Canada, between 2002 and 2012. We included patients aged 66 years or older (median age 73 years) who received an outpatient prescription for subcutaneous low molecular weight heparin (n = 11 471) or oral rivaroxaban (n = 12 850) on hospital discharge after a total knee or hip arthroplasty. The two coprimary outcomes assessed within 30 days of the prescription date were emergency department visit or hospitalization with venous thromboembolism (either deep vein thrombosis or pulmonary embolism; primary efficacy outcome) and a hospitalization with non-traumatic major hemorrhage (primary safety outcome). Rivaroxaban use increased over the study period. Compared to low molecular weight heparin, rivaroxaban was associated with a lower 30-day risk of hospitalization with venous thromboembolism (0.47% vs. 0.81%; relative risk 0.58; 95% confidence interval 0.42-0.81; P = 0.001) with no significant difference in hospitalizations for major bleeding (0.18% vs. 0.20%; relative risk 0.89; 95% confidence interval 0.50-1.59; P = 0.700). In routine practice, anticoagulant prophylaxis with rivaroxaban compared to low molecular weight heparin after hospital discharge from total hip or knee arthroplasty is associated with a lower risk of symptomatic venous thromboembolism with no difference in the risk of bleeding. © 2014 International Society on Thrombosis and Haemostasis.
Jo, Woo-Lam; Lee, Young-Kyun; Ha, Yong-Chan; Lee, Kyung-Min; Kang, Bun-Jung; Koo, Kyung-Hoi
Intermittent Pneumatic Compression (IPC) device has been used to prevent venous thromboembolism (VTE). This study investigated the effectiveness of IPC device. We evaluated incidences of deep vein thrombosis (DVT) and pulmonary embolism (PE) in total hip arthroplasty (THA) patients after use of IPC device, and compared with historical incidences from our institution. We applied IPC device in 741 patients who underwent 870 elective primary THAs from January 2010 to December 2013, DVT was detected in 3 patients (0.3%) by sonography, and one (0.1%) of them was symptomatic. Symptomatic PE occurred in 1 patient (0.1%) and there were no cases of fatal PE. The incidence of symptomatic DVT was significantly lower than the historical control (P = 0.042). The IPC is a safe and effective prophylaxis of VTE after primary THA in Korea.
Skillman, Joanna; Thomas, Sunil
When intermittent compression devices (ICDs) are used to prevent venous thromboembolism (VTE) they can cause pressure sores in a selected group of women, undergoing long operations. A prospective audit pre and post intervention showed a reduced risk with an alternative device, without increasing the risk of VTE.
Kubota, Y; London, S J; Cushman, M; Chamberlain, A M; Rosamond, W D; Heckbert, S R; Zakai, N; Folsom, A R
Essentials The association of lung function with venous thromboembolism (VTE) is unclear. Chronic obstructive pulmonary disease (COPD) patterns were associated with a higher risk of VTE. Symptoms were also associated with a higher risk of VTE, but a restrictive pattern was not. COPD may increase the risk of VTE and respiratory symptoms may be a novel risk marker for VTE.
Girard, P; Penaloza, A; Parent, F; Gable, B; Sanchez, O; Durieux, P; Hausfater, P; Dambrine, S; Meyer, G; Roy, P-M
Essentials The reproducibility of Clinical Events Committee (CEC) adjudications is almost unexplored. A random selection of events from a venous thromboembolism trial was blindly re-adjudicated. 'Unexplained sudden deaths' (possible fatal embolism) explained most discordant adjudications. A precise definition for CEC adjudication of this type of events is needed and proposed.
Duan, Qianglin; Lv, Wei; Yang, Minjun; Yang, Fan; Zhu, Yongqiang; Kang, Hui; Song, Haoming; Wang, Shengyue; Dong, Hui; Wang, Lemin
Aim: This study was to carry out exome sequencing in a Han Chinese family with venous thromboembolism. Methods: Three venous thromboembolism (VTE) patients and five members from a Han Chinese family were evaluated by exome sequencing. Results: Among the 3 VTE patients, mutations of 2 genes including PRF1 and HTR2A were identified and predicted to be functionally damaged to their encoded proteins. In addition, the PRF1 mutation and the HTR2A mutation identified in our study were absent in 100 non-related controls, indicating that venous thromboembolism has a genetic component. The R357W mutation is located in the membrane attack complex/perforin domain of PRF1 protein, which exists in both the perforin. The steps of killing foreign or pathological antigen cells by NK cells, CD8 +T cells and the membrane attack complex include membrane perforation and release of the granzyme, either of which is abnormal can lead to immune dysfunction. Conclusions: The mutations of immune related genes in familial VTE might provide new understanding of the pathogenesis of familial venous thromboembolism. PMID:26221353
Wawrzyńska, L; Hajduk, B; Kober, J; Filipecki, S
We have attempted to determine the outcome of 87 out-patients who were lost from follow-up. Several factors have been assessed: causes of lost from follow-up duration of oral anticoagulation, recurrent venous thromboembolic events, cause of death (if applicable).
Samama, C M
The overall thromboembolic risk is the resultant of patient-related risk and surgical risk. The surgical risk is decreasing, especially with the introduction of new procedures (fast-track surgery). The value of prophylaxis has been firmly established. Mechanical prophylaxis is to be used as first-line prophylaxis when there is a risk of bleeding. Combining this with drugs increases the antithrombotic efficacy. However, the effectiveness of prophylaxis on pulmonary embolism and mortality has not been demonstrated. Renal function needs to be evaluated when low molecular weight heparins, fondaparinux, rivaroxaban or dabigatran are prescribed. An age of over 75 years and low body weight (<50 kg) have to be taken into account. There is a risk of spinal or epidural hematoma in patients receiving anticoagulants. Caution should be taken especially when administering the newer agents. Patients undergoing surgery that involves a moderate or high overall risk should receive prophylaxis until full mobilization. Patients who have undergone a total hip replacement, surgery for hip fracture, or major abdominal surgery should receive prophylaxis for about 5 weeks longer. The relevance of distal vein thromboses is debated. Surrogate venographic end-points should be gradually replaced by a combination of ultrasound and clinical criteria. The new antithrombotic agents will probably modify prevention in the years to come but currently there are very few long-term data for these products for which - it should be reminded - no antagonists are available.
Monahan, M; Ensor, J; Moore, D; Fitzmaurice, D; Jowett, S
Essentials Correct duration of treatment after a first unprovoked venous thromboembolism (VTE) is unknown. We assessed when restarting anticoagulation was worthwhile based on patient risk of recurrent VTE. When the risk over a one-year period is 17.5%, restarting is cost-effective. However, sensitivity analyses indicate large uncertainty in the estimates. Background Following at least 3 months of anticoagulation therapy after a first unprovoked venous thromboembolism (VTE), there is uncertainty about the duration of therapy. Further anticoagulation therapy reduces the risk of having a potentially fatal recurrent VTE but at the expense of a higher risk of bleeding, which can also be fatal. Objective An economic evaluation sought to estimate the long-term cost-effectiveness of using a decision rule for restarting anticoagulation therapy vs. no extension of therapy in patients based on their risk of a further unprovoked VTE. Methods A Markov patient-level simulation model was developed, which adopted a lifetime time horizon with monthly time cycles and was from a UK National Health Service (NHS)/Personal Social Services (PSS) perspective. Results Base-case model results suggest that treating patients with a predicted 1 year VTE risk of 17.5% or higher may be cost-effective if decision makers are willing to pay up to £20 000 per quality adjusted life year (QALY) gained. However, probabilistic sensitivity analysis shows that the model was highly sensitive to overall parameter uncertainty and caution is warranted in selecting the optimal decision rule on cost-effectiveness grounds. Univariate sensitivity analyses indicate variables such as anticoagulation therapy disutility and mortality risks were very influential in driving model results. Conclusion This represents the first economic model to consider the use of a decision rule for restarting therapy for unprovoked VTE patients. Better data are required to predict long-term bleeding risks during therapy in this
Lestienne, B; Vergnes, M-C; Audibert, G; Faillot, T; Bosson, J-L; Payen, J-F; Bruder, N
There are few studies of poor methodological quality on the risk of thromboembolism in head and neck surgery. The incidence of symptomatic deep vein thrombosis is estimated between, 0.1% and 0.6%. The patient's risk factors (cancer, alcoholism, smoking, malnutrition) determine for the assessment of the potential benefit of thromboembolism prophylaxis. No method can be recommended based on the literature. In patients receiving anticoagulant therapy undergoing superficial head and neck surgery or dental extraction, the literature suggest to continue anticoagulation throughout the perioperative period.
Thromboembolic disease is a rare, but important, complication of pregnancy that remains a leading non-obstetric cause of maternal death. The prevention and management of venous thromboembolism (VTE) in pregnant women is a complex area of medicine: a balance must be found between protecting the health of the mother and minimizing the risk to the unborn fetus. Until now, unfractionated heparin has been regarded as the drug of choice for the prevention and treatment of VTE during pregnancy. However, because of its significant side effects (osteoporosis and heparin-induced thrombocytopenia), the inconvenient mode of administration and need for monitoring, unfractionated heparin is now being replaced by low-molecular-weight heparin (LMWH). There is a convincing body of clinical evidence from well-designed studies and prospective case series that supports the efficacy and safety of LMWH in pregnant women. There are also encouraging observations on the efficacy of LMWH in the prevention of severe obstetric complications, which are frequently associated with inherited or acquired thrombophilias. The recently-published guidelines of The American College of Chest Physicians (ACCP), summarized in this review, allows the development of higher clinical standards. However, there is concern over the greater cost of LMWH compared with unfractionated heparin and oral anticoagulants, and cost-effectiveness studies are needed.
Bleau, Nathalie; Patenaude, Valerie; Abenhaim, Haim A
The objective of this study is to evaluate the effect of autoimmune disease on the risk of venous thromboembolism (VTE) including deep vein thrombosis (DVT) and pulmonary embolism (PE) in pregnant women. Using the Health Care Cost and Utilization Project, Nationwide Inpatient Sample database from 2003 to 2011, the risk of developing DVT, PE, and VTE among pregnant patients with selected autoimmune diseases was estimated using unconditional logistic regression analysis. Our study cohort consisted of 7 917 453 women of which 43 523 had underlying autoimmune diseases. Risk of VTE was high in pregnant women with systemic lupus erythematosus, dermatomyositis, rheumatoid arthritis, type 1 diabetes mellitus, ulcerative colitis, and Crohn's disease. Most autoimmune diseases considerably increase the risk of VTE. Thromboprophylaxis may be considered in pregnancies with autoimmune disease, particularly those with systemic lupus erythematosus and dermatomyositis. © The Author(s) 2014.
Pangilinan, Joanna Maudlin
Clinicians must always maintain a heightened suspicion for the development of venous thromboembolism (VTE) in the cancer patient population. VTE is common in this population and often results in morbidity and mortality. The pathophysiology is complex and likely multifactorial. Risk factors for VTE include patient-associated, cancer-associated, and treatment-associated factors as well as biomarkers. Low-molecular-weight heparin (LMWH) is a cornerstone for VTE prophylaxis and treatment. Studies have shown that LMWH may decrease VTE recurrence and impart a survival benefit. Organizational guidelines are available to assist the clinician in choosing appropriate anticoagulant agents, dosing, and duration of prophylaxis and treatment. Pharmacists serve an important role for the safe and effective management of anticoagulation in this complex patient population. In addition, pharmacists can be important providers of patient education about VTE and anticoagulation.
Gon, Yasufumi; Sakaguchi, Manabu; Takasugi, Junji; Mochizuki, Hideki
Direct oral anticoagulants (DOACs) are at least as efficacious as conventional anticoagulation therapy for the initial and long-term treatment of cancer patients with venous thromboembolism (VTE). Whether DOACs are non-inferior to low-molecular-weight heparin for the management of cancer patients with VTE is under investigation. In addition, the efficacy of DOACs for the treatment of cancer patients with arterial thrombosis (e.g., ischemic stroke) remains unclear. Herein, we report on two cancer patients admitted to our hospital with Stage IV gastric adenocarcinoma who were being treated with DOACs due to a history of VTE and had developed their first ever ischemic stroke, which was diagnosed due to cancer-related hypercoagulation. Notably, neither patient had recurrence of VTE during the course of their disease. In cancer-related thrombosis, DOACs effectively reduce VTE, but may be insufficient for preventing ischemic stroke. Copyright © 2017 Elsevier Ltd. All rights reserved.
Thorogood, M; Mann, J; Murphy, M; Vessey, M
A case-control study of fatal venous thromboembolism in young women is described. Sixty women aged between 16 and 39 who died from thromboembolism in England and Wales between 1986 and 1988 were included in the study. Two living controls matched for age and marital status were sought from the records of the general practitioner with whom each case was registered. Some 115 controls were included in the study. The cases had a significantly higher prevalence of a history of major illness, particularly thrombotic episodes, than the controls. The odds ratio (OR) of a fatal thromboembolism in women who had a history of venous thrombosis was 4.0 (95% Cl: 1.4-11.5). There was also a significantly higher frequency of a recent operation or accident amongst the cases than the controls (OR = 11.1, 95% Cl: 1.3-92.5). There was no significant excess or oral contraceptive use amongst the cases. The overall OR associated with current use of oral contraceptives was 1.6 (95% Cl: 0.7-3.4), while the corresponding OR for 'idiopathic' diseases was 2.1 (95% Cl: 0.8-5.2). These risks are considerably smaller than those observed in previous studies. The observed risk may be low because the dosage of oestrogen in modern oral contraceptive preparations has been reduced, but it may also be because the cases of fatal venous thromboembolism included in this study represent only a small proportion of all cases of venous thrombeombolism; a disease which is rarely fatal in young women. These results cannot necessarily be extrapolated to nonfatal venous thromboembolism.
Westerlund, Eli; Wallén, Håkan; Brandt, Lena; Hovatta, Outi; Ekbom, Anders
Objective To estimate the risk of pulmonary embolism and venous thromboembolism in pregnant women after in vitro fertilisation. Design Cross sectional study. Setting Sweden. Participants 23 498 women who had given birth after in vitro fertilisation between 1990 and 2008 and 116 960 individually matched women with natural pregnancies. Main outcome measures Risk of pulmonary embolism and venous thromboembolism (identified by linkage to the Swedish national patient register) during the whole pregnancy and by trimester. Results Venous thromboembolism occurred in 4.2/1000 women (n=99) after in vitro fertilisation compared with 2.5/1000 (n=291) in women with natural pregnancies (hazard ratio 1.77, 95% confidence interval 1.41 to 2.23). The risk of venous thromboembolism was increased during the whole pregnancy (P<0.001) and differed between the trimesters (P=0.002). The risk was particularly increased during the first trimester, at 1.5/1000 after in vitro fertilisation versus 0.3/1000 (hazard ratio 4.22, 2.46 to 7.26). The proportion of women experiencing pulmonary embolism during the first trimester was 3.0/10 000 after in vitro fertilisation versus 0.4/10 000 (hazard ratio 6.97, 2.21 to 21.96). Conclusions In vitro fertilisation is associated with an increased risk of pulmonary embolism and venous thromboembolism during the first trimester. The risk of pulmonary embolism is low in absolute terms but because the condition is a leading cause of maternal mortality and clinical suspicion is critical for diagnosis, an awareness of this risk is important. Trial registration ClinicalTrials.gov NCT01524393. PMID:23321489
Henriksson, Peter; Westerlund, Eli; Wallén, Håkan; Brandt, Lena; Hovatta, Outi; Ekbom, Anders
To estimate the risk of pulmonary embolism and venous thromboembolism in pregnant women after in vitro fertilisation. Cross sectional study. Sweden. 23,498 women who had given birth after in vitro fertilisation between 1990 and 2008 and 116,960 individually matched women with natural pregnancies. Risk of pulmonary embolism and venous thromboembolism (identified by linkage to the Swedish national patient register) during the whole pregnancy and by trimester. Venous thromboembolism occurred in 4.2/1000 women (n=99) after in vitro fertilisation compared with 2.5/1000 (n=291) in women with natural pregnancies (hazard ratio 1.77, 95% confidence interval 1.41 to 2.23). The risk of venous thromboembolism was increased during the whole pregnancy (P<0.001) and differed between the trimesters (P=0.002). The risk was particularly increased during the first trimester, at 1.5/1000 after in vitro fertilisation versus 0.3/1000 (hazard ratio 4.22, 2.46 to 7.26). The proportion of women experiencing pulmonary embolism during the first trimester was 3.0/10,000 after in vitro fertilisation versus 0.4/10,000 (hazard ratio 6.97, 2.21 to 21.96). In vitro fertilisation is associated with an increased risk of pulmonary embolism and venous thromboembolism during the first trimester. The risk of pulmonary embolism is low in absolute terms but because the condition is a leading cause of maternal mortality and clinical suspicion is critical for diagnosis, an awareness of this risk is important. ClinicalTrials.gov NCT01524393.
Bird, Steven T.; Hartzema, Abraham G.; Brophy, James M.; Etminan, Mahyar; Delaney, Joseph A.C.
Background: There is an increased risk of venous thromboembolism among women taking oral contraceptives. However, whether there is an additional risk among women with polycystic ovary syndrome (PCOS) is unknown. Methods: We developed a population-based cohort from the IMS LifeLink Health Plan Claims Database, which includes managed care organizations in the United States. Women aged 18–46 years taking combined oral contraceptives and who had a claim for PCOS (n = 43 506) were matched, based on a propensity score, to control women (n = 43 506) taking oral contraceptives. Venous thromboembolism was defined using administrative coding and use of anticoagulation. We used Cox proportional hazards models to assess the relative risk (RR) of venous thromboembolism among users of combined oral contraceptives with and without PCOS. Results: The incidence of venous thromboembolism among women with PCOS was 23.7/10 000 person-years, while that for matched controls was 10.9/10 000 person-years. Women with PCOS taking combined oral contraceptives had an RR for venous thromboembolism of 2.14 (95% confidence interval [CI] 1.41–3.24) compared with other contraceptive users. The incidence of venous thromboembolism was 6.3/10 000 person-years among women with PCOS not taking oral contraceptives; the incidence was 4.1/10 000 person-years among matched controls. The RR of venous thromboembolism among women with PCOS not taking oral contraceptives was 1.55 (95% CI 1.10–2.19). Interpretation: We found a 2-fold increased risk of venous thromboembolism among women with PCOS who were taking combined oral contraceptives and a 1.5-fold increased risk among women with PCOS not taking oral contraceptives. Physicians should consider the increased risk of venous thromboembolism when prescribing contraceptive therapy to women with PCOS. PMID:23209115
Hurst, Katherine V; O’Callaghan, John Matthew; Handa, Ashok
The new generation of target-specific oral anticoagulants is being prescribed for increasing numbers of patients at risk of stroke or venous thromboembolism (VTE). These drugs offer valuable benefits due to fast onset anticoagulation, a fixed anticoagulation effect (allowing administration of specified doses), and no requirement for routine monitoring. Edoxaban is a fast-acting oral anticoagulant, approved for use in the prevention of stroke in patients with nonvalvular atrial fibrillation (AF) and in the treatment of acute VTE. Like many of the new oral anticoagulants, it selectively inhibits factor Xa, in a concentration-dependent manner. Multiple Phase II clinical trials have shown edoxaban to be noninferior to vitamin K antagonists in the prevention of stroke and VTE, with a good safety profile. To date, the pivotal studies to endorse edoxaban’s clinical use have been ENGAGE AF-TIMI and Hokusai-VTE, both of which have compared its efficacy to standard warfarin treatment. This paper aims at reviewing the use of edoxaban in the management of stroke and thromboembolic disease, highlighting the key study results that have led to its current license. PMID:27563246
Pinède, L; Ninet, J; Boissel, J P; Pasquier, J
Every clinician managing a patient with venous thromboembolism of the lower limbs is faced with two opposing problems: first the risk of antivitamin K induced haemorrhage requires adequate but not excessive hypocoaguability of limited duration (international normalized ratio between 2 and 3); second the threat of recurrence requiring an adequate level of hypocoaguability of sufficient duration. Recently reported clinical data have greatly changed management attitudes. Current recommendations favour a 6 week regimen of antivitamin K for distal venous thrombosis in patients with thromboembolism of lower limb veins without any other aggravating factor and a 12 week regimen for proximal vein thrombosis or pulmonary emboli, although the therapeutic efficacity and risk remain to be demonstrated with precision. In France, we are conducting a multicentric controlled study with sufficient power (1800 patients) comparing parallel groups of patients: those with distal deep venous thrombosis treated 6 versus 12 week regimens, those with proximal deep venous thrombosis and/or pulmonary emboli treated 12 versus 24 week regimens. The "DOTAVK" study (Durée Optimale du Traitement Antivitamine K) involves patients with first time venous thrombosis or pulmonary emboli and no underlying neoplasia or coagulation disease. The two criteria of outcome are haemorrhage complications and thromboembolic recurrence during treatment and the first year after treatment withdrawal.
Baratloo, Alireza; Safari, Saeed; Rouhipour, Alaleh; Hashemi, Behrooz; Rahmati, Farhad; Motamedi, Maryam; Forouzanfar, Mohammadmehdi; Haroutunian, Pauline
Introduction: Oral contraceptives (OCs) are considered as one of the most common risk factor of venous thromboembolism (VTE) in childbearing age. Some of the recent researches indicate that the odds of VTE may be even higher with newer generations of OCs. The present meta-analysis was designed to evaluate the effect of different generation of OCs on the occurrence of VTE. Methods: Two researchers independently ran a thorough search in Pubmed, ISI Web of Science, EMBASE, CINAHL and Scopus databases regarding study keywords including thromboembolic event, thromboembolism, embolism, thromboembolic, thrombotic and thrombosis, combined with oral contraceptive. The outcomes were the incidence of diagnosed thromboembolism, such as deep vein thrombosis, pulmonary embolism and cerebral venous thrombosis. Based on the heterogeneity of the studies, random effect model was used and pooled odds ratio was reported. Results: Three cohort and 17 case-control studies with 13,265,228 subjects were entered into meta-analysis. Analysis showed that the odds of VTE in women taking OCs are more than three-fold (OR=3.13; 95% CI: 2.61-3.65). The risk of VTE in women taking first-, second- and third-generation OCs are 3.5 fold (OR=3.48; 95% CI: 2.01-4.94), 3 fold (OR=3.08; 95% CI: 2.43-3.74) and 4.3 fold (OR=4.35; CI: 3.69‒5.01), respectively. Conclusion: It seems that the risk of VTE is not same between different generations of OCs, so that third-generation has highest risk. Taking second and third-generation OCs increases the risk of VTE up to 3 and 4.3 fold, respectively. The researchers of the present study suggest that more trials be designed in relation to the effect of newer generations of OCs in different communities. PMID:26495334
Alsayegh, Faisal; Al-Jassar, Waleed; Wani, Salima; Tahlak, Muna; Al-Bahar, Awatef; Al-Kharusi, Lamya; Al-Tamimi, Halima; El-Taher, Faten; Mahmood, Naeema; Al-Zakwani, Ibrahim
Objectives: To estimate the prevalence of venous thromboembolism (VTE) risk factors in pregnancy and the proportion of pregnancies at risk of VTE that received the recommended prophylaxis according to the American College of Chest Physicians (ACCP) 2012 published guidelines in antenatal clinics in the Arabian Gulf. Methods: The evaluation of venous thromboembolism (EVE)-Risk project was a non-interventional, cross-sectional, multi-centre, multi-national study of all eligible pregnant women (≥17 years) screened during antenatal clinics from 7 centres in the Arabian Gulf countries (United Arab Emirates, Kuwait, Bahrain, Qatar and Oman). Pregnant women were recruited during a 3-month period between September and December 2012. Results: Of 4,131 screened pregnant women, 32% (n=1,337) had ≥1 risk factors for VTE. Common VTE risk factors included obesity (76%), multiparity (33%), recurrent miscarriages (9.1%), varicose veins (6.9%), thrombophilia (2.6%), immobilization (2.0%), sickle cell disease (2.8%) and previous VTE (1.6%). Only 8.3% (n=111) of the high risk patients were on the recommended VTE prophylaxis. Enoxaparin was used in 80% (n=89) of the cases followed by tinzaparin (4%; n=4). Antiplatelet agents were prescribed in 11% (n=149) of pregnant women. Of those on anticoagulants (n=111), 59% (n=66) were also co-prescribed antiplatelet agents. Side effects (mainly local bruising at the injection site) were reported in 12% (n=13) of the cases. Conclusion: A large proportion of pregnant women in the Arabian Gulf countries have ≥1 VTE risk factor with even a smaller fraction on prophylaxis. VTE risk assessment must be adopted to identify those at risk who would need VTE prophylaxis. PMID:26517701
Liu, Bo; Ding, Fengxia; Zhang, Deying; Wei, Guang-Hui
The reported incidence of arterial and venous thromboembolic events varies markedly between VEGFR-TKI-related clinical trials. Here, we performed a meta-analysis to determine the incidence and the relative risk (RR) of venous thromboembolism events (VTEs) and arterial thromboembolic events (ATEs) associated with these agents. Databases (PubMed, Web of Science) were searched for relevant studies. Statistical analyses were conducted to calculate the summary incidences, RRs and 95% confidence intervals (CIs) using either random-effects or fixed-effects models according to the heterogeneity of the included studies. A total of 24,855 patients from 48 studies were included. The overall incidence of all-grade and high-grade VTEs associated with VEGFR-TKIs was 3.6% (95% CI 2.3-5.2%) and 1.6% (95% CI 1.0-2.4%), respectively. The use of VEGFR-TKIs did not significantly increase the risk of developing all-grade (RR 0.91; 95% CI 0.68-1.22; P = 0.558) and high-grade (RR 1.05; 95% CI 0.84-1.31; P = 0.769) VTEs. The overall incidence of all-grade and high-grade ATEs associated with VEGFR-TKIs was 2.7% (95% CI 1.7-3.6%) and 0.6% (95% CI 0.2-1.2%), respectively. The use of VEGFR-TKIs significantly increase the risk of developing all-grade (RR 3.09; 95% CI 1.41-6.76; P = 0.033) ATEs, and a tendency to increase the risk of high-grade (RR 1.49; 95% CI 0.99-2.24; P = 0.101) ATEs was also detected. Patients with cancer that receive VEGFR-TKIs are at high risk of developing ATEs. Physicians should be aware of these adverse effects and should monitor cancer patients receiving VEGFR-TKIs.
Sánchez-Siles, Mariano; Rosa-Salazar, Vladimir; Salazar-Sánchez, Noemi; Camacho-Alonso, Fabio
In recent years, periodontal disease has been related to a large number of systemic disorders. To study the possible relationship between periodontal disease and high levels of D-dimer in a group of patients with venous thromboembolic disease. A study was made of 142 patients diagnosed with unprovoked venous thromboembolic disease. All patients underwent oral examination consecutively and randomly. Finally, two groups were obtained: (a) patients with periodontal disease (n = 71); and (b) patients without periodontal disease (n = 71). All patients were subjected to periodontal study, with evaluation of the number of teeth, bleeding index, gingival index, simplified oral hygiene index, community periodontal index of treatment needs, clinical attachment level, probe depth, number of pockets ≥4 mm, number of pockets ≥6 mm. The D-dimer values were evaluated in both groups. D-dimer values were higher in the study group than the control group, with statistically significant differences (p = 0.010). A relationship is observed between the presence of periodontal disease and high D-dimer levels. Patients with venous thromboembolic disease and periodontal disease could have more risk of a new thromboembolism episode.
Jensvoll, Hilde; Blix, Kristine; Brækkan, Sigrid K.; Hansen, John-Bjarne
Background Elevated platelet count is associated with risk of venous thromboembolism in cancer patients initiating chemotherapy. It is not known whether this risk by platelet count is causal or merely reflects the malignant disease. We investigated whether pre-cancer platelet count alone or together with high leukocyte count was associated with risk of venous thromboembolism in subjects who did and did not develop cancer during follow-up in a population-based cohort study. Methods Platelet count and other baseline characteristics were measured in 25160 initially cancer-free subjects who participated in the Tromsø Study in 1994–1995. Incident cancer and symptomatic venous thromboembolism events were registered up to December 31st, 2009. Multivariable Cox regression models were used to calculate hazard ratio for venous thromboembolism across categories of platelet count (<40th, 40–80th, and >80th percentile) with 95% confidence interval. Results During follow-up, 2082 subjects were diagnosed with cancer. Platelet count was measured on average 8.3 years before the cancer diagnosis. There were 129 venous thromboembolism events in the cancer cohort (13.5 per 1000 person-years) and 377 in the non-cancer cohort (1.2 per 1000 person-years). In cancer patients, pre-cancer platelet count above the 80th percentile (≥295×109/L) was associated with a 2-fold higher risk of venous thromboembolism (Hazard ratio: 1.98, 95% confidence interval 1.21–3.23) compared to platelet count below the 40th percentile (<235×109/L). Concomitant high platelet and leukocyte counts showed a synergistic effect on the VTE risk. In cancer-free subjects, no association was found. Comment In conclusion, pre-cancer platelet count was associated with risk of symptomatic venous thromboembolism in cancer patients, but not in cancer-free subjects. Our findings suggest that platelet count and platelet-leukocyte interactions may play a role in the pathogenesis of cancer-related venous
Jensvoll, Hilde; Blix, Kristine; Brækkan, Sigrid K; Hansen, John-Bjarne
Elevated platelet count is associated with risk of venous thromboembolism in cancer patients initiating chemotherapy. It is not known whether this risk by platelet count is causal or merely reflects the malignant disease. We investigated whether pre-cancer platelet count alone or together with high leukocyte count was associated with risk of venous thromboembolism in subjects who did and did not develop cancer during follow-up in a population-based cohort study. Platelet count and other baseline characteristics were measured in 25160 initially cancer-free subjects who participated in the Tromsø Study in 1994-1995. Incident cancer and symptomatic venous thromboembolism events were registered up to December 31st, 2009. Multivariable Cox regression models were used to calculate hazard ratio for venous thromboembolism across categories of platelet count (<40th, 40-80th, and >80th percentile) with 95% confidence interval. During follow-up, 2082 subjects were diagnosed with cancer. Platelet count was measured on average 8.3 years before the cancer diagnosis. There were 129 venous thromboembolism events in the cancer cohort (13.5 per 1000 person-years) and 377 in the non-cancer cohort (1.2 per 1000 person-years). In cancer patients, pre-cancer platelet count above the 80th percentile (≥295×10(9)/L) was associated with a 2-fold higher risk of venous thromboembolism (Hazard ratio: 1.98, 95% confidence interval 1.21-3.23) compared to platelet count below the 40th percentile (<235×10(9)/L). Concomitant high platelet and leukocyte counts showed a synergistic effect on the VTE risk. In cancer-free subjects, no association was found. In conclusion, pre-cancer platelet count was associated with risk of symptomatic venous thromboembolism in cancer patients, but not in cancer-free subjects. Our findings suggest that platelet count and platelet-leukocyte interactions may play a role in the pathogenesis of cancer-related venous thromboembolism.
Ouaissi, Mehdi; Frasconi, Cecilia; Mege, Diane; Panicot-Dubois, Laurence; Boiron, Laurence; Dahan, Laetitia; Debourdeau, Philippe; Dubois, Christophe; Farge, Dominique; Sielezneff, Igor
Few studies have analyzed the effect of venous thromboembolism (VTE) events on the prognosis of pancreatic cancer, but their results were conflicting. The present study was undertaken to determine the effect of VTE on pancreatic adenocarcinoma (PA) outcomes. All consecutive patients diagnosed with PA from May 2004 to January 2012 in a single oncology center were retrospectively studied. Clinical, radiological and histological data at time of diagnosis or within the first 3 months after surgery, including the presence (+) or absence (-) of VTE were collected. VTE was defined as radiological evidence of either pulmonary embolism (PE), deep venous thrombosis without infection or catheter-related thrombosis. PA with and without PE was compared for survival using the Kaplan-Meier method to estimate overall survival. Among 162 PA patients with a median follow-up of 15 (3-92) months after diagnosis, 28 demonstrated VTE (+). PA patients with and without PE were similar for age, American Society of Anesthesiologist score, body mass index, and history of treatment. The distribution of cancer stages was similar between the two groups VTE (+) and VTE (-). The median duration of survival was significantly worse in the VTE (+) group vs VTE (-) (12 vs 18 months, P=0.010). In multivariate analysis, the presence of VTE and surgical treatment were independent prognostic factors for overall survival. VTE (+) at time of diagnosis or within the first 3 months after surgery during treatment is an independent factor of poor prognosis in PA.
Increasing age and renal impairment are risk factors for venous thrombosis but also for anticoagulant-induced bleeding. In large-scale phase III trials, non-VKA oral anticoagulants (NOACs) were at least as effective and safe for the treatment of acute venous thromboembolism as warfarin. Here, we review the efficacy and safety of dabigatran, rivaroxaban, apixaban and edoxaban in the subgroups of elderly patients (≥75 years) and patients with impaired renal function (creatinine clearance ≤50 ml/min). In all phase III trials, the efficacy of NOACs in the prevention of recurrent VTE was conserved both in the elderly subgroup and in the subgroup with impaired renal function. In a meta-analysis of the pooled results, NOACs reduced VTE recurrence compared with warfarin in elderly patients. In elderly patients and patients with impaired renal function, the safety of NOACs was in line with the results of the overall study. NOACs may offer an effective, safer and more convenient alternative for VKAs also in the elderly. However, the efficacy/safety profile of NOACs in the aged population needs to be confirmed in real-life. PMID:25650285
Qureshi, Waqas; Ali, Zeeshan; Amjad, Waseem; Alirhayim, Zaid; Farooq, Hina; Qadir, Shayan; Khalid, Fatima; Al-Mallah, Mouaz H
Cancer patients are at major risk of developing venous thromboembolism (VTE), resulting in increased morbidity and economic burden. While a number of theories try to explain its pathophysiology, its risk stratification can be broadly done in cancer-related, treatment-related, and patient-related factors. Studies report the prophylactic use of thrombolytic agents to be safe and effective in decreasing VTE-related mortality/morbidity especially in postoperative cancer patients. Recent data also suggest the prophylactic use of low molecular weight Heparins (LMWHs) and Warfarin to be effective in reducing VTEs related to long-term central venous catheter use. In a double-blind, multicenter trial, a new ultra-LMWH Semuloparin has shown to be efficacious in preventing chemotherapy-associated VTE's along with other drugs, such as Certoparin and Nadoparin. LMWHs are reported to be very useful in preventing recurrent VTEs in advanced cancers and should be preferred over full dose Warfarin. However, their long-term safety beyond 6 months has not been established yet. Furthermore, this paper discusses the safety and efficacy of different drugs used in the treatment and prevention of recurrent VTEs, including Bemiparin, Semuloparin, oral direct thrombin inhibitors, parenteral and direct oral factor Xa inhibitors.
Qureshi, Waqas; Ali, Zeeshan; Amjad, Waseem; Alirhayim, Zaid; Farooq, Hina; Qadir, Shayan; Khalid, Fatima; Al-Mallah, Mouaz H.
Cancer patients are at major risk of developing venous thromboembolism (VTE), resulting in increased morbidity and economic burden. While a number of theories try to explain its pathophysiology, its risk stratification can be broadly done in cancer-related, treatment–related, and patient-related factors. Studies report the prophylactic use of thrombolytic agents to be safe and effective in decreasing VTE-related mortality/morbidity especially in postoperative cancer patients. Recent data also suggest the prophylactic use of low molecular weight Heparins (LMWHs) and Warfarin to be effective in reducing VTEs related to long-term central venous catheter use. In a double-blind, multicenter trial, a new ultra-LMWH Semuloparin has shown to be efficacious in preventing chemotherapy-associated VTE’s along with other drugs, such as Certoparin and Nadoparin. LMWHs are reported to be very useful in preventing recurrent VTEs in advanced cancers and should be preferred over full dose Warfarin. However, their long-term safety beyond 6 months has not been established yet. Furthermore, this paper discusses the safety and efficacy of different drugs used in the treatment and prevention of recurrent VTEs, including Bemiparin, Semuloparin, oral direct thrombin inhibitors, parenteral and direct oral factor Xa inhibitors. PMID:27517038
Gross, Michael; Anderson, David R.; Nagpal, Seema; O’Brien, Bernie
Objective To determine the pharmacologic and physical modalities used by orthopedic surgeons in Canada to prevent venous thromboembolism (deep venous thrombosis and pulmonary embolism) after total hip or knee arthroplasty. Design Mail survey sent to all members of the Canadian Orthopaedic Association. Setting A nation-wide study. Methods A total of 828 questionnaires, designed to identify the type and frequency of prophylaxis against venous thromboembolism that were used after hip and knee arthroplasty were mailed to orthopedic surgeons. Outcome measures Demographic data and the frequency and type of thromboprophylaxis. Results Of the 828 surveys mailed 445 (54%) were returned, and 397 were included in this analysis. Of the respondents, 97% used prophylaxis routinely for patients who undergo total hip or knee arthroplasty. Three of the 397 (0.8%) did not use any method of prophylaxis. Warfarin was the most common agent used (46%), followed by low-molecular-weight heparin (LMWH) (36%). Combination therapy with both mechanical and pharmacologic methods were used in 39% of patients. Objective screening tests were not frequently performed before discharge. Extended prophylaxis beyond the duration of hospitalization was used by 36% of physicians. Conclusion Prophylaxis for venous thromboembolism with warfarin or LMWH has become standard care after total hip or knee arthroplasty in Canada. PMID:10593248
Venous thromboembolism (VTE) is still an important problem of Public Health, due to its impact in terms of morbidity, mortality, resource allocation and associated costs. In the prevention and treatment of VTE, pharmacological therapy is well defined and efficacious but has some inconveniences that leave space for improvement. Several new oral anticoagulants are being developed and tested for the prevention and treatment of VTE. The better studied are the selective Factor Xa inhibitors apixaban, rivaroxaban and edoxaban, and the thrombin antagonist dabigatran. They all are orally administrated, don't have important interactions with food or other drugs, have a convenient fixed-dose regimen and a predictable action, and dispense routine monitoring of their anticoagulant effect. The major part of them has phase III studies concluded and published. Some of them are already approved by de European Medicines Agency (EMA) and the Food and Drug Administration (FDA) and recommended by the international guidelines. Rivaroxaban is approved by the EMA for the treatment of deep venous thrombosis (DVT) and for the prevention of recurrences of DVT and pulmonary embolism. In this article the available evidences are reviewed, the place of the new oral anticoagulants is discussed and future perspectives regarding the prevention and treatment of VTE are outlined. Copyright © 2012 Sociedade Portuguesa de Cardiologia. Published by Elsevier España. All rights reserved.
Zahid, Mohammad Faizan; Murad, M Hassan; Litzow, Mark R; Hogan, William J; Patnaik, Mrinal S; Khorana, Alok; Spyropoulos, Alex C; Hashmi, Shahrukh K
Venous thromboembolism (VTE) is a common complication of hematopoietic stem cell transplantation (HSCT). Graft-versus-host disease (GVHD) is another complication of HSCT that may modify the risk of VTE. Our objective was to explore the incidence of VTE (deep venous thrombosis and pulmonary embolism) following HSCT and to evaluate its association with GVHD. A comprehensive search of Medline In-Process & Other Non-Indexed Citations, MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and Scopus was conducted to search for both retrospective and prospective HSCT studies which had reported VTE. Random-effects meta-analysis was used to pool incidence rates. We included 17 studies reporting on allogeneic- and 10 on autologous-HSCT; enrolling 6693 patients; of which 5 were randomized. The overall incidence of VTE after HSCT was 5 % (4-7 %). Incidence in allogeneic-HSCT was 4 % (2-6 %) and in autologous-HSCT was 4 % (1-15 %). Eleven and nine studies reported data on acute and chronic GVHD, respectively. The incidence of VTE in chronic GVHD was 35 % (20-54 %), whereas in acute GVHD it was 47 % (32-62 %). Based on the results of this meta-analysis, VTE is a fairly common complication after HSCT, emphasizing the importance of assimilating guidelines for both treatment and prophylaxis in this patient population.
Streiff, Michael B
Cancer is associated with a four to sevenfold increased risk of venous thromboembolism (VTE). This risk is influenced by the site and extent of cancer and its treatment. Despite its availability, effective VTE prophylaxis is used in less than 50% of oncology patients. Pharmacologic VTE prophylaxis should be administered to all hospitalized medical and surgical oncology patients for the duration of their hospitalization or up to 10-14 days, whichever is longer. Extended duration (up to 4 weeks post-operation) VTE prophylaxis is recommended for high-risk surgical oncology patients. Routine use of prophylaxis in ambulatory medical oncology patients awaits prospective testing of VTE risk assessment models. Routine prophylactic dose anticoagulation to prevent central venous catheter (CVC) thrombosis is ineffective and not indicated. Low molecular weight heparin is the first line choice for acute and chronic therapy of VTE in cancer patients. Therapy should continue for at least 3 months or the duration of the malignancy, whichever is longer. Anticoagulation is indicated for at least 3 months or the duration of the catheter for CVC thrombosis. Preliminary data indicate that some cancer patients with pulmonary embolism may be managed as outpatients. Prospective validation of these studies and testing of current risk assessment strategies in oncology patients is warranted. Management of recurrent VTE and unsuspected VTE in the cancer patient are also reviewed.
Méan, Marie; Limacher, Andreas; Stalder, Odile; Angelillo-Scherrer, Anne; Alberio, Lorenzo; Fontana, Pierre; Beer, Hans-Jürg; Rodondi, Nicolas; Lämmle, Bernhard; Aujesky, Drahomir
The value of genetic thrombophilia testing in elderly patients with an unprovoked venous thromboembolism is unclear. We assessed whether the Factor V Leiden and the prothrombin G20210A mutation are associated with recurrent venous thromboembolism in elderly patients in a prospective multicenter cohort study. We genotyped the Factor V Leiden and the prothrombin G20210A mutation in 354 consecutive in- and outpatients aged ≥65 years with a first unprovoked venous thromboembolism from 9 Swiss hospitals. Patients and managing physicians were blinded to testing results. The outcome was recurrent symptomatic venous thromboembolism during follow-up. We examined the association between the Factor V Leiden and the prothrombin G20210A mutation and venous thromboembolism recurrence using competing risk regression, adjusting for age, sex, and periods of anticoagulation as a time-varying covariate. Overall, 9.0% of patients had a Factor V Leiden and 3.7% had a prothrombin G20210A mutation. At 36 months of follow-up, patients with a Factor V Leiden and a prothrombin G20210A mutation had a cumulative incidence of recurrent venous thromboembolism of 12.9% (95% confidence interval [CI], 5.1%-30.8%) and 18.5% (95% CI, 4.9%-56.5%), respectively, compared with 16.7% (95% CI, 12.5%-22.1%) of patients without mutation (P = .91 by the log-rank test). After adjustment, neither the Factor V Leiden (sub-hazard ratio 0.98; 95% CI, 0.35-2.77) nor the prothrombin G20210A mutation (sub-hazard ratio 1.15; 95% CI, 0.25-5.19) was associated with recurrent venous thromboembolism. Our results suggest that testing for genetic thrombophilia may not be beneficial in elderly patients with a first unprovoked venous thromboembolism. Copyright © 2017 Elsevier Inc. All rights reserved.
Janssen, Rob Paulus Augustinus; Reijman, Max; Janssen, Daan Martijn; van Mourik, Jan Bernardus Antonius
AIM To summarize the current knowledge on vascular complications and deep venous thrombosis (DVT) prophylaxis after anterior cruciate ligament (ACL) reconstruction. METHODS A systematic review was conducted according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses statement. MEDLINE, EMBASE, Cochrane, Web of Science, CINAHL, PubMed publisher, and Google scholar medical literature databases were searched up to November 10, 2015. Any arthroscopic surgical method of primary or revision intra-articular ACL reconstruction of all graft types in humans was included. A risk of bias assessment was determined. RESULTS Fourty-seven studies were included in the review. Pseudaneurysms were the most frequently reported arterial complication after ACL reconstruction, irrespective of graft type or method of graft fixation with an incidence of 0.3%. The time to diagnosis of arterial complications after ACL reconstruction varied from days to mostly weeks but even years. After ACL reconstruction without thromboprophylaxis, the incidence of DVT was 9.7%, of which 2.1% was symptomatic. The incidence of pulmonary embolism was 0.1%. Tourniquet time > 2 h was related to venous thromboembolism. Thromboprophylaxis is indicated in patients with risk factors for venous thromboembolism. CONCLUSION After ACL reconstruction, the incidence of arterial complications, symptomatic DVT and pulmonary embolism was 0.3%, 2.1% and 0.1% respectively. Arterial complications may occur with all types of arthroscopic ACL reconstruction, methods of graft fixation as well as any type of graft. Patients considered to be at moderate or high risk of venous thromboembolism should routinely receive thromboprophylaxis after ACL reconstruction. PMID:27672574
Abbas, Mohamed Sayed
Critically ill patients are considered a high-risk group for developing venous thromboembolism (VTE). Due to their impaired cardiopulmonary reserve, these VTEs may result in significant morbidity and mortality. In this study, we compared two types of low molecular weight heparin, enoxaparin, and bemiparin, as regards to their efficacy and safety in VTE prevention among Intensive Care Unit (ICU) patients. This study was a prospective, randomized trial of 100 critically ill patients who are at high risk for developing VTE were included in this study and assigned to receive subcutaneous injections of either 3500 international units (IU) anti-factor Xa of bemiparin sodium or 40 mg of enoxaparin given once a day and patient were followed for 60 days after initiation of anticoagulant therapy for the development of documented deep venous thrombosis (DVT) using bilateral lower limb venous duplex, documented pulmonary embolism using computed tomography pulmonary angiography, and complications related to injectant anticoagulant. Confirmed DVT was observed in two patients (4%) in the bemiparin group compared with 10 patients (20%) in the enoxaparin group with P < 0.05. Confirmed pulmonary embolism (PE) was observed in seven patients (14%) in the enoxaparin group with no recorded cases of confirmed PE in the bemiparin group (P < 0.05). No deaths were recorded in either group. Adverse events such as ecchymosis or hematoma at the injection site were observed in one patient (2%) in the bemiparin group and eight patients (16%) in the enoxaparin group (P < 0.05). There was no significant statistical difference between both groups as regards other adverse effects and complications related to the injectant anticoagulant. Bemiparin was superior to enoxaparin as a prophylactic anticoagulant for VTE in critically ill patients with less adverse local complications at the injection site. The study was registered on www.clinicaltrials.gov. Registration ID: NCT02795065. Registered June 8
Samuelson, Bethany; Go, Alan S; Sung, Sue Hee; Fan, Dongjie; Fang, Margaret C
Although superficial thrombophlebitis (SVTE) is generally considered a benign, self-limited disease, accumulating evidence suggests that it often leads to more serious forms of venous thromboembolism. We reviewed the medical charts of 329 subjects with SVTE from the Cardiovascular Research Network Venous Thromboembolism cohort study to collect information on the acute treatment of SVTE and subsequent diagnosis of deep venous thrombosis within 1 year. All participants received care within Kaiser Permanente Northern California, a large, integrated healthcare delivery system. Fourteen (4.3%) subjects with SVTE received anticoagulants, 148 (45.0%) were recommended antiplatelet agents or nonsteroidal anti-inflammatory drugs, and in 167 (50.8%) there was no documented antithrombotic therapy. In the year after SVTE diagnosis, 19 (5.8%) patients had a subsequent diagnosis of a deep venous thrombosis or pulmonary embolism. In conclusion, clinically significant venous thrombosis within a year after SVTE was uncommon in our study despite infrequent use of antithrombotic therapy. Journal of Hospital Medicine 2016;11:432-434. © 2016 Society of Hospital Medicine. © 2016 Society of Hospital Medicine.
Dimakakos, Evangelos; Vathiotis, Ioannis; Papaspiliou, Aggeliki; Panagiotarakou, Meropi; Manolis, Emmanouil; Syrigos, Konstantinos
We describe the clinical and imaging characteristics of 7 cases with polymerase chain reaction-confirmed novel influenza A H1N1 virus (pH1N1) infection who developed venous thromboembolic events (VTEs) while being hospitalized for influenza pneumonia. Pulmonary embolism (PE) without deep vein thrombosis (DVT) was observed in 6 of 7 cases (85.7%); PE with underlying DVT was found in 1 patient (14.3%). PMID:28018924
Lee, J H; Lee, J; Yhim, H-Y; Oh, D; Bang, S-M
Essentials Data on venous thromboembolism (VTE) after L-asparaginase (L-asp) in Asian lymphoma are scarce. This is a population-based study in Asian patients with lymphoid disease and L-asp-related VTE. The overall incidence of L-asp-associated VTE was similar to reports on Caucasians. This first and largest study in Asians shows that mainly adult patients are at risk of thrombosis.
Vassalini, Marzia; Verzeletti, Andrea; De Ferrari, Francesco
Concerning recent Italian laws and jurisprudential statements, guidelines application involves several difficulties in clinical practice, regarding prevention, diagnosis and therapy of venous thromboembolism. International scientific community systematically developed statements about this disease in order to optimize the available resources in prophylaxis, diagnosis and therapy. Incongruous prevention, missed or delayed diagnosis and/or inadequate treatment of this disease can frequently give rise to medico-legal litigation.
Bertoletti, Laurent; Robin, Philippe; Jara-Palomare, Luis; Tromeur, Cécile; Pastre, Jean; Prevot-Bitot, Nathalie; Mouneh, Thomas; Le Gal, Grégoire; Salaun, Pierre-Yves
Most recent trials evaluating extensive screening strategies for occult cancer in patients with unprovoked venous thromboembolism failed, among other explanations because of an overall low rate of occult cancer. The RIETE investigators recently proposed a score aiming to identify a sub-group at higher risk. We retrospectively computed the RIETE score for all patients included in the MVTEP study, which evaluated the accuracy of FDG-PET in the screening of occult cancer in patients with unprovoked venous thromboembolism. Performance of the RIETE score was assessed by the proportion of patients classified in each risk group, and the corresponding rate of cancer diagnosis. Among the 386 patients included in the analysis, 136 patients (35.3%) were classified as high risk by the RIETE score. Cancer was diagnosed in 16 (11.8%) of them, while it was diagnosed in 9 (3.6%) of the 250 patients with a low RIETE cancer score: odds ratio 3.6 (95% CI 1.53 to 8.32). The area under the ROC curve was 0.63 (95% CI 0.51 to 0.74). the RIETE score seems to be able to identify a sub-group at high risk for cancer (10%), in our specific data-set of patients with unprovoked venous thromboembolism. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
Lecumberri, R; Panizo, E; Gomez-Guiu, A; Varea, S; García-Quetglas, E; Serrano, M; García-Mouriz, A; Marqués, M; Gómez-Outes, A; Páramo, J A
The prevention of venous thromboembolism (VTE) is a priority for improved safety in hospitalised patients. Worldwide, there is growing concern over the undersuse of appropriate thromboprophylaxis. Computerised decision support improves the implementation of thromboprophylaxis and reduces inpatient VTE. However, an economic assessment of this approach has not yet been performed. To evaluate the economic impact of an electronic alert (e-alert) system to prevent VTE in hospitalised patients over a 4year period. All hospitalised patients at a single institution during the first semesters of 2005-2009 (n=32280) were included. All cases of VTE developed during hospitalisation were followed and direct costs of diagnosis and management collected. E-alerts achieved a sustained reduction of the incidence of in-hospital VTE, OR 0.50 (95% CI, 0.29-0.84), the impact being especially significant in medical patients, OR 0.44 (95% CI, 0.22-0.86). No increase in prophylaxis-related bleeding was observed. In our setting, the mean direct cost (during hospitalisation and after discharge) of an in-hospital VTE episode is €7058. Direct costs per single hospitalised patient were reduced after e-alerts from €21.6 to €11.8, while the increased use of thromboprophylaxis and the development of e-alerts meant €3 and €0.35 per patient, respectively. Thus, the implementation of e-alerts led to a net cost saving of €6.5 per hospitalised patient. Should all hospitalised patients in Spain be considered, total yearly savings would approach €30million. E-alerts are useful and cost-effective tools for thromboprophylaxis strategy in hospitalised patients. Fewer thromboembolic complications and lower costs are achieved by its implementation. © 2011 International Society on Thrombosis and Haemostasis.
Kim, Dae Sik; Park, Keun-Myoung; Won, Yong Sung; Kim, Jang Yong; Lee, Jin Kwon; Kim, Jun Gi; Oh, Seong Taek; Jung, Sang Seol; Kang, Won Kyung
Purpose: Colorectal cancer (CRC) has a high risk for postoperative thromboembolic complications such as venous thromboembolism (VTE) compared to other surgical diseases, but the relationship between VTE and CRC in Asian patients remains poorly understood. The present study examined the incidence of symptomatic VTE in Korean patients who underwent surgery for CRC. We also identified risk factors, incidence and survival rate for VTE in these patients Materials and Methods: The patients were identified from the CRC database treated from January 2011 to December 2012 in a single institution. These patients were classified into VTE and non-VTE groups, their demographic features were compared, and the factors which had significant effects on VTE and mortality between the two groups were analyzed. Results: We analyzed retrospectively a total of 840 patients and the incidence of VTE was 3.7% (31 patients) during the follow-up period (mean, 17.2 months). Histologic subtype (mucinous adenocarcinoma) and previous history of VTE affected the incidence of VTE on multivariate analysis. There was a statistically significant difference in survival rate between the VTE and non-VTE group, but VTE wasn’t the factor affecting survival rate on multivariate analysis. Comparing differences in survival rate for each pathologic stage, there was only a significant difference in stage II patients. Conclusion: Among CRC patients after surgery, the incidence of VTE was approximately 3% within 1 year and development of VTE wasn’t a significant risk factor for death in our study but these findings are not conclusive due to our small sample size. PMID:26217616
O'Shaughnessy, Fergal; Donnelly, Jennifer C; Cooley, Sharon M; Deering, Mary; Raman, Ajita; Gannon, Geraldine; Hickey, Jane; Holland, Alan; Hayes, Niamh; Bennett, Kathleen; Áinle, Fionnuala Ní; Cleary, Brian
Venous thromboembolism risk assessment (VTERA) is recommended in all pregnant and postpartum women. Our objective was to develop, pilot and implement a user-friendly electronic VTERA tool MATERIALS AND METHODS: We developed 'Thrombocalc', an electronic VTERA tool using Microsoft Excel(™) . Thrombocalc was designed as a score-based tool to facilitate rapid assessment of all women after childbirth. Calculation of a total score estimated risk of venous thromboembolism in line with consensus guidelines. Recommendations for thromboprophylaxis were included in the VTERA output. Implementation was phased. Uptake of the VTERA tool was prospectively assessed by monitoring the proportion of women who gave birth in our institution and had a completed risk assessment. Factors affecting completion and accuracy of risk assessments were also assessed RESULTS: Thrombocalc was used to prospectively risk assess 8380 women between September 2014 and December 2015. Compliance with this tool increased dramatically throughout the study period; over 92% of women were risk assessed in the last quarter of data collection. Compliance was not adversely affected if delivery took place out of working hours (aOR 1.14, 95% CI; 1.04-1.25). Risk assessment was less likely in the case of caesarean deliveries (aOR=0.66, 95% CI 0.60-0.73) and stillborn infants (aOR=0.48, 95% CI; 0.29-0.79). Misclassification of risk factors led to approximately 207 (2.5%) inaccurate thromboprophylaxis recommendations CONCLUSION: Our electronic, score-based VTERA tool, provides a highly effective mechanism for rapid, assessment of individual postpartum venous thromboembolism risk in a high throughput environment. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
Suenaga, Mitsukuni; Mizunuma, Nobuyuki; Shinozaki, Eiji; Matsusaka, Satoshi; Ozaka, Masato; Ogura, Mariko; Chin, Keisho; Yamaguchi, Toshiharu
Background Doppler ultrasound imaging is useful for management of venous thromboembolism associated with a subclavicular implantable central venous access system in patients receiving bevacizumab (Bev). We investigated the efficacy and safety of our anticoagulant regimen based on Doppler findings. Methods Patients aged ≤75 years with metastatic colorectal cancer, no history of thromboembolism, and no prior use of Bev received chemotherapy plus Bev. Doppler ultrasound imaging of the deep venous system to detect thrombosis was performed after the first course of Bev and repeated after the third course in patients with asymptomatic thrombosis. Indications for anticoagulant therapy in patients with asymptomatic thrombosis were as follows: enlarging thrombus (E), thrombus >40 mm in diameter (S), thrombus involving the superior vena cava (C), and decreased blood flow (V). Results Among 79 patients enrolled in this study, asymptomatic thrombosis was detected in 56 patients (70.9%) by Doppler ultrasound imaging after the first course of Bev and there was no thrombus in 23 patients (29.1%). Of these 56 patients, 11 (19.6%) received anticoagulant therapy with warfarin, including eight after the first course and three after follow-up imaging. S + V was observed in four of 11 patients (36.4%), as well as V in two (18.2%), S + V + C in one (9.1%), E + S + V in one (9.1%), E + C in one (9.1%), E in one (9.1%), and C in one (9.1%). All patients resumed chemotherapy, including seven who resumed Bev. Improvement or stabilization of thrombi was achieved in ten patients (90.9%). Only one patient had symptomatic thromboembolism. Mild bleeding due to anticoagulant therapy occurred in six patients (54.5%), but there were no treatment-related severe adverse events or deaths. Severe thromboembolism was not observed in the other 68 patients. Conclusion Our anticoagulant protocol for asymptomatic thrombosis detected by Doppler ultrasound imaging was effective at preventing severe
Cook, Deborah; McMullin, Joseph; Hodder, Richard; Heule, Mark; Pinilla, Jaime; Dodek, Peter; Stewart, Thomas
Background Venous thromboembolism (VTE) confers considerable morbidity and mortality in hospitalized patients, although few studies have focused on the critically ill population. The objective of this study was to understand current approaches to the prevention and diagnosis of deep venous thrombosis (DVT) and pulmonary embolism (PE) among patients in the intensive care unit (ICU). Design Mailed self-administered survey of ICU Directors in Canadian university affiliated hospitals. Results Of 29 ICU Directors approached, 29 (100%) participated, representing 44 ICUs and 681 ICU beds across Canada. VTE prophylaxis is primarily determined by individual ICU clinicians (20/29, 69.0%) or with a hematology consultation for challenging patients (9/29, 31.0%). Decisions are usually made on a case-by-case basis (18/29, 62.1%) rather than by preprinted orders (5/29, 17.2%), institutional policies (6/29, 20.7%) or formal practice guidelines (2/29, 6.9%). Unfractionated heparin is the predominant VTE prophylactic strategy (29/29, 100.0%) whereas low molecular weight heparin is used less often, primarily for trauma and orthopedic patients. Use of pneumatic compression devices and thromboembolic stockings is variable. Systematic screening for DVT with lower limb ultrasound once or twice weekly was reported by some ICU Directors (7/29, 24.1%) for specific populations. Ultrasound is the most common diagnostic test for DVT; the reference standard of venography is rarely used. Spiral computed tomography chest scans and ventilation–perfusion scans are used more often than pulmonary angiograms for the diagnosis of PE. ICU Directors recommend further studies in the critically ill population to determine the test properties and risk:benefit ratio of VTE investigations, and the most cost-effective methods of prophylaxis in medical–surgical ICU patients. Interpretation Unfractionated subcutaneous heparin is the predominant VTE prophylaxis strategy for critically ill patients, although
Kearon, Clive; O'Donnell, Martin
Pulmonary embolism is the most common preventable cause of death in hospital patients and prevention of venous thromboembolism (VTE) is cost-saving in high-risk patients. Low-dose anticoagulation is very effective at preventing VTE but increases bleeding. Graduated compression stockings and intermittent pneumatic compression devices are also used to prevent VTE and do not increase bleeding, which makes their use appealing in patients who cannot tolerate bleeding, such as patients with acute stroke. Studies that evaluated mechanical methods of preventing VTE were small and mainly used asymptomatic deep vein thrombosis (DVT), detected using screening tests, as the study outcome. The recently published CLOTS Trial 1 (Clots in Legs Or sTockings after Stroke) compared thigh-level compression stockings with no stockings in about 2500 patients with stroke and immobility, and found that thigh-level stockings were not effective. Indirectly, the findings of this study question the ability of stockings to prevent VTE in other patient groups, including those after surgery. CLOTS 1 compared thigh-level and below-knee stockings in about 3000 patients with acute stroke. Given that thigh-level stockings were ineffective in CLOTS 1, it is surprising that they were more effective than below-knee stockings in CLOTS Trial 2. A possible explanation is that below-knee stockings increase DVT, although this seems unlikely. CLOTS 1 and CLOTS 2 question whether graduated compression stockings prevent VTE and suggest the need for further trials evaluating their efficacy in medical and surgical patients.
Healy, Bridget; Cameron, Laird; Weatherall, Mark; Beasley, Richard
Objective To examine the association between venous thromboembolism and prolonged work- and computer-related seated immobility. Design A case-control study. Participants and setting Cases were 200 patients attending venous thromboembolism clinics with a history of deep vein thrombosis and/or pulmonary embolism in the past six months, and controls were 200 patients treated in fracture clinic for an upper limb injury in the past six months. Main outcome measures Logistic regression was used to estimate the association between venous thromboembolism and prolonged work- and computer-related seated immobility in the 28 days before the index event. Prolonged work- and computer-related seated immobility was defined firstly as a categorical variable with at least 10 h seated in a 24-h period, including at least 2 h without getting up; and secondly as the actual time spent seated in a 24-h period. Results Prolonged work- and computer-related seated immobility (categorical variable) was present in 36 (18%) cases and 31 (15.5%) controls. In multivariate analysis, there was no significant association between prolonged seated immobility and venous thromboembolism, odds ratio 1.18 (95% CI 0.56 to 2.48), P = 0.67. For the mean and maximum number of hours seated in a 24-h period, the odds ratios for the association per additional hour seated with venous thromboembolism were 1.08 (95% CI 1.01 to 1.6), P = 0.02 and 1.04 (95% CI 0.99 to 1.09), P = 0.08, respectively. Conclusion This study found a weak association between venous thromboembolism and prolonged work- and computer-related seated immobility, with increasing mean hours seated associated with a higher risk of venous thromboembolism. PMID:27540486
Dickmann, Boris; Ahlbrecht, Jonas; Ay, Cihan; Dunkler, Daniela; Thaler, Johannes; Scheithauer, Werner; Quehenberger, Peter; Zielinski, Christoph; Pabinger, Ingrid
Advanced cancer is a risk factor for venous thromboembolism. However, lymph node metastases are usually not considered an established risk factor. In the framework of the prospective, observational Vienna Cancer and Thrombosis Study we investigated the association between local (N0), regional (N1–3), and distant (M1) cancer stages and the occurrence of venous thromboembolism. Furthermore, we were specifically interested in the relationship between stage and biomarkers that have been reported to be associated with venous thromboembolism. We followed 832 patients with solid tumors for a median of 527 days. The study end-point was symptomatic venous thromboembolism. At study inclusion, 241 patients had local, 138 regional, and 453 distant stage cancer. The cumulative probability of venous thromboembolism after 6 months in patients with local, regional and distant stage cancer was 2.1%, 6.5% and 6.0%, respectively (P=0.002). Compared to patients with local stage disease, patients with regional and distant stage disease had a significantly higher risk of venous thromboembolism in multivariable Cox-regression analysis including age, newly diagnosed cancer (versus progression of disease), surgery, radiotherapy, and chemotherapy (regional: HR=3.7, 95% CI: 1.5–9.6; distant: HR=5.4, 95% CI: 2.3–12.9). Furthermore, patients with regional or distant stage disease had significantly higher levels of D-dimer, factor VIII, and platelets, and lower hemoglobin levels than those with local stage disease. These results demonstrate an increased risk of venous thromboembolism in patients with regional disease. Elevated levels of predictive biomarkers in patients with regional disease underpin the results and are in line with the activation of the hemostatic system in the early phase of metastatic dissemination. PMID:23585523
Hebbeler, Sara L; Marciniak, Christina M; Crandall, Susan; Chen, David; Nussbaum, Steven; Mendelewski, Susan
Subcutaneous administration of low molecular weight heparin (eg, enoxaparin) has been shown to be safe and effective in the prevention of acute venous thromboembolic (TE) disease following acute spinal cord injury (SCI) in the rehabilitation setting. However, emerging evidence suggests that different dosing strategies may be equivalent. To determine whether subcutaneous enoxaparin, 40 mg once daily, when compared with subcutaneous enoxaparin, 30 mg twice daily, is equally safe and effective in the prevention of venous TE disease in patients with SCI. Retrospective chart review. A freestanding, inpatient, acute, rehabilitation hospital. One hundred and twenty-nine patients admitted from June 2000 through June 2002 for inpatient rehabilitation following an acute SCI who received either enoxaparin, 40 mg once daily, or enoxaparin, 30 mg twice daily, for prophylaxis for TE disease. Equivalent prophylaxis efficacy was seen in both enoxaparin groups. Symptomatic venous thromboembolism did not differ, with deep vein thromboses occurring in 1 of 49 (2.0%) patients receiving twice-daily enoxaparin, and 1 of 80 (1.25%) patients receiving once-daily enoxaparin (chi2 = 0.125, NS). Pulmonary embolism was seen in 1 of 49 (2.0%) patients treated with twice-daily enoxaparin and in none of the patients in the once-daily group (chi2 = 1.64, NS). Bleeding complications also did not differ between the 2 treatment groups; these were observed in 2 of 49 (4.1%) patients receiving twice-daily enoxaparin and in 5 of 80 (6.3%) patients receiving once-daily enoxaparin (chi2 = 0.228, NS). Subcutaneous enoxaparin administered once or twice daily is equally effective for the prevention of venous TE disease. Both dosing strategies are associated with a low incidence of bleeding in patients with SCI who are undergoing rehabilitation.
Arcelus, Juan I; Domènech, Pere; Fernández-Capitan, Ma Del Carmen; Guijarro, Ricardo; Jiménez, David; Jiménez, Sonia; Lozano, Francisco S; Monreal, Manel; Nieto, José A; Páramo, José A
Anticoagulation therapy is the standard treatment of patients with symptomatic venous thromboembolism (VTE), including deep vein thrombosis and pulmonary embolism. Until recently, treatment of VTE was based on parenteral or low-molecular-weight heparin for initial therapy (5-10 days) and oral vitamin K antagonists for long-term therapy. Those treatments have some limitations, including parenteral administration (heparins), the need for frequent monitoring and dose adjustments, interactions with several medications, and dietary restrictions (vitamin K antagonists). Rivaroxaban is a new oral direct factor Xa inhibitor with a wide therapeutic window, predictable anticoagulant effect, no food interactions, and few drug interactions. Consequently, no periodic monitoring of anticoagulation is needed, and fixed doses can be prescribed. EINSTEIN program demonstrated that rivaroxaban was as effective as and significantly safer than standard therapy for treatment of VTE. Rivaroxaban was recently authorized so doubts exist about how to use it in daily clinical practice. This document aims to clarify common questions formulated by clinicians regarding the use of this new drug. © The Author(s) 2014.
Hanison, Esther; Corbett, Kevin
To assess the relative clinical efficacy of different forms of non-pharmacological prophylaxis, intermittent pneumatic compression and graduated compression stockings in reducing the incidence of venous thromboembolism (VTE) in patients hospitalised following acute stroke. This was a thematic synthesis of literature retrieved from a structured bibliographic search of: Medline, the Cumulative Index to Nursing and Allied Health Literature (CINAHL), Summon, British Nursing Index, NHS Evidence, Internurse.com, PubMed, Ovid and the websites of other health information resources, such as the Nursing and Midwifery Council, National Institute for Health and Care Excellence and the World Health Organization. Citations were also searched for using: Web of Science, Google Scholar, the Cochrane Central Register of Controlled Trials, Current Controlled Trials, Stroke Trials Registry and Clinical Trials. Intermittent pneumatic compression (IPC) showed a small but statistically significant (P = 0.001) reduction in rates of deep vein thrombosis (DVT), in both symptomatic and asymptomatic DVT, involving proximal or calf veins, with fewer adverse effects such as skin breakdown and ulcers attributed to IPC, as compared to graduated compression stockings. No single intervention was the most effective for VTE prevention. More reliable evidence is required. Clear and extensive guidelines are necessary to ensure high-quality care for patients with acute stroke to improve their quality of life, and reduce morbidity and mortality rates.
Di Blasi, A; Di Blasi, L; Manferoce, O; Napoli, P
The venous thromboembolism can clinically show itself as deep venous thrombosis or as pulmonary embolism. Both serious and potentially fatal, for this high incidence, they assume importance in social economic sphere. The authors take into account the medicolegal diagnostics methodology of the deep venous thrombosis and of the pulmonary embolism, the traumatic and post traumatic etiology, to determine the connection of causality and the estimating parameters of the damage to a person in the sphere of civil responsibility. To attain to a certain diagnosis of thromboembolism, since its difficult cause of paucisymtomaticity or asymtomaticity of the pathology after an attentive evaluation of symptoms, clinic manifestations and factors of risk, it can't be disregarded to utilize scientific diagnostic criteria, and instrumental ascertainments, serial too, helped by conventional means of standardization, such as the new American system of classification CEAP. The following phases of medicolegal ascertainment consist in identifying the causal connection between disease and event and in estimating of the damage to a person, with rigorous and objective methodology and using tabular orientation guides, that have to indicate the percentage incidence of the undergone disablement on the person's validity for indemnity. It is showed the particular delicacy of the medical examiner's evaluation in thromboembolic disease, in the sphere of civil responsibility, both for the difficulties of the diagnostic identification of the deep venous thrombosis, and of the pulmonary embolism, and for the determination of the connection of causality with traumatic events and with following operation of orthopedics-traumatology and neurosurgery (sector on which the most difficult problems of professional responsibility can connect) and finally for the real evaluation of the consequent damage to a persons, in order to its indemnity.
Zhou, Lin; Song, Haoming; Xu, Wenjun; Xu, Jiahong; Jiang, Jinfa; Gong, Zhu; Liu, Yang; Yan, Wenwen; Wang, Lemin
Recent studies have shown that the major risk factors for arterial thrombotic diseases are closely associated with venous thromboembolism (VTE). This study aimed to investigate the expression of CD3, CD4 and CD8 in T lymphocytes, the CD4/CD8 ratio and high-sensitivity C-reactive protein (hs-CRP) levels in patients with VTE, coronary artery atherosclerosis (CAA) and healthy subjects. A total of 82 healthy subjects, 51 VTE patients and 114 CAA patients were recruited, and the expression of CD3, CD4 and CD8 in T lymphocytes and the CD4/CD8 ratio were determined. Serum hs-CRP was also measured. Compared to healthy subjects, VTE patients had significantly reduced CD3 expression (p=0.019), comparable CD4 expression (p=0.868), significantly reduced CD8 expression (p<0.001) and increased CD4/CD8 ratio (p=0.044). However, VTE patients had comparable expression of CD3, CD4 and CD8 and CD4/CD8 ratio to CAA patients. In addition, among patients with VTE or CAA, the proportion of patients with reduced CD3+ and CD8+ T lymphocytes or increased CD4/CD8 ratio was significantly higher than in healthy subjects. In addition, hs-CRP in both VTE and CAA groups was significantly higher than in healthy subjects. The antigen recognition and signal transduction activation of T cells is significantly reduced in patients with VTE or CAA, and the killing effect of T cells on pathogens, including viruses, is also significantly compromised. In addition, inflammatory and immune mechanisms are involved in the occurrence and development of venous and arterial thrombosis. Copyright © 2013 Sociedade Portuguesa de Cardiologia. Published by Elsevier España. All rights reserved.
Gómez-Outes, Antonio; Suárez-Gea, M Luisa; Lecumberri, Ramón; Terleira-Fernández, Ana Isabel; Vargas-Castrillón, Emilio; Rocha, Eduardo
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. PMID:23674896
Gómez-Outes, Antonio; Suárez-Gea, M Luisa; Lecumberri, Ramón; Terleira-Fernández, Ana Isabel; Vargas-Castrillón, Emilio; Rocha, Eduardo
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.
Nobili, Elisabetta; Di Cicilia, Roberto; Di Battista, Monica; Morselli-Labate, Antonio Maria; Paragona, Marco; Corbelli, Jody; Macchini, Marina; Prandoni, Paolo; Biasco, Guido; Brandi, Giovanni
Venous thromboembolism (VTE) may occur during the natural history of neoplastic disease and is a common cause of mortality and morbidity in cancer patients. Major risk factors for VTE in cancer patients include surgery, immobilization, hospitalization, and the administration of granulopoietic and/or erythropoietic (stimulatory) agents. Chemotherapy is a supplementary independent risk factor for VTE and the use of central venous catheters (CVC) in clinical practice has increased the risk of thromboembolic events. We conducted a retrospective study to evaluate CVC-related thrombosis and the VTE rate in 145 consecutive metastatic colorectal cancer patients. We observed only 2 cases of symptomatic CVC- related thrombotic events (1.38%) and 10 cases of thromboembolic events (6.9%) in our series. Only surgery for metastases was found to be significantly related to the development of VTE, with an incidence of 16.1% vs. 4.4 in patients who did not undergo surgery (p = 0.037). In addition, a history of VTE seems to be a supplementary risk factor for CVC-related thrombosis (p = 0.055).
Risk of non-fatal venous thromboembolism in women using oral contraceptives containing drospirenone compared with women using oral contraceptives containing levonorgestrel: case-control study using United States claims data.
Jick, Susan S; Hernandez, Rohini K
To compare the risk of non-fatal venous thromboembolism in women receiving oral contraceptives containing drospirenone with that in women receiving oral contraceptives containing levonorgestrel. Nested case-control and cohort study. The study was based on information from PharMetrics, a United States based company that collects information on claims paid by managed care plans. The study encompassed all women aged 15 to 44 years who received an oral contraceptive containing either drospirenone or levonorgestrel after 1 January 2002. Cases were women with current use of a study oral contraceptive and a diagnosis of venous thromboembolism in the absence of identifiable clinical risk factors (idiopathic venous thromboembolism). Up to four controls were matched to each case by age and calendar time. Odds ratios comparing the risk of non-fatal venous thromboembolism in users of the two contraceptives; incidence rates and rate ratios of non-fatal venous thromboembolism for users of each of the study contraceptives. 186 newly diagnosed, idiopathic cases of venous thromboembolism were identified in the study population and matched with 681 controls. In the case-control analysis, the conditional odds ratio for venous thromboembolism comparing use of oral contraceptives containing drospirenone with use of those containing levonorgestrel was 2.3 (95% confidence interval 1.6 to 3.2). The incidence rates for venous thromboembolism in the study population were 30.8 (95% confidence interval 25.6 to 36.8) per 100,000 woman years among users of oral contraceptives containing drospirenone and 12.5 (9.61 to 15.9) per 100,000 woman years among users of oral contraceptives containing levonorgestrel. The age adjusted incidence rate ratio for venous thromboembolism for current use of oral contraceptives containing drospirenone compared with those containing levonorgestrel was 2.8 (2.1 to 3.8). The risk of non-fatal venous thromboembolism among users of oral contraceptives containing
Risk of non-fatal venous thromboembolism in women using oral contraceptives containing drospirenone compared with women using oral contraceptives containing levonorgestrel: case-control study using United States claims data
Hernandez, Rohini K
non-fatal venous thromboembolism among users of oral contraceptives containing drospirenone seems to be around twice that of users of oral contraceptives containing levonorgestrel, after the effects of potential confounders and prescribing biases have been taken into account. PMID:21511805
Patel, Niyant V.; Wagner, Douglas S.
Background: Venous thromboembolism (VTE) risk models including the Davison risk score and the 2005 Caprini risk assessment model have been validated in plastic surgery patients. However, their utility and predictive value in breast reconstruction has not been well described. We sought to determine the utility of current VTE risk models in this population and the VTE rate observed in various methods of breast reconstruction. Methods: A retrospective review of breast reconstructions by a single surgeon was performed. One hundred consecutive transverse rectus abdominis myocutaneous (TRAM) patients, 100 consecutive implant patients, and 100 consecutive latissimus dorsi patients were identified over a 10-year period. Patient demographics and presence of symptomatic VTE were collected. 2005 Caprini risk scores and Davison risk scores were calculated for each patient. Results: The TRAM reconstruction group was found to have a higher VTE rate (6%) than the implant (0%) and latissimus (0%) reconstruction groups (P < 0.01). Mean Davison risk scores and 2005 Caprini scores were similar across all reconstruction groups (P > 0.1). The vast majority of patients were stratified as high risk (87.3%) by the VTE risk models. However, only TRAM reconstruction patients demonstrated significant VTE risk. Conclusions: TRAM reconstruction appears to have a significantly higher risk of VTE than both implant and latissimus reconstruction. Current risk models do not effectively stratify breast reconstruction patients at risk for VTE. The method of breast reconstruction appears to have a significant role in patients’ VTE risk. PMID:26090287
Huang, Qianxin; Zhang, Qingqiao; Xu, Hao; Zu, Maoheng; Gu, Yuming; Wei, Ning; Xu, Wei; Cui, Yanfeng
To evaluate the safety and efficacy of suprarenal inferior vena cava (IVC) filter implantation in patients with venous thromboembolism (VTE). Between May 2006 and December 2014, 28 patients with VTE underwent suprarenal IVC filter implantation, anticoagulant treatment and/or catheter-directed thrombolysis at the affiliated hospital of Xuzhou medical college. Follow up examination with color Doppler ultrasound was taken after treatment to eassess the patency of IVC. One filter was successfully implanted in suprarenal IVC in each patient intraoperatively. The filter was retrieved in 26 patients after indwelling of 5 to 17 (mean 11 ± 3) days. The filter was permanently indwelled in 2 patients. There were no complications of filter tilt and migration in all cases. Twenty eight patients were followed up for 2 to 104 (mean 34 ± 34) months. None of the 2 patients whose filters were permanently indwelled presented complications of recurrent pulmonary embolism and IVC occlusion due to the filter. Among 26 patients whose filters were retrieved, the IVC was patent. Suprarenal IVC filter placement is a safe and effective method in the treatment of VTE.
Uchiyama, Hidetoshi; Inoue, Yoshinori; Uchimura, Isao; Nakamura, Tomomasa; Kudo, Toshifumi; Muneta, Takeshi; Kawano, Tatsuyuki
Venous thromboembolism (VTE) including deep vein thrombosis (DVT) and pulmonary embolism (PE) frequently occurs in patients undergoing total knee arthroplasty (TKA). This study aimed to evaluate the efficacy of dielectric blood coagulometry (DBCM) as a new technique for predicting postoperative VTE. Thirty patients undergoing TKA were enrolled. DVT was diagnosed by ultrasonography preoperatively and on the fourth or fifth postoperative day. Enhanced computed tomography was performed to detect PE on the fourth postoperative day. The day after surgery, a blood sample was measured by DBCM. All patients received fondaparinux or low-molecular-weight heparin for postoperative thromboprophylaxis. Eighteen of the 30 patients had DVT postoperatively, and 10 had asymptomatic PE. Seven patients had both DVT and PE. The patterns of permittivity as a function of time and frequency from the DBCM measurement were different between patients with and without VTE. The sensitivity and specificity of the parameter constructed from a set of permittivities at the frequencies of 2.5 kHz, 1 MHz, and 10 MHz were 90% and 78%, respectively. DBCM was effective and efficient for predicting VTE after TKA. Copyright © 2016 Elsevier Inc. All rights reserved.
Markel, Arie; Gavish, Israel; Kfir, Hila; Rimbrot, Sofia
Venous thromboembolism (VTE) is the third most common cause of death and the leading cause of sudden death in hospitalized medical patients. Despite the existence of guidelines for prevention and treatment of this disorder, their implementation in everyday life is not always accomplished. We performed a survey among directors of Internal Medicine departments in our country in order to evaluate their attitude and approach to this issue. A questionnaire with pertinent questions regarding prevention and treatment of VTE, including deep vein thrombosis (DVT) and pulmonary embolism (PE) was sent to each one of the directors of Internal Medicine Departments around the country. Sixty-nine out of 97 (71%) of the Internal Medicine departments directors responded the questionnaire. We found that several of the current guidelines were followed in a reasonable way. On the other hand, heterogeneity of responses was also present and the performance of current guidelines was imperfectly followed, and showed to be deficient in several aspects. An effort should be done in order to reemphasize and put in effect current guidelines for the prevention and treatment of VTE among hospitalists and Internal Medicine practitioners.
Fanola, Christina L
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.
Maynard, Greg; Jenkins, Ian H; Merli, Geno J
Hospital-associated nonsurgical venous thromboembolism (VTE) is an important problem addressed by new guidelines from the American College of Physicians (ACP) and American College of Chest Physicians (AT9). Narrative review and critique. Both guidelines discount asymptomatic VTE outcomes and caution against overprophylaxis, but have different methodologies and estimates of risk/benefit. Guideline complexity and lack of consensus on VTE risk assessment contribute to an implementation gap. Methods to estimate prophylaxis benefit have significant limitations because major trials included mostly screening-detected events. AT9 relies on a single Italian cohort study to conclude that those with a Padua score ≥4 have a very high VTE risk, whereas patients with a score <4 (60% of patients) have a very small risk. However, the cohort population has less comorbidity than US inpatients, and over 1% of patients with a score of 3 suffered pulmonary emboli. The ACP guideline does not endorse any risk-assessment model. AT9 includes the Padua model and Caprini point-based system for nonsurgical inpatients and surgical inpatients, respectively, but there is no evidence they are more effective than simpler risk-assessment models. New VTE prevention guidelines provide varied guidance on important issues including risk assessment. If Padua is used, a threshold of 3, as well as 4, should be considered. Simpler VTE risk-assessment models may be superior to complicated point-based models in environments without sophisticated clinical decision support. © 2013 Society of Hospital Medicine.
Donnellan, E.; Kevane, B.; Bird, B.R. Healey; Ainle, F. Ni
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. PMID:24940094
Ungprasert, Patompong; Srivali, Narat; Kittanamongkolchai, Wonngarm
Background: Several immune-mediated inflammatory disorders, such as rheumatoid arthritis, psoriatic arthritis, and systemic lupus erythematosus have been linked to an increased risk of venous thromboembolism (VTE). However, the data on ankylosing spondylitis (AS) are limited. Methods: We conducted a systematic review and meta-analysis of observational studies that reported odds ratio, relative risk, hazard ratio, or standardized incidence ratio comparing the risk of VTE and possible pulmonary embolism (PE) in patients with AS versus non-AS participants. Pooled risk ratio and 95% confidence intervals were calculated using a random-effect, generic inverse variance method of DerSimonian and Laird. Results: Of 423 potentially relevant articles, three studies met our inclusion criteria and thus, were included in the data analysis. The pooled risk ratio of VTE in patients with AS was 1.60 (95% confidence interval: 1.05–2.44). The statistical heterogeneity of this study was high with an I2 of 93%. Conclusion: Our study demonstrated a statistically significant increased VTE risk among patients with AS. PMID:27890993
Al-Qahtani, Ali S
The aim of this study was to benchmark our guidelines of prevention of venous thromboembolism (VTE) in ENT surgical population against ENT.UK guidelines, and also to encourage healthcare providers to utilize benchmarking as an effective method of improving performance. The study design is prospective descriptive analysis. The setting of this study is tertiary referral centre (Assir Central Hospital, Abha, Saudi Arabia). In this study, we are benchmarking our practice guidelines of the prevention of VTE in the ENT surgical population against that of ENT.UK guidelines to mitigate any gaps. ENT guidelines 2010 were downloaded from the ENT.UK Website. Our guidelines were compared with the possibilities that either our performance meets or fall short of ENT.UK guidelines. Immediate corrective actions will take place if there is quality chasm between the two guidelines. ENT.UK guidelines are evidence-based and updated which may serve as role-model for adoption and benchmarking. Our guidelines were accordingly amended to contain all factors required in providing a quality service to ENT surgical patients. While not given appropriate attention, benchmarking is a useful tool in improving quality of health care. It allows learning from others' practices and experiences, and works towards closing any quality gaps. In addition, benchmarking clinical outcomes is critical for quality improvement and informing decisions concerning service provision. It is recommended to be included on the list of quality improvement methods of healthcare services.
Smythe, Maureen A; Priziola, Jennifer; Dobesh, Paul P; Wirth, Diane; Cuker, Adam; Wittkowsky, Ann K
Venous thromboembolism (VTE) is a serious and often fatal medical condition with an increasing incidence. Despite the changing landscape of VTE treatment with the introduction of the new direct oral anticoagulants many uncertainties remain regarding the optimal use of traditional parenteral agents. This manuscript, initiated by the Anticoagulation Forum, provides clinical guidance based on existing guidelines and consensus expert opinion where guidelines are lacking. This specific chapter addresses the practical management of heparins including low molecular weight heparins and fondaparinux. For each anticoagulant a list of the most common practice related questions were created. Each question was addressed using a brief focused literature review followed by a multidisciplinary consensus guidance recommendation. Issues addressed included initial anticoagulant dosing recommendations, recommended baseline laboratory monitoring, managing dose adjustments, evidence to support a relationship between laboratory tests and meaningful clinical outcomes, special patient populations including extremes of weight and renal impairment, duration of necessary parenteral therapy during the transition to oral therapy, candidates for outpatient treatment where appropriate and management of over-anticoagulation and adverse effects including bleeding and heparin induced thrombocytopenia. This article concludes with a concise table of clinical management questions and guidance recommendations to provide a quick reference for the practical management of heparin, low molecular weight heparin and fondaparinux.
van Ommen, C. Heleen; Nowak-Göttl, Ulrike
Venous thromboembolic disease in childhood is a multifactorial disease. Risk factors include acquired clinical risk factors such as a central venous catheter and underlying disease and inherited thrombophilia. Inherited thrombophilia is defined as a genetically determined tendency to develop venous thromboembolism. In contrast to adults, acquired clinical risk factors play a larger role than inherited thrombophilia in the development of thrombotic disease in children. The contributing role of inherited thrombophilia is not clear in many pediatric thrombotic events, especially catheter-related thrombosis. Furthermore, identification of inherited thrombophilia will not often influence acute management of the thrombotic event as well as the duration of anticoagulation. In some patients, however, detection of inherited thrombophilia may lead to identification of other family members who can be counseled for their thrombotic risk. This article discusses the potential arguments for testing of inherited thrombophilia, including factor V Leiden mutation, prothrombin mutation, and deficiencies of antithrombin, protein C, or protein S and suggests some patient groups in childhood, which may be tested. PMID:28352625
van Ommen, C Heleen; Nowak-Göttl, Ulrike
Venous thromboembolic disease in childhood is a multifactorial disease. Risk factors include acquired clinical risk factors such as a central venous catheter and underlying disease and inherited thrombophilia. Inherited thrombophilia is defined as a genetically determined tendency to develop venous thromboembolism. In contrast to adults, acquired clinical risk factors play a larger role than inherited thrombophilia in the development of thrombotic disease in children. The contributing role of inherited thrombophilia is not clear in many pediatric thrombotic events, especially catheter-related thrombosis. Furthermore, identification of inherited thrombophilia will not often influence acute management of the thrombotic event as well as the duration of anticoagulation. In some patients, however, detection of inherited thrombophilia may lead to identification of other family members who can be counseled for their thrombotic risk. This article discusses the potential arguments for testing of inherited thrombophilia, including factor V Leiden mutation, prothrombin mutation, and deficiencies of antithrombin, protein C, or protein S and suggests some patient groups in childhood, which may be tested.
Kim, Kwang-Kyoun; Won, Ye-Yeon
Purpose The aim of this study was to investigate the efficacy of low-molecular-weight heparin (LMWH) for the prevention of venous thromboembolism in Korean patients who underwent hip fracture surgery (HFS). Materials and Methods Prospectively, a total 181 cases were classified into the LMWH user group (116 cases) and LMWH non-user group (65 cases). Each group was sub-classified according to fracture types as follows: 81 cases of intertrochanteric fracture (group A: 49, group B: 32) and 100 cases of neck fracture (group C: 67, group D: 33). We compared the incidence of deep vein thrombosis (DVT) and pulmonary embolism (PE) according to LMWH use. Results Of the 181 cases, four DVTs were found in the LMWH user groups (1 in group A, and 3 in group C). One case of PE was found in LMWH non-user group D. The incidences of DVT and PE showed no statistically significant differences between the LMWH user and non-user groups (p=0.298 and 0.359, respectively). In subgroup analysis, no statistically significant differences were found between groups A and B and between groups C and D. Conclusion The administration of LMWH was not effective in the prevention of venous thromboembolism and PE in the Korean patients who underwent HFS. PMID:27401653
Hereditary and acquired thrombophilias are known risk factors for a first venous thromboembolism (VTE). In contrast, the relative risk of VTE recurrence in presence of hereditary thrombophilia seems to be at most moderately elevated. However, thrombophilia still contributes to a greater extent to the absolute risk of VTE recurrence. This is explained by the 20-50-fold increased risk of VTE in a subject after a first VTE when compared to the state without previous VTE. Testing for thrombophilia may therefore be helpful in patients at intermediate risk of recurrence in whom the finding of a "strong" thrombophilia can bring about a decision for long-term anticoagulation.
Faramarzalian, Ali; Armitage, Keith B.; Kapoor, Baljendra; Kalva, Sanjeeva P.
The rapid expansion of minimally invasive image-guided procedures has led to their extensive use in the interdisciplinary management of patients with vascular, hepatobiliary, genitourinary, and oncologic diseases. Given the increased availability and breadth of these procedures, it is important for physicians to be aware of common complications and their management. In this article, the authors describe management of select common complications from interventional radiology procedures including tumor lysis syndrome, acute on chronic postprocedural pain, and venous thromboembolism. These complications are discussed in detail and their medical management is outlined according to generally accepted practice and evidence from the literature. PMID:26038627
Silvariño, Ricardo; Danza, Álvaro; Mérola, Valentina; Bérez, Adriana; Méndez, Enrique; Espinosa, Gerard; Cervera, Ricard
Systemic autoimmune diseases are conditions of unknown etiology, characterized by the simultaneous or successive involvement of most organs and systems, as well as the presence of autoantibodies as biological markers. Venous thromboembolic disease has a higher incidence in this population when compared to healthy individuals. This responds to the increase in congenital and acquired risk factors in this group. One of the main risk factors is linked to the presence of antiphospholipid antibodies, whose prevalence is increased among patients with such conditions. Copyright © 2012 Elsevier B.V. All rights reserved.
Nou, M; Laroche, J-P
Cancer and venous thrombo-embolic disease (VTE) are closely related. Indeed, cancer can reveal VTE and VTE can be the first sign of cancer. Low molecular weight heparin (LWMH) is now the first line treatment in cancer patients. Compliance with marketing authorizations and guidelines are crucial for patient-centered decision-making. This work deals with the prescription of LWMH in patients who develop VTE during cancer in order to better recognize what should or should not be done. The patient's wishes must be taken into consideration when making the final therapeutic decision. The other treatments are discussed: vitamin K antagonists and direct oral anticoagulants (DOACs) may be useful.
Peters, Bradley J; Dierkhising, Ross A; Mara, Kristin C
Background. Obesity is a significant issue in the critically ill population. There is little evidence directing the dosing of venous thromboembolism (VTE) prophylaxis within this population. We aimed to determine whether obesity predisposes medical intensive care unit patients to venous thromboembolism despite standard chemoprophylaxis with 5000 international units of subcutaneous heparin three times daily. Results. We found a 60% increased risk of venous thromboembolism in the body mass index (BMI) ≥ 30 kg/m(2) group compared to the BMI < 30 kg/m(2) group; however, this difference did not reach statistical significance. After further utilizing our risk model, neither obesity nor mechanical ventilation reached statistical significance; however, vasopressor administration was associated with a threefold risk. Conclusions. We can conclude that obesity did increase the rate of VTE, but not to a statistically significant level in this single center medical intensive care unit population.
Kwak, Hong Suk; Cho, Jai Ho; Kim, Jung Taek; Yoo, Jeong Joon
Background Venous thromboembolism (VTE) is a relatively common and potentially life threatening complication after major hip surgery. There are two main types of prophylaxis: chemical and mechanical. Chemical prophylaxis is very effective but causes bleeding complications in surgical wounds and remote organs. On the other hand, mechanical methods are free of hemorrhagic complications but are less effective. We hypothesized that mechanical prophylaxis is effective enough for Asians in whom VTE occurs less frequently. This study evaluated the effect of intermittent pneumatic compression (IPC) in the prevention of VTE after major hip surgery. Methods Incidences of symptomatic VTE after primary total hip arthroplasty with and without application of IPC were compared. A total of 379 patients were included in the final analysis. The IPC group included 233 patients (106 men and 127 women) with a mean age of 54 years. The control group included 146 patients (80 men and 66 women) with a mean age of 53 years. All patients took low-dose aspirin for 6 weeks after surgery. IPC was applied to both legs just after surgery and maintained all day until discharge. When a symptom or a sign suspicious of VTE, such as swelling or redness of the foot and ankle, Homans' sign, and dyspnea was detected, computed tomography (CT) angiogram or duplex ultrasonogram was performed. Results Until 3 months after surgery, symptomatic VTE occurred in three patients in the IPC group and in 6 patients in the control group. The incidence of VTE was much lower in the IPC group (1.3%) than in the control group (4.1%), but the difference was not statistically significant. Complications associated with the application of IPC were not detected in any patient. Patients affected by VTE were older and hospitalized longer than the unaffected patients. Conclusions The results of this study suggest that IPC might be an effective and safe method for the prevention of postoperative VTE. PMID:28261425
Tzoran, Inna; Papadakis, Manolis; Brenner, Benjamin; Fidalgo, Ángeles; Rivas, Agustina; Wells, Philip S; Gavín, Olga; Adarraga, María Dolores; Moustafa, Farès; Monreal, Manuel
Individuals with factor V Leiden or prothrombin G20210A mutations are at a higher risk to develop venous thromboembolism. However, the influence of these polymorphisms on patient outcome during anticoagulant therapy has not been consistently explored. We used the Registro Informatizado de Enfermedad TromboEmbólica database to compare rates of venous thromboembolism recurrence and bleeding events occurring during the anticoagulation course in factor V Leiden carriers, prothrombin mutation carriers, and noncarriers. Between March 2001 and December 2015, 10,139 patients underwent thrombophilia testing. Of these, 1384 were factor V Leiden carriers, 1115 were prothrombin mutation carriers, and 7640 were noncarriers. During the anticoagulation course, 160 patients developed recurrent deep vein thrombosis and 94 patients developed pulmonary embolism (16 died); 154 patients had major bleeding (10 died), and 291 patients had nonmajor bleeding. On multivariable analysis, factor V Leiden carriers had a similar rate of venous thromboembolism recurrence (adjusted hazard ratio [HR], 1.16; 95% confidence interval [CI], 0.82-1.64), half the rate of major bleeding (adjusted HR, 0.50; 95% CI, 0.25-0.99) and a nonsignificantly lower rate of nonmajor bleeding (adjusted HR, 0.66; 95% CI, 0.43-1.01) than noncarriers. Prothrombin mutation carriers and noncarriers had a comparable rate of venous thromboembolism recurrence (adjusted HR, 1.00; 95% CI, 0.68-1.48), major bleeding (adjusted HR, 0.75; 95% CI, 0.42-1.34), and nonmajor bleeding events (adjusted HR, 1.10; 95% CI, 0.77-1.57). During the anticoagulation course, factor V Leiden carriers had a similar risk for venous thromboembolism recurrence and half the risk for major bleeding compared with noncarriers. This finding may contribute to decision-making regarding anticoagulation duration in selected factor V Leiden carriers with venous thromboembolism. Copyright © 2017. Published by Elsevier Inc.
Al-Hameed, Fahad M.; Al-Dorzi, Hasan M.; Abdelaal, Mohamed A.; Alaklabi, Ali; Bakhsh, Ebtisam; Alomi, Yousef A.; Baik, Mohammad Al; Aldahan, Salah; Schünemann, Holger; Brozek, Jan; Wiercioch, Wojtek; Darzi, Andrea J.; Waziry, Reem; Akl, Elie A.
Venous thromboembolism (VTE), including deep vein thrombosis (DVT) and pulmonary embolism (PE), is a preventable disease. Long distant travelers are prone to variable degree to develop VTE. However, the low risk of developing VTE among long-distance travelers and which travelers should receive VTE prophylaxis, and what prophylactic measures should be used led us to develop these guidelines. These clinical practice guidelines are the result of an initiative of the Ministry of Health of the Kingdom of Saudi Arabia involving an expert panel led by the Saudi Association for Venous Thrombo Embolism (a subsidiary of the Saudi Thoracic Society). The McMaster University Guideline working group provided the methodological support. The expert panel identified 5 common questions related to the thromboprophylaxis in long-distance travelers. The corresponding recommendations were made following the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach. PMID:28042639
Yusuf, Hussain R; Reyes, Nimia; Zhang, Qing C; Okoroh, Ekwutosi M; Siddiqi, Azfar-E-Alam; Tsai, James
We assessed the rates, trends, and factors associated with venous thromboembolism (VTE) diagnosis among hospitalizations of adults ≥60 years of age during the period 2001 to 2010. Data from the National Hospital Discharge Survey were used for this study. During the period 2001 to 2010, the estimated annual number of hospitalizations in which a VTE diagnosis was recorded, among adults ≥ 60 years of age, ranged from approximately 2 70 000 in 2001 to 4 23 000 in 2010. The rate of such hospitalizations per 1 00 000 US population ≥60 years of age ranged from 581 in 2001 to 739 in 2010. During the period 2001 to 2004, there was a significant increasing trend in the rate of hospitalizations with VTE among women ≥60 years of age. The factors positively associated with an increased risk of VTE diagnosis were female sex, summer and autumn seasons (compared with spring), venous catheterization, cancer, and greater length of hospital stay.
Gupta, Amitesh; Mrigpuri, Parul; Faye, Abhishek; Bandyopadhyay, Debdutta; Singla, Rupak
One-third of patients with symptomatic venous thromboembolism (VTE) manifest pulmonary embolism, whereas two-thirds manifest deep vein thrombosis (DVT). Overall, 25%–50% of patients with first-time VTE have an idiopathic condition, without a readily identifiable risk factor, and its association with tuberculosis (TB) is a rare occurrence. Deep venous thrombosis has been associated with 1.5%–3.4% cases of TB. Early initiation of anti-TB treatment along with anticoagulant therapy decreases the overall morbidity and mortality associated with the disease. We report three cases of DVT associated with pulmonary TB who were diagnosed due to high index of suspicion as the risk factors for the development of DVT were present in these cases. PMID:28144063
Gonzalez-Billalabeitia, Enrique; Castellano, Daniel; Sobrevilla, Nora; Guma, Josep; Hervas, David; Luengo, Maria I; Aparicio, Jorge; Sanchez-Muñoz, Alfonso; Mellado, Begoña; Saenz, Alberto; Valverde, Claudia; Fernandez, Antonio; Margeli, Mireia; Duran, Ignacio; Fernandez, Sara; Sastre, Javier; Ros, Silverio; Maroto, Pablo; Manneh, Ray; Cerezuela, Pablo; Carmona-Bayonas, Alberto; Ayala de la Peña, Francisco; Aguilar, Jose Luis; Rivera, Samuel; García del Muro, Xavier; Germà-Lluch, Jose R
Disseminated germ cell cancers are at high risk of developing thromboembolic complications. We evaluated the prognostic value of venous thromboembolic events (VTE) in disseminated germ cell cancer. Patients with germ cell cancer receiving upfront platinum-containing chemotherapy between 2004 and 2014 were pooled from the Spanish Germ Cell Cancer Group (SGCCG) registry and reviewed for the presence of VTE. Results were validated in an independent international group of patients. We used a penalized Cox proportional hazards model including VTE as a time-varying covariate to identify and validate prognostic factors. All statistical tests were two-sided. The SGCCG registry identified 416 patients from 14 referral institutions. With a median follow-up of 49 months, VTEs were observed in 9% of patients (n = 38). Events occurred at diagnosis, during chemotherapy, and after chemotherapy in 2.6%, 5.0%, and 1.4% of patients, respectively. VTE was associated with shorter progression-free survival (PFS; hazard ratio [HR] = 2.29, 95% confidence interval [CI] = 1.18 to 4.47, P = .02) and overall survival (OS; HR = 5.14, 95% CI = 2.22 to 11.88, P < .001). In multivariable analysis, the effect was consistent in the intermediate-risk group, both for PFS (HR = 9.52 95% CI = 2.48 to 36.58, P < .001) and OS (HR = 12.84, 95% CI = 2.01 to 82.02, P = .007). VTE at diagnosis is also an adverse prognostic variable for progression-free survival (HR = 4.64, 95% CI = 2.04 to 10.54, P < .001) and for overall survival (HR = 6.28, 95% CI = 1.68 to 17.10, P = .01). These results were validated in an independent international cohort that included 241 patients from four hospitals. VTE is an independent adverse prognostic factor in disseminated germ cell cancers, in particular for the intermediate prognostic group of the International Germ Cell Cancer Collaborative Group classification. The presence of VTE at diagnosis has also prognostic significance and
Tooher, Rebecca; Gates, Simon; Dowswell, Therese; Davis, Lucy-Jane
Background Venous thromboembolic disease (TED), although rare, is a major cause of maternal mortality and morbidity, hence methods of prophylaxis are often used for women at risk. This may include women delivered by caesarean section, those with a personal or family history of TED and women with inherited or acquired thrombophilias (conditions that predispose people to thrombosis). Many methods of prophylaxis carry a risk of side effects, and as the risk of TED is low, it is possible that the benefits of thromboprophylaxis may be outweighed by harm. Current guidelines for clinical practice are based on expert opinion only, rather than high quality evidence from randomised trials. Objectives To determine the effects of thromboprophylaxis in women who are pregnant or have recently delivered and are at increased risk of TED on the incidence of venous TED and side effects of treatment. Search methods We searched the Cochrane Pregnancy and Childbirth Group’s Trials Register (May 2009). Selection criteria Randomised trials comparing one method of thromboprophylaxis with placebo or no treatment, and randomised trials comparing two (or more) methods of thromboprophylaxis. Data collection and analysis Two review authors extracted data independently and resolved any discrepancies by discussion. Main results Sixteen trials met the inclusion criteria but only 13 trials, involving 1774 women, examining a range of methods of thromboprophylaxis, contributed data for the outcomes of interest. Four of them compared methods of antenatal prophylaxis: low molecular weight heparin (LMWH) versus unfractionated heparin (UFH) (two studies), and heparin versus no treatment (two studies). Eight studies assessed postnatal prophylaxis after caesarean section; one compared hydroxyethyl starch with unfractionated heparin; four compared heparin with placebo; and the other three compared UFH with LMWH. One study examined prophylaxis in the postnatal period. The small number of statistically
MUSSELWHITE, Laura W.; SHEIKH, Virginia; NORTON, Thomas D.; RUPERT, Adam; PORTER, Brian O.; PENZAK, Scott R.; SKINNER, Jeff; MICAN, JoAnn M.; HADIGAN, Colleen; SERETI, Irini
Objective HIV infection is associated with coagulation abnormalities and significantly increased risk of venous thrombosis. It has been shown that higher plasma levels of coagulation and inflammatory biomarkers predicted mortality in HIV. We investigated the relationship between venous thrombosis and HIV-related characteristics, traditional risk factors of hypercoagulability and pre-event levels of biomarkers. Design A retrospective case-control study of 23 HIV-infected individuals who experienced an incident venous thromboembolic (VTE) event while enrolled in National Institutes of Health studies from 1995–2010 and 69 age and sex-matched HIV-infected individuals without known VTE. Methods Biomarkers of inflammation, endothelial dysfunction, coagulation, tissue fibrosis, and cytomegalovirus (CMV) reactivation were assessed by ELISA-based assays and PCR using plasma obtained prior to the event. Results VTE events were related to nadir CD4 count, lifetime history of multiple opportunistic infections, CMV disease, CMV viremia, immunological AIDS, active infection and provocation (i.e. recent hospitalization, surgery or trauma). VTE events were independently associated with increased plasma levels of P-selectin, P=0.002; D-dimer, P=0.01; and hyaluronic acid, P=0.009 in a multivariate analysis. No significant differences in antiretroviral or interleukin 2 exposures, plasma HIV viremia, or other traditional risk factors were observed. Conclusion Severe immunodeficiency, active infection and provocation are associated with venous thromboembolic disease in HIV. Biomarkers of endothelial dysfunction, coagulation and tissue fibrosis may help identify HIV-infected patients at elevated risk of VTE. PMID:21412059
Mezei, Zoltán A; Katona, Éva; Kállai, Judit; Bereczky, Zsuzsanna; Somodi, Laura; Molnár, Éva; Kovács, Bettina; Miklós, Tünde; Ajzner, Éva; Muszbek, László
The association of plasma factor XIII (FXIII) level with venous thromboembolism (VTE) is still controversial and the effect of sex and FXIII B subunit (FXIII-B) polymorphisms in this respect have not been explored. 1/ To determine FXIII activity and antigen levels in patients with a history of VTE and how they are influenced by sex and FXIII-B polymorphisms. 2/ To explore the association of FXIII levels and FXIII-B polymorphisms with the risk of VTE. 218 VTE patients and equal number of age and sex matched controls were enrolled in the study. FXIII activity was measured by ammonia release assay; FXIII-A2B2 and FXIII-B levels were determined by ELISAs. FXIII-B polymorphisms were identified by RT-PCR using melting point analysis. Adjusted FXIII activity and FXIII-A2B2 antigen levels were significantly higher in females with a history of VTE than in the respective controls. FXIII-B levels were significantly lower in male VTE patients than in controls. FXIII-A2B2 antigen levels in the upper tertile increased the risk of VTE in females (adjusted OR: 2.52; CI: 1.18-5.38). Elevated FXIII-B antigen level had a protective effect only in males (adjusted OR: 0.19; CI: 0.08-0.46). FXIII-B Intron K c.1952+144 C>G polymorphism significantly lowered FXIII activity, FXIII-A2B2 and FXIII-B antigen levels in both groups. FXIII-B polymorphisms did not influence the risk of VTE. In VTE patients the changes of FXIII level and their effect on the risk of VTE show considerable sex-specific differences. Intron K polymorphism results in decreased FXIII levels, but does not influence the risk of VTE. Copyright © 2017. Published by Elsevier Ltd.
White, C Whitney; Thomason, Angela R; Prince, Valerie
To report a patient case identifying risk for recurrent venous thromboembolism (VTE) associated with heterozygous Factor V Leiden mutation. A 54-year-old Caucasian male was diagnosed with heterozygous Factor V Leiden mutation in 2008 after experiencing a deep vein thrombosis (DVT) and bilateral pulmonary embolism. The patient was treated appropriately and started on anticoagulation therapy with warfarin through an anticoagulation management clinic. After approximately 17 months of warfarin therapy without incident, warfarin was discontinued. Within 2 months after discontinuation of anticoagulation therapy, the patient experienced his second DVT and left pulmonary artery embolus. The risk of recurrent venous thromboembolism (VTE) in patients with heterozygous Factor V Leiden mutation is documented as an approximate 1.4-fold increase compared to patients without thrombophilia. However, the risk increases dramatically when nonreversible (age) or reversible risk factors (obesity, smoking, and long air flights) are present in this population. Based on recent literature, heterozygous Factor V Leiden mutation exponentially increases the risk of recurrent VTE, especially in the presence of other risk factors. Health care providers should complete a comprehensive review of the patients' other risk factors when deciding on duration of anticoagulation therapy for patients with positive heterozygous Factor V Leiden mutation.
Currently venous thromboembolic disease (VTE), i.e. deep venous thrombosis and pulmonary embolism, remains a major cause of morbidity and mortality all around the world. The Hokusai-VTE study is a randomized, double-blind trial to evaluate whether initial heparin (5 days) followed by the oral Xa factor inhibitor edoxaban (60 mg once daily) may be an alternative to the standard therapy, i.e. heparin (5 days) followed by warfarin (INR of 2.0-3.0) for the prevention of recurrent thromboembolism in patients with acute symptomatic VTE. In patients with VTE, including pulmonary embolism with right ventricular dysfunction, treatment with heparin followed by oral edoxaban 60 mg once daily was non inferior to the standard treatment with respect to efficacy and superior with respect to bleeding (fewer fatal and intracranial bleeds, but no statistical significance regarding major bleeding). Reducing the dosage of edoxaban to 30 mg once daily is safe in case of renal impairment and low body weight.
Al-Hameed, Fahad M.; Al-Dorzi, Hasan M.; Al-Momen, Abdulkarim M.; Algahtani, Farjah H.; Al-Zahrani, Hazzaa A.; Al-Saleh, Khalid A.; Al-Sheef, Mohammed A.; Owaidah, Tarek M.; Alhazzani, Waleed; Neumann, Ignacio; Wiercioch, Wojtek; Brozek, Jan; Schünemann, Holger; Akl, Elie A.
Venous thromboembolism (VTE) including deep vein thrombosis (DVT) and pulmonary embolism (PE) is commonly encountered in daily clinical practice. After diagnosis, its management frequently carries significant challenges to the clinical practitioner. Treatment of VTE with the inappropriate modality and/or in the inappropriate setting may lead to serious complications and have life-threatening consequences. As a result of an initiative of the Ministry of Health of the Kingdom of Saudi Arabia, an expert panel led by the Saudi Association for Venous Thrombo-Embolism (a subsidiary of the Saudi Thoracic Society) and the Saudi Scientific Hematology Society with the methodological support of the McMaster University Guideline working group, this clinical practice guideline was produced to assist health care providers in VTE management. Two questions were identified and were related to the inpatient versus outpatient treatment of acute DVT, and the early versus standard discharge from hospital for patients with acute PE. The corresponding recommendations were made following the GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) approach. PMID:26219456
Ndzengue, Albert; Rafal, Richard B.; Balmir, Simon; Rai, Dinker B.; Jaffe, Eric A.
Klippel–Trenaunay syndrome (KTS) is a congenital condition redefined by Oduber et al (2008) by the coexistence of vascular malformations and disturbed soft tissue or bony growth, including hypertrophy or hypotrophy in the same or opposite sides of the body. The anomalies may involve part of a limb, a whole limb, a limb girdle, or a hemibody. Vascular malformations may involve veins, capillaries, or lymphatics although venous or capillary malformations are essential for the diagnosis. Associated venous anomalies include dysplasia, valvular malformations, and varicosities. Congenital venous anomalies are often associated with disturbances of blood flow and should be considered as prothrombotic states. However, such anomalies are not considered in Wells scores and used to determine the risk for venous thromboembolism (VTE). We present the case of a male with unrecognized crossed dissociated form of KTS and unsuspected VTE. The pathophysiology and the treatment of VTE in KTS are discussed. We suggest physicians to be aware of KTS and that its recognition in a critically ill patient should prompt consideration for appropriate prophylaxis for high-risk category for VTE. Dedicated duplex sonography should be obtained if VTE is suspected. We also suggest a modification of the Wells scores to reflect the association of KTS and VTE. PMID:24293983
Meyer, R Michael; Larkin, M Benjamin; Szuflita, Nicholas S; Neal, Chris J; Tomlin, Jeffrey M; Armonda, Rocco A; Bailey, Jeffrey A; Bell, Randy S
OBJECTIVE Traumatic brain injury (TBI) is independently associated with deep vein thrombosis (DVT) and pulmonary embolism (PE). Given the numerous studies of civilian closed-head injury, the Brain Trauma Foundation recommends venous thromboembolism chemoprophylaxis (VTC) after severe TBI. No studies have specifically examined this practice in penetrating brain injury (PBI). Therefore, the authors examined the safety and effectiveness of early VTC after PBI with respect to worsening intracranial hemorrhage and DVT or PE. METHODS The Kandahar Airfield neurosurgery service managed 908 consults between January 2010 and March 2013. Eighty of these were US active duty members with PBI, 13 of whom were excluded from analysis because they presented with frankly nonsurvivable CNS injury or they died during initial resuscitation. This is a retrospective analysis of the remaining 67 patients. RESULTS Thirty-two patients received early VTC and 35 did not. Mean time to the first dose was 24 hours. Fifty-two patients had blast-related PBI and 15 had gunshot wounds (GSWs) to the head. The incidence of worsened intracranial hemorrhage was 16% after early VTC and 17% when it was not given, with the relative risk approaching 1 (RR = 0.91). The incidence of DVT or PE was 12% after early VTC and 17% when it was not given (RR = 0.73), though this difference was not statistically significant. CONCLUSIONS Early VTC was safe with regard to the progression of intracranial hemorrhage in this cohort of combat-related PBI patients. Data in this study suggest that this intervention may have been effective for the prevention of DVT or PE but not statistically significantly so. More research is needed to clarify the safety and efficacy of this practice.
Parpia, S; Julian, J A; Thabane, L; Lee, A Y Y; Rickles, F R; Levine, M N
Patients with malignant disease enrolled in trials of thrombotic disorders may experience competing events such as death. The occurrence of a competing event may prevent the thrombotic event from being observed. Standard survival analysis techniques ignore competing risks, resulting in possible bias and distorted inferences. To assess the impact of competing events on the results of a previously reported trial comparing low molecular weight heparin (LMWH) with oral anticoagulant (OAC) therapy for the prevention of recurrent venous thromboembolism (VTE) in patients with advanced cancer, we compare the results from standard survival analysis with those from competing risk techniques which are based on the cumulative incidence function (CIF) and Gray's test. The Kaplan-Meier method overestimates the risk of recurrent VTE (17.2% in the OAC group and 8.7% in the LMWH group). Risk of recurrence using the CIF is 12.0% and 6.0% in the OAC and LMWH groups, respectively. Both the log-rank test (p=0.002) and Gray's test (p=0.006) suggest evidence in favor of LMWH. The overestimation of risk is 30% in each treatment group, resulting in a similar relative treatment effect; using the Cox model the hazard ratio (HR) is 0.48 (95% confidence interval [CI], 0.30 to 0.78) and HR=0.47 (95% CI, 0.29 to 0.74) using the CIF model. Failing to account for competing risks may lead to incorrect interpretations of the probability of recurrent VTE. However, when the distribution of competing risks is similar within each treatment group, standard and competing risk methods yield comparable relative treatment effects.
Christiansen, Christian Fynbo
Venous thromboembolism (VTE) is a potentially serious complication occurring in 1%-2% of hospitalized medical patients. Despite this low absolute risk, as many as 82% of medical patients are considered to be at increased risk of developing VTE and are eligible for medical thromboprophylaxis. In this commentary, The author will discuss the main findings of a recent paper published in Clinical Epidemiology that questions the large proportion of individuals who are eligible for medical thromboprophylaxis, and also discuss the potential implications for the prevention of VTE. The recent paper demonstrated that when a population is divided into high- and low-risk groups, the maximum absolute risk depends on the inverse of the proportion of patients that is considered to be high risk. Consequently, even an effective treatment will only result in a small reduction in the absolute risk when the high-risk group comprises the largest proportion of this population. For medical thromboprophylaxis, this implies that even patients considered to be at high-risk for developing VTE have a maximum absolute VTE risk of 2% when the overall risk is 1.6%. Therefore, even an effective preventive initiative will only result in a small risk reduction. This small potential benefit should be weighed against potential harms associated with prophylaxis, mainly bleeding events. Still, there may be a reasonable overall balance between prevention of pulmonary embolism and major bleeding, mainly because major bleeding events are rare. Nonetheless, this discussion underscores that future risk prediction models should aim to predict the benefits and harms in individual patients in order to provide optimal care for the right patients.
Phan, Minh; John, Sonia; Casanegra, Ana I.; Rathbun, Suman; Mansfield, Aaron; Stoner, Julie A.; Tafur, Alfonso J.
Venous thromboembolism (VTE) is a leading cause of death among outpatient chemotherapy patients. However the VTE preventive measures for outpatients are not widely advocated. We did a meta-analysis to evaluate the outpatient VTE prevention's effectiveness and safety. We searched electronic databases until the end of December 2012 and reviewed the abstracts and manuscripts following the PRISMA guidelines. Occurrence of first VTE event was the efficacy outcome. The safety end point was major bleeding. We calculated Q statistic and a homogeneity formal test. The odds ratio (OR) estimates were pooled by using the Mantel–Haenszel fixed-effects method in the absence of heterogeneity. Data were analyzed using the R META package). We identified 1,485 articles and reviewed 37 articles based on initial screening. The number of patients included in 11 selected trials was 7,805. The odds of VTE was lower in the prophylaxis group (OR 0.56; 95 % CI 0.45–0.71) and improved when heparin-based prevention was analyzed (OR 0.53; 95 % CI 0.41–0.70). We found strong prevention among patients with lung cancer (OR 0.46; 95 % CI 0.29–0.74) and pancreatic cancer (OR 0.33; 95 % CI 0.16–0.67). Major bleeding events were frequent in the intervention group (OR 1.65; 95 % CI 1.12–2.44). Thromboprophylaxis reduced VTE episodes. The VTE events were reduced by 47 % in heparin-based prophylaxis trials compared to placebo. The patients receiving heparin-based prophylaxis had a 60 % increase in bleeding events. Improving risk stratification tools to personalize prevention strategies may enhance the VTE prevention applicability in cancer patients. PMID:24233387
Guermaz, R; Belhamidi, S; Amarni, A
PROMET is an observational study aimed to assess the management of patients at venous thromboembolism risk in the Algerian hospitals and to evaluate the proportion of at-risk patients treated with an adequate prophylaxis. Following the ENDORSE study achieved five years before with a similar protocol, PROMET included 435hospitalized patients (229 in medical units and 206 in surgical units). Compared to the ENDORSE results, the PROMET data reflect progress in the management of venous thromboembolism: 73.3% of at-risk patients received prophylaxis (57.6% of medical patients and 90.8% of surgical patients). In 93.1% of cases, this prophylaxis was provided by a low molecular weight heparin, mainly at the dose of one injection per day. In medical population, the prescription was triggered by long-term immobilization (P=0.01; OR=5.8 95%CI [1.5-23.0]), associated risk factors (P=0.025; OR=4.13 [1.2-14.2]) and the cause of hospitalization (P=0.056). In surgical departments, the therapeutic decision depended on the nature of the surgical intervention and was influenced by the presence of a contraindication for prophylaxis (P<0.001; OR=0.02 [0.00-0.14]) or a high hemorrhagic risk (P<0.001; OR=0.02). The assessment and management of thromboembolic risk were in accordance with ACCP recommendations for surgical patients. However efforts are needed for medical patients for whom the risk is underestimated and insufficiently supported. Unlike surgery where procedures are well established, there are real difficulties in medicine to define the at-risk patients who will benefit from thromboprophylaxis. The process of preventive treatment (particularly the optimal duration) needs to be clarified.
Tricotel, Aurore; Raguideau, Fanny; Collin, Cédric; Zureik, Mahmoud
Purpose To estimate the number of venous thromboembolic events and related-premature mortality (including immediate in-hospital lethality) attributable to the use of combined oral contraceptives in women aged 15 to 49 years-old between 2000 and 2011 in France. Methods French data on sales of combined oral contraceptives and on contraception behaviours from two national surveys conducted in 2000 and 2010 were combined to estimate the number of exposed women according to contraceptives generation and age. Absolute risk of first time venous thromboembolism in non-users of hormonal contraception and increased risk of thromboembolism in users vs. non-users of hormonal contraception were estimated on the basis of literature data. Finally, immediate in-hospital lethality due to pulmonary embolism and premature mortality due to recurrent venous thromboembolism were estimated from the French national database of hospitalisation and literature data. Results In France, more than four million women are daily exposed to combined oral contraceptives. The mean annual number of venous thromboembolic events attributable to their use was 2,529 (778 associated to the use of first- and second-generation contraceptives and 1,751 to the use of third- and fourth-generation contraceptives), corresponding to 20 premature deaths (six with first- and second-generation contraceptives and fourteen with third- and fourth-generation contraceptives), of which there were eight to nine immediate in-hospital deaths. As compared to the use of first- and second-generation contraceptives, exposure to third- and fourth-generation contraceptives led to a mean annual excess of 1,167 venous thromboembolic events and nine premature deaths (including three immediate in-hospital deaths). Conclusions Corrective actions should be considered to limit exposure to third- and fourth-generation contraceptives, and thus optimise the benefit-risk ratio of combined oral contraception. PMID:24751717
Michtalik, Henry J.; Carolan, Howard T.; Haut, Elliott R.; Lau, Brandyn D.; Streiff, Michael B.; Finkelstein, Joseph; Pronovost, Peter J.; Durkin, Nowella; Brotman, Daniel J.
Background Despite safe and cost-effective venous thromboembolism (VTE) prevention measures, VTE prophylaxis rates are often suboptimal. Healthcare reform efforts emphasize transparency through programs to report performance, and payment incentives through programs to pay-for-performance. Objective To sequentially examine an individualized physician dashboard and pay-for-performance program to improve VTE prophylaxis rates amongst hospitalists. Design Retrospective analysis of 3144 inpatient admissions. After a baseline observation period, VTE prophylaxis compliance was compared during both interventions. Setting 1060-bed tertiary care medical center. Participants 38 part- and full-time academic hospitalists. Interventions A Web-based hospitalist dashboard provided VTE prophylaxis feedback. After 6 months of feedback only, a pay-for-performance program was incorporated, with graduated payouts for compliance rates of 80-100%. Measurements Prescription of American College of Chest Physicians guideline-compliant VTE prophylaxis and subsequent pay-for-performance payments. Results Monthly VTE prophylaxis compliance rates were 86% (95% CI: 85, 88), 90% (95% CI: 88, 93), and 94% (95% CI: 93, 96) during the baseline, dashboard, and combined dashboard/pay-for-performance periods, respectively. Compliance significantly improved with the use of the dashboard (p=0.01) and addition of the pay-for-performance program (p=0.01). The highest rate of improvement occurred with the dashboard (1.58%/month; p=0.01). Annual individual physician performance payments ranged from $53 to $1244 (mean $633; SD ±350). Conclusions Direct feedback using dashboards was associated with significantly improved compliance, with further improvement after incorporating an individual physician pay-for-performance program. Real-time dashboards and physician-level incentives may assist hospitals in achieving higher safety and quality benchmarks. PMID:25545690
Kaelber, David C; Foster, Wendy; Gilder, Jason; Love, Thomas E; Jain, Anil K
To demonstrate the potential of de-identified clinical data from multiple healthcare systems using different electronic health records (EHR) to be efficiently used for very large retrospective cohort studies. Data of 959 030 patients, pooled from multiple different healthcare systems with distinct EHR, were obtained. Data were standardized and normalized using common ontologies, searchable through a HIPAA-compliant, patient de-identified web application (Explore; Explorys Inc). Patients were 26 years or older seen in multiple healthcare systems from 1999 to 2011 with data from EHR. Comparing obese, tall subjects with normal body mass index, short subjects, the venous thromboembolic events (VTE) OR was 1.83 (95% CI 1.76 to 1.91) for women and 1.21 (1.10 to 1.32) for men. Weight had more effect then height on VTE. Compared with Caucasian, Hispanic/Latino subjects had a much lower risk of VTE (female OR 0.47, 0.41 to 0.55; male OR 0.24, 0.20 to 0.28) and African-Americans a substantially higher risk (female OR 1.83, 1.76 to 1.91; male OR 1.58, 1.50 to 1.66). This 13-year retrospective study of almost one million patients was performed over approximately 125 h in 11 weeks, part time by the five authors. As research informatics tools develop and more clinical data become available in EHR, it is important to study and understand unique opportunities for clinical research informatics to transform the scale and resources needed to perform certain types of clinical research. With the right clinical research informatics tools and EHR data, some types of very large cohort studies can be completed with minimal resources.
Schulman, Sam; Kakkar, Ajay K; Goldhaber, Samuel Z; Schellong, Sebastian; Eriksson, Henry; Mismetti, Patrick; Christiansen, Anita Vedel; Friedman, Jeffrey; Le Maulf, Florence; Peter, Nuala; Kearon, Clive
Dabigatran and warfarin have been compared for the treatment of acute venous thromboembolism (VTE) in a previous trial. We undertook this study to extend those findings. In a randomized, double-blind, double-dummy trial of 2589 patients with acute VTE treated with low-molecular-weight or unfractionated heparin for 5 to 11 days, we compared dabigatran 150 mg twice daily with warfarin. The primary outcome, recurrent symptomatic, objectively confirmed VTE and related deaths during 6 months of treatment occurred in 30 of the 1279 dabigatran patients (2.3%) compared with 28 of the 1289 warfarin patients (2.2%; hazard ratio, 1.08; 95% confidence interval [CI], 0.64-1.80; absolute risk difference, 0.2%; 95% CI, -1.0 to 1.3; P<0.001 for the prespecified noninferiority margin for both criteria). The safety end point, major bleeding, occurred in 15 patients receiving dabigatran (1.2%) and in 22 receiving warfarin (1.7%; hazard ratio, 0.69; 95% CI, 0.36-1.32). Any bleeding occurred in 200 dabigatran (15.6%) and 285 warfarin (22.1%; hazard ratio, 0.67; 95% CI, 0.56-0.81) patients. Deaths, adverse events, and acute coronary syndromes were similar in both groups. Pooled analysis of this study RE-COVER II and the RE-COVER trial gave hazard ratios for recurrent VTE of 1.09 (95% CI, 0.76-1.57), for major bleeding of 0.73 (95% CI, 0.48-1.11), and for any bleeding of 0.70 (95% CI, 0.61-0.79). Dabigatran has similar effects on VTE recurrence and a lower risk of bleeding compared with warfarin for the treatment of acute VTE. www.clinicaltrials.gov. Unique identifiers: NCT00680186 and NCT00291330.
Martinelli, Ida; Lensing, Anthonie W A; Middeldorp, Saskia; Levi, Marcel; Beyer-Westendorf, Jan; van Bellen, Bonno; Bounameaux, Henri; Brighton, Timothy A; Cohen, Alexander T; Trajanovic, Mila; Gebel, Martin; Lam, Phuong; Wells, Philip S; Prins, Martin H
Women receiving vitamin K antagonists (VKAs) require adequate contraception because of the potential for fetal complications. It is unknown whether the use of hormonal therapy, especially those containing estrogens, is associated with recurrent venous thromboembolism (VTE) during anticoagulation. Despite the absence of data, World Health Organization guidelines state that use of estrogen-containing contraceptives confers an "unacceptable health risk" during established anticoagulation for VTE. We compared the incidences of recurrent VTE and abnormal uterine bleeding with and without concomitant hormonal therapy in women aged <60 years who were receiving anticoagulation with rivaroxaban or enoxaparin/VKA for confirmed VTE. Incidence densities in percentage per year were computed for the on and off estrogen-containing or progestin-only therapy periods. Cox regression models were fitted, with hormonal therapy (on vs off) as a time-dependent variable to derive the hazard ratio (HR) for the effects on recurrent VTE and abnormal uterine bleeding. In total, 1888 women were included. VTE incidence densities on and off hormonal therapy were 3.7%/year and 4.7%/year (adjusted HR, 0.56; 95% confidence interval [CI], 0.23-1.39), respectively, and were 3.7%/year and 3.8%/year, respectively, for estrogen-containing and progestin-only therapy. The adjusted HR for all abnormal uterine bleeding (on vs off hormonal therapy) was 1.02 (95% CI, 0.66-1.57). Abnormal uterine bleeding occurred more frequently with rivaroxaban than with enoxaparin/VKA (HR, 2.13; 95% CI, 1.57-2.89). Hormonal therapy was not associated with an increased risk of recurrent VTE in women receiving therapeutic anticoagulation. The observed increased risk of abnormal uterine bleeding with rivaroxaban needs further exploration. © 2016 by The American Society of Hematology.
Lensing, Anthonie W. A.; Middeldorp, Saskia; Levi, Marcel; Beyer-Westendorf, Jan; van Bellen, Bonno; Bounameaux, Henri; Brighton, Timothy A.; Cohen, Alexander T.; Trajanovic, Mila; Gebel, Martin; Lam, Phuong; Wells, Philip S.; Prins, Martin H.
Women receiving vitamin K antagonists (VKAs) require adequate contraception because of the potential for fetal complications. It is unknown whether the use of hormonal therapy, especially those containing estrogens, is associated with recurrent venous thromboembolism (VTE) during anticoagulation. Despite the absence of data, World Health Organization guidelines state that use of estrogen-containing contraceptives confers an “unacceptable health risk” during established anticoagulation for VTE. We compared the incidences of recurrent VTE and abnormal uterine bleeding with and without concomitant hormonal therapy in women aged <60 years who were receiving anticoagulation with rivaroxaban or enoxaparin/VKA for confirmed VTE. Incidence densities in percentage per year were computed for the on and off estrogen-containing or progestin-only therapy periods. Cox regression models were fitted, with hormonal therapy (on vs off) as a time-dependent variable to derive the hazard ratio (HR) for the effects on recurrent VTE and abnormal uterine bleeding. In total, 1888 women were included. VTE incidence densities on and off hormonal therapy were 3.7%/year and 4.7%/year (adjusted HR, 0.56; 95% confidence interval [CI], 0.23-1.39), respectively, and were 3.7%/year and 3.8%/year, respectively, for estrogen-containing and progestin-only therapy. The adjusted HR for all abnormal uterine bleeding (on vs off hormonal therapy) was 1.02 (95% CI, 0.66-1.57). Abnormal uterine bleeding occurred more frequently with rivaroxaban than with enoxaparin/VKA (HR, 2.13; 95% CI, 1.57-2.89). Hormonal therapy was not associated with an increased risk of recurrent VTE in women receiving therapeutic anticoagulation. The observed increased risk of abnormal uterine bleeding with rivaroxaban needs further exploration. PMID:26696010
Lecumberri, Ramón; Marqués, Margarita; Panizo, Elena; Alfonso, Ana; García-Mouriz, Alberto; Gil-Bazo, Ignacio; Hermida, José; Schulman, Sam; Páramo, José A
Many cancer patients are at high risk of venous thromboembolism (VTE) during hospitalisation; nevertheless, thromboprophylaxis is frequently underused. Electronic alerts (e-alerts) have been associated with improvement in thromboprophylaxis use and a reduction of the incidence of VTE, both during hospitalisation and after discharge, particularly in the medical setting. However, there are no data regarding the benefit of this tool in cancer patients. Our aim was to evaluate the impact of a computer-alert system for VTE prevention in patients with cancer, particularly in those admitted to the Oncology/Haematology ward, comparing the results with the rest of inpatients at a university teaching hospital. The study included 32,167 adult patients hospitalised during the first semesters of years 2006 to 2010, 9,265 (28.8%) with an active malignancy. Appropriate prophylaxis in medical patients, significantly increased over time (from 40% in 2006 to 57% in 2010) and was maintained over 80% in surgical patients. However, while e-alerts were associated with a reduction of the incidence of VTE during hospitalisation in patients without cancer (odds ratio [OR] 0.31; 95% confidence interval [CI], 0.15-0.64), the impact was modest in cancer patients (OR 0.89; 95% CI, 0.42-1.86) and no benefit was observed in patients admitted to the Oncology/Haematology Departments (OR 1.11; 95% CI, 0.45-2.73). Interestingly, 60% of VTE episodes in cancer patients during recent years developed despite appropriate prophylaxis. Contrary to the impact on hospitalised patients without cancer, implementation of e-alerts for VTE risk did not prevent VTE effectively among those with malignancies.
Duff, Jed; Walker, Kim; Omari, Abdullah; Middleton, Sandy; McInnes, Elizabeth
Venous thromboembolism (VTE) is a significant cause of morbidity and mortality in hospitalized medical patients. Evidence-based guidelines exist for preventing VTE; unfortunately, these guidelines are not always adhered to by clinicians. The aim of this study was to evaluate the acceptability, utility and clinical impact of an educational outreach visit (EOV) on nurses' provision of mechanical prophylaxis to hospitalized medical patients using a prospective, uncontrolled, before-and-after design. Nurses received a 1-to-1 educational session on mechanical VTE prevention by a trained nurse facilitator. The EOV intervention was designed by a multidisciplinary group of healthcare professionals using social marketing theory. Eighty-five of the 120 eligible nurses (71%) attended the EOV. The median length of each visit was 11.5 minutes (interquartile range [IQR], 10-15) and the median time spent arranging and conducting each visit was 63 minutes (IQR, 49-85). Eighty-four (99%) of the 85 participants gave a verbal commitment to trial the new evidence-based mechanical VTE prevention practices. However, there were no measurable improvements in the proportion of patients risk assessed (-1.7% improvement; 95% confidence interval [CI], -7.0 to 10.3; P = .68) or provided appropriate mechanical prophylaxis (-0.3% improvement; 95% CI, -13.4 to 14; P = .96). Researchers conclude that EOV should not be used to improve nurses' use of mechanical VTE prevention because it has no measurable impact on clinical practice and is resource intensive, requiring 4.5 minutes of preparation for every minute spent face to face with participants. Further research into the specific mechanism of action is required to explain the variability in clinical effect seen with this intervention. Copyright © 2013 Society for Vascular Nursing, Inc. Published by Mosby, Inc. All rights reserved.
Monreal, Manuel; Falgá, Conxita; Valle, Reina; Barba, Raquel; Bosco, Juan; Beato, José Luís; Maestre, Ana
Current guidelines make no specific recommendations for venous thromboembolism (VTE) treatment in patients with renal insufficiency, but some experts recommend some reduction in heparin dose. Registro Informatizado de Enfermedad TromboEmbólica (RIETE) is an ongoing, prospective registry of consecutively enrolled patients with objectively confirmed, symptomatic, acute VTE. In this analysis we retrospectively analyzed the effect of renal insufficiency on the incidence of fatal pulmonary embolism (PE) and fatal bleeding within 15 days of diagnosis. Up to March 2005, 10,526 patients with acute VTE were enrolled in RIETE, of whom 9234 (88%) had a creatinine clearance (CrCl) greater than 60 mL/min, 704 (6.7%) had a CrCl 30 to 60 mL/min, and 588 (5.6%) had a CrCl less than 30 mL/min. The incidence of fatal PE during the study period was 1.0%, 2.6%, and 6.6%, respectively. Fatal bleeding occurred in 0.2%, 0.3%, and 1.2% of the patients, respectively. On multivariate analysis, patients with a CrCl less than 30 mL/min were independently associated with an increased risk for fatal PE and fatal bleeding. In addition, initial diagnosis of PE, immobility for 4 days or more, cancer, and initial therapy with unfractionated heparin were independent predictors of fatal PE; whereas immobility for 4 days or more and cancer were independent predictors of fatal bleeding. Patients with VTE who have renal insufficiency had an increased incidence of both fatal PE and fatal bleeding, but the risk of fatal PE far exceeded that of fatal bleeding. Our data support the use of full-dose anticoagulant therapy, even in patients with a CrCl less than 30 mL/min.
Hansen-Krone, Ida J; Brækkan, Sigrid K; Enga, Kristin F; Wilsgaard, Tom; Hansen, John-Bjarne
Moderate alcohol consumption has been shown to protect against cardiovascular diseases. The association between alcohol consumption, especially types of alcoholic beverages, and venous thromboembolism (VTE) is less well described. The aim of this study was to investigate the impact of alcohol consumption and different alcoholic beverages on risk of VTE. Information on alcohol consumption was collected by a self-administrated questionnaire in 26,662 subjects, aged 25-97 years, who participated in the Tromsø Study, in 1994-1995. Subjects were followed through September 1, 2007 with incident VTE as the primary outcome. There were 460 incident VTE-events during a median of 12.5 years of follow-up. Total alcohol consumption was not associated with risk of incident VTE. However, subjects consuming ≥ 3 units of liquor per week had 53% increased risk of VTE compared to teetotalers in analyses adjusted for age, sex, body mass index, smoking, diabetes, cancer, previous cardiovascular disease, physical activity and higher education (HR: 1.53, 95% CI: 1.00-2.33). Contrary, subjects with a wine intake of ≥ 3 units/week had 22% reduced risk of VTE (HR: 0.78, 95% CI: 0.47-1.30), further adjustment for liquor and beer intake strengthened the protective effect of wine (HR: 0.53, 95% CI: 0.30-1.00). Frequent binge drinkers (≥ 1/week) had a 17% increased risk of VTE compared to teetotallers (HR 1.17, 95% CI: 0.66-2.09), and a 47% increased risk compared to non-binge drinkers (HR 1.47, 95% CI: 0.85-2.54). In conclusion, liquor consumption and binge drinking was associated with increased risk of VTE, whereas wine consumption was possibly associated with reduced risk of VTE.
Yu, Irene; Chen, Leo; Ruan, Jenny Y; Chang, Jennifer T; Cheung, Winson Y
Bevacizumab may potentiate the risk of venous thromboembolisms (VTEs) in cancer patients, who are already predisposed to pro-thrombotic states. We aimed to characterize the incidence of VTEs in a population-based cohort of metastatic colorectal cancer (mCRC) patients treated with bevacizumab, describe patient and treatment factors associated with VTEs, and examine how VTEs are managed. Patients diagnosed with mCRC from 2006 to 2009 and offered bevacizumab were included. Descriptive statistics were used to describe VTE occurrences and management. Univariate and multivariate regression models were constructed to explore associations between clinical factors and VTEs. We identified 541 mCRC patients: 27 never started bevacizumab and 15 were lost to follow-up. Of the 499 evaluable patients, median age was 61, 59.3% were men, 88.1% had ECOG 0/1, and 5.2% reported previous VTEs. Mean number of bevacizumab doses was 13.3 cycles. After receiving bevacizumab, 81 patients developed 93 cases of VTEs, with 9 patients experiencing >1 event. Individuals who experienced VTEs were more likely to have had pre-existing cardiovascular disease (OR 2.259, p = 0.0245), resection of primary cancer (OR 3.262, p = 0.0269), pre-chemotherapy platelet count ≥350,000/μL (OR 2.295, p = 0.0293), and received >12 bevacizumab cycles (OR 2.172, p = 0.0158). Use of bevacizumab varied after occurrence of VTE where it was discontinued in 34.4%, continued in 34.4%, and temporarily held in 1.1%. VTE risk can be high, especially in patients with specific pre-treatment risk factors as well as in those who received more bevacizumab, suggesting a potential dose-related effect. Management of bevacizumab-related VTEs was variable.
Streiff, Michael B; Carolan, Howard T; Hobson, Deborah B; Kraus, Peggy S; Holzmueller, Christine G; Demski, Renee; Lau, Brandyn D; Biscup-Horn, Paula; Pronovost, Peter J
Problem Venous thromboembolism (VTE) is a common cause of potentially preventable mortality, morbidity, and increased medical costs. Risk-appropriate prophylaxis can prevent most VTE events, but only a small fraction of patients at risk receive this treatment. Design Prospective quality improvement programme. Setting Johns Hopkins Hospital, Baltimore, Maryland, USA. Strategies for change A multidisciplinary team established a VTE Prevention Collaborative in 2005. The collaborative applied the four step TRIP (translating research into practice) model to develop and implement a mandatory clinical decision support tool for VTE risk stratification and risk-appropriate VTE prophylaxis for all hospitalised adult patients. Initially, paper based VTE order sets were implemented, which were then converted into 16 specialty-specific, mandatory, computerised, clinical decision support modules. Key measures for improvement VTE risk stratification within 24 hours of hospital admission and provision of risk-appropriate, evidence based VTE prophylaxis. Effects of change The VTE team was able to increase VTE risk assessment and ordering of risk-appropriate prophylaxis with paper based order sets to a limited extent, but achieved higher compliance with a computerised clinical decision support tool and the data feedback which it enabled. Risk-appropriate VTE prophylaxis increased from 26% to 80% for surgical patients and from 25% to 92% for medical patients in 2011. Lessons learnt A computerised clinical decision support tool can increase VTE risk stratification and risk-appropriate VTE prophylaxis among hospitalised adult patients admitted to a large urban academic medical centre. It is important to ensure the tool is part of the clinician’s normal workflow, is mandatory (computerised forcing function), and offers the requisite modules needed for every clinical specialty. PMID:22718994
Foster, Wendy; Gilder, Jason; Love, Thomas E; Jain, Anil K
Objective To demonstrate the potential of de-identified clinical data from multiple healthcare systems using different electronic health records (EHR) to be efficiently used for very large retrospective cohort studies. Materials and methods Data of 959 030 patients, pooled from multiple different healthcare systems with distinct EHR, were obtained. Data were standardized and normalized using common ontologies, searchable through a HIPAA-compliant, patient de-identified web application (Explore; Explorys Inc). Patients were 26 years or older seen in multiple healthcare systems from 1999 to 2011 with data from EHR. Results Comparing obese, tall subjects with normal body mass index, short subjects, the venous thromboembolic events (VTE) OR was 1.83 (95% CI 1.76 to 1.91) for women and 1.21 (1.10 to 1.32) for men. Weight had more effect then height on VTE. Compared with Caucasian, Hispanic/Latino subjects had a much lower risk of VTE (female OR 0.47, 0.41 to 0.55; male OR 0.24, 0.20 to 0.28) and African-Americans a substantially higher risk (female OR 1.83, 1.76 to 1.91; male OR 1.58, 1.50 to 1.66). This 13-year retrospective study of almost one million patients was performed over approximately 125 h in 11 weeks, part time by the five authors. Discussion As research informatics tools develop and more clinical data become available in EHR, it is important to study and understand unique opportunities for clinical research informatics to transform the scale and resources needed to perform certain types of clinical research. Conclusions With the right clinical research informatics tools and EHR data, some types of very large cohort studies can be completed with minimal resources. PMID:22759621
Prediction of risk of recurrence of venous thromboembolism following treatment for a first unprovoked venous thromboembolism: systematic review, prognostic model and clinical decision rule, and economic evaluation.
Ensor, Joie; Riley, Richard D; Jowett, Sue; Monahan, Mark; Snell, Kym Ie; Bayliss, Susan; Moore, David; Fitzmaurice, David
Unprovoked first venous thromboembolism (VTE) is defined as VTE in the absence of a temporary provoking factor such as surgery, immobility and other temporary factors. Recurrent VTE in unprovoked patients is highly prevalent, but easily preventable with oral anticoagulant (OAC) therapy. The unprovoked population is highly heterogeneous in terms of risk of recurrent VTE. The first aim of the project is to review existing prognostic models which stratify individuals by their recurrence risk, therefore potentially allowing tailored treatment strategies. The second aim is to enhance the existing research in this field, by developing and externally validating a new prognostic model for individual risk prediction, using a pooled database containing individual patient data (IPD) from several studies. The final aim is to assess the economic cost-effectiveness of the proposed prognostic model if it is used as a decision rule for resuming OAC therapy, compared with current standard treatment strategies. Standard systematic review methodology was used to identify relevant prognostic model development, validation and cost-effectiveness studies. Bibliographic databases (including MEDLINE, EMBASE and The Cochrane Library) were searched using terms relating to the clinical area and prognosis. Reviewing was undertaken by two reviewers independently using pre-defined criteria. Included full-text articles were data extracted and quality assessed. Critical appraisal of included full texts was undertaken and comparisons made of model performance. A prognostic model was developed using IPD from the pooled database of seven trials. A novel internal-external cross-validation (IECV) approach was used to develop and validate a prognostic model, with external validation undertaken in each of the trials iteratively. Given good performance in the IECV approach, a final model was developed using all trials data. A Markov patient-level simulation was used to consider the economic cost-effectiveness
Risk of venous thromboembolism associated with single and combined effects of Factor V Leiden, Prothrombin 20210A and Methylenetethraydrofolate reductase C677T: a meta-analysis involving over 11,000 cases and 21,000 controls.
Simone, Benedetto; De Stefano, Valerio; Leoncini, Emanuele; Zacho, Jeppe; Martinelli, Ida; Emmerich, Joseph; Rossi, Elena; Folsom, Aaron R; Almawi, Wassim Y; Scarabin, Pierre Y; den Heijer, Martin; Cushman, Mary; Penco, Silvana; Vaya, Amparo; Angchaisuksiri, Pantep; Okumus, Gulfer; Gemmati, Donato; Cima, Simona; Akar, Nejat; Oguzulgen, Kivilcim I; Ducros, Véronique; Lichy, Christoph; Fernandez-Miranda, Consuelo; Szczeklik, Andrzej; Nieto, José A; Torres, Jose Domingo; Le Cam-Duchez, Véronique; Ivanov, Petar; Cantu-Brito, Carlos; Shmeleva, Veronika M; Stegnar, Mojka; Ogunyemi, Dotun; Eid, Suhair S; Nicolotti, Nicola; De Feo, Emma; Ricciardi, Walter; Boccia, Stefania
Genetic and environmental factors interact in determining the risk of venous thromboembolism (VTE). The risk associated with the polymorphic variants G1691A of factor V (Factor V Leiden, FVL), G20210A of prothrombin (PT20210A) and C677T of methylentetrahydrofolate reductase (C677T MTHFR) genes has been investigated in many studies. We performed a pooled analysis of case-control and cohort studies investigating in adults the association between each variant and VTE, published on Pubmed, Embase or Google through January 2010. Authors of eligible papers, were invited to provide all available individual data for the pooling. The Odds Ratio (OR) for first VTE associated with each variant, individually and combined with the others, were calculated with a random effect model, in heterozygotes and homozygotes (dominant model for FVL and PT20210A; recessive for C677T MTHFR). We analysed 31 databases, including 11,239 cases and 21,521 controls. No significant association with VTE was found for homozygous C677T MTHFR (OR: 1.38; 95 % confidence intervals [CI]: 0.98-1.93), whereas the risk was increased in carriers of either heterozygous FVL or PT20210 (OR = 4.22; 95 % CI: 3.35-5.32; and OR = 2.79;95 % CI: 2.25-3.46, respectively), in double heterozygotes (OR = 3.42; 95 %CI 1.64-7.13), and in homozygous FVL or PT20210A (OR = 11.45; 95 %CI: 6.79-19.29; and OR: 6.74 (CI 95 % 2.19-20.72), respectively). The stratified analyses showed a stronger effect of FVL on individuals ≤ 45 years (p value for interaction = 0.036) and of PT20210A in women using oral contraceptives (p-value for interaction = 0.045). In this large pooled analysis, inclusive of large studies like MEGA, no effect was found for C677T MTHFR on VTE; FVL and PT20210A were confirmed to be moderate risk factors. Notably, double carriers of the two genetic variants produced an impact on VTE risk significantly increased but weaker than previously thought.
Risk of venous thromboembolism associated with single and combined effects of Factor V Leiden, Prothrombin 20210A and Methylenetethraydrofolate reductase C677T: a meta-analysis involving over 11,000 cases and 21,000 controls
Simone, B; De Stefano, V; Leoncini, E; Zacho, J; Martinelli, I; Emmerich, J; Rossi, E; Folsom, AR; Almawi, WY; Scarabin, PY; den Heijer, M; Cushman, M; Penco, S; Vaya, A; Angchaisuksiri, P; Okumus, G; Gemmati, D; Cima, S; Akar, N; Oguzulgen, KI; Ducros, V; Lichy, C; Fernandez-Miranda, C; Szczeklik, A; Nieto, JA; Torres, JD; Le Cam-Duchez, V; Ivanov, P; Cantu, C; Shmeleva, VM; Stegnar, M; Ogunyemi, D; Eid, SS; Nicolotti, N; De Feo, E; Ricciardi, W; Boccia, S
BACKGROUND Genetic and environmental factors interact in determining the risk of venous thromboembolism (VTE). The risk associated with the polymorphic variants G1691A of factor V (Factor V Leiden,FVL), G20210A of prothrombin (PT20210A) and C677T of methylentetrahydrofolate reductase (C677T MTHFR) genes has been investigated in many studies. METHODS We performed a pooled analysis of case-control and cohort studies investigating in adults the association between each variant and VTE, published on Pubmed, Embase or Google through January 2010. Authors of eligible papers, were invited to provide all available individual data for the pooling. The Odds Ratio (OR) for first VTE associated with each variant, individually and combined with the others, were calculated with a random effect model, in heterozygotes and homozygotes (dominant model for FVL and PT20210A; recessive for C677T MTHFR). RESULTS We analysed 31 databases, including 11,239 cases and 21,521 controls. No significant association with VTE was found for homozygous C677T MTHFR (OR: 1.38; 95% confidence intervals [CI]: 0.98–1.93), whereas the risk was increased in carriers of either heterozygous FVL or PT20210 (OR=4.22; 95% CI: 3.35–5.32; and OR=2.79;95% CI: 2.25–3.46, respectively), in double hterozygotes (OR=3.42; 95%CI 1.64-7.13), and in homozygous FVL or PT20210A (OR=11.45; 95%CI: 6.79-19.29; and OR: 2.79; 95%CI: 2.25 – 3.46, respectively). The stratified analyses showed a stronger effect of FVL on individuals ≤45 years (p-value for interaction = 0.036) and of PT20210A in women using oral contraceptives (p-value for interaction = 0.045). CONCLUSIONS In this large pooled analysis, inclusive of large studies like MEGA, no effect was found for C677T MTHFR on VTE; FVL and PT20210A were confirmed to be moderate risk factors. Notably, double carriers of the two genetic variants produced an impact on VTE risk significantly increased but weaker than previously thought. PMID:23900608
The cost-effectiveness of oral direct factor Xa inhibitors compared with low-molecular-weight heparin for the prevention of venous thromboembolism prophylaxis in total hip or knee replacement surgery.
Mahmoudi, Mandana; Sobieraj, Diana M
Major orthopedic surgery is associated with a high risk of venous thromboembolism (VTE). Anticoagulants are recommended to prevent VTE, and recently an oral direct factor Xa inhibitor (FXaI) was approved for this indication. We compared the cost-effectiveness of FXaIs with low-molecular-weight heparin (LMWH) in patients undergoing total hip replacement (THR) or total knee replacement (TKR) surgery. A decision-tree model was developed to compare the cost-effectiveness of oral direct FXaIs (rivaroxaban, apixaban, and edoxaban) to subcutaneous LMWHs (enoxaparin and dalteparin), with separate models for THR and TKR. The analysis was conducted over a 180-day postoperative time horizon from the U.S. Medicare perspective. The model was developed using TreeAge Pro 2011 (TreeAge Software Inc., Williamstown, MA, USA). Efficacy and safety data (probabilities of distal and proximal deep vein thrombosis, symptomatic pulmonary embolism, and major bleeding) were derived from a systematic review and meta-analysis of phase II and III clinical trials. Costs and quality-adjusted life-years (QALYs) are reported. One-way and probabilistic sensitivity analyses were performed to evaluate parameter uncertainty. In the THR model, the average costs per patient for FXaIs and LMWHs were $18,762 and $18,897, respectively, and the QALYs were 0.938 and 0.932. In the TKR model, the average cost per patient for FXaIs and LMWHs were $18,804 and $18,991, respectively, and the QALYs were 0.935 and 0.931. In both models, FXaIs dominated LMWH (less costly and more efficacious). Neither model was sensitive to changes in any of the variables in the one-way sensitivity analyses. Probabilistic sensitivity analysis indicated that FXaIs were cost-effective in more than 99% of iterations in the THR population and in 98% of iterations in the TKR population assuming a willingness-to-pay threshold of $50,000/QALY. Oral direct FXaIs may be an economically dominant strategy compared with LMWHs for VTE prophylaxis
Efficiency and effectiveness of the use of an acenocoumarol pharmacogenetic dosing algorithm versus usual care in patients with venous thromboembolic disease initiating oral anticoagulation: study protocol for a randomized controlled trial
Background Hemorrhagic events are frequent in patients on treatment with antivitamin-K oral anticoagulants due to their narrow therapeutic margin. Studies performed with acenocoumarol have shown the relationship between demographic, clinical and genotypic variants and the response to these drugs. Once the influence of these genetic and clinical factors on the dose of acenocoumarol needed to maintain a stable international normalized ratio (INR) has been demonstrated, new strategies need to be developed to predict the appropriate doses of this drug. Several pharmacogenetic algorithms have been developed for warfarin, but only three have been developed for acenocoumarol. After the development of a pharmacogenetic algorithm, the obvious next step is to demonstrate its effectiveness and utility by means of a randomized controlled trial. The aim of this study is to evaluate the effectiveness and efficiency of an acenocoumarol dosing algorithm developed by our group which includes demographic, clinical and pharmacogenetic variables (VKORC1, CYP2C9, CYP4F2 and ApoE) in patients with venous thromboembolism (VTE). Methods and design This is a multicenter, single blind, randomized controlled clinical trial. The protocol has been approved by La Paz University Hospital Research Ethics Committee and by the Spanish Drug Agency. Two hundred and forty patients with VTE in which oral anticoagulant therapy is indicated will be included. Randomization (case/control 1:1) will be stratified by center. Acenocoumarol dose in the control group will be scheduled and adjusted following common clinical practice; in the experimental arm dosing will be following an individualized algorithm developed and validated by our group. Patients will be followed for three months. The main endpoints are: 1) Percentage of patients with INR within the therapeutic range on day seven after initiation of oral anticoagulant therapy; 2) Time from the start of oral anticoagulant treatment to achievement of a
Efficiency and effectiveness of the use of an acenocoumarol pharmacogenetic dosing algorithm versus usual care in patients with venous thromboembolic disease initiating oral anticoagulation: study protocol for a randomized controlled trial.
Carcas, Antonio J; Borobia, Alberto M; Velasco, Marta; Abad-Santos, Francisco; Díaz, Manuel Quintana; Fernández-Capitán, Carmen; Ruiz-Giménez, Nuria; Madridano, Olga; Sillero, Pilar Llamas
Hemorrhagic events are frequent in patients on treatment with antivitamin-K oral anticoagulants due to their narrow therapeutic margin. Studies performed with acenocoumarol have shown the relationship between demographic, clinical and genotypic variants and the response to these drugs. Once the influence of these genetic and clinical factors on the dose of acenocoumarol needed to maintain a stable international normalized ratio (INR) has been demonstrated, new strategies need to be developed to predict the appropriate doses of this drug. Several pharmacogenetic algorithms have been developed for warfarin, but only three have been developed for acenocoumarol. After the development of a pharmacogenetic algorithm, the obvious next step is to demonstrate its effectiveness and utility by means of a randomized controlled trial. The aim of this study is to evaluate the effectiveness and efficiency of an acenocoumarol dosing algorithm developed by our group which includes demographic, clinical and pharmacogenetic variables (VKORC1, CYP2C9, CYP4F2 and ApoE) in patients with venous thromboembolism (VTE). This is a multicenter, single blind, randomized controlled clinical trial. The protocol has been approved by La Paz University Hospital Research Ethics Committee and by the Spanish Drug Agency. Two hundred and forty patients with VTE in which oral anticoagulant therapy is indicated will be included. Randomization (case/control 1:1) will be stratified by center. Acenocoumarol dose in the control group will be scheduled and adjusted following common clinical practice; in the experimental arm dosing will be following an individualized algorithm developed and validated by our group. Patients will be followed for three months. The main endpoints are: 1) Percentage of patients with INR within the therapeutic range on day seven after initiation of oral anticoagulant therapy; 2) Time from the start of oral anticoagulant treatment to achievement of a stable INR within the therapeutic
Cohen, Alexander T; Harrington, Robert; Goldhaber, Samuel Z; Hull, Russell; Gibson, C Michael; Hernandez, Adrian F; Kitt, Michael M; Lorenz, Todd J
Randomized clinical trials have identified a population of acute medically ill patients who remain at risk for venous thromboembolism (VTE) beyond the standard duration of therapy and hospital discharge. The aim of the APEX study is to determine whether extended administration of oral betrixaban (35-42 days) is superior to a standard short course of prophylaxis with subcutaneous enoxaparin (10 ± 4 days followed by placebo) in patients with known risk factors for post-discharge VTE. Patients initially are randomized to receive either betrixaban or enoxaparin (and matching placebo) in a double dummy design. Following a standard duration period of enoxaparin treatment (with placebo tablets) or betrixaban (with placebo injections), patients receive only betrixaban (or alternative matching placebo). Patients are considered for enrollment if they are older than 40 years, have a specified medical illness, and restricted mobility. They must also meet the APEX criteria for increased VTE risk (aged ≥75 years, baseline D-Dimer ≥2× upper the limit of "normal", or 2 additional ancillary risk factors for VTE). The primary efficacy end point is the composite of asymptomatic proximal deep venous thrombosis, symptomatic deep venous thrombosis, non-fatal (pulmonary embolus) pulmonary embolism, or VTE-related death through day 35. The primary safety outcome is the occurrence of major bleeding. We hypothesize that extended duration betrixaban VTE prophylaxis will be safe and more effective than standard short duration enoxaparin in preventing VTE in acute medically ill patients with known risk factors for post hospital discharge VTE.
Brotman, Daniel J; Segal, Jodi B; Jani, Jayesh T; Petty, Brent G; Kickler, Thomas S
To determine the utility and limitations of D-dimer testing for the evaluation of venous thromboembolism in hospitalized patients. We performed D-dimer testing by four different methods in unselected inpatients undergoing radiologic evaluation for possible venous thromboembolism. We included patients with a history of malignancy, recent surgery, thrombosis, and anticoagulation treatment. C-reactive protein levels were assayed as a measure of inflammation. Of 45 patients with radiographically proven proximal deep venous thrombosis or pulmonary embolism, 43 had elevated D-dimer levels by enzyme-linked immunosorbent assay (ELISA) (sensitivity, 96%); the specificity of the test was 23% (36/157). The qualitative non-ELISA tests had higher specificities, but their sensitivities were <70%. Nineteen patients (42%) with thrombosis had false-negative D-dimer tests by at least one assay. The specificity of the tests decreased with increasing duration of hospitalization, increasing age, and increasing C-reactive protein levels. D-dimer testing had little or no utility in distinguishing patients with thrombosis from those without in patients who had been hospitalized for more than 3 days, were older than 60 years, or had C-reactive protein levels in the highest quartile. In unselected inpatients, D-dimer testing has limited clinical utility because of its poor specificity. This is particularly true for older patients, those who have undergone prolonged hospitalization, and those with markedly elevated C-reactive protein levels. In some patient subsets, a negative non-ELISA D-dimer test cannot discriminate between inpatients with and without thrombosis.
Carrillo-Esper, Raúl; Alcántar-Luna, Ernesto; Herrera-Cornejo, Martín Alberto; Jaimovich, David; Ramos-Corrales, Marco Antonio; Villagómez-Ortiz, Asisclo
Venous thromboembolic disease is a major cause of morbidity and hospital mortality worldwide. Although exact figures are unknown in Mexico, achieving uniformity of criteria among the specialties involved in the prophylaxis and treatment will offer a clearer picture and contribute to a more rational and interdisciplinary approach in order to improve the quality of care for patients and increase the level of awareness of this entity. For the preparation of this document, a total of 11 medical specialists from Mexico City and the interior of the country met along with a highly experienced professional from Chicago, IL, USA with wide experience in the field and knowledge of methodology for the development of a management algorithm for prophylaxis in at-risk patients of venous thromboembolic disease. The expert group met in plenary working sessions, managed uniform criteria and reached consensus agreement by issuing a series of useful recommendations for the care of patients with venous thromboembolism in Mexican hospitals. In Mexico there is the need to develop and disseminate guidelines on thromboprophylaxis and treatment of venous thromboembolic disease because of the wide disparity of views or simple misinformation, leading to diagnostic and treatment behaviors unique to each institution.
Choi, Chang Won; Kim, Heon Min; Park, Hye Won
Background While venous thromboembolism (VTE) is uncommon, its incidence is increasing in children. We aimed to evaluate the incidence, risk factors, treatment, and outcome of pediatric VTE cases at a single tertiary hospital in Korea. Methods We retrospectively analyzed the records of consecutive pediatric VTE patients admitted to the Seoul National University Bundang Hospital between April 2003 and March 2016. Results Among 70,462 hospitalizations, 25 pediatric VTE cases were identified (3.27 cases per 10,000 admissions). Fifteen patients (60%) were male, 8 were neonates (32%), and the median age at diagnosis was 10.9 years (range, 0 days‒17 yr). Doppler ultrasonography was the most frequently used imaging modality. Thrombosis occurred in the intracerebral (20%), upper venous (64%), lower venous (12%), and combined upper and lower venous systems (4%). Twenty patients (80%) had underlying clinical conditions including venous catheterization (24%), malignancy (20%), and systemic diseases (12%). Protein C, protein S, and antithrombin deficiencies occurred in 2 of 13, 4 of 13, and 1 of 14 patients tested, respectively. Six patients were treated with heparin followed by warfarin, while 4 were treated with heparin or warfarin. Thrombectomy and inferior vena cava filter and/or thrombolysis were performed in 5 patients. Two patients died of pulmonary embolism, and 2 developed a post-thrombotic syndrome. Conclusion Compared with the reports from Western countries, VTE occurrence was lower in the Korean pediatric population under study, although similar clinical characteristics including bimodal age distribution, underlying diseases, treatment pattern, and outcomes were observed. PMID:27722126
Pirtskhelani, N; Kochiashvili, N; Makhaldiani, L; Pargalava, N; Gaprindashvili, E; Kartvelishvili, K
Inherited thrombophilia means a predisposition of an individual to thrombosis caused by genetic disorders of homeostasis system. Purpose of the conducted study was to establish the role of point mutations of prothrombin (PGM) - 20210G/A; Factor V Leiden (FVL) - 1691G/A and methylenetetrahydrofolate reductase (MTHFR) - 677C/T genes, i.e. inherited thrombophilia in the pathogenesis of primary and recurrent venous thromboembolism in patients of the Georgian population. The above mentioned mutations were detected by PCR and single nucleotide primer extension reaction, followed by Enzyme Linked Immuno-Sorbent Assay (ELISA) in 93 patients with venous thromboembolism, out of which: 56 patients were diagnosed with unprovoked, primary thromboembolism confirmed by objective studies and 37 patients were diagnosed with recurrent thromboembolism. According to statistical analysis of the results, incidence of FVL mutation in the group of patients with recurrent thrombosis was significantly higher compared to patients with primary thrombosis - respectively 0.21 and 0.44 (p=0.0164<0.05). It should also be mentioned that homozygous carriage of FVL mutation was confirmed only with patients having recurrent thrombosis. Similar tendency was observed during study of prothrombin gene; however the difference was not statistically significant. Similar tendencies were not observed in case of homozygous carriage of MTHFR gene C677T mutation. Double and triple heterozygous/homozygous carriage of studied mutations (total of 20 cases) was observed in patients of both groups. Distribution of these genotypes in the recurrent thrombosis group was higher compared to patients with primary thrombosis - respectively 27% and 17.9%. Herewith, it should be mentioned that the patients with primary thrombosis were much younger than those with recurrent thrombosis and their age did not exceed 50 years. According to the results obtained by us, it is possible to consider Leiden mutation, especially its
Folsom, Aaron R; Tang, Weihong; Roetker, Nicholas S; Heckbert, Susan R; Cushman, Mary; Pankow, James S
Elevated plasma concentrations of coagulation factor XI may increase risk of venous thromboembolism (VTE), but prospective data are limited. We studied prospectively the associations of plasma factor XI and a key F11 genetic variant with incident VTE in whites and African-Americans. We measured factor XI in 16,299 participants, initially free of VTE, in two prospective population cohorts. We also measured the F11 single nucleotide polymorphism rs4241824, which a genome-wide association study had linked to factor XI concentration. During follow-up, we identified 606 VTEs. The age, race, sex, and study-adjusted hazard ratio of VTE increased across factor XI quintiles (P < 0.001 for trend), and the hazard ratio was 1.51 (95% CI 1.16, 1.97) for the highest versus lowest quintile overall, and was 1.42 (95% CI 1.03, 1.95) in whites and 1.72 (95% CI 1.08, 2.73) in African-Americans. In whites, the F11 variant was associated with both factor XI concentration and VTE incidence (1.15-fold greater incidence of VTE per risk allele). In African-Americans, these associations were absent. In conclusion, this cohort study documented that an elevated plasma factor XI concentration is a risk factor for VTE over extended follow-up, not only in whites but also in African-Americans. In whites, the association of the F11 genetic variant with VTE suggests a causal relation, but we did not observe this genetic relation in African-Americans. © 2015 Wiley Periodicals, Inc.
Folsom, Aaron R.; Tang, Weihong; Roetker, Nicholas S.; Heckbert, Susan R.; Cushman, Mary; Pankow, James S.
Elevated plasma concentrations of coagulation factor XI may increase risk of venous thromboembolism (VTE), but prospective data are limited. We studied prospectively the associations of plasma factor XI and a key F11 genetic variant with incident VTE in whites and African Americans. We measured factor XI in 16,299 participants, initially free of VTE, in two prospective population cohorts. We also measured the F11 single nucleotide polymorphism rs4241824, which a genome-wide association study had linked to factor XI concentration. During follow-up, we identified 606 VTEs. The age, race, sex, and study-adjusted hazard ratio of VTE increased across factor XI quintiles (p<0.001 for trend), and the hazard ratio was 1.51 (95% CI 1.16, 1.97) for the highest versus lowest quintile overall, and was 1.42 (95% CI 1.03, 1.95) in whites and 1.72 (95% CI 1.08, 2.73) in African Americans. In whites, the F11 variant was associated with both factor XI concentration and VTE incidence (1.15-fold greater incidence of VTE per risk allele). In African Americans, these associations were absent. In conclusion, this cohort study documented that an elevated plasma factor XI concentration is a risk factor for VTE over extended follow-up, not only in whites but also in African Americans. In whites, the association of the F11 genetic variant with VTE suggests a causal relation, but we did not observe this genetic relation in African Americans. PMID:26260105
Lecumberri, Ramón; Alfonso, Ana; Jiménez, David; Fernández Capitán, Carmen; Prandoni, Paolo; Wells, Philip S; Vidal, Gemma; Barillari, Giovanni; Monreal, Manuel
In patients with venous thromboembolism (VTE), assessment of the risk of fatal recurrent VTE and fatal bleeding during anticoagulation may help to guide intensity and duration of therapy. We aimed to provide estimates of the case-fatality rate (CFR) of recurrent VTE and major bleeding during anticoagulation in a 'real life' population, and to assess these outcomes according to the initial presentation of VTE and its etiology. The study included 41,826 patients with confirmed VTE from the RIETE registry who received different durations of anticoagulation (mean 7.8 ± 0.6 months). During 27,110 patient-years, the CFR was 12.1% (95% CI, 10.2-14.2) for recurrent VTE, and 19.7% (95% CI, 17.4-22.1) for major bleeding. During the first three months of anticoagulant therapy, the CFR of recurrent VTE was 16.1% (95% CI, 13.6-18.9), compared to 2.0% (95% CI, 0-4.2) beyond this period. The CFR of bleeding was 20.2% (95% CI, 17.5-23.1) during the first three months, compared to 18.2% (95% CI, 14.0-23.2) beyond this period. The CFR of recurrent VTE was higher in patients initially presenting with PE (18.5%; 95% CI, 15.3-22.1) than in those with DVT (6.3%; 95% CI, 4.5-8.6), and in patients with provoked VTE (16.3%; 95% CI, 13.6-19.4) than in those with unprovoked VTE (5.5%; 95% CI, 3.5-8.0). In conclusion, the CFR of recurrent VTE decreased over time during anticoagulation, while the CFR of major bleeding remained stable. The CFR of recurrent VTE was higher in patients initially presenting with PE and in those with provoked VTE.
Oral anticoagulants for primary prevention, treatment and secondary prevention of venous thromboembolic disease, and for prevention of stroke in atrial fibrillation: systematic review, network meta-analysis and cost-effectiveness analysis.
Sterne, Jonathan Ac; Bodalia, Pritesh N; Bryden, Peter A; Davies, Philippa A; López-López, Jose A; Okoli, George N; Thom, Howard Hz; Caldwell, Deborah M; Dias, Sofia; Eaton, Diane; Higgins, Julian Pt; Hollingworth, Will; Salisbury, Chris; Savović, Jelena; Sofat, Reecha; Stephens-Boal, Annya; Welton, Nicky J; Hingorani, Aroon D
BACKGROUND Warfarin is effective for stroke prevention in atrial fibrillation (AF), but anticoagulation is underused in clinical care. The risk of venous thromboembolic disease during hospitalisation can be reduced by low-molecular-weight heparin (LMWH): warfarin is the most frequently prescribed anticoagulant for treatment and secondary prevention of venous thromboembolism (VTE). Warfarin-related bleeding is a major reason for hospitalisation for adverse drug effects. Warfarin is cheap but therapeutic monitoring increases treatment costs. Novel oral anticoagulants (NOACs) have more rapid onset and offset of action than warfarin, and more predictable dosing requirements. OBJECTIVE To determine the best oral anticoagulant/s for prevention of stroke in AF and for primary prevention, treatment and secondary prevention of VTE. DESIGN Four systematic reviews, network meta-analyses (NMAs) and cost-effectiveness analyses (CEAs) of randomised controlled trials. SETTING Hospital (VTE primary prevention and acute treatment) and primary care/anticoagulation clinics (AF and VTE secondary prevention). PARTICIPANTS Patients eligible for anticoagulation with warfarin (stroke prevention in AF, acute treatment or secondary prevention of VTE) or LMWH (primary prevention of VTE). INTERVENTIONS NOACs, warfarin and LMWH, together with other interventions (antiplatelet therapy, placebo) evaluated in the evidence network. MAIN OUTCOME MEASURES Efficacy Stroke, symptomatic VTE, symptomatic deep-vein thrombosis and symptomatic pulmonary embolism. Safety Major bleeding, clinically relevant bleeding and intracranial haemorrhage. We also considered myocardial infarction and all-cause mortality and evaluated cost-effectiveness. DATA SOURCES MEDLINE and PREMEDLINE In-Process & Other Non-Indexed Citations, EMBASE and The Cochrane Library, reference lists of published NMAs and trial registries. We searched MEDLINE and PREMEDLINE In-Process & Other Non-Indexed Citations, EMBASE and The
Lippi, Giuseppe; Cervellin, Gianfranco; Mattiuzzi, Camilla
Venous thromboembolism (VTE) is a highly prevalent condition worldwide, which can be triggered by a combination of inherited and acquired risk factors, including diet. Several lines of evidence suggest that consumption of red and processed meat is associated with a significant risk of colorectal cancer, cardiovascular disease and diabetes. Therefore, an electronic search was conducted to identify clinical studies investigating the potential association between the risk of venous thrombosis and consumption of red or processed meat. Seven articles were finally included in this review, 6 prospective studies and 1 case-control investigation. Taken together, the evidence of the current scientific literature suggests that whether or not a pathophysiological link may exist between red or processed meat consumption and venous thrombosis, the association is definitely weak, since it was found to be non-statistically significant in four prospective cohort studies, marginally significant in one prospective cohort study and highly significant in the remaining prospective cohort study. In the single case-control study, the risk was also found to be non-statistically significant. Although further studies will be needed to definitely establish the existence of a thrombotic risk associated with different subtypes of red or processed meat, it seems premature to conclude that a reduced consumption of red and processed meat lowers the risk of VTE.
Arbeit, J.M.; Lowry, S.F.; Line, B.R.; Jones, D.C.; Brennan, M.F.
Deep venous thromboembolism (DVT) was studied in 44 patients with clinical Stage I, II, and III melanoma undergoing staging and therapeutic inguinal lymph node dissection. The ability of two noninvasive methods of surveillance, the phleborheograph (PRG) and the /sup 125/I fibrinogen scan to detect deep venous thrombosis was determined by comparison with prospective bilateral lower extremity venograms. In addition, the therapeutic impact, both beneficial and detrimental, of low dose heparin, 5000 units administered subcutaneously two hours prior to and every eight hours after operation was determined in a double blind study. The sensitivity of the PRG and /sup 125/I fibrinogen scan were both 20%. There were five deep venous thrombi, and two pulmonary emboli for a combined incidence of DVT of 13.6% for the entire patient population. However, there was no significant difference in the incidence of DVT between the two groups. The heparin-treated patients had an increased total volume (796 +/- 516 versus 388 +/- 208 ml; p less than 0.05), and duration of wound drainage (9 +/- 4 versus 13 +/- 6 days; p less than 0.05).
Arbeit, J.M.; Lowry, S.F.; Line, B.R.
Deep venous thromboembolism (DVT) was studied in 44 patients with clinical Stage I, II, and III melanoma undergoing staging and therapeutic inguinal lymph node dissection. The ability of two noninvasive methods of surveillance, the phleborheograph (PRG) and the /sup 125/I fibrinogen scan to detect deep venous thrombosis was determined by comparison with prospective bilateral lower extremity venograms. In addition, the therapeutic impact, both beneficial and detrimental, of low dose heparin, 5000 units administered subcutaneously two hours prior to and every eight hours after operation was determined in a double blind study. The sensitivity of the PRG and /sup 125/I fibrinogen scan were both 20%. There were five deep venous thrombi, and two pulmonary emboli for a combined incidence of DVT of 13.6% for the entire patient population. However, there was no significant difference in the incidence of DVT between the two groups. The heparin-treated patients had an increased total volume (796 +/- 516 versus 388 +/- 208 ml; p < 0.05), and duration of wound drainage (9 +/- 4 versus 13 +/- 6 days; p < 0.05).
Tamaki, Hiromichi; Khasnis, Atul
Venous thromboembolism (VTE) is a prevalent multifactorial health condition associated with significant morbidity and mortality. Population-based epidemiological studies have revealed an association between systemic autoimmune diseases and deep venous thrombosis (DVT)/VTE. The etiopathogenesis of increased risk of VTE in systemic autoimmune diseases is not entirely clear but multiple contributors have been explored, especially in the context of systemic inflammation and disordered thrombogenesis. Epidemiologic data on increased risk of VTE in patients with primary systemic vasculitides (PSV) have accumulated in recent years and some of these studies suggest the increased risk while patients have active diseases. This could lead us to hypothesize that venous vascular inflammation has a role to play in this phenomenon, but this is unproven. The role of immunosuppressive agents in modulating the risk of VTE in patients with PSV is not yet clear except for Behçet's disease, where most of the studies are retrospective. Sensitizing physicians to this complication has implications for prevention and optimal management of patients with these complex diseases. This review will focus on the epidemiology and available evidence regarding pathogenesis, and will attempt to summarize the best available data regarding evaluation and treatment of these patients.
Pinto, Shanti M; Galang, Gary
The aim of this study was to investigate the impact of venous thromboembolism (VTE) on rate of acute care hospital transfer, inpatient rehabilitation (IPR) length of stay (LOS), and functional outcomes. This was a retrospective cohort study of 2312 consecutive patient discharges from a single IPR facility over an 18-month period. When age, sex, reason for admission, and admission Functional Independence Measure (FIM) scores were controlled for, those with VTE had nearly 2 times greater odds for transfer to acute care hospital than did those without a diagnosis of VTE. Inpatient rehabilitation LOS was 4.700 days (95% confidence interval [CI], 2.956-6.445 days) longer for those with a diagnosis of VTE prior to IPR admission and 2.287 days (95% CI, 1.026-3.547 days) longer for those with a diagnosis of VTE during IPR admission compared with those without a diagnosis of VTE. There was no difference in FIM change based on VTE diagnosis. Venous thromboembolism diagnosis during IPR was associated with a significant decrease in FIM efficiency (-0.358; 95% CI, -0.654 to -0.062) if diagnosed during IPR admission, but there was no difference in FIM efficiency if VTE was diagnosed prior to IPR. Patients with a diagnosis of VTE were more likely to be transferred to the acute care hospital and have longer IPR LOS independent of admission FIM scores. It is important to prevent development of VTE. Complete the self-assessment activity and evaluation online at http://www.physiatry.org/JournalCME CME OBJECTIVES: Upon completion of this article, the reader should be able to: (1) understand the association of venous thromboembolism (VTE) diagnosis with acute hospital transfer and inpatient rehabilitation length of stay; (2) identify reasons for acute hospital transfer in patients diagnosed with VTE; and (3) understand the relationship between VTE diagnosis and functional outcomes during inpatient rehabilitation. Advanced ACCREDITATION: The Association of Academic Physiatrists is
Rosenfeld, Hannah; Byard, Roger W
Venous stasis predisposes to thrombosis. One hundred and sixty cases of fatal pulmonary thromboembolism were reviewed to determine how many cases had deep venous thromboses associated with venous blood flow reduction caused by external pressure from benign pelvic masses. Three cases were identified, representing 2% of cases overall (3/160): a 44-year-old woman with a large uterine leiomyoma (1048 g); a 74-year-old man with prostatomegaly and bladder distension (containing 1 L of urine); and a 70-year-old man with prostatomegaly and bladder distension (containing 3 L of urine). Although a rare cause of fatal deep venous thrombosis and pulmonary thromboembolism, space-occupying pelvic lesions can lead to extrinsic pressure on adjacent veins reducing blood flow and causing stasis and thrombosis. Individuals with large pelvic masses may, therefore, be at increased risk of pulmonary thromboembolism from deep venous thrombosis, particularly in the presence of concurrent risk factors such as immobility, thrombophilias, malignancy, and significant cardiopulmonary disease.
Gigante, A; Di Mario, F; Pierucci, A; Amoroso, A; Pignataro, F S; Napoleone, L; Basili, S; Raparelli, V
The risk of venous thromboembolism (VTE) is increased across the spectrum of chronic kidney disease (CKD), from mild to more advanced CKD, and typically characterizes nephrotic syndrome (NS). VTE risk in patients with kidney disease may be due to underlying hemostatic abnormalities, including activation of pro-thrombotic factors, inhibition of endogenous anticoagulation systems, enhanced platelet activation and aggregation, and decreased fibrinolytic activity. The mechanisms involved differ depending on the cause of the kidney impairment (i.e. presence of NS or CKD stage). Sex and gender differences, as well as, environmental factors or comorbidities may play a modulating role; however, specific sex and gender data on this topic are still rare. The aim of the present review is to discuss the VTE risk associated with impairment of kidney function, the potential mechanism accounting for it and the impact of sex differences in this clinical setting.
Miljic, Dragana; Miljic, Predrag; Doknic, Mirjana; Pekic, Sandra; Stojanovic, Marko; Petakov, Milan; Popovic, Vera
Adipsic diabetes insipidus (ADI) is a rare disorder. It can occur after transcranial surgery for craniopharyngeoma, suprasellar pituitary adenoma and anterior communicating artery aneurysm but also with head injury, toluene exposure and developmental disorders. It is often associated with significant hypothalamic dysfunction and complications like obesity, sleep apnea, thermoregulatory disorders, seizures and venous thromboembolism (VTE). Morbidity and mortality data have been reported as single case reports with only one large series suggesting increased risk for VTE in patients with ADI. Here we report a mini-series of four patients with ADI and VTE. Post-surgery immobilization, obesity, infection, with prolonged hospitalization, hemoconcentration and changes in coagulation which might be induced by inadequate hormone treatment in the postoperative period (high doses of glucocorticoids, sex steroids and DDAVP replacement) may all contribute to the pathogenesis of VTE. Thromboprophylactic treatment after pituitary surgery and during episodes of hypernatremia is therefore warranted.
Venous thromboembolism (VTE) is a common cause of morbidity and mortality. This is especially true for hospitalized patients. Pulmonary embolism (PE) is the leading preventable cause of in-hospital mortality. The preferred method of both treatment and prophylaxis for VTE is anticoagulation. However, in a subset of patients, anticoagulation therapy is contraindicated or ineffective, and these patients often receive an inferior vena cava (IVC) filter. The sole purpose of an IVC filter is prevention of clinically significant PE. IVC filter usage has increased every year, most recently due to the availability of retrievable devices and a relaxation of thresholds for placement. Much of this recent growth has occurred in the trauma patient population given the high potential for VTE and frequent contraindication to anticoagulation. Retrievable filters, which strive to offer the benefits of permanent filters without time-sensitive complications, come with a new set of challenges including methods for filter follow-up and retrieval. PMID:23997414
Gallo-Vallejo, J L; Naveiro-Fuentes, M; Puertas-Prieto, A; Gallo-Vallejo, F J
After noting that there are a number of risk factors for venous thromboembolism disease during pregnancy, it emphasizes primary prevention and treatment of this serious condition during pregnancy and the postpartum period are essential to reduce maternal morbidity and mortality. Low molecular-weight heparins are under the anticoagulant of choice in pregnancy. Your prescription may make both the primary care physician, as the hematologist and obstetrician. As for prescribing terms, an application protocol in both primary and specialized, multidisciplinary care, based on the existing literature on the subject is presented, which indicated that the hypercoagulable disorders associated with some of the risk factors, forced to do thromboprophylaxis with low molecular-weight heparins throughout pregnancy and the postpartum period presented. Copyright Â© 2016 Sociedad Española de Médicos de Atención Primaria (SEMERGEN). Publicado por Elsevier España, S.L.U. All rights reserved.
Zalpour, Ali; Oo, Thein Hlaing
Anticoagulation with heparin and vitamin K antagonist has been the mainstay of prevention and treatment of venous thromboembolism (VTE) for many years. In recent years, novel oral anticoagulants such as dabigatran etexilate (a direct thrombin inhibitor) and rivaroxaban, apixaban, and edoxaban (a direct factor Xa inhibitor) have emerged for the prevention and treatment of VTE. Novel oral anticoagulants have been shown to be noninferior to vitamin K antagonist or heparin in the prevention and treatment of VTE. This review specifically examines the role of apixaban in the prevention and treatment of VTE based on the available literature. The management of apixaban in the perioperative setting is also explored because some patients on apixaban may require surgical intervention. Finally, we discuss the management of apixaban-induced major bleeding complications, the relevance of drug–drug interactions, and patient education. PMID:25395835
Conard, J; Horellou, M H; Samama, M M
Guidelines concerning the prevention and treatment of pregnancy-associated venous thromboembolism (VTE) have been elaborated by the American College of Chest Physicians and published in Chest in 2008. In this review, they have been compared with European guidelines and discussed taking into account the papers published since 2008.Most recommendations are of low grade of evidence because randomized studies are lacking during pregnancy and many reflect guidelines proposed by experts. The decisions on the most appropriate prophylaxis, dose to be administered and moment of pregnancy for starting prophylaxis are often decided case by case after careful assessment of the risk of pregnancy-associated VTE, on one hand, and the risk for the mother, on the other.Risk factors (age >or= 35, obesity, history of VTE with or without sequellae, in vitro fertilization)or thrombophilia have to be taken into account. Scores have been proposed to improve standardisation and evaluation of the risk of VTE and they should be validated.
Ruiz-Bailén, Manuel; Ramos-Cuadra, Jose Angel; Machado-Casas, Juan; Rucabado-Aguilar, Luis
We describe a case report observed via an echocardiography of a venous thromboembolism (VTE) that crosses through the patent foramen ovale to the left atrium and is successfully treated with alteplase. This is a case report of a tertiary care hospital without cardiac surgery facilities. An 81-year-old female seeking medical attention for dyspnoea, arriving at hospital with hypoxaemia, hypotension and prerenal failure. A computed tomographic (CT) pulmonary angiography was carried out, revealing a VTE. A transesophageal echocardiography (TEE) was carried out, exposing emboli in the right cavities, said thrombus crossing through the patent foramen ovale to the left atrium. A systemic thrombolysis is carried out using alteplase which improves the patient's condition and results in the disappearance of thrombotic images in the various cardiac cavities. The evolution is positive and there is no evidence of embolic or haemorrhagic complications. When a paradoxical embolism is present, in the context of a serious VTE, carrying out thrombolysis could be a therapeutic option.
Charters, Michael A; Frisch, Nicholas B; Wessell, Nolan M; Dobson, Christopher; Les, Clifford M; Silverton, Craig D
The oral Factor Xa inhibitor rivaroxaban (Xarelto) has been the pharmacologic agent used for venous thromboembolism (VTE) prophylaxis after primary hip and knee arthroplasty (THA/TKA) at our institution since February 2012. The purpose of our study was to compare rates of VTE and major bleeding between rivaroxaban and our previous protocol of enoxaparin after THA/TKA. A retrospective cohort study was performed including 2406 consecutive patients at our institution between 1/1/11 and 9/30/13. Patients who did not have unilateral primary THA/TKA or who received other anticoagulants were excluded. Of the 1762 patients included, 1113 patients (63.2%) received enoxaparin and 649 patients (36.8%) received rivaroxaban. This study found no demonstrable differences between these two anticoagulants in rates of VTE, infection, reoperation, transfusion, or major bleeding. Therapeutic, Retrospective comparative study, Level III. Copyright © 2015 Elsevier Inc. All rights reserved.
Cui, Guoce; Wang, Xiaofeng; Yao, Weiwei; Li, Huashan
The objective of this study was to systematically compare the incidence of postoperative venous thromboembolism (VTE; deep vein thrombosis and/or pulmonary embolism) in patients with colorectal cancer after laparoscopic surgery and conventional open surgery. A systematic search of Medline, EMBASE, and the Cochrane Central Register of Controlled Trials was conducted. Eleven randomized control trials involving 3058 individuals who reported VTE outcomes were identified, of whom 1677 were treated with laparoscopic therapy and 1381 underwent open surgery. The combined results of the individual trials showed no statistically significant difference in the odds ratio for overall VTE (odds ratio 0.64, 95% confidence interval, 0.33-1.23, P=0.18), as well as in subgroups of deep vein thrombosis and anticoagulant prophylaxis between these 2 approaches. In conclusion, laparoscopic resection could achieve similar outcomes in terms of the incidence of VTE, which are associated with long-term benefits of the patients.
Lai, J M; Yablon, S A; Ivanhoe, C B
Venous thromboembolism (VTE) is a potentially life-threatening complication among patients with traumatic brain injury (TBI). However, few reports describe the incidence of this important disease. We reviewed the incidence of symptomatic VTE among 124 consecutive admissions with TBI to a free-standing rehabilitation hospital over an 18-month period. Four patients manifested evidence of VTE within 2 months of injury: two with leg swelling, one with an oedematous arm, and one with respiratory distress. None of the patients with suspected VTE received prophylactic anticoagulant therapy. Diagnosis of VTE was confirmed with venograph in two of the four patients. Although VTE is frequently asymptomatic, the incidence of symptomatic VTE (1.6%) among this series of rehabilitation inpatients with TBI still appears surprisingly low. These results have implications regarding the utility of non-invasive diagnostic screening of asymptomatic VTE and routine anticoagulant prophylaxis of high-risk patients with TBI.
Naina, H V; Pruthi, R K; Inwards, D J; Dingli, D; Litzow, M R; Ansell, S M; William, H J; Dispenzieri, A; Buadi, F K; Elliott, M A; Gastineau, D A; Gertz, M A; Hayman, S R; Johnston, P B; Lacy, M Q; Micallef, I N; Porrata, L F; Kumar, S
The use of erythropoietic agents has been associated with an increased risk of venous thromboembolic events (VTEs), especially in patients with underlying malignancies. However, it is not known whether there is an increased risk of VTE associated with granulocyte growth factors. We reviewed 621 patients undergoing PBSC mobilization using granulocyte growth factors, alone or in combination with CY. Patients with a diagnosis of AL amyloidosis (AL: 114; 18%), multiple myeloma (MM: 278; 44%) Hodgkin lymphoma (HL: 20; 3%) or non-Hodgkin lymphoma (NHL: 209; 33%) were included. Symptomatic VTE occurred in six (0.97%) patients: two AL, two MM and two NHL. Of the six patients, two had pulmonary embolism, one developed deep vein thrombosis and three developed symptomatic catheter related thrombosis. Two patients with AL had heparin-induced thrombocytopenia and thrombosis. We found a low incidence of VTE among patients undergoing PBSC mobilization.
Xie, Ruiqiang; Li, Lei; Chen, Lina; Li, Wan; Chen, Binbin; Jiang, Jing; Huang, Hao; Li, Yiran; He, Yuehan; Lv, Junjie; He, Weiming
Venous thromboembolism (VTE) is a common, fatal and frequently recurrent disease. Changes in the activity of different coagulation factors serve as a pathophysiological basis for the recurrent risk of VTE. Systems biology approaches provide a better understanding of the pathological mechanisms responsible for recurrent VTE. In this study, a novel computational method was presented to identify the recurrent risk modules (RRMs) based on the integration of expression profiles and human signaling network, which hold promise for achieving new and deeper insights into the mechanisms responsible for VTE. The results revealed that the RRMs had good classification performance to discriminate patients with recurrent VTE. The functional annotation analysis demonstrated that the RRMs played a crucial role in the pathogenesis of VTE. Furthermore, a variety of approved drug targets in the RRM M5 were related to VTE. Thus, the M5 may be applied to select potential drug targets for combination therapy and the extended treatment of VTE.
Piazza, Gregory; Goldhaber, Samuel Z.
Case Presentation A 76-year-old woman with coronary artery disease, left ventricular systolic dysfunction (ejection fraction = 30%), obesity, and a history of deep vein thrombosis presents with dyspnea and hypoxemia. The combination of physical examination findings of an S3, rales in the lower half of both lung fields, and peripheral edema, chest x-ray evidence of cardiomegaly and pulmonary edema, and a pro-brain-type natriuretic peptide level of 2,150 pg/mL (normal <350 pg/mL) confirms the diagnosis of decompensated heart failure. She is admitted to the Cardiology Service for diuretic therapy and optimization of her heart failure regimen. Although she is written for bedrest, her admission orders do not include venous thromboembolism (VTE) prophylaxis. While entering orders, the Medical House Officer caring for the patient receives an electronic alert identifying the patient as high-risk for VTE and recommending that she be prescribed prophylaxis. PMID:19770412
Bell, Alison D; Hockenberry, Marilyn; Landier, Wendy; Ewing, Nadia
No widely accepted method exists to evaluate pediatric hematology oncology patients for the risk of venous thromboembolism (VTE) and the need for prophylaxis. The use of a VTE risk-assessment tool and standardized guidelines for prophylaxis could increase the use of appropriate prophylaxis and reduce the number of VTEs in patients, thereby decreasing morbidity, mortality, hospitalization, and cost. The purpose of this project was to implement and assess the compliance of a pediatric-specific VTE risk-assessment tool in hospitalized pediatric, adolescent, and young adult hematology oncology patients. From the 114 pediatric, adolescent, and young adult patients requiring assessment, 91 (80%) VTE assessments were completed and 87 (96%) were completed accurately. Eighty percent of the at-risk patients were ordered VTE prophylaxis. The use of a VTE risk-assessment tool in pediatric hematology oncology patients is a feasible way to assess patients for their risk of developing a VTE.
Xie, Ruiqiang; Chen, Binbin; Huang, Hao; Li, Yiran; He, Yuehan; Lv, Junjie; He, Weiming; Chen, Lina
Identifying the genes involved in venous thromboembolism (VTE) recurrence is important not only for understanding the pathogenesis but also for discovering the therapeutic targets. We proposed a novel prioritization method called Function-Interaction-Pearson (FIP) by creating gene-disease similarity scores to prioritize candidate genes underling VTE. The scores were calculated by integrating and optimizing three types of resources including gene expression, gene ontology and protein-protein interaction. As a result, 124 out of top 200 prioritized candidate genes had been confirmed in literature, among which there were 34 antithrombotic drug targets. Compared with two well-known gene prioritization tools Endeavour and ToppNet, FIP was shown to have better performance. The approach provides a valuable alternative for drug targets discovery and disease therapy. PMID:27050193
Venous thromboembolism (VTE) that includes deep vein thrombosis and/or pulmonary embolism is a frequent, severe, and potentially lethal disease. After a first episode, VTE has a strong tendency to recur. While VTE is an acute disease, it may have variable outcomes in early and late phases after initial presentation. Furthermore, the incidence of late, clinically important consequences (postthrombotic syndrome and/or chronic thromboembolic pulmonary hypertension) increases in case of recurrent events. The aims of the present review are (i) to analyze the incidence and risk factors for recurrence of VTE (either those related to the type of first thrombotic event or to the patients), the risks associated with occurrence of recurrent events, and the problems linked to the diagnosis, not always easy, of recurrent events; (ii) to discuss whether or not it is possible to predict the individual risk of recurrence after a first event, by stratifying patients at high or low risk of recurrence, and how this can influence their treatment; (iii) to comment what the current guidelines and guidance suggest/recommend about anticoagulant treatment after a first VTE event and, finally, to propose practical indications on how to manage individual patients affected by VTE. PMID:24278687
Ungprasert, Patompong; Koster, Matthew J; Thongprayoon, Charat; Warrington, Kenneth J
To investigate the possible association between systemic vasculitis and risk of venous thromboembolism (VTE), two investigators independently searched published studies indexed in MEDLINE, EMBASE, and the Cochrane database from inception to April 2016 using the terms for each type of vasculitis in conjunction with the terms for venous thromboembolism. The inclusion criteria were as follows: (1) observational studies published as original studies to evaluate the association between vasculitis and VTE, (2) odds ratios, relative risk or hazard ratio or standardized incidence ratio with 95 % confidence intervals (CI) were provided, and (3) participants without vasculitis were used as comparators for cohort studies and cross-sectional studies while participants without VTE were used as comparators for case-control studies. RevMan 5.3 software was used for the data analysis. Point estimates and standard errors were extracted from individual studies and were combined by the generic inverse variance method of DerSimonian and Laird. Seven studies investigating the risk of VTE among patients with systemic vasculitis were identified. At least one study was available for three specific forms of vasculitis (polyarteritis nodosa [PAN], granulomatosis with polyangiitis [GPA], and giant cell arteritis [GCA]). An increased risk of VTE was seen in all three vasculitides (GPA, pooled RR 3.94, 95 % CI 1.11-14.01; PAN, pooled RR 3.00, 95 % CI 2.20-4.09; GCA, pooled RR 2.26, 95 % CI 1.38-3.71). This meta-analysis demonstrates that patients with systemic vasculitis may have a significantly increased risk of VTE.
Ho, K M; Tan, J A; Burrell, M; Rao, S; Misur, P
The ideal thromboprophylaxis in patients at risk of bleeding is uncertain. This retrospective cohort study assessed the risk factors for complications after using retrievable inferior vena cava (IVC) filters for primary or secondary thromboembolism prophylaxis in patients after major trauma. Using data from radiology, trauma and death registries, the incidence of and risk factors for subsequent deep venous thrombosis (DVT), venous thromboembolism (VTE), and mechanical complications related to retrievable IVC filters in patients, admitted between 2007 and 2012, were assessed in a single trauma centre. Of the 2940 major trauma patients admitted during the study period, a retrievable IVC filter was used in 223 patients (7.6%). Thirty-six patients (16%) developed DVT or VTE subsequent to placement of IVC filters (median 20 days, interquartile range 9-33), including 27 with lower limb (DVT), 8 upper limb DVT, and 4 pulmonary embolism. A high Injury Severity Score, tibial/fibular fractures, and a delay in initiating pharmacological thromboprophylaxis after insertion of the filters (14 vs 7 days, P=0.001) were significant risk factors. Thirty patients were lost to follow-up (13%) and their filters were not retrieved. Mechanical complications-including filters adherent to the wall of IVC (4.9%), IVC thrombus (4.0%), and displaced or tilted filters (2.2%)-were common when the filters were left in situ for >50 days. A delay in initiating pharmacological thromboprophylaxis or filter removal were associated with an increased risk of subsequent DVT, VTE, and mechanical complications of retrievable IVC filters in patients after major trauma. © The Author 2014. Published by Oxford University Press on behalf of the British Journal of Anaesthesia. All rights reserved. For Permissions, please email: email@example.com.
Mokri, Bahareh; Mariani, Andrea; Heit, John A.; Weaver, Amy L.; McGree, Michaela E.; Martin, Janice R.; Lemens, Maureen A.; Cliby, William A.; Bakkum-Gamez, Jamie N.
Objective The aim of this study was to determine the incidence and the risk factors of venous thromboembolism (VTE) within 30 days after primary surgery for epithelial ovarian cancer (EOC). Methods In a historical cohort study, we estimated the postoperative 30-day cumulative incidence of VTE among consecutive Mayo Clinic patients undergoing primary cytoreduction for EOC between January 2, 2003, and December 29, 2008. We tested perioperative patient characteristics and process-of-care variables (defined by the National Surgical Quality Improvement Program, >130 variables) as potential predictors of postoperative VTE using the Cox proportional hazards modeling. Results Among 569 cases of primary EOC cytoreduction and/or staging and no recent VTE, 35 developed symptomatic VTE within 30 days after surgery (cumulative incidence = 6.5%; 95% confidence interval, 4.4%–8.6%). Within the cohort, 95 (16.7%) received graduated compression stockings (GCSs), 367 (64.5%) had sequential compression devices + GCSs, and 69 (12.1%) had sequential compression devices + GCSs + postoperative heparin, with VTE rates of 1.1%, 7.4%, and 5.8%, respectively (P = 0.07, χ2 test). The remaining 38 (6.7%) received various other chemical and mechanical prophylaxis regimens. In the multivariate analysis, current or past tobacco smoking, longer hospital stay, and a remote history of VTE significantly increased the risk for postoperative VTE. Conclusions Venous thromboembolism is a substantial postoperative complication among women with EOC, and the high cumulative rate of VTE within 30 days after primary surgery suggests that a more aggressive strategy is needed for VTE prevention. In addition, because longer hospital stay is independently associated with a higher risk for VTE, methods to decrease length of stay and minimize factors that contribute to prolonged hospitalization are warranted. PMID:24172104
Sweetland, Siân; Green, Jane; Liu, Bette; Berrington de González, Amy; Canonico, Marianne; Reeves, Gillian
Objective To examine the duration and magnitude of increased risk of venous thromboembolism after different types of surgery. Design Prospective cohort study (Million Women Study). Setting Questionnaire data from the Million Women Study linked with hospital admission and death records. Participants 947 454 middle aged women in the United Kingdom recruited in 1996-2001 and followed by record linkage to routinely collected NHS data on hospital admissions and deaths. During follow-up 239 614 admissions were for surgery; 5419 women were admitted, and a further 270 died, from venous thromboembolism. Main outcome measures Adjusted relative risks and standardised incidence rates for hospital admission or death from venous thromboembolism (pulmonary embolism or deep vein thrombosis), by time since and type of surgery. Results Compared with not having surgery, women were 70 times more likely to be admitted with venous thromboembolism in the first six weeks after an inpatient operation (relative risk 69.1, 95% confidence interval 63.1 to 75.6) and 10 times more likely after a day case operation (9.6, 8.0 to 11.5). The risks were lower but still substantially increased 7-12 weeks after surgery (19.6, 16.6 to 23.1 and 5.5, 4.3 to 7.0, respectively). This pattern of risk was similar for pulmonary embolism (n=2487) and deep venous thrombosis (n=3529). The postoperative risks of venous thromboembolism varied considerably by surgery type, with highest relative risks after inpatient surgery for hip or knee replacement and for cancer—1-6 weeks after surgery the relative risks were, respectively, 220.6 (187.8 to 259.2) and 91.6 (73.9 to 113.4). Conclusion The risk of deep vein thrombosis and pulmonary embolism after surgery is substantially increased in the first 12 postoperative weeks, and varies considerably by type of surgery. An estimated 1 in 140 middle aged women undergoing inpatient surgery in the UK will be admitted with venous thromboembolism during the 12 weeks after
Paiva, Edison F; Rocha, Ana T C
The objective of this manuscript is to discuss the existing barriers for the dissemination of medical guidelines, and to present strategies that facilitate the adaptation of the recommendations into clinical practice. The literature shows that it usually takes several years until new scientific evidence is adopted in current practice, even when there is obvious impact in patients' morbidity and mortality. There are some examples where more than thirty years have elapsed since the first case reports about the use of a effective therapy were published until its utilization became routine. That is the case of fibrinolysis for the treatment of acute myocardial infarction. Some of the main barriers for the implementation of new recommendations are: the lack of knowledge of a new guideline, personal resistance to changes, uncertainty about the efficacy of the proposed recommendation, fear of potential side-effects, difficulties in remembering the recommendations, inexistence of institutional policies reinforcing the recommendation and even economical restrains. In order to overcome these barriers a strategy that involves a program with multiple tools is always the best. That must include the implementation of easy-to-use algorithms, continuous medical education materials and lectures, electronic or paper alerts, tools to facilitate evaluation and prescription, and periodic audits to show results to the practitioners involved in the process. It is also fundamental that the medical societies involved with the specific medical issue support the program for its scientific and ethical soundness. The creation of multidisciplinary committees in each institution and the inclusion of opinion leaders that have pro-active and lasting attitudes are the key-points for the program's success. In this manuscript we use as an example the implementation of a guideline for venous thromboembolism prophylaxis, but the concepts described here can be easily applied to any other guideline
Yao, Feng-Juan; Zeng, Wu-Tao; Zheng, Dong-Dan; Dong, Yu-Gang; Wu, Su-Hua
Background 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. Conclusions 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 PMID
Horvei, Lars Daae; Brækkan, Sigrid K.; Hansen, John-Bjarne
Background Obesity is a major risk factor for venous thromboembolism (VTE), but it is unknown to what extent weight change over time affects VTE risk. Aims To investigate the association between weight change and risk of incident VTE in a population-based cohort with repeated measurements. Methods Participant data were collected from the Tromsø 3 (1986–87), 4 (1994–95), 5 (2000–01) and 6 (2007–08) surveys. Subjects who attended two subsequent or more surveys were included (n = 17802), and weight change between the surveys was calculated. Person-time at risk was accrued from the second of two subsequent vists until the next survey, the date of an incident VTE, migration, death or study end (December 31st 2012), whichever came first. Cox regression models were used to calculate risk of VTE according to change in body weight. Results There were 302 incident VTE events during a median of 6.0 years of follow-up. Subjects who gained most weight (7.5–40.0 kg weight gain) had a 1.9-fold higher risk of VTE compared to those with no or a moderate (0–7.4 kg) weight gain (HR 1.92; 95% CI 1.38–2.68). The VTE risk by ≥7.5 kgs over no or moderate (0–7.4 kg) weight gain was highest (HR 3.75; 95% 1.83–7.68) in subjects with baseline body mass index (BMI) ≥30 kg/m2. There was a joint effect of weight gain and baseline BMI on VTE risk. Those with BMI ≥30 who gained ≥7.5 kgs had a 6.6-fold increased risk (HR 6.64; 95% CI 3.61–12.22) compared to subjects with BMI <25 and no or moderate (0–7.4 kg) weight gain. Conclusions Our findings imply that further weight gain is a considerable risk factor for VTE, particularly in obese individuals. PMID:27997594
Horvei, Lars Daae; Brækkan, Sigrid K; Hansen, John-Bjarne
Obesity is a major risk factor for venous thromboembolism (VTE), but it is unknown to what extent weight change over time affects VTE risk. To investigate the association between weight change and risk of incident VTE in a population-based cohort with repeated measurements. Participant data were collected from the Tromsø 3 (1986-87), 4 (1994-95), 5 (2000-01) and 6 (2007-08) surveys. Subjects who attended two subsequent or more surveys were included (n = 17802), and weight change between the surveys was calculated. Person-time at risk was accrued from the second of two subsequent vists until the next survey, the date of an incident VTE, migration, death or study end (December 31st 2012), whichever came first. Cox regression models were used to calculate risk of VTE according to change in body weight. There were 302 incident VTE events during a median of 6.0 years of follow-up. Subjects who gained most weight (7.5-40.0 kg weight gain) had a 1.9-fold higher risk of VTE compared to those with no or a moderate (0-7.4 kg) weight gain (HR 1.92; 95% CI 1.38-2.68). The VTE risk by ≥7.5 kgs over no or moderate (0-7.4 kg) weight gain was highest (HR 3.75; 95% 1.83-7.68) in subjects with baseline body mass index (BMI) ≥30 kg/m2. There was a joint effect of weight gain and baseline BMI on VTE risk. Those with BMI ≥30 who gained ≥7.5 kgs had a 6.6-fold increased risk (HR 6.64; 95% CI 3.61-12.22) compared to subjects with BMI <25 and no or moderate (0-7.4 kg) weight gain. Our findings imply that further weight gain is a considerable risk factor for VTE, particularly in obese individuals.
Durinka, Joel B; Hecht, Todd Eh; Layne, Andrew J; Jackson, Benjamin M; Woo, Edward Y; Fairman, Ronald M; Rohrbach, Jeffery I; Wang, Grace J
Venous thromboembolism (VTE) is a potentially preventable complication following surgery. There is variation with regard to the most effective mode of prophylaxis. We sought to determine if an aggressive approach to VTE prophylaxis would reduce VTE rates on the inpatient vascular surgical service. Vascular inpatients from a single institution from July 2010 to March 2013 were included in the analysis. A protocol for VTE prophylaxis was implemented on the inpatient vascular surgical service in November 2011. This included subcutaneous (SQ) heparin initiation within 24 h of admission unless deemed inappropriate by the attending, as well as intermittent compression devices (ICD) and compression stockings (CS). The rate of VTE was compared prior to and following the intervention. Patients were compared using AHRQ comorbidity categories, APR-DRG severity of illness, insurance status, and principle procedure. T-tests were used to compare continuous variables and chi-square analysis used to compare categorical variables. There were 1483 vascular patients in the pre-intervention group and 1652 patients in the post-intervention group. The rate of pharmacologic prophylaxis was 52.57% pre-intervention compared to 69.33% post-intervention (p < 0.001). The rate of pharmacologic or mechanical prophylaxis was 91.76% pre-intervention compared to 93.10% post-intervention (p = 0.54). The overall rate of VTE prior to the intervention was 1.49% compared to after intervention which was 0.38% (p = 0.033). The DVT rate prior to intervention was 1.09% vs 0.189% after intervention (p = 0.0214). The rate of pulmonary embolism trended towards a significant reduction with the intervention (0.681% vs 0.189%, p = 0.095). There were no statistically significant differences in patient groups based on gender, comorbidity category, severity of illness, or insurance type. The overall rate of VTE was reduced by 75% after the initiation of a standard protocol for pharmacologic
Kaplan, Gilaad G; Lim, Allen; Seow, Cynthia H; Moran, Gordon W; Ghosh, Subrata; Leung, Yvette; Debruyn, Jennifer; Nguyen, Geoffrey C; Hubbard, James; Panaccione, Remo
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
Easaw, J.C.; Shea–Budgell, M.A.; Wu, C.M.J.; Czaykowski, P.M.; Kassis, J.; Kuehl, B.; Lim, H.J.; MacNeil, M.; Martinusen, D.; McFarlane, P.A.; Meek, E.; Moodley, O.; Shivakumar, S.; Tagalakis, V.; Welch, S.; Kavan, P.
Patients with cancer are at increased risk of venous thromboembolism (vte). Anticoagulation therapy is used to treat vte; however, patients with cancer have unique clinical circumstances that can often make decisions surrounding the administration of therapeutic anticoagulation complicated. No national Canadian guidelines on the management of established cancer-associated thrombosis have been published. We therefore aimed to develop a consensus-based, evidence-informed guideline on the topic. PubMed was searched for clinical trials and meta-analyses published between 2002 and 2013. Reference lists of key articles were hand-searched for additional publications. Content experts from across Canada were assembled to review the evidence and make recommendations. Low molecular weight heparin is the treatment of choice for cancer patients with established vte. Direct oral anticoagulants are not recommended for the treatment of vte at this time. Specific clinical scenarios, including the presence of an indwelling venous catheter, renal insufficiency, and thrombocytopenia, warrant modifications in the therapeutic administration of anticoagulation therapy. Patients with recurrent vte should receive extended (>3 months) anticoagulant therapy. Incidental vte should generally be treated in the same manner as symptomatic vte. There is no evidence to support the monitoring of anti–factor Xa levels in clinically stable cancer patients receiving prophylactic anticoagulation; however, levels of anti–factor Xa could be checked at baseline and periodically thereafter in patients with renal insufficiency. Follow-up and education about the signs and symptoms of vte are important components of ongoing patient care. PMID:25908913
Lodders, J N; Parmar, S; Stienen, N L M; Martin, T J; Karagozoglu, K H; Heymans, M W; Forouzanfar, T
We retrospectively analysed the incidence of symptomatic venous thromboembolism (VTE) and associated risk factors in operations under general anaesthesia for cancer of the oral cavity. To identify symptoms related to deep venous thrombosis (DVT) and pulmonary embolism (PE), together with associated risk factors, we reviewed medical records of patients operated on in the department of oral and maxillofacial surgery at the Queen Elizabeth Hospital, Birmingham, United Kingdom, between June 2007 and October 2012. All patients were categorised according to their level of risk of VTE. The incidence of VTE was calculated with univariate associations and odds ratios with related 95% confidence intervals, where possible. In total, 233 patients were included, comprising 244 operations (mean (SD) age at operation 60.9 (13) years). Almost all patients (97%) were classified as having the highest risk of VTE. Swelling of an extremity, expectoration of blood, and tightness of the chest were the most common symptoms for suspected cases. An incidence of 0.41% was found for symptomatic VTE; one man developed a PE 2 days after operation. Associations between the analysed factors and symptomatic VTE were not significant. The development of the complication in oncological oral and maxillofacial operations seems to be rare, even in patients with a high risk. We cannot recommend the use of routine thromboprophylaxis, but it could be advocated in patients with obvious serious risk factors. Copyright © 2015. Published by Elsevier Ltd.
Easaw, J C; Shea-Budgell, M A; Wu, C M J; Czaykowski, P M; Kassis, J; Kuehl, B; Lim, H J; MacNeil, M; Martinusen, D; McFarlane, P A; Meek, E; Moodley, O; Shivakumar, S; Tagalakis, V; Welch, S; Kavan, P
Patients with cancer are at increased risk of venous thromboembolism (vte). Anticoagulation therapy is used to treat vte; however, patients with cancer have unique clinical circumstances that can often make decisions surrounding the administration of therapeutic anticoagulation complicated. No national Canadian guidelines on the management of established cancer-associated thrombosis have been published. We therefore aimed to develop a consensus-based, evidence-informed guideline on the topic. PubMed was searched for clinical trials and meta-analyses published between 2002 and 2013. Reference lists of key articles were hand-searched for additional publications. Content experts from across Canada were assembled to review the evidence and make recommendations. Low molecular weight heparin is the treatment of choice for cancer patients with established vte. Direct oral anticoagulants are not recommended for the treatment of vte at this time. Specific clinical scenarios, including the presence of an indwelling venous catheter, renal insufficiency, and thrombocytopenia, warrant modifications in the therapeutic administration of anticoagulation therapy. Patients with recurrent vte should receive extended (>3 months) anticoagulant therapy. Incidental vte should generally be treated in the same manner as symptomatic vte. There is no evidence to support the monitoring of anti-factor Xa levels in clinically stable cancer patients receiving prophylactic anticoagulation; however, levels of anti-factor Xa could be checked at baseline and periodically thereafter in patients with renal insufficiency. Follow-up and education about the signs and symptoms of vte are important components of ongoing patient care.
Kuipers, S; Venemans-Jellema, A; Cannegieter, S C; van Haften, M; Middeldorp, S; Büller, H R; Rosendaal, F R
Airline pilots may be at increased risk of venous thromboembolism (VTE) because air travel has recently been established as a risk factor for VTE. The aim of this study was to assess the risk of VTE in a cohort of Dutch airline pilots. Airline pilots who had been active members of the Dutch aviation society (VNV) were questioned for the occurrence of VTE, presence of risk factors for VTE and number of flight hours per year and rank. Incidence rates among pilots were compared with those of the general Dutch population and with a population of frequently flying employees of multinational organizations. A total of 2630 male pilots were followed-up for a total of 20420 person-years (py). Six venous thromboses were reported, yielding an incidence rate of 0.3 per 1000 py. The standardized morbidity ratio, comparing these pilots with the general Dutch population adjusted for age, was 0.8. Compared with the international employee cohort, the standardized morbidity ratio was 0.7 when all employees were included and 0.6 when only the frequently travelling employees were included. The incidence rate did not increase with number of flight hours per year and did not clearly vary by rank. We conclude that the risk of VTE is not increased amongst airline pilots. © 2014 International Society on Thrombosis and Haemostasis.
Sibai, H.; Seki, J.T.; Wang, T.Q.; Sakurai, N.; Atenafu, E.G.; Yee, K.W.L.; Schuh, A.C.; Gupta, V.; Minden, M.D.; Schimmer, A.D.; Brandwein, J.M.
Background Venous thromboembolism (vte) is a recognized complication in patients treated with asparaginase-containing chemotherapy regimens; the optimal preventive strategy is unclear. We assessed the safety and efficacy of prophylaxis using low-dose low molecular weight heparin in adult patients with acute lymphoblastic leukemia in complete remission treated with an asparaginase-based post-remission chemotherapy regimen. Methods As part of the intensification phase of the Dana-Farber Cancer Institute 91-01 regimen, asparaginase was administered weekly to 41 consecutive patients for 21–30 weeks; these patients also received prophylaxis with enoxaparin 40 mg daily (60 mg for patients ≥80 kg). Outcomes were assessed against outcomes in a comparable cohort of 99 patients who received the same chemotherapy regimen without anticoagulation prophylaxis. Results The overall rate of symptomatic venous thrombosis was not significantly different in the prophylaxis and non-prophylaxis cohorts (18.92% and 21.74% respectively). Among patients receiving prophylaxis, vte occurred in higher proportion in those who weighed at least 80 kg (42.86% vs. 4.35%, p = 0.0070). No major bleeding complications occurred in the prophylaxis group (minor bleeding: 8.1%). Conclusions Prophylaxis with low-dose enoxaparin during the intensification phase was safe, but was not associated with a lower overall proportion of vte. PMID:27536184
Brown, Joshua D.; Adams, Val R.; Moga, Daniela C.
Multiple myeloma (MM) has one of the highest risks of venous thromboembolism (VTE) of all cancers due to pathologic changes and treatment-related exposures. This study assessed the one-year incidence of VTE in newly diagnosed MM and to determine the baseline and time-varying treatment-related factors associated with VTE risk in a U.S.-based cohort. MM patients were identified and age, gender, and baseline comorbidities were determined. Treatment-related exposures included thalidomide derivatives (IMIDs), proteasome inhibitors, cytotoxic chemotherapy, steroids, erythropoietin-stimulating agents (ESAs), stem cell transplants (SCT), hospitalizations, infection, and central venous catheters (CVC). Multiple statistical models were used including a baseline competing risks model, a time-varying exposure Cox proportional hazard (CPH) model, and a case-time-control analysis. The overall incidence of VTE was 107.2 per 1000 person-years with one-half of the VTEs occurring in the first 90 days. The baseline model showed that increasing age, heart failure, and hypertension were associated with one-year incidence of VTE. MM-specific IMID treatment had lower than expected associations with VTE based on prior literature. Instead, exposure to ESAs, SCT, CVC, and infection had higher associations. Based on these results, VTE risk in MM may be less straightforward than considering only chemotherapy exposures, and other treatment-related exposures should be considered to determine patient risk. PMID:27999418
Nakamura, Mashio; Yamada, Norikazu; Oda, Eisei; Matsubayashi, Daisuke; Ota, Kaori; Kobayashi, Masafumi; Matsushita, Yasuyuki; Kaburagi, Jumpei; Ibusuki, Kei; Takita, Atsushi; Iwashita, Mikio; Yamaguchi, Takuhiro
Treatment to prevent the recurrence of venous thromboembolism (VTE) and prevent bleeding events should be given to patients with VTE in an appropriate balance in relation to relevant predictors. We elucidated the current medical care in a real world setting and quantified predictors using a Japanese healthcare database. The study included 3578 patients who were diagnosed with VTE between April 2008 and September 2013 at a Japanese acute-care hospital and included in the hospital database. Twenty-four patients who had a VTE event during the 180-day period after enrollment were excluded. We analyzed the incidence of recurrent VTE, incidence of bleeding events, and predictors in VTE patients. Events were defined by disease, medication, imaging, and laboratory testing, among other factors. The rate of recurrence of VTE events was 7.2 per 100 patient-years. The incidence rate of bleeding events was 8.3 per 100 patient-years. The presence of malignant disease, antipsychotic drugs, and nonsteroidal anti-inflammatory drugs increased the risk for recurrent VTE. The predictors for bleeding events were malignant disease, central venous catheterization, cancer chemotherapy, stroke, and diabetes. These findings obtained from healthcare database suggest predictors either for recurrent VTE and bleeding that should be considered when selecting treatment to reduce the risk of recurrent VTE and mitigate bleeding. Copyright © 2016. Published by Elsevier Ltd.
Background Venous thromboembolic events (VTE), including deep venous thrombosis and pulmonary embolism, are common in older age. It has been suggested that statins might reduce the risk of VTE however positive results from studies of middle aged subjects may not be generalisable to elderly people. We aimed to determine the effect of pravastatin on incident VTE in older people; we also studied the impact of clinical and plasma risk variables. Methods This study was an analysis of incident VTE using data from the Prospective Study of Pravastatin in the Elderly at Risk (PROSPER), a randomized, double-blind, placebo-controlled trial of pravastatin in men and women aged 70-82. Mean follow-up was 3.2 years. Risk for VTE was examined in non-warfarin treated pravastatin (n = 2834) and placebo (n = 2865) patients using a Cox's proportional hazard model, and the impact of other risk factors assessed in a multivariate forward stepwise regression analysis. Baseline clinical characteristics, blood biochemistry and hematology variables, plasma levels of lipids and lipoproteins, and plasma markers of inflammation and adiposity were compared. Plasma markers of thrombosis and hemostasis were assessed in a nested case (n = 48) control (n = 93) study where the cohort was those participants, not on warfarin, for whom data were available. Results There were 28 definite cases (1.0%) of incident VTE in the pravastatin group recipients and 20 cases (0.70%) in placebo recipients. Pravastatin did not reduce VTE in PROSPER compared to placebo [unadjusted hazard ratio (95% confidence interval) 1.42 (0.80, 2.52) p = 0.23]. Higher body mass index (BMI) [1.09 (1.02, 1.15) p = 0.0075], country [Scotland vs Netherlands 4.26 (1.00, 18.21) p = 0.050 and Ireland vs Netherlands 6.16 (1.46, 26.00) p = 0.013], lower systolic blood pressure [1.35 (1.03, 1.75) p = 0.027] and lower baseline Mini Mental State Examination (MMSE) score [1.19 (1.01, 1.41) p = 0.034] were associated with an increased risk of
Gherman; Goodwin; Leung; Byrne; Montoro
Objective: To determine the incidence, timing, and associated clinical characteristics of objectively diagnosed pregnancy-associated venous thromboembolism (VTE).Methods: A retrospective review of VTE cases occurring between 1978 and 1996 was performed. Cases of deep venous thrombosis (DVT) and pulmonary embolism (PE) were identified by ICD-9 discharge diagnosis code and review of antepartum and coagulation laboratory databases. Study inclusion criteria required the objective diagnosis of VTE with either Doppler ultrasound, impedance plethysmography, pulmonary angiography, ventilation-perfusion scanning, or CT/MRI.Results: Among 268,525 deliveries there were 165 (0.06%) episodes of VTE (1/1627 births). There were 127 cases of DVT and 38 cases of PE. Only 14% (23/165) had a prior history of DVT or PE. Most DVTs occurred in the left leg (104/127, 81.9%). Nearly three quarters of the DVTs (95/127, 74.8%) occurred in the antepartum period. Among the antepartum DVT cases, half were detected prior to 15 weeks of gestation (47/95, 49.5%), with only 28 cases occurring after 20 weeks (P <.0001). The majority of the PEs occurred in the postpartum period (23/38, 60.5%). There were only 3 maternal deaths due to PE, all associated with cesarean section. Only 1 patient developed PE while on heparin therapy for DVT while 11 others had complications attributable to heparin use.Conclusion: Most pregnancy-related VTE occurs in the antepartum period. The risk of deep venous thrombosis appears to begin early in pregnancy, even before the second trimester. The highest risk period for pulmonary embolism is after cesarean delivery. Maternal complications of heparin anticoagulation during pregnancy are rare.
Wittmann, P H; Wittmann, F W; Ring, P A
A retrospective study of the morbidity and mortality from deep vein thrombosis (DVT) and pulmonary embolus (PE) in 490 consecutive patients undergoing uncemented total hip replacement was carried out in a district general hospital. Special diagnostic tests for DVT and PE were not available. Patients were followed up for one year. There were three deaths in hospital and eight further deaths during the first year, all unrelated to DVT and PE. The clinical incidence of venous thromboembolism was 2.04%. While clinical diagnosis of venous thromboembolic disease probably underestimates its incidence, the figures for mortality are accurate. With every patient accounted for one year after operation, there were no deaths attributable to PE in this series. PMID:1941855
Bertoletti, Laurent; Ollier, Edouard; Duvillard, Cécile; Delavenne, Xavier; Beyens, Marie-Noëlle; De Magalhaes, Elodie; Bellet, Florelle; Basset, Thierry; Mismetti, Patrick; Laporte, Silvy
The treatment of acute venous thromboembolism (VTE) is being completely modified with the development of direct oral anticoagulants (DOACs). Rivaroxaban, apixaban and edoxaban directly inhibit factor Xa, whereas dabigatran inhibits factor IIa. All these drugs are proposed orally, and share pharmacological similarities: fixed doses without any therapeutic drug monitoring, key role of the transporter proteins P-glycoprotein for all of them and metabolism mediated by CYP3A4 for the anti-Xa, short half-life with variable rate of renal elimination. More than 25 000 patients with acute VTE were included in phase-III studies. Rivaroxaban and apixaban challenged all the conventional therapy (parenteral heparins followed by anti-vitamin K antagonists) whereas edoxaban and dabigatran challenged only anti-vitamin K antagonists. All the DOACs met the non-inferiority efficacy endpoint (recurrent VTE during treatment), whereas the large non-inferiority margin was debated for dabigatran. However, they were associated with better safety and a decreased risk of major bleeding. According to indirect comparisons, there were no statistically significant differences between DOACs in terms of efficacy but some differences are not excluded in term of safety. Although DOACs allow for simplification of treatment in the majority of patients with acute VTE, their risk/benefit ratio is questioned in elderly patients, patients with mild-to-severe renal impairment, and in some clinical subgroups such as cancer or chronic thromboembolic pulmonary hypertension. Validated reversal strategies (potentially based on laboratory monitoring) are expected for patients with major bleeding, overdose or with a need for surgery.
Murphy, Patrick B.; Sothilingam, Niroshan; Stewart, Tanya Charyk; Batey, Brandon; Moffat, Brad; Gray, Daryl K.; Parry, Neil G.; Vogt, Kelly N.
Background The optimal timing of initiating low–molecular weight heparin (LMWH) in patients who have undergone nonoperative management (NOM) of blunt solid organ injuries (SOIs) remains controversial. We describe the safety of early initiation of chemical venous thromboembolism (VTE) prophylaxis among patients undergoing NOM of blunt SOIs. Methods We retrospectively studied severely injured adults who sustained blunt SOI without significant intracranial hemorrhage and underwent an initial NOM at a Canadian lead trauma hospital between 2010 and 2014. Safety was assessed based on failure of NOM, defined as the need for operative intervention, in patients who received early (< 48 h) or late LMWH (≥48 h, or early dischar