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. PMID:24436666
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.
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.
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
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
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
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.
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.
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.
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
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.
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
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.
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.
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
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
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.
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".
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
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.
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.
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.
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
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.
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.
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.
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
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.
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
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
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.
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.
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
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
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.
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
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.
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.
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.
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.
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.
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.
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
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.
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.
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.
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
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.
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.
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
Zöller, Bengt; Li, Xinjun; Sundquist, Jan; Sundquist, Kristina
Arterial cardiovascular disease and neighborhood deprivation are associated. However, no study has determined whether neighborhood deprivation is associated with venous thromboembolism (VTE). We aimed to determine whether there is an association between neighborhood deprivation and hospitalization for VTE, and whether effects vary across sociodemographic groups. The entire Swedish population aged 25-74 was followed from January 1, 2000 until hospitalization for VTE, death, emigration, or the end of the study period (December 31, 2008). Data were analyzed by multilevel logistic regression, with individual-level characteristics (age, marital status, family income, educational attainment, immigration status, urban/rural status, mobility, and comorbidity) at the first level and level of neighborhood deprivation at the second level. Neighborhood deprivation was significantly associated with VTE hospitalization rate in both men (OR = 1.09) and women (OR = 1.38). In the full model, which took account of individual-level socioeconomic characteristics and comorbidities, the odds of VTE remained significant only in women (OR = 1.12, 95 % CI 1.06-1.20) in the most deprived neighborhoods. Neighborhood characteristics affect odds of hospitalization for VTE, particularly in women. Thus, neighborhood deprivation is a common risk factor for both arterial cardiovascular disease and VTE. This study adds to knowledge of the negative effects of neighborhood deprivation on cardiovascular health.
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.
Gupta, Neha; Ashraf, Mohammad Z
There are several genetic and acquired risk factors for venous thromboembolism. Exposure to high altitude (HA), either during air travel, ascension of mountains, or while engaging in sports activities, has been observed to result in a hypercoagulable state, thus predisposing to thromboembolic events. Although several previous studies have suggested that conditions present at HAs contribute to establish a prothrombotic milieu, published reports are contradictory and the exact underlying mechanism remains poorly understood. Results from HA studies also show that environmental conditions at HA such as hypoxia, dehydration, hemoconcentration, low temperature, use of constrictive clothing as well as enforced stasis due to severe weather, would support the occurrence of thrombotic disorders. The three leading factors of Virchow triad, that is, venous stasis, hypercoagulability, and vessel-wall injury, all appear to be present at HA. In synthesis, the large list of environmental variables suggests that a single cause of HA-induced thromboembolic disorders (TED) may not exist, so that this peculiar phenomenon should be seen as a complex or multifactorial trait. Further investigation is needed to understand the risk of TED at HA as well as the possible underlying mechanisms.
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
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
Objectif : Présenter une approche, fondée sur les données actuelles, envers le diagnostic, la prise en charge et la thromboprophylaxie de la thromboembolie veineuse pendant la grossesse et la période postpartum. Résultats : La littérature publiée a été récupérée par l’intermédiaire de recherches menées dans PubMed, Medline, CINAHL et The Cochrane Library entre novembre 2011 et juillet 2013 au moyen d’un vocabulaire contrôlé (p. ex. « pregnancy », « venous thromboembolism », « deep vein thrombosis », « pulmonary embolism », « pulmonary thrombosis ») et de mots clés (p. ex. « maternal morbidity », « pregnancy complications », « thromboprophylaxis », « antithrombotic therapy ») appropriés. Les résultats ont été restreints aux analyses systématiques, aux essais comparatifs randomisés / essais cliniques comparatifs et aux études observationnelles publiés en anglais ou en français. Aucune restriction n’a été imposée en matière de dates. La littérature grise (non publiée) a été identifiée par l’intermédiaire de recherches menées dans les sites Web d’organismes s’intéressant à l’évaluation des technologies dans le domaine de la santé et d’organismes connexes, dans des collections de directives cliniques, dans des registres d’essais cliniques et auprès de sociétés de spécialité médicale nationales et internationales. Valeurs : La qualité des résultats est évaluée au moyen des critères décrits dans le rapport du Groupe d’étude canadien sur les soins de santé préventifs (Tableau). Recommandations 1. La tenue d’un examen objectif s’avère requise lorsque la présence d’une thrombose veineuse profonde ou d’une embolie pulmonaire est soupçonnée sur le plan clinique. (II-2A) 2. Pour diagnostiquer la présence d’une thrombose veineuse profonde, il est recommandé d’avoir recours à une échographie; lorsque l’examen initial donne des résultats n
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.
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.
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
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.
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
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.
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.
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.
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.
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
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
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.
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.
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.
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.
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.
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.
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.
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
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.
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
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
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.
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.
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
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
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
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.
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.
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
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.
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
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
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.
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.
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.
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
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
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
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
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
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.
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
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.
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
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.
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.
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).
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.
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.
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.
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
Ross SE. Pulmonary embolism in major trauma patients. J Trauma 1990;30:748.  Goldhaber SZ, Bounameaux H. Pulmonary embolism and deep vein thrombosis...vein thrombosis in high risk trauma patients. Am Surg 2003;69:459.  Major KM, Wilson M, Nishi GK, et al. The incidence of thromboembolism in the
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
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
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.
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
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.
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.
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
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.
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
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
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
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
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.
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.
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).
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.
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
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
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
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
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
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
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.
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
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.
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
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.
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
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.
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
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.
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
BACKGROUND 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. OBJECTIVES 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. METHODS 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
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.
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
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
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
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.
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
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).
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.
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.
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
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.
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.
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.
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.
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
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.
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.
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
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.
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.
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.
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.
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
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
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
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
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
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
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
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
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 discharge [< 72 h] without LMWH). Results We included 162 patients in our analysis. Most were men (69%), and the average age was 42 ± 18 years. The median injury severity score was 17, and splenic injuries were most common (97 [60%], median grade 2), followed by liver (57 [35%], median grade 2) and kidney injuries (31 [19%], median grade 1). Combined injuries were present in 14% of patients. A total of 78 (48%) patients received early LMWH, while 84 (52%) received late LMWH. The groups differed only in percent of high-grade splenic injury (14% v. 32%). Overall 2% of patients failed NOM, none after receiving LMWH. Semielective angiography was performed in 23 (14%) patients. The overall rate of confirmed VTE on imaging was 1.9%. Conclusion Early initiation of medical thromboembolic prophylaxis appears safe in select patients with isolated SOI following blunt trauma. A prospective multicentre study is warranted. PMID:26820318
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.
Bergmann, Jean-Francois; Cohen, Alexander T; Tapson, Victor F; Goldhaber, Samuel Z; Kakkar, Ajay K; Deslandes, Bruno; Huang, Wei; Anderson, Frederick A
Limited data are available regarding the risk for venous thromboembolism (VTE) and VTE prophylaxis use in hospitalised medically ill patients. We analysed data from the global ENDORSE survey to evaluate VTE risk and prophylaxis use in this population according to diagnosis, baseline characteristics, and country. Data on patient characteristics, VTE risk, and prophylaxis use were abstracted from hospital charts. VTE risk and prophylaxis use were evaluated according to the 2004 American College of Chest Physicians (ACCP) guidelines. Multivariable analysis was performed to identify factors associated with use of ACCP-recommended prophylaxis. Data were evaluated for 37,356 hospitalised medical patients across 32 countries. VTE risk varied according to medical diagnosis, from 31.2% of patients with gastrointestinal/hepatobiliary diseases to 100% of patients with acute heart failure, active non-infectious respiratory disease, or pulmonary infection (global rate, 41.5%). Among those at risk for VTE, ACCP-recommended prophylaxis was used in 24.4% haemorrhagic stroke patients and 40-45% of cardiopulmonary disease patients (global rate, 39.5%). Large differences in prophylaxis use were observed among countries. Markers of disease severity, including central venous catheters, mechanical ventilation, and admission to intensive care units, were strongly associated with use of ACCP-recommended prophylaxis. In conclusion, VTE risk varies according to medical diagnosis. Less than 40% of at-risk hospitalised medical patients receive ACCP-recommended prophylaxis. Prophylaxis use appears to be associated with disease severity rather than medical diagnosis. These data support the necessity to improve implementation of available guidelines for evaluating VTE risk and providing prophylaxis to hospitalised medical patients.
Kimmell, Kristopher T; Jahromi, Babak S
OBJECT Patients undergoing craniotomy are at risk for developing venous thromboembolism (VTE). The safety of anticoagulation in these patients is not clear. The authors sought to identify risk factors predictive of VTE in patients undergoing craniotomy. METHODS The authors reviewed a national surgical quality database, the American College of Surgeons National Surgical Quality Improvement Program. Craniotomy patients were identified by current procedural terminology code. Clinical factors were analyzed to identify associations with VTE. RESULTS Four thousand eight hundred forty-four adult patients who underwent craniotomy were identified. The rate of VTE in the cohort was 3.5%, including pulmonary embolism in 1.4% and deep venous thrombosis in 2.6%. A number of factors were found to be statistically significant in multivariate binary logistic regression analysis, including craniotomy for tumor, transfer from acute care hospital, age ≥ 60 years, dependent functional status, tumor involving the CNS, sepsis, emergency surgery, surgery time ≥ 4 hours, postoperative urinary tract infection, postoperative pneumonia, on ventilator ≥ 48 hours postoperatively, and return to the operating room. Patients were assigned a score based on how many of these factors they had (minimum score 0, maximum score 12). Increasing score was predictive of increased VTE incidence, as well as risk of mortality, and time from surgery to discharge. CONCLUSIONS Patients undergoing craniotomy are at low risk of developing VTE, but this risk is increased by preoperative medical comorbidities and postoperative complications. The presence of more of these clinical factors is associated with progressively increased VTE risk; patients possessing a VTE Risk Score of ≥ 5 had a greater than 20-fold increased risk of VTE compared with patients with a VTE score of 0.
Colwell, Clifford; Mouret, Patrick
Patients undergoing major lower-extremity orthopedic surgery such as total hip replacement (THR) and total knee replacement (TKR) are at an increased risk of venous thromboembolism (VTE). Routine prophylaxis is necessary to reduce the risk of deep vein thrombosis (DVT), which may progress to potentially fatal pulmonary embolism and secondary complications such as postthrombotic syndrome, recurrent DVT, and chronic pulmonary hypertension. Prophylaxis in patients undergoing TKR, THR, and hip fracture surgery is now standard practice and generally involves anticoagulant treatment with either low-molecular-weight heparin (LMWH) or warfarin for a period of 7 to 10 days, with extended prophylaxis in those with ongoing risk factors such as obesity, cancer, or previous VTE. Data from clinical practice suggest that there is a general trend toward longer postsurgical prophylaxis and shorter hospital stays, making practicality of treatment an important consideration. LMWH is effective for the prophylaxis of VTE, but the parenteral route of administration is not convenient for use in the outpatient setting. Warfarin, on the other hand, can be administered orally but requires the infrastructure for careful patient monitoring and dose adjustments because of its unpredictable dose-response relationship. The development of new anticoagulants has been pursued with the aim of improving efficacy, predictability, consistency of response, safety, and convenience. A recently approved anticoagulant, fondaparinux, has been proven to provide superior efficacy for the prevention of VTE compared with LMWH, but this agent requires parenteral administration and does not overcome the convenience issue. Ximelagatran is the oral form of the direct thrombin inhibitor melagatran, which is available for subcutaneous administration. Ximelagatran has a consistent anticoagulant response allowing fixed oral dosing without the need for coagulation monitoring. The efficacy and safety profile of melagatran
Bemiparin sodium (Hibor, Ivor, Zivor, Badyket, Laboratorios Farmaceuticos Rovi SA) is a new second-generation low molecular weight heparin (LMWH). Bemiparin has the lowest mean molecular weight (3600 Da), the longest half-life (5.3 h) and the largest antifactor Xa:antifactor IIa ratio (8:1) of all LMWHs. Bemiparin promotes a greater release of tissue factor pathway inhibitor than unfractionated heparin (UFH) or dalteparin. These properties could result in a more favourable efficacy:safety ratio than the currently marketed LMWHs. Bemiparin 2500 IU/day was as effective as UFH for preventing venous thromboembolism (VTE) in moderate risk abdominal surgery. Bemiparin 3500 IU/day significantly reduced VTE compared to UFH in high-risk hip replacement surgery. Bemiparin 3500 IU/day started postoperatively was as effective as enoxaparin 4000 IU/day started preoperatively in total knee arthroplasty, with a trend towards a lower rate of proximal deep vein thrombosis (DVT), pulmonary embolism and symptomatic VTE. In patients with acute DVT, bemiparin was more effective than UFH in thrombus mass reduction and at least as effective as UFH for the prevention of clinical recurrence. Bemiparin was as effective as UFH for clot prevention during haemodialysis. The use of bemiparin was associated with a lower incidence of major and minor bleeding as compared to UFH in abdominal surgery. When compared with enoxaparin in orthopaedic surgery, a lower rate of complications at injection site was observed.
Kim, Nam Ki; Kim, Tae Kyun; Kim, Jong Min
Purpose The purpose of this study is to provide information on the actual status and prevailing trend of prophylaxis for venous thromboembolism (VTE) following total knee arthroplasty (TKA) in South Korea. Materials and Methods The Korean Knee Society (KKS) developed a questionnaire with 6 clinical questions on VTE. The questionnaire was distributed to all members of KKS by both postal and online mail. Participants were asked to supply details on their specialty and to select methods of prophylaxis they employ. Of the total members of KKS, 27.9% participated in the survey. Results The percentage of surgeons who routinely performed prophylaxis for VTE was 60.4%; 19.4% performed prophylaxis depending on the patient's health condition; and the remaining 20.2% never implemented prophylaxis after surgery. The common prophylactic methods among the responders were compression stocking (72.9%), pneumatic leg compression (63.3%), perioral direct factor Xa inhibitor (46.9%), and low-molecular-weight heparin (39.5%). For the respondents who did not perform prophylaxis, the main reason (51.5%) was the low risk of postoperative VTE considering the low incidences in Asians. Conclusions The present study involving members of the KKS will help to comprehend the actual status of VTE prevention in South Korea. The results of this study may be useful to design VTE guidelines appropriate for Koreans in the future. PMID:27595074
Witt, Daniel M; Clark, Nathan P; Kaatz, Scott; Schnurr, Terri; Ansell, Jack E
Venous thromboembolism (VTE) is a serious and often fatal medical condition with an increasing incidence. The treatment of VTE is undergoing tremendous changes with the introduction of the new direct oral anticoagulants and clinicians need to understand new treatment paradigms. This article, initiated by the Anticoagulation Forum, provides clinical guidance based on existing guidelines and consensus expert opinion where guidelines are lacking. Well-managed warfarin therapy remains an important anticoagulant option and it is hoped that anticoagulation providers will find the guidance contained in this article increases their ability to achieve optimal outcomes for their patients with VTE Pivotal practical questions pertaining to this topic were developed by consensus of the authors and were derived from evidence-based consensus statements whenever possible. The medical literature was reviewed and summarized using guidance statements that reflect the consensus opinion(s) of all authors and the endorsement of the Anticoagulation Forum's Board of Directors. In an effort to provide practical and implementable information about VTE and its treatment, guidance statements pertaining to choosing good candidates for warfarin therapy, warfarin initiation, optimizing warfarin control, invasive procedure management, excessive anticoagulation, subtherapeutic anticoagulation, drug interactions, switching between anticoagulants, and care transitions are provided.
Boiko, Olga; Sheaff, Rod; Child, Susan; Gericke, Christian A
Drawing on wider sociologies of risk, this article examines the complexity of clinical risks and their management, focusing on risk management systems, expert decision-making and safety standards in health care. At the time of this study preventing venous thromboembolism (VTE) among in-patients was one of the top priorities for hospital safety in the English National Health Service (NHS). An analysis of 50 interviews examining hospital professionals' perceptions about VTE risks and prophylaxis illuminates how National Institute for Health and Clinical Excellence (NICE) guidelines influenced clinical decision-making in four hospitals in one NHS region. We examine four themes: the identification of new risks, the institutionalisation and management of risk, the relationship between risk and danger and the tensions between risk management systems and expert decision-making. The implementation of NICE guidelines for VTE prevention extended managerial control over risk management but some irreducible clinical dangers remained that were beyond the scope of the new VTE risk management systems. Linking sociologies of risk with the realities of hospital risk management reveals the capacity of these theories to illuminate both the possibilities and the limits of managerialism in health care.
Parker, S G; McGlone, E R; Knight, W R; Sufi, P; Khan, O A
A best evidence topic in surgery was written according to a structured protocol. The question addressed was: which is the best regimen of enoxaparin thromboprophylaxis for patients undergoing bariatric surgery? One hundred and twenty-five papers were identified using the reported literature search, of which four represented the best evidence to answer the clinical question. The authors, country and date of publication, patient groups, relevant outcomes and results of these papers were tabulated. All four studies are non-randomized cohort studies examining venous thromboembolism rates and major postoperative bleeding following varying regimens of Enoxaparin thromboprophylaxis. There is no level 1 evidence which significantly favors any particular thromboprophylaxis regimen. There is some evidence that extended duration of treatment of ten days after discharge significantly reduces the incidence of VTE compared to in-hospital treatment only, and that a higher incidence of post-operative bleeding occurs with a regimen that includes a pre-operative dose of Enoxaparin. With regard to dosage, for in-hospital treatment the higher dosage of 40 mg twice daily as opposed to 30 mg seems to significantly reduce the incidence of VTE without significantly affecting bleeding rate.
Fisher, W D; Agnelli, G; George, D J; Kakkar, A K; Lassen, M R; Mismetti, P; Mouret, P; Turpie, A G G
There is currently limited information available on the benefits and risks of extended thromboprophylaxis after hip fracture surgery. SAVE-HIP3 was a randomised, double-blind study conducted to evaluate the efficacy and safety of extended thromboprophylaxis with the ultra-low molecular-weight heparin semuloparin compared with placebo in patients undergoing hip fracture surgery. After a seven- to ten-day open-label run-in phase with semuloparin (20 mg once daily subcutaneously, initiated post-operatively), patients were randomised to once-daily semuloparin (20 mg subcutaneously) or placebo for 19 to 23 additional days. The primary efficacy endpoint was a composite of any venous thromboembolism (VTE; any deep-vein thrombosis and non-fatal pulmonary embolism) or all-cause death until day 24 of the double-blind period. Safety parameters included major and clinically relevant non-major bleeding, laboratory data, and treatment-emergent adverse events (TEAEs). Extended thromboprophylaxis with semuloparin demonstrated a relative risk reduction of 79% in the rate of any VTE or all-cause death compared with placebo (3.9% vs 18.6%, respectively; odds ratio 0.18 (95% confidence interval 0.07 to 0.45), p < 0.001). Two patients in the semuloparin group and none in the placebo group experienced clinically relevant bleeding. TEAE rates were similar in both groups. In conclusion, the SAVE-HIP3 study results demonstrate that patients undergoing hip fracture surgery benefit from extended thromboprophylaxis.
Riess, Hanno; Habbel, Piet; Jühling, Anja; Sinn, Marianne; Pelzer, Uwe
Venous thromboembolism event (VTE) is a common and morbid complication in cancer patients. Patients with gastrointestinal cancers often suffer from symptomatic or incidental splanchnic vein thrombosis, impaired liver function and/or thrombocytopenia. These characteristics require a thorough risk/benefit evaluation for individual patients. Considering the risk factors for the development of VTE and bleeding events in addition to recent study results may be helpful for correct initiation of primary pharmacological prevention and treatment of cancer-associated thrombosis (CAT), preferably with low molecular weight heparins (LMWH). Whereas thromboprophylaxis is most often recommended in hospitalized surgical and non-surgical patients with malignancy, there is less agreement as to its duration. With regard to ambulatory cancer patients, the lack of robust data results in low grade recommendations against routine use of anticoagulant drugs. Anticoagulation with LMWH for the first months is the evidence-based treatment for acute CAT, but duration of secondary prevention and the drug of choice are unclear. Based on published guidelines and literature, this review will focus on prevention and treatment strategies of VTE in patients with gastrointestinal cancers. PMID:26989461
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 has been shown to prevent vte; however, unique clinical circumstances in patients with cancer can often complicate the decisions surrounding the administration of prophylactic anticoagulation. No national Canadian guidelines on the prevention of 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 can be used prophylactically in cancer patients at high risk of developing vte. Direct oral anticoagulants are not recommended for vte prophylaxis at this time. Specific clinical scenarios, including renal insufficiency, thrombocytopenia, liver disease, and obesity can warrant modifications in the administration of prophylactic anticoagulant therapy. There is no evidence to support the monitoring of anti–factor Xa levels in clinically stable cancer patients receiving prophylactic anticoagulation; however, factor Xa levels could be checked at baseline and periodically in patients with renal insufficiency. The use of anticoagulation therapy to prolong survival in cancer patients without the presence of risk factors for vte is not recommended. PMID:25908912
Papa, Alfredo; Gerardi, Viviana; Marzo, Manuela; Felice, Carla; Rapaccini, Gian Lodovico; Gasbarrini, Antonio
Inflammatory bowel disease (IBD) patients have an increased risk of venous thromboembolism (VTE), which represents a significant cause of morbidity and mortality. The most common sites of VTE in IBD patients are the deep veins of the legs and pulmonary system, followed by the portal and mesenteric veins. However, other sites may also be involved, such as the cerebrovascular and retinal veins. The aetiology of VTE is multifactorial, including both inherited and acquired risk factors that, when simultaneously present, multiply the risk to the patient. VTE prevention involves correcting modifiable risk factors, such as disease activity, vitamin deficiency, dehydration and prolonged immobilisation. The role of mechanical and pharmacological prophylaxis against VTE using anticoagulants is also crucial. However, although guidelines recommend thromboprophylaxis for IBD patients, this method is still poorly implemented because of concerns about its safety and a lack of awareness of the magnitude of thrombotic risk in these patients. Further efforts are required to increase the rate of pharmacological prevention of VTE in IBD patients to avoid preventable morbidity and mortality. PMID:24695669
Kuderer, Nicole M.; Lyman, Gary H.
The association between cancer and thrombosis has been recognized for more than 150 years. Not only are patients with cancer at a substantially increased risk of developing venous thromboembolism (VTE), the link between several coagulation factors and tumor growth, invasion, and the development of metastases has been established. Reported rates of VTE in patients with cancer have increased in recent years likely reflecting, in part, improved diagnosis with sophisticated imaging techniques as well as the impact of more aggressive cancer diagnosis, staging, and treatment. Various therapeutic interventions, such as surgery, chemotherapy, hormonal therapy, targeted therapeutic strategies as well as the frequent use of indwelling catheters and other invasive procedures also place cancer patients at increased risk of VTE. The increasing risk of VTE, the multitude of risk factors, and the greater risk of VTE recurrence and death among patients with cancer represent considerable challenges in modern clinical oncology. The American Society of Clinical Oncology (ASCO) originally developed guidelines for VTE in patients with cancer in 2007. ASCO recently updated clinical practice guidelines on the treatment and prevention of VTE in patients with cancer following an extensive systematic review of the literature. Revised 2013 guidelines have now been presented and will be discussed in this review. Although several new studies were identified and considered, many important questions remain regarding the relationship between thrombosis and cancer and the optimal care of patients at risk for VTE. PMID:24862132
Thibodeau, Jennifer T; Mishkin, Joseph D; Patel, Parag C; Kaiser, Patricia A; Ayers, Colby R; Mammen, Pradeep P A; Markham, David W; Ring, W Steves; Peltz, Matthias; Drazner, Mark H
Sirolimus is an immunosuppressive agent increasingly used in cardiac transplant recipients in the setting of allograft vasculopathy or worsening renal function. Recently, sirolimus has been associated with increased risk of venous thromboembolism (VTE) in lung transplant recipients. To investigate whether this association is also present in cardiac transplant recipients, we retrospectively reviewed the charts of 67 cardiac transplant recipients whose immunosuppressive regimen included sirolimus and 134 matched cardiac transplant recipients whose regimen did not include sirolimus. Rates of VTE were compared. Multivariable Cox proportional hazards models tested the association of sirolimus use with VTE. A higher incidence of VTE was seen in patients treated with vs. without sirolimus (8/67 [12%] vs. 9/134 [7%], log-rank statistic: 4.66, p=0.03). Lower body mass index (BMI) and total cholesterol levels were also associated with VTE (p<0.05). The association of sirolimus with VTE persisted when adjusting for BMI (hazard ratio [95% confidence interval]: 2.96 [1.13, 7.75], p=0.03) but not when adjusting for total cholesterol (p=0.08). These data suggest that sirolimus is associated with an increased risk of VTE in cardiac transplant recipients, a risk possibly mediated through comorbid conditions. Larger, more conclusive studies are needed. Until such studies are completed, a heightened level of awareness for VTE in cardiac transplant recipients treated with sirolimus appears warranted.
Werth, Sebastian; Halbritter, Kai; Beyer-Westendorf, Jan
Over the last 15 years, low-molecular-weight heparins (LMWHs) have been accepted as the “gold standard” for pharmaceutical thromboprophylaxis in patients at high risk of venous thromboembolism (VTE) in most countries around the world. Patients undergoing major orthopedic surgery (MOS) represent a population with high risk of VTE, which may remain asymptomatic or become symptomatic as deep vein thrombosis or pulmonary embolism. Numerous trials have investigated LMWH thromboprophylaxis in this population and demonstrated high efficacy and safety of these substances. However, LMWHs have a number of disadvantages, which limit the acceptance of patients and physicians, especially in prolonged prophylaxis up to 35 days after MOS. Consequently, new oral anticoagulants (NOACs) were developed that are of synthetic origin and act as direct and very specific inhibitors of different factors in the coagulation cascade. The most developed NOACs are dabigatran, rivaroxaban, and apixaban, all of which are approved for thromboprophylaxis in MOS in a number of countries around the world. This review is focused on the pharmacological characteristics of apixaban in comparison with other NOACs, on the impact of NOAC on VTE prophylaxis in daily care, and on the management of specific situations such as bleeding complications during NOAC therapy. PMID:22547932
Shea–Budgell, M.A.; Wu, C.M.J.; Easaw, J.C.
Venous thromboembolism (vte) is a serious, life-threatening complication of cancer. Anticoagulation therapy such as low molecular weight heparin (lmwh) has been shown to treat and prevent vte. Cancer therapy is often complex and ongoing, making the management of vte less straightforward in patients with cancer. There are no published Canadian guidelines available to suggest appropriate strategies for the management of vte in patients with solid tumours. We therefore aimed to develop a clear, evidence-based guideline on this topic. A systematic review of clinical trials and meta-analyses published between 2002 and 2013 in PubMed was conducted. Reference lists were hand-searched for additional publications. The National Guidelines Clearinghouse was searched for relevant guidelines. Recommendations were developed based on the best available evidence. In patients with solid tumours, lmwh is recommended for those with established vte and for those without established vte but with a high risk for developing vte. Options for lmwh include dalteparin, enoxaparin, and tinzaparin. No one agent can be recommended over another, but in the setting of renal insufficiency, tinzaparin is preferred. Unfractionated heparin can be used under select circumstances only (that is, when rapid clearance of the anticoagulant is desired). The most common adverse event is bleeding, but major events are rare, and with appropriate follow-up care, bleeding can be monitored and appropriately managed. PMID:24940110
Pérez-de-Llano, Luis A; Leiro-Fernández, Virginia; Golpe, Rafael; Núñez-Delgado, Jose M; Palacios-Bartolomé, Ana; Méndez-Marote, Lidia; Colomé-Nafria, Esteve
The objective of the present study was to evaluate the efficacy, safety and healthcare resource utilization of long-term treatment with tinzaparin in symptomatic patients with acute pulmonary embolism as compared to standard therapy. In this open-label trial, 102 patients with objectively confirmed pulmonary embolism were randomized to receive, after initial treatment with tinzaparin, either tinzaparin (175 IU/kg/day) or international normalized ratio-adjusted acenocoumarol for 6 months. Clinical endpoints were assessed during the 6 months of treatment. A pharmacoeconomic analysis was carried out to evaluate the cost of the long-term treatment with tinzaparin in comparison with the standard one. In an intention-to-treat analysis, one of 52 patients developed recurrent venous thromboembolism in the tinzaparin group compared with none of the 50 patients in the acenocoumarol group. One patient in each group had a major haemorrhagic complication. Six patients in the acenocoumarol group had minor bleeding compared with none in the tinzaparin group (P = 0.027). Median hospital length of stay was shorter in the tinzaparin group compared to the acenocoumarol group (7 versus 9 days; P = 0.014). When all the direct and indirect cost components were combined for the entire population, we found a slight, nonstatistically significant (mean difference €345; 95% CI 1382-2071; P = 0.69) reduction in total cost with tinzaparin. Symptomatic acute pulmonary embolism treatment with full therapeutic doses of tinzaparin for 6 months is a feasible alternative to conventional treatment with vitamin K antagonists.
Weiss, Thomas W; Rohla, Miklos; Dieplinger, Benjamin; Domanovits, Hans; Fries, Dietmar; Vosko, Milan R; Gary, Thomas; Ay, Cihan
Edoxaban is the most recent available representative of the Non-Vitamin K antagonist oral anticoagulants (NOAC). The approval was based on the largest phase III trials of NOACs for stroke prevention in patients with non-valvular atrial fibrillation (AF, ENGAGE-AF), and for the treatment of venous thromboembolism (VTE, HOKUSAI-VTE). In both trials, edoxaban was associated with similar efficacy and a significant reduction in bleeding events with respect to the pre-defined primary safety endpoints, as compared to warfarin.Additionally, the once daily dosing of edoxaban, the clinically investigated strategy for dose-reduction based on clearly defined criteria and the favorable pharmacokinetic profile might further support the clinical applicability of the substance.In the light of recent data, this expert consensus document aims to summarize the latest clinical trial results while providing a concise overview of current guideline recommendations on the management of patients with non-valvular AF and VTE.
Gándara, Esteban; Kovacs, Michael J; Kahn, Susan R; Wells, Philip S; Anderson, David A; Chagnon, Isabelle; Le Gal, Grégoire; Solymoss, Susan; Crowther, Mark; Carrier, Marc; Langlois, Nicole; Kovacs, Judy; Little Ma, Julian; Carson, Nancy; Ramsay, Tim; Rodger, Marc A
The role of ABO blood type as a risk factor for recurrent venous thromboembolism (VTE) in patients with a first unprovoked VTE who complete oral anticoagulation therapy is unknown. The aim of this study was to determine if non-OO blood type is a risk factor for recurrent VTE in patients with a first unprovoked VTE who completed 5-7 months of anticoagulant therapy. In an ongoing cohort study of patients with unprovoked VTE who discontinued oral anticoagulation after 5-7 months of therapy, six single nucleotide polymorphisms sites were tested to determine ABO blood type using banked DNA. The main outcome was objectively proven recurrent VTE. Mean follow-up for the cohort was 4.19 years (SD 2.16). During 1,553 patient-years of follow-up, 101 events occurred in 380 non-OO patients (6.5 events per 100 patient years; 95% CI 5.3-7.7) compared to 14 events during 560 patient years of follow-up in 129 OO patients (2.5 per 100 patient years; 95% CI 1.2-3.7), the adjusted hazard ratio was 1.98 (1.2-3.8). In conclusion, non-OO blood type is associated with a statistically significant and clinically relevant increased risk of recurrent VTE following discontinuation of anticoagulant therapy for a first episode of unprovoked VTE.
Meza Reyes, Gilberto Eduardo; Esquivel Gómez, Ricardo; Martínez del Campo Sánchez, Antonio; Espinosa-Larrañaga, Francisco; Martínez Guzmán, Miguel Ángel Enrique; Torres González, Rubén; de la Fuente Zuno, Juan Carlos; Méndez Huerta, Juan Vicente; Villalobos Garduño, Enrique; Cymet Ramírez, José; Ibarra Hirales, Efrén; Díaz Borjón, Efraín; Aguilera Zepeda, José Manuel; Valles Figueroa, Juan Francisco; Majluf-Cruz, Abraham
Venous thromboembolism (VTE) is a worldwide public health problem, with an annual incidence of 1-2 cases/1,000 individuals in the general population and a 1-5% associated mortality. Orthopedic surgery is a major surgical risk factor for VTE, but the problem is more important for patients with hip and knee joint replacement, multiple traumatisms, severe damage to the spine, or large fractures. Thromboprophylaxis is defined as the strategy and actions necessary to diminish the risk of VTE in high-risk orthopedic surgery. Antithrombotics may prevent VTE. At the end of this paper, we describe a proposal of thromboprophylaxis actions for patients requiring high-risk orthopedic surgery, based on the opinion of specialists in Orthopedics and Traumatology who work with high-risk orthopedic surgery patients. A search for evidence about this kind of surgery was performed and a 100-item inquiring instrument was done in order to know the opinions of the participants. Then, recommendations and considerations were built. In conclusion, this document reviews the problem of VTE in high-risk orthopedic surgery patients and describes the position of the Colegio Mexicano de Ortopedia y Traumatología related to VTE prevention in this setting.
Kourlaba, Georgia; Relakis, John; Mylonas, Charalambos; Kapaki, Vasiliki; Kontodimas, Stathis; Holm, Majbrit V; Maniadakis, Nikos
The objective of this study was to present evidence on the epidemiology, health outcomes and economic burden of cancer-related venous thromboembolism (VTE). Medline, Cochrane Central Register of Controlled Trials, Econlit, Science Direct, JSTOR, Oxford Journals and Cambridge Journals were searched. The systematic literature search was limited to manuscripts published from January 2000 to December 2012. On the basis of the literature, cancer patients experience between two-fold and 20-fold higher risk of developing VTE than noncancer patients. They are more likely to experience a VTE event during the first 3-6 months after cancer diagnosis. In addition, an increased risk of VTE in patients with distant metastases and certain types of cancer (i.e. pancreatic or lung) was revealed. VTE was found to be a leading cause of mortality in cancer patients. The annual average total cost for cancer patients with VTE was found to be almost 50% higher than that of cancer patients without VTE. Inpatient care costs accounted for more than 60% of total cost. The existing evidence assessed in the present review demonstrated the significant health and economic consequences of cancer-related VTE, which make a strong case for the importance of its proper and efficient prevention and management.
Baker, Dustin; Sherrod, Brandon; McGwin, Gerald; Ponce, Brent; Gilbert, Shawn
Introduction The risk of morbidity associated with venous thromboembolism (VTE) after pediatric orthopaedic surgery remains unclear despite increased use of thromboprophylaxis measures. Methods The American College of Surgeons National Surgical Quality Improvement Program, Pediatric database was queried for patients undergoing an orthopaedic surgical procedure between 2012 and 2013. Upper extremity and skin/subcutaneous surgeries were excluded. Associations between VTE and procedure, demographics, comorbidities, preoperative laboratory values, and 30-day postoperative outcomes were evaluated. Results Of 14,776 cases, 15 patients (0.10%) experienced postoperative VTE. Deep vein thrombosis (DVT) occurred in 13 patients (0.09%), and pulmonary embolism developed in 2 patients (0.01%). The procedure with the highest VTE rate was surgery for infection (1.2%). Patient factors associated with the development of VTE included hyponatremia (P = 0.003), abnormal partial thromboplastin time (P = 0.046), elevated aspartate transaminase level (P = 0.004), and gastrointestinal (P = 0.011), renal (P = 0.016), and hematologic (P = 0.019) disorders. Nearly half (46.2%) of DVTs occurred postdischarge. Complications associated with VTE included prolonged hospitalization (P = <0.001), pneumonia (P = <0.001), unplanned intubation (P = 0.003), urinary tract infection (P = 0.003), and central line-associated bloodstream infection (P = <0.001). Most of the postoperative complications (66.7%) occurred before VTE diagnosis, and no patients with VTE died. Conclusion In the absence of specified risk factors, thromboprophylaxis may be unnecessary for this population. PMID:26855119
Background Studies describing venous thromboembolic event (VTEE) and atrial fibrillation (AF) in South American populations are limited. The aim of this cross-sectional study was to describe the characteristics of Venezuelan patients admitted and treated for these conditions. Methods A retrospective medical record review of 1397 consecutive patients admitted to three private hospitals or clinics between January 2000 and December 2005 was performed. Data was collected on demographics, anthropometrics, hospital visit, comorbidities and treatment. Results Among 401 VTEE and 996 AF patients, men were more likely to have AF (58%) while more women experienced a VTEE (58%). Most patients were admitted via the emergency room (87%) and had only one event during the study period (83%). Common comorbidities included hypertension (46%), heart failure (17%), diabetes (12%) and congestive heart failure (11%). Characteristics of Venezuelan patients with VTEE and AF are similar to that reported in the literature for other populations. Conclusions These results provide background characteristics for future studies assessing risk factors for AF and VTEE in South American populations. PMID:21627817
Hooper, W Craig
Among the cardiovascular diseases and after ischemic heart disease and stroke, venous thromboembolism (VTE) is the third leading cause of death in the U.S. (3). Although VTE is seen across most ethnic groups in the U.S. as well as throughout the world, the rate varies. In the U.S., American Indians/Alaskan Natives as well as Asians have been reported to have a significantly lower rate of deep vein thrombosis (DVT) and pulmonary embolism (PE) as compared to blacks and whites. In sharp conrast blacks appear to have much higher rates than whites. Although these rate differences are thought in part by some to be attributable to disparities in diagnosis and care as well as genetics, it nevertheless is important to define as well as to understand the true incidence and impact so that both public health and clinical resources can be maximally utilized. The purpose of this commentary is to review the VTE burden in the U.S. with respect to ethnicity in terms of clinical demographics and genetics with particular emphasis on blacks.
T Rocha, Ana; F Paiva, Edison; Lichtenstein, Arnaldo; Milani, Rodolfo; Cavalheiro-Filho, Cyrillo; H Maffei, Francisco
The risk for venous thromboembolism (VTE) in medical patients is high, but risk assessment is rarely performed because there is not yet a good method to identify candidates for prophylaxis. Purpose To perform a systematic review about VTE risk factors (RFs) in hospitalized medical patients and generate recommendations (RECs) for prophylaxis that can be implemented into practice. Data sources A multidisciplinary group of experts from 12 Brazilian Medical Societies searched MEDLINE, Cochrane, and LILACS. Study selection Two experts independently classified the evidence for each RF by its scientific quality in a standardized manner. A risk-assessment algorithm was created based on the results of the review. Data synthesis Several VTE RFs have enough evidence to support RECs for prophylaxis in hospitalized medical patients (eg, increasing age, heart failure, and stroke). Other factors are considered adjuncts of risk (eg, varices, obesity, and infections). According to the algorithm, hospitalized medical patients ≥40 years-old with decreased mobility, and ≥1 RFs should receive chemoprophylaxis with heparin, provided they don’t have contraindications. High prophylactic doses of unfractionated heparin or low-molecular-weight-heparin must be administered and maintained for 6–14 days. Conclusions A multidisciplinary group generated evidence-based RECs and an easy-to-use algorithm to facilitate VTE prophylaxis in medical patients. PMID:17969384
Venous thromboembolism (VTE), comprising life-threatening pulmonary embolism (PE) and its precursor deep-vein thrombosis (DVT), is commonly encountered problem. Although most patients survive DVT, they often develop serious and costly long-term complications. Both unfractionated heparin and low molecular weight heparins significantly reduce the incidence of VTE and its associated complications. Despite the evidence demonstrating significant benefit of VTE prophylaxis in acutely ill medical patients, several registries have shown significant underutilization. This underutilization indicates the need for educational and audit programs in order to increase the number of medical patients receiving appropriate prophylaxis. Many health advocacy groups and policy makers are paying more attention to VTE prophylaxis; the National Quality Forum and the Joint Commission recently endorsed strict VTE risk assessment evaluation for each patient upon admission and regularly thereafter. In the article, all major studies addressing this issue in medical patients have been reviewed from the PubMed. The current status of VTE prophylaxis in hospitalized medical patients is addressed and some improvement strategies are discussed. PMID:20981179
Lee, Huang L.; Yang, Ian A.; Masel, Philip J.
Background Clinical practice of thrombophilia testing those with venous thrombo-embolism (VTE) in public hospitals may not be consistent with the international guidelines. This study aims to assess whether practice of thrombophilia testing in two public hospitals are consistent with international guidelines, and to assess whether certain groups of patients were more likely to benefit from testing. Methods A retrospective audit on patients who presented to two Queensland public hospitals from August 2011 to September 2012 with VTE. Data were collected on demographics, yield of the test, and whether the result of the test changed the duration of anticoagulation. Group analysis was performed to identify patients who were more likely to yield positive results. Results Of the 152 patients, 49% were tested for thrombophilia, of whom 31% returned a positive result. 38% of patients with provoked VTE were tested for thrombophilia, inconsistent with guideline recommendations. In 1.2% of cases there were documented changes to duration of anticoagulation with positive results. The rates of positive results were 45% in unprovoked VTE cases compared with 29% in provoked VTE cases (P=0.054). The rates of positive results were 52% in recurrent VTE cases compared with 27% in those cases with first episode of VTE (P=0.007). Conclusions The practice of thrombophilia testing in public hospitals was frequently inconsistent with guidelines, and did not significantly influence clinical decisions. There was higher yield of testing in patients with recurrent episodes of VTE and possibly in patients with unprovoked VTE. PMID:28149566
Izadi, Morteza; Alemzadeh-Ansari, Mohammad Javad; Kazemisaleh, Davood; Moshkani-Farahani, Maryam; Shafiee, Akbar
International travel has become increasingly common and accessible, and it is part of everyday life in pregnant women. Venous thromboembolism (VTE) is a serious public health disorder that occurs following long-haul travel, especially after air travel. The normal pregnancy is accompanied by a state of hypercoagulability and hypofibrinolysis. Thus, it seems that pregnant women are at a higher risk of VTE following air travel, and, if they have preexisting risk factors, this risk would increase. There is limited data about travel-related VTE in pregnant women; therefore, in the present study, we tried to evaluate the pathogenesis of thrombosis, association of thrombosis and air travel, risk factors and prevention of VTE in pregnant women based on available evidences. Pregnancy is associated with a five- to 10-fold increased risk of VTE compared with nonpregnant women; however, during the postpartum period, this risk would increase to 20–80-fold. Furthermore, the risk of thrombosis is higher in individuals with preexisting risk factors, and the most common risk factor for VTE during pregnancy is a previous history of VTE. Pregnant women are at a higher risk for thrombosis compared with other women. Thus, the prevention of VTE and additional risk factors should be considered for all pregnant women who travel by plane. PMID:25802829
Werth, Sebastian; Halbritter, Kai; Beyer-Westendorf, Jan
Over the last 15 years, low-molecular-weight heparins (LMWHs) have been accepted as the "gold standard" for pharmaceutical thromboprophylaxis in patients at high risk of venous thromboembolism (VTE) in most countries around the world. Patients undergoing major orthopedic surgery (MOS) represent a population with high risk of VTE, which may remain asymptomatic or become symptomatic as deep vein thrombosis or pulmonary embolism. Numerous trials have investigated LMWH thromboprophylaxis in this population and demonstrated high efficacy and safety of these substances. However, LMWHs have a number of disadvantages, which limit the acceptance of patients and physicians, especially in prolonged prophylaxis up to 35 days after MOS. Consequently, new oral anticoagulants (NOACs) were developed that are of synthetic origin and act as direct and very specific inhibitors of different factors in the coagulation cascade. The most developed NOACs are dabigatran, rivaroxaban, and apixaban, all of which are approved for thromboprophylaxis in MOS in a number of countries around the world. This review is focused on the pharmacological characteristics of apixaban in comparison with other NOACs, on the impact of NOAC on VTE prophylaxis in daily care, and on the management of specific situations such as bleeding complications during NOAC therapy.
O'Connell, Casey L; Liebman, Howard A
Venous thromboembolism (VTE) is a frequent clinical complication of cancer and its treatment. Although much of the epidemiologic data regarding this complication have been based on symptomatic events, the use of multidetector row CT scanner technology has led to increased identification of VTE on scans ordered primarily for staging or restaging of malignancy. These incidentally discovered VTEs are variously referred to in the literature as incidental, asymptomatic, unexpected, or unsuspected VTE. A recent guidance paper by the Hemostasis and Malignancy Subcommittee of the International Society on Thrombosis and Haemostasis provided recommendations regarding this terminology (now termed incidental) and reporting of incidental VTE for clinical trials. A growing number of retrospective and case-controlled reports have described the prevalence, prognostic implications, and treatment options for these incidentally discovered VTE events, and have reported similar clinical outcomes for patients with incidental and symptomatic VTE. Because most reported patients with incidental VTE have been treated in a manner similar to those with symptomatic events, the present recommendations, except in rare circumstances, support the use of standard anticoagulation in the management of incidental deep vein thrombosis and pulmonary embolism.
Ahmad, Aminah Noor; Byrne, Megan Leyla; Imambaccus, Nazia; Hubert, Dawid; Gateley, Anna; Abdullahi Idle, Salwa; Lloyd, Jilly
Venous thromboembolism (VTE) is one of the leading causes of maternal mortality in the UK. Therefore, timely VTE risk assessment is essential in all obstetrics patients. The Commissioning for Quality and Innovation (CQUIN) payment framework set a target for trusts to complete a VTE risk assessment within 24 hours of admission for 95% of patients. A combination of factors, including lack of integration between multiple IT systems, means that this CQUIN target is currently not being met for obstetric patients in the Hospital Birth Centre at Guys and St Thomas' NHS Trust. This project aims to increase staff awareness of this issue and educate them regarding the correct procedure for VTE assessment. Trialled methods included reminders at staff handovers, use of magnets on the patient whiteboard, posters and stickers displayed around the unit and a loyalty card scheme as incentive to complete assessments. Initial average completion rate was 20.7%, which increased to 67.5% after the first plan, do, study, act (PDSA) cycle with a slight drop to 65.7% after the second cycle. Completion rates increased to 92.3% on the last day of the third PDSA cycle. Although we did not reach the 95% target, we have raised awareness of the importance of recording VTE assessment on electronic systems, and hope we have created sustainable change. PMID:27933149
Abstract Despite the frequency and morbidity of venous thromboembolism (VTE) development after traumatic brain injury (TBI), no national standard of care exists to guide TBI caregivers for the use of prophylactic anticoagulation. Fears of iatrogenic propagation of intracranial hemorrhage patterns have led to a dearth of research in this field, and it is only relatively recently that studies dedicated to this question have been performed. These have generally been limited to retrospective and/or observational studies in which patients are classified in a binary fashion as having the presence or absence of intracranial blood. This methodology does not account for the fact that smaller injury patterns stabilize more rapidly, and thus may be able to safely tolerate earlier initiation of prophylactic anticoagulation than larger injury patterns. This review seeks to critically assess the literature on this question by examining the existing evidence on the safety and efficacy of pharmacologic VTE prophylaxis in the setting of elective craniotomy (as this is the closest model available from which to extrapolate) and after TBI. In doing so, we critique studies that approach TBI as a homogenous or a heterogenous study population. Finally, we propose our own theoretical protocol which stratifies patients into low, moderate, and high risk for the likelihood of natural progression of their hemorrhage pattern, and which allows one to tailor a unique VTE prophylaxis regimen to each individual arm. PMID:22651698
Gerotziafas, Grigoris T; Mahé, Isabelle; Elalamy, Ismail
Patients with cancer have a 6–7-fold higher risk of venous thromboembolism (VTE) as compared with non-cancer patients. Effective and safe anticoagulation for the prevention and treatment of VTE is the cornerstone of the management of patients with cancer, aiming to decrease morbidity and mortality and to improve quality of life. Unfractionated heparin, low molecular weight heparins, fondaparinux and vitamin K antagonists (VKAs) are used in the prevention and treatment of VTE in cancer patients. Heparins and fondaparinux are administered subcutaneously. VKAs are orally active, but they have a narrow therapeutic window, numerous food and drug interactions, and treatment requires regular laboratory monitoring and dose adjustment. These limitations among others have important negative impact on the quality of life of patients and decrease adherence to the treatment. New orally active anticoagulant (NOAC) agents are specific inhibitors of activated factor Xa (FXa) (rivaroxaban and apixaban) or thrombin (dabigatran). It is expected that NOACs will improve antithrombotic treatment. Cancer patients are a particular group that could benefit from treatment with NOACs. However, NOACs present some significant interactions with drugs frequently used in cancer patients, which might influence their pharmacokinetics, compromising their efficacy and safety. In the present review, we analyzed the available data from the subgroups of patients with active cancer who were included in Phase III clinical trials that assessed the efficacy and safety of NOACs in the prevention and treatment of VTE. The data from the Phase III trials in prophylaxis of VTE by rivaroxaban or apixaban highlight that these two agents, although belonging to the same pharmacological group (direct inhibitors of factor Xa), have substantially different profiles of efficacy and safety, especially in hospitalized acutely ill medical patients with active cancer. A limited number of patients with VTE and active
Farmer, R D; Lawrenson, R A; Thompson, C R; Kennedy, J G; Hambleton, I R
Four studies published since December 1995 have reported an increased risk of venous thromboembolism (VTE) in women using oral contraceptives (OCs) containing the third-generation progestogens gestodene and desogestrel compared to users of OCs containing second-generation progestogens. The results of these studies could have been compromised, however, by bias and confounding. To reassess this association with a more rigorous study design, computerized medical records from 143 general practices in the UK of about 540,000 women born from 1941 to 1981 were reviewed and 83 cases of deep-vein thrombosis, venous thrombosis not otherwise specified, and pulmonary embolus (all treated with an anticoagulant) were identified. Two women were using a progestogen-only OC. Of the 83 VTE cases associated with combined OC use, 43 were diagnosed as deep-vein thrombosis, 35 as pulmonary thrombosis, and 5 as venous thrombosis not otherwise specified. The crude rate of VTE per 10,000 woman-years was 4.10 in current users of any OC, 3.10 in users of second-generation OCs, and 4.96 in users of third-generation OCs. After exact age matching of cases and controls, the odds ratio of VTE in users of third-generation compared to second-generation OCs was 1.68 (95%, confidence interval, 1.04-2.75). Logistic regression revealed no significant difference in VTE risk between users of the 2 groups of OCs. Using all second-generation OCs as the reference, the VTE risk was higher for third-generation OCs containing desogestrel and 20 grams of ethinyl estradiol than for those containing desogestrel or gestodene and 30 grams of ethinyl estradiol--an implausible finding presumed to reflect preferential prescribing of the former OCs to older women. The previously reported increased VTE risk associated with third-generation OCs likely reflects residual confounding by age. Exact age-matching is recommended for all future studies to ensure that controls are representative of the population from which cases
Ashrani, Aneel A.; Barsoum, Michel K.; Crusan, Daniel J.; Petterson, Tanya M.; Bailey, Kent R.; Heit, John A.
Introduction The independent effect of lipid lowering therapy (LLT) on venous thromboembolism (VTE) risk is uncertain. Objective To test statin and non-statin LLT as potential VTE risk factors. Methods Using Rochester Epidemiology Project resources, we identified all Olmsted County, MN residents with objectively diagnosed incident VTE (cases) over the 13-year period, 1988–2000 (n=1340), and one to two matched controls (n=1538). We reviewed their complete medical records for baseline characteristics previously identified as independent VTE risk factors, and for statin and non-statin LLT. Using conditional logistic regression, we tested the overall effect of LLT on VTE risk and also separately explored the role of statin versus that of non-statin LLT, adjusting for other baseline characteristics. Results Among cases and controls, 74 and 111 received statin LLT, and 32 and 50 received non-statin LLT, respectively. Univariately, and after individually controlling for other potential VTE risk factors (i.e., BMI, trauma/fracture, leg paresis, hospitalization for surgery or medical illness, nursing home residence, active cancer, central venous catheter, varicose veins, prior superficial vein thrombosis, diabetes, congestive heart failure, angina/myocardial infarction, stroke, peripheral vascular disease, smoking, anticoagulation), LLT was associated with decreased odds of VTE (unadjusted OR= 0.73; p= 0.03). When considered separately, statin and non-statin LLT were each associated with moderate, non-significant lower odds of VTE. After adjusting for angina/myocardial infarction, each was significantly associated with decreased odds of VTE (OR= 0.63, p< 0.01 and OR= 0.61, p=0.04, respectively). Conclusions LLT is associated with decreased VTE risk after adjusting for known risk factors. PMID:25891841
Obernosterer, Andrea; Aschauer, Manuela; Portugaller, Horst; Köppel, Herwig; Lipp, Rainer W
Pulmonary embolism and deep venous thrombosis are individual manifestations of a single entity, venous thromboembolic disease. This study aimed to assess the feasibility of 3-dimensional gadolinium-enhanced magnetic resonance angiography used as an "one-stop shop'' imaging procedure visualizing both the pulmonary arteries and the deep lower venous system within a single investigation. The inclusion criterion was a proven or excluded venous thromboembolism. Diagnosis was based on an imaging work-up for pulmonary embolism including either perfusion lung scan or contrast-enhanced spiral computed tomography, or both, and an imaging work-up for deep venous thrombosis including either venous color-coded duplex sonography or ascending phlebography, or both. A gadolinium-enhanced "one-stop shop'' magnetic resonance angiography was performed within 24 hours of completed diagnostic imaging work-up for pulmonary embolism and deep venous thrombosis in 20 patients. Results of pulmonary magnetic resonance angiography were concordant with perfusion lung scan and/or computed tomography in 90% of patients. Magnetic resonance angiography results of the deep lower venous system were concordant with venous duplex sonography and/or phlebography in 75% of patients and seemed to be more precise in 25% of patients. The "one-stop shop'' imaging procedure using gadolinium-enhanced magnetic resonance angiography was feasible and proved to offer a reliable and rapid diagnostic approach in thromboembolic disease, sparing patients' exposure to ionizing radiation and iodinated contrast media.
van Es, Nick; Di Nisio, Marcello; Bleker, Suzanne M; Segers, Annelise; Mercuri, Michele F; Schwocho, Lee; Kakkar, Ajay; Weitz, Jeffrey I; Beyer-Westendorf, Jan; Boda, Zoltan; Carrier, Marc; Chlumsky, Jaromir; Décousus, Hervé; Garcia, David; Gibbs, Harry; Kamphuisen, Pieter W; Monreal, Manuel; Ockelford, Paul; Pabinger, Ingrid; Verhamme, Peter; Grosso, Michael A; Büller, Harry R; Raskob, Gary E
Direct oral anticoagulants may be effective and safe for treatment of venous thromboembolism (VTE) in cancer patients, but they have not been compared with low-molecular-weight heparin (LMWH), the current recommended treatment for these patients. The Hokusai VTE-cancer study is a randomised, open-label, clinical trial to evaluate whether edoxaban, an oral factor Xa inhibitor, is non-inferior to LMWH for treatment of VTE in patients with cancer. We present the rationale and some design features of the study. One such feature is the composite primary outcome of recurrent VTE and major bleeding during a 12-month study period. These two complications occur frequently in cancer patients receiving anticoagulant treatment and have a significant impact. The evaluation beyond six months will fill the current gap in the evidence base for the long-term treatment of these patients. Based on the observation that the risk of recurrent VTE in patients with active cancer is similar to that in those with a history of cancer, the Hokusai VTE-cancer study will enrol patients if whose cancer was diagnosed within the past two years. In addition, patients with incidental VTE are eligible because their risk of recurrent VTE is similar to that in patients with symptomatic disease. The unique design features of the Hokusai VTE-cancer study should lead to enrolment of a broad spectrum of cancer patients with VTE who could benefit from oral anticoagulant treatment.
Lidegaard, Øjvind; Edström, Birgitte; Kreiner, Svend
The objective of this study was to assess the influence of oral contraceptives (OCs) on the risk of venous thromboembolism (VTE) in young women. A 5-year case-control study including all Danish hospitals was conducted. All women 15-44 years old, suffering a first ever deep venous thrombosis or a first pulmonary embolism (PE) during the period January 1, 1994, to December 30, 1998, were included. Controls were selected annually, 600 per year in 1994-1995 and 1200 per year 1996-1998. Response rates for cases and controls were 87.2% and 89.7%, respectively. After exclusion of nonvalid diagnoses, pregnant women, and women with previous thrombotic disease, 987 cases and 4054 controls were available for analysis. A multivariate, matched analysis was performed. Controls were matched to cases within 1-year age bands. Adjustment was made for confounding influence (if any) from the following variables: age, year, body mass index, length of OC use, family history of VTE, cerebral thrombosis or myocardial infarction, coagulopathies, diabetes, years of schooling, and previous birth. The risk of VTE among current users of OCs was primarily influenced by duration of use, with significantly decreasing odds ratios (OR) over time: <1 year, 7.0 (5.1-9.6); 1-5 years, 3.6 (2.7-4.8); and >5 years, 3.1 (2.5-3.8), all compared with nonusers of OCs. After adjustment for confounders, current use of OCs with second- (levonorgestrel or norgestimate) and third- (desogestrel or gestodene) generation progestins when compared with nonuse resulted in ORs for VTE of 2.9 (2.2-3.8) and 4.0 (3.2-4.9), respectively. After adjusting for progestin types and length of use, the risk decreased significantly with decreasing estrogen dose. With 30-40 microg as reference, 20 and 50 microg products implied ORs of 0.6 (0.4-0.9) and 1.6 (0.9-2.8), respectively (p(trend) = 0.02). After correction for duration of use and differences in estrogen dose, the third/second-generation risk ratio was 1.3 (1.0-1.8; p <0
Sindet-Pedersen, Caroline; Bruun Oestergaard, Louise; Gundlund, Anna; Fosbøl, Emil Loldrup; Aasbjerg, Kristian; Langtved Pallisgaard, Jannik; Gislason, Gunnar; Torp-Pedersen, Christian; Bjerring Olesen, Jonas
Background 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. Objectives To examine the relative rate of VTE in first-degree relatives compared with the general population. Methods 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. Results 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). Conclusion A family history of VTE was associated with a significantly increased rate of VTE among first-degree relatives compared with the general population. PMID:28033406
Stuck, Anna K; Spirk, David; Schaudt, Jil; Kucher, Nils
Although the use of thromboprophylaxis is recommended for acutely ill medical patients at increased risk of venous thromboembolism (VTE), it remains unclear which risk assessment model (RAM) should be routinely used to identify at-risk patients requiring thromboprophylaxis. We therefore aimed to describe existing RAMs, and to compare these tools in terms of validity and applicability for clinical decision-making. We performed a comprehensive systematic search in MEDLINE from the date of initiation until May 2016 for studies in acutely ill medical patients investigating validity of RAMs for VTE. Two reviewers independently screened the title, abstract, and full text, and evaluated the characteristics of studies, and the composition, evidence of validation, and results on validity of the RAMs. We included 11 studies assessing eight RAMs: 4-Element RAM, Caprini RAM, a full logistic model, Geneva risk score, IMPROVE-RAM, Kucher Model, a "Multivariable Model", and Padua Prediction Score. The 4-Element RAM, IMPROVE-RAM, Multivariable Model, and full logistic model had derivation by identifying factors with predictive power. The other four RAMs were empirically generated based on consensus guidelines, published data, and clinical expertise. The Kucher Model, the Padua Prediction Score, the Geneva Risk Score and the IMPROVE-RAM underwent multicenter external validation. The Kucher Model, the Padua Prediction Score, and the Geneva Risk Score improved rates of thromboprophylaxis or clinical outcomes. In conclusion, existing RAMs to evaluate the need of thromboprophylaxis in acutely ill medical patients are difficult to compare and none fulfills the criteria of an ideal RAM. Nevertheless, the adequacy of thromboprophylaxis may be improved by implementing one of the validated RAMs.
Ay, C; Pabinger, I
Cancer is a major and independent risk factor of venous thromboembolism (VTE). In clinical practice, a high number of VTE events occurs in patients with cancer, and treatment of cancer-associated VTE differs in several aspects from treatment of VTE in the general population. However, treatment in cancer patients remains a major challenge, as the risk of recurrence of VTE as well as the risk of major bleeding during anticoagulation is substantially higher in patients with cancer than in those without cancer. In several clinical trials, different anticoagulants and regimens have been investigated for treatment of acute VTE and secondary prophylaxis in cancer patients to prevent recurrence. Based on the results of these trials, anticoagulant therapy with low-molecular-weight heparins (LMWH) has become the treatment of choice in cancer patients with acute VTE in the initial period and for extended and long-term anticoagulation for 3-6 months. New oral anticoagulants directly inhibiting thrombin or factor Xa, have been developed in the past decade and studied in large phase III clinical trials. Results from currently completed trials are promising and indicate their potential use for treatment of VTE also in cancer patients. However, the role of the new oral thrombin and factor Xa inhibitors for VTE treatment in cancer patients still has to be clarified in further studies specifically focusing on cancer-associated VTE. This brief review will summarize the current strategies of initial and long-term VTE treatment in patients with cancer and discuss the potential use of the new oral anticoagulants.
Apixaban, a direct orally active anticoagulant (selective, direct factor Xa inhibitor) is approved for (primary) prevention of venous thromboembolism (VTE) in patients undergoing elective total-hip or total-knee arthroplasty, for acute treatment/prevention of recurrent events in patients with VTE, and extended prophylaxis in patients with a history of VTE. Another approved use is prevention of stroke and systemic embolism in patients with nonvalvular atrial fibrillation. The present overview focuses on the safety of apixaban specifically in the VTE setting. Apixaban displays favorable pharmacokinetic properties: simple twice-daily dosing, low inter- and intrasubject variability, dose and time linearity, and multiple elimination pathways not critically dependent on either renal or metabolic mechanisms. An extensive nonclinical program and the overall clinical development program (all approved and tested indications) provided no signal that would indicate any particular specific safety concern related to apixaban apart from the increased risk of bleeding. With regard to the approved VTE indications, safety (and efficacy) was assessed in five large pivotal Phase III trials. In comparison to currently recommended standard treatments, apixaban shows superior efficacy, while at the same time no excess risk of bleeding in patients undergoing total-hip or total-knee arthroplasty. In treatment of VTE, apixaban shows noninferior efficacy and a reduced risk of bleeding, whereas in extended prophylaxis it reduced the risk of VTE/VTE-related deaths, with no increased risk of relevant bleedings in comparison to placebo. Documented clinical experience with apixaban in daily practice is currently sparse. However, its use is progressively increasing, and there has been no signal so far that would materially change the perception of its safety profile as defined in the premarketing trials.
Piper, Keaton; Algattas, Hanna; DeAndrea-Lazarus, Ian A; Kimmell, Kristopher T; Li, Yan Michael; Walter, Kevin A; Silberstein, Howard J; Vates, G Edward
OBJECTIVE Patients undergoing spinal surgery are at risk for developing venous thromboembolism (VTE). The authors sought to identify risk factors for VTE in these patients. METHODS The American College of Surgeons National Surgical Quality Improvement Project database for the years 2006-2010 was reviewed for patients who had undergone spinal surgery according to their primary Current Procedural Terminology code(s). Clinical factors were analyzed to identify associations with VTE. RESULTS Patients who underwent spinal surgery (n = 22,434) were identified. The rate of VTE in the cohort was 1.1% (pulmonary embolism 0.4%; deep vein thrombosis 0.8%). Multivariate binary logistic regression analysis revealed 13 factors associated with VTE. Preoperative factors included dependent functional status, paraplegia, quadriplegia, disseminated cancer, inpatient status, hypertension, history of transient ischemic attack, sepsis, and African American race. Operative factors included surgery duration > 4 hours, emergency presentation, and American Society of Anesthesiologists Class III-V, whereas postoperative sepsis was the only significant postoperative factor. A risk score was developed based on the number of factors present in each patient. Patients with a score of ≥ 7 had a 100-fold increased risk of developing VTE over patients with a score of 0. The receiver-operating-characteristic curve of the risk score generated an area under the curve of 0.756 (95% CI 0.726-0.787). CONCLUSIONS A risk score based on race, preoperative comorbidities, and operative characteristics of patients undergoing spinal surgery predicts the postoperative VTE rate. Many of these risks can be identified before surgery. Future protocols should focus on VTE prevention in patients who are predisposed to it.
Chopra, Vineet; Bernstein, Steven J.; Hofer, Timothy P.; Flanders, Scott A.
Background The optimal approach to assess risk of venous thromboembolism (VTE) in hospitalized medical patients is unknown. We examined how well the Caprini risk assessment model (RAM) predicts VTE in hospitalized medical patients. Methods Between January 2011 and March 2014, VTE events and risk factors were collected from non-intensive care unit (ICU) medical patients hospitalized in facilities across Michigan. Following calculation of the Caprini score for each patient, mixed logistic spline regression was used to determine the predicted probabilities of 90-day VTE by receipt of pharmacologic prophylaxis across the Caprini risk continuum. Results A total of 670 (1.05%) of 63,548 eligible patients experienced a VTE event within 90 days of hospital admission. The mean Caprini risk score was 4.94 (range 0 - 28). Predictive modeling revealed a consistent linear increase in VTE for Caprini scores between 1-10; estimates beyond a score of 10 were unstable. Receipt of pharmacologic prophylaxis resulted in a modest decrease in VTE risk (odds ratio=0.85; 95% confidence interval 0.72 - 0.99, p = 0.04). However, the low overall incidence of VTE led to large estimates of numbers needed to treat in order to prevent a single VTE event. A Caprini cut-point demonstrating clear benefit of prophylaxis was not detected. Conclusions Although a linear association between the Caprini RAM and risk of VTE was noted, an extremely low incidence of VTE events in non-ICU medical patients was observed. The Caprini RAM was unable to identify a subset of medical patients who benefit from pharmacologic prophylaxis. PMID:26551977
The UK's prescription drug regulatory agency warned the public and health care providers about the possible increased risk of venous thromboembolism (VTE) among users of the combined oral contraceptives (OCs) containing desogestrel or gestodene. Data from three large not-yet-published studies served as the basis for the warning. The studies found about a 2-fold increased risk of VTE for these OC users when compared to users of OCs with other progestins. Yet the observational studies are subject to inherent biases (e.g., hospitalized cases and selection bias), which may explain the increased risk. Assuming the increased risk to be true, the risk of VTE is still lower than that linked to pregnancy (30 vs. 60 VTE cases per 100,000). The risk of VTE for users of OCs containing older progestins is about 15 VTE cases and that among healthy, nonpregnant, nonusers is about 4 VTE cases. The mortality risk associated with VTE among users of OCs containing desogestrel or gestodene is 1-1.5 deaths/1 million woman-years. The US Food and Drug Administration has examined the data and has concluded that the risk is not high enough to justify switching to other OCs or stopping use of OCs containing desogestrel or gestodene. It recommends that users of the OCs in question discuss the OCs with their providers and make an informed choice based on the benefits and risks and individual preferences. It might consider changes in labeling, but not pulling the OCs off the market. In Germany, women aged less than 30 were temporarily advised not to begin use of desogestrel- or gestodene-containing OCs. Women using them were advised to continue their use, however. The European Union announced that bias or chance could account for the findings and thus did not recommend changes in prescribing desogestrel- or gestodene-containing OCs.
BAJENARU, Ovidiu; ANTOCHI, Florina; BALASA, Rodica; BURAGA, Ioan; PATRICHI, Sanda; SIMU, Mihaela; SZABOLCS, Szatmari; TIU, Cristina; ZAHARIA, Cornelia
The authors present the data of a medical registry which evaluated if the physicians assess VTE risk in stroke patients, during hospitalization period and at hospital discharge and if the thromboprophylaxis is used according to National Guidelines for VTE Prophylaxis. 884 patients with acute ischemic stroke patients were enrolled between June 2010 and December 2011, from 62 centers, 51.4% male and 48.6% female with mean age 70.07 years (68.25 years in the male group and 71.92 years in the female one). There were two co-primary endpoints: the percentage of patients at risk for VTE at hospital admission assessed by the physician, and the percentage of patients with risk factors for VTE that persist at hospital discharge from the total number of patients hospitalized with ischemic stroke. The secondary endpoints were: the percentage of hospitalized patients receiving prophylaxis according to the National Guidelines of VTE Prophylaxis from the total number of patients at risk of VTE, the percentage of hospitalized patients with VTE risk receiving recommendation for thromboprophylaxis at discharge, the duration and the type of VTE prophylaxis in hospitalized patients, the duration and the type of VTE prophylaxis at discharge. Results: 879 (99.4%) of the total number of patients at risk of VTE have received prophylaxis during hospitalization. The most frequently types of prophylaxis used during hospitalisation were LMWH in 96.3% of the patients and mechanic method in 16.6% that were in accordance with the National Guidelines of VTE Prophylaxis recommendations. Conclusions: There is a clear improvement in both assessment and thromprophylaxis recommendation in acute stroke patients with restricted mobility at VTE risk and in our country. LMWH is preferred to unfractionated heparin for venous thromboembolism prophylaxis in this high-risk patient population in view of its better clinical benefits to risk ratio and convenience of once daily administration. PMID:25553119
Dowling, N F; Austin, H; Dilley, A; Whitsett, C; Evatt, B L; Hooper, W C
The aim of this study was to assess, comprehensively, medical and genetic attributes of venous thromboembolism (VTE) in a multiracial American population. The Genetic Attributes and Thrombosis Epidemiology (GATE) study is an ongoing case-control study in Atlanta, Georgia, designed to examine racial differences in VTE etiology and pathogenesis. Between 1998 and 2001, 370 inpatients with confirmed VTE, and 250 control subjects were enrolled. Data collected included blood specimens for DNA and plasma analysis and a medical lifestyle history questionnaire. Comparing VTE cases, cancer, recent surgery, and immobilization were more common in caucasian cases, while hypertension, diabetes, and kidney disease were more prevalent in African-American cases. Family history of VTE was reported with equal frequency by cases of both races (28-29%). Race-adjusted odds ratios for the associations of factor V Leiden and prothrombin G20210A mutations were 3.1 (1.5, 6.7) and 1.9 (0.8, 4.4), respectively. Using a larger external comparison group, the odds ratio for the prothrombin mutation among Caucasians was a statistically significant 2.5 (1.4, 4.3). A case-only analysis revealed a near significant interaction between the two mutations among Caucasians. We found that clinical characteristics of VTE patients differed across race groups. Family history of VTE was common in white and black patients, yet known genetic risk factors for VTE are rare in African-American populations. Our findings underscore the need to determine gene polymorphisms associated with VTE in African-Americans.
Jiang, Jun; Liu, Kang; Zou, Junjie; Ma, Hao; Yang, Hongyu; Zhang, Xiwei; Jiao, Yuanyong
Abstract Background: Recently, several studies showed that the polymorphisms in the coagulation-related genes might be associated with venous thromboembolism (VTE); however, the results were still controversial. We performed a meta-analysis with trial sequential analysis to investigate the associations between the endothelial cell-activated protein C receptor (EPCR) rs9574, F11 rs2289252, F11 rs2036914, FGG rs2066865, FGG rs1049636, CYP4V2 rs13146272, SERPINC1 rs2227589, and GP6 rs1613662 polymorphisms with the risk of VTE. Methods: We searched both the common English-language databases and the Chinese literature databases. Two authors selected studies according to inclusion and exclusion criteria. Crude odds ratios with 95% confidence intervals (CI) were calculated to estimate the strength of this association. Between-study heterogeneity was assessed with the chi-square-based Q test and the I2 statistic. Results: Overall, a total of 20 studies were included. The meta-analysis revealed that the F11 rs2289252, F11 rs2036914, FGG rs2066865, and CYP4V2 rs13146272 polymorphisms were closely related to the development of VTE in the white race under the best genetic models after multiple testing adjustments. The EPCR rs9574, FGG rs1049636, SERPINC1 rs2227589, and GP6 rs1613662 polymorphisms might be potential candidates in the pathogenesis of VTE, but trial sequential analyses and sensitivity analyses indicated that the evidences were limited. Larger scale studies were demanded to avoid false-positive outcomes. Conclusions: Finally, our study demonstrated the important role of rs2289252, rs2036914, rs2066865, and rs13146272 polymorphisms in the development of VTE in the white race. Rs9574, rs1049636, rs2227589 and rs1613662 polymorphisms might be risk factors of VTE. However, more studies involving diverse races are needed to probe the ethnic difference and the underlying mechanisms of significant associations. PMID:28353616
Apixaban, a direct orally active anticoagulant (selective, direct factor Xa inhibitor) is approved for (primary) prevention of venous thromboembolism (VTE) in patients undergoing elective total-hip or total-knee arthroplasty, for acute treatment/prevention of recurrent events in patients with VTE, and extended prophylaxis in patients with a history of VTE. Another approved use is prevention of stroke and systemic embolism in patients with nonvalvular atrial fibrillation. The present overview focuses on the safety of apixaban specifically in the VTE setting. Apixaban displays favorable pharmacokinetic properties: simple twice-daily dosing, low inter- and intrasubject variability, dose and time linearity, and multiple elimination pathways not critically dependent on either renal or metabolic mechanisms. An extensive nonclinical program and the overall clinical development program (all approved and tested indications) provided no signal that would indicate any particular specific safety concern related to apixaban apart from the increased risk of bleeding. With regard to the approved VTE indications, safety (and efficacy) was assessed in five large pivotal Phase III trials. In comparison to currently recommended standard treatments, apixaban shows superior efficacy, while at the same time no excess risk of bleeding in patients undergoing total-hip or total-knee arthroplasty. In treatment of VTE, apixaban shows noninferior efficacy and a reduced risk of bleeding, whereas in extended prophylaxis it reduced the risk of VTE/VTE-related deaths, with no increased risk of relevant bleedings in comparison to placebo. Documented clinical experience with apixaban in daily practice is currently sparse. However, its use is progressively increasing, and there has been no signal so far that would materially change the perception of its safety profile as defined in the premarketing trials. PMID:26937206
Mahé, Isabelle; Sterpu, Raluca; Bertoletti, Laurent; López-Jiménez, Luciano; Mellado Joan, Meritxell; Trujillo-Santos, Javier; Ballaz, Aitor; Hernández Blasco, Luis Manuel; Marchena, Pablo Javier; Monreal, Manuel
Current guidelines of antithrombotic therapy suggest early initiation of vitamin K antagonists (VKA) in non-cancer patients with venous thromboembolism (VTE), and long-term therapy with low-molecular weight heparin (LMWH) for those with cancer. We used data from RIETE (international registry of patients with VTE) to report the use of long-term anticoagulant therapy over time and to identify predictors of anticoagulant choice (regarding international guidelines) in patients with- and without cancer. Among 35,280 patients without cancer, 82% received long-term VKA (but 17% started after the first week). Among 4,378 patients with cancer, 66% received long term LMWH as monotherapy. In patients without cancer, recent bleeding (odds ratio [OR] 2.70, 95% CI 2.26–3.23), age >70 years (OR 1.15, 95% CI 1.06–1.24), immobility (OR 2.06, 95% CI 1.93–2.19), renal insufficiency (OR 2.42, 95% CI 2.15–2.71) and anemia (OR 1.75, 95% CI 1.65–1.87) predicted poor adherence to guidelines. In those with cancer, anemia (OR 1.83, 95% CI 1.64–2.06), immobility (OR 1.51, 95% CI 1.30–1.76) and metastases (OR 3.22, 95% CI 2.87–3.61) predicted long-term LMWH therapy. In conclusion, we report practices of VTE therapy in real life and found that a significant proportion of patients did not receive the recommended treatment. The perceived increased risk for bleeding has an impact on anticoagulant treatment decision. PMID:26076483
Wang, Kang-Ling; Chu, Pao-Hsien; Lee, Cheng-Han; Pai, Pei-Ying; Lin, Pao-Yen; Shyu, Kou-Gi; Chang, Wei-Tien; Chiu, Kuan-Ming; Huang, Chien-Lung; Lee, Chung-Yi; Lin, Yen-Hung; Wang, Chun-Chieh; Yen, Hsueh-Wei; Yin, Wei-Hsian; Yeh, Hung-I; Chiang, Chern-En; Lin, Shing-Jong; Yeh, San-Jou
Deep vein thrombosis (DVT) is a potentially catastrophic condition because thrombosis, left untreated, can result in detrimental pulmonary embolism. Yet in the absence of thrombosis, anticoagulation increases the risk of bleeding. In the existing literature, knowledge about the epidemiology of DVT is primarily based on investigations among Caucasian populations. There has been little information available about the epidemiology of DVT in Taiwan, and it is generally believed that DVT is less common in Asian patients than in Caucasian patients. However, DVT is a multifactorial disease that represents the interaction between genetic and environmental factors, and the majority of patients with incident DVT have either inherited thrombophilia or acquired risk factors. Furthermore, DVT is often overlooked. Although symptomatic DVT commonly presents with lower extremity pain, swelling and tenderness, diagnosing DVT is a clinical challenge for physicians. Such a diagnosis of DVT requires a timely systematic assessment, including the use of the Wells score and a D-dimer test to exclude low-risk patients, and imaging modalities to confirm DVT. Compression ultrasound with high sensitivity and specificity is the front-line imaging modality in the diagnostic process for patients with suspected DVT in addition to conventional invasive contrast venography. Most patients require anticoagulation therapy, which typically consists of parenteral heparin bridged to a vitamin K antagonist, with variable duration. The development of non-vitamin K oral anticoagulants has revolutionized the landscape of venous thromboembolism treatment, with 4 agents available,including rivaroxaban, dabigatran, apixaban, and edoxaban. Presently, all 4 drugs have finished their large phase III clinical trial programs and come to the clinical uses in North America and Europe. It is encouraging to note that the published data to date regarding Asian patients indicates that such new therapies are safe and
Sticchi, Elena; Magi, Alberto; Kamstrup, Pia R.; Marcucci, Rossella; Prisco, Domenico; Martinelli, Ida; Mannucci, Pier Mannuccio; Abbate, Rosanna; Giusti, Betti
In addition to the established association between high lipoprotein(a) [Lp(a)] concentrations and coronary artery disease, an association between Lp(a) and venous thromboembolism (VTE) has also been described. Lp(a) is controlled by genetic variants in LPA gene, coding for apolipoprotein(a), including the kringle-IV type 2 (KIV-2) size polymorphism. Aim of the study was to investigate the role of LPA gene KIV-2 size polymorphism and single nucleotide polymorphisms (SNPs) (rs1853021, rs1800769, rs3798220, rs10455872) in modulating VTE susceptibility. Five hundred and sixteen patients with VTE without hereditary and acquired thrombophilia and 1117 healthy control subjects, comparable for age and sex, were investigated. LPA KIV-2 polymorphism, rs3798220 and rs10455872 SNPs were genotyped by TaqMan technology. Concerning rs1853021 and rs1800769 SNPs, PCR-RFLP assay was used. LPA KIV-2 repeat number was significantly lower in patients than in controls [median (interquartile range) 11(6–17) vs 15(9–25), p<0.0001]. A significantly higher prevalence of KIV-2 repeat number ≤7 was observed in patients than in controls (33.5% vs 15.5%, p<0.0001). KIV-2 repeat number was independently associated with VTE (p = 4.36 x10-9), as evidenced by the general linear model analysis adjusted for transient risk factors. No significant difference in allele frequency for all SNPs investigated was observed. Haplotype analysis showed that LPA haplotypes rather than individual SNPs influenced disease susceptibility. Receiver operating characteristic curves analysis showed that a combined risk prediction model, including KIV-2 size polymorphism and clinical variables, had a higher performance in identifying subjects at VTE risk than a clinical-only model, also separately in men and women. PMID:26900838
Sticchi, Elena; Magi, Alberto; Kamstrup, Pia R; Marcucci, Rossella; Prisco, Domenico; Martinelli, Ida; Mannucci, Pier Mannuccio; Abbate, Rosanna; Giusti, Betti
In addition to the established association between high lipoprotein(a) [Lp(a)] concentrations and coronary artery disease, an association between Lp(a) and venous thromboembolism (VTE) has also been described. Lp(a) is controlled by genetic variants in LPA gene, coding for apolipoprotein(a), including the kringle-IV type 2 (KIV-2) size polymorphism. Aim of the study was to investigate the role of LPA gene KIV-2 size polymorphism and single nucleotide polymorphisms (SNPs) (rs1853021, rs1800769, rs3798220, rs10455872) in modulating VTE susceptibility. Five hundred and sixteen patients with VTE without hereditary and acquired thrombophilia and 1117 healthy control subjects, comparable for age and sex, were investigated. LPA KIV-2 polymorphism, rs3798220 and rs10455872 SNPs were genotyped by TaqMan technology. Concerning rs1853021 and rs1800769 SNPs, PCR-RFLP assay was used. LPA KIV-2 repeat number was significantly lower in patients than in controls [median (interquartile range) 11(6-17) vs 15(9-25), p<0.0001]. A significantly higher prevalence of KIV-2 repeat number ≤7 was observed in patients than in controls (33.5% vs 15.5%, p<0.0001). KIV-2 repeat number was independently associated with VTE (p = 4.36 x10-9), as evidenced by the general linear model analysis adjusted for transient risk factors. No significant difference in allele frequency for all SNPs investigated was observed. Haplotype analysis showed that LPA haplotypes rather than individual SNPs influenced disease susceptibility. Receiver operating characteristic curves analysis showed that a combined risk prediction model, including KIV-2 size polymorphism and clinical variables, had a higher performance in identifying subjects at VTE risk than a clinical-only model, also separately in men and women.
Jain, Varsha; Wotring, Virginia
Venous thromboembolism (VTE) is a common and serious condition affecting approximately 1-2 per 1000 people in the USA every year. There have been no documented case reports of VTE in female astronauts during spaceflight in the published literature. Some female astronauts use hormonal contraception to control their menstrual cycles and it is currently unknown how this affects their risk of VTE. Current terrestrial risk prediction models do not account for the spaceflight environment and the physiological changes associated with it. We therefore aim to estimate a specific risk score for female astronauts who are taking hormonal contraception for menstrual cycle control, to deduce whether they are at an elevated risk of VTE. A systematic review of the literature was conducted in order to identify and quantify known terrestrial risk factors for VTE. Studies involving analogues for the female astronaut population were also reviewed, for example, military personnel who use the oral contraceptive pill for menstrual suppression. Well known terrestrial risk factors, for example, obesity or smoking would not be applicable to our study population as these candidates would have been excluded during astronaut selection processes. Other risk factors for VTE include hormonal therapy, lower limb paralysis, physical inactivity, hyperhomocysteinemia, low methylfolate levels and minor injuries, all of which potentially apply to crew members LSAH data will be assessed to identify which of these risk factors are applicable to our astronaut population. Using known terrestrial risk data, an overall estimated risk of VTE for female astronauts using menstrual cycle control methods will therefore be calculated. We predict this will be higher than the general population but not significantly higher requiring thromboprophylaxis. This study attempts to delineate what is assumed to be true of our astronaut population, for example, they are known to be a healthy fit cohort of individuals, and
Farge, Dominique; Trujillo-Santos, Javier; Debourdeau, Philippe; Bura-Riviere, Alessandra; Rodriguez-Beltrán, Eva Maria; Nieto, Jose Antonio; Peris, Maria Luisa; Zeltser, David; Mazzolai, Lucia; Hij, Adrian; Monreal, Manuel
Abstract In cancer patients treated for venous thromboembolism (VTE), including deep-vein thrombosis (DVT) and pulmonary embolism (PE), analyzing mortality associated with recurrent VTE or major bleeding is needed to determine the optimal duration of anticoagulation. This was a cohort study using the Registro Informatizado de Enfermedad TromboEmbólica (RIETE) Registry database to compare rates of fatal recurrent PE and fatal bleeding in cancer patients receiving anticoagulation for VTE. As of January 2013, 44,794 patients were enrolled in RIETE, of whom 7911 (18%) had active cancer. During the course of anticoagulant therapy (mean, 181 ± 210 days), 178 cancer patients (4.3%) developed recurrent PE (5.5 per 100 patient-years; 95% CI: 4.8–6.4), 194 (4.7%) had recurrent DVT (6.2 per 100 patient-years; 95% confidence interval [CI]: 5.3–7.1), and 367 (8.9%) bled (11.3 per 100 patient-years; 95% CI: 10.2–12.5). Of 4125 patients initially presenting with PE, 43 (1.0%) died of recurrent PE and 45 (1.1%) of bleeding; of 3786 patients with DVT, 19 (0.5%) died of PE, and 55 (1.3%) of bleeding. During the first 3 months of anticoagulation, there were 59 (1.4%) fatal PE recurrences and 77 (1.9%) fatal bleeds. Beyond the third month, there were 3 fatal PE recurrences and 23 fatal bleeds. In RIETE cancer patients, the rate of fatal recurrent PE or fatal bleeding was much higher within the first 3 months of anticoagulation therapy. PMID:26266353
Yusuf, Hussain R; Hooper, W Craig; Beckman, Michele G; Zhang, Qing C; Tsai, James; Ortel, Thomas L
Previous research has suggested autoimmune diseases are risk factors for developing venous thromboembolism (VTE). We assessed whether having diagnoses of selected autoimmune diseases associated with antiphospholipid antibodies--autoimmune hemolytic anemia (AIHA), immune thrombocytopenic purpura (ITP), rheumatoid arthritis (RA), and systemic lupus erythematosus (SLE)--were associated with having a VTE diagnosis among US adult hospitalizations. A cross-sectional study was conducted using the 2010 Nationwide Inpatient Sample of the Healthcare Cost and Utilization Project, Agency for Healthcare Research and Quality. VTE and autoimmune diseases were identified using International Classification of Diseases, Ninth Revision, Clinical Modification coded diagnoses information. The percentages of hospitalizations with a VTE diagnosis among all non-maternal adult hospitalizations without any of the four autoimmune diseases of interest and among those with AIHA, ITP, RA, and SLE diagnoses were 2.28, 4.46, 3.35, 2.65 and 2.77%, respectively. The adjusted odds ratios (OR) for having a diagnosis of VTE among non-maternal adult hospitalizations with diagnoses of AIHA, ITP, RA, and SLE were 1.25 [95% confidence interval (CI) 1.05-1.49], 1.20 (95% CI 1.07-1.34), 1.17 (95% CI 1.13-1.21), and 1.23 (95% CI 1.15-1.32), respectively, when compared to those without the corresponding conditions. The adjusted OR for a diagnosis of VTE associated with a diagnosis of any of the four autoimmune diseases was 1.20 (95% CI 1.16-1.24). The presence of a diagnosis of AIHA, ITP, RA, and SLE was associated with an increased likelihood of having a VTE diagnosis among the group of all non-maternal adult hospitalizations.
Streiff, Michael B; Lau, Brandyn D; Hobson, Deborah B; Kraus, Peggy S; Shermock, Kenneth M; Shaffer, Dauryne L; Popoola, Victor O; Aboagye, Jonathan K; Farrow, Norma A; Horn, Paula J; Shihab, Hasan M; Pronovost, Peter J; Haut, Elliott R
Venous thromboembolism (VTE) is an important cause of preventable harm in hospitalized patients. The critical steps in delivery of optimal VTE prevention care include (1) assessment of VTE and bleeding risk for each patient, (2) prescription of risk-appropriate VTE prophylaxis, (3) administration of risk-appropriate VTE prophylaxis in a patient-centered manner, and (4) continuously monitoring outcomes to identify new opportunities for learning and performance improvement. To ensure that every hospitalized patient receives VTE prophylaxis consistent with their individual risk level and personal care preferences, we organized a multidisciplinary task force, the Johns Hopkins VTE Collaborative. To achieve the goal of perfect prophylaxis for every patient, we developed evidence-based, specialty-specific computerized clinical decision support VTE prophylaxis order sets that assist providers in ordering risk-appropriate VTE prevention. We developed novel strategies to improve provider VTE prevention ordering practices including face-to-face performance reviews, pay for performance, and provider VTE scorecards. When we discovered that prescription of risk-appropriate VTE prophylaxis does not ensure its administration, our multidisciplinary research team conducted in-depth surveys of patients, nurses, and physicians to design a multidisciplinary patient-centered educational intervention to eliminate missed doses of pharmacologic VTE prophylaxis that has been funded by the Patient Centered Outcomes Research Institute. We expect that the studies currently underway will bring us closer to the goal of perfect VTE prevention care for every patient. Our learning journey to eliminate harm from VTE can be applied to other types of harm. Journal of Hospital Medicine 2016;11:S8-S14. © 2016 Society of Hospital Medicine.
Agzarian, John; Linkins, Lori-Ann; Schneider, Laura; Hanna, Waël C.; Finley, Christian J.; Schieman, Colin; De Perrot, Marc; Crowther, Mark; Douketis, James
Background The incidence of venous thromboembolic events (VTE) after resection of thoracic malignancies can reach 15%, but prophylaxis guidelines are yet to be established. We aimed to survey Canadian practitioners regarding perioperative risk factors for VTE, impact of those factors on extended prophylaxis selection, type of preferred prophylaxis, and timing of initiation and duration of thromboprophylaxis. Methods A modified Delphi survey was undertaken over three rounds with thoracic surgeons, thoracic anesthesiologists and thrombosis experts across Canada. Participants were asked to rate each parameter on a ten-point scale. Agreement was determined a priori as an item reaching a coefficient of variation of ≤30% (0.3), with the item then discontinued from later rounds. Results In total, 72, 57 and 50 respondents participated in three consecutive rounds, respectively. Consensus was reached on previous VTE, age, cancer diagnosis, thrombophilia, poor mobilization, extended resections, and pre-operative chemotherapy as risk factors. Consensus on risk factors impacting extended prophylaxis decisions was achieved on cancer diagnosis, obesity, previous VTE and poor mobilization. With respect to perioperative prophylaxis, once daily low-molecular-weight heparin (LMWH) was the only parameter that demonstrated agreement as a common practice pattern. No agreement was achieved regarding the role of mechanical prophylaxis, unfractionated heparin (UFH) or timing of initiation of peri-operative treatment. VTE prophylaxis until discharge reached agreement but there was substantial variability regarding the role of extended prophylaxis. Conclusions There is agreement between Canadian clinicians treating patients with thoracic malignancies regarding most risk factors for VTE, but there is no agreement on timing of initiation of prophylaxis, the agents used or factors mandating usage of extended prophylaxis. PMID:28203409
Hotoleanu, Cristina; Trifa, Adrian; Popp, Radu; Fodor, Daniela
Background: Methylenetetrahydrofolate reductase (MTHFR) polymorphisms have recently raised the interest as a possible thrombophilic factors. Aims: We aimed to assess the frequency of the methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C polymorphisms in idiopathic venous thromboembolism (VTE) in a Romanian population and the associated risk of VTE. Study Design: We performed a case-control transversal study including 90 patients diagnosed with VTE and 75 sex- and age-matched controls. Methods: MTHFR C677T and A1298C polymorphisms were detected using PCR-RFLP method. Results: The homozygous MTHFR 677TT genotype, present in 18.8% of patients with VTE versus 6.6% of controls, was significantly associated with VTE (p= 0.021, OR= 3.26, 95%CI (1.141–9.313)). The heterozygous MTHFR A1298C genotype, presenting the highest prevalence in the VTE group (34.4%) as well as in controls (37.3%), was not associated with VTE (p=0.7). No associations were found for heterozygous MTHFR C677T (with a frequency of 32.2% in VTE and 37.3% in controls, p=0.492), respective homozygous MTHFR A1298C genotype (with a frequency of 1.1% in VTE and 2.6% in controls, p=0.456). Conclusion: Among MTHFR polymorphisms, only homozygosity for MTHFR 677TT may be considered a risk factor for VTE; the MTHFR A1298C polymorphism is not significantly associated with an increased risk of VTE. PMID:25207100
Farmer, R D; Todd, J C; Lewis, M A; MacRae, K D; Williams, T J
This study investigated the risk of venous thromboembolic disease (VTE) between second and third generation combined oral contraceptives, using the German MediPlus database of patient records. Women studied included 42 patients between the ages of 18 and 49 years, with a diagnosis of VTE treated with an anticoagulant, who were exposed to an oral contraceptive (OC). Four controls per patient (168), matched by year of birth and exposure to an OC on the even day, were identified. More women were users of second generation than third generation OC, and none were using progestogen-only pills. There was no significant difference between patients and control subjects with respect to the type of OC used on the event day (unadjusted odds ratio for third versus second generation users was 0.77; 95% confidence interval [CI] 0.38-1.57). There was no significant age difference between second and third generation users among patients or control subjects. Between January 1 and the event date, there was no significant difference between the patients and control subjects in terms of the number of oral contraceptive prescriptions, number of consultations for psychotherapeutic complaints, or mixed physical and psychotherapeutic consultations; however, patients did demonstrate significantly more consultations for purely physical complaints compared with control subjects (p < 0.0001). There were no significant consultation differences between patients with pulmonary emboli (n = 6) and other VTE patients (n = 36). No significant differences with respect to VTE risk between users of second and third generation oral contraceptives were found in this study. Consultations (physical) for patients were higher than for control subjects before the VTE event. If consultation rate relates to the general health status of a person, this might indicate that VTE risk is higher among women of poorer health, but that this is not related to the type of progestogen in the oral contraceptive that they use.
Gerhardt, Andrea; Scharf, Rüdiger E; Greer, Ian A; Zotz, Rainer B
Venous thromboembolism (VTE) is a leading cause of maternal mortality. Few studies have evaluated the individual risk of gestational VTE associated with heritable thrombophilia and current recommendations for antenatal thromboprophylaxis in women with severe thrombophilia such as homozygous factor V Leiden mutation (FVL) depend on a positive family history of VTE. To better stratify thromboprophylaxis in pregnancy, we aimed to estimate the individual probability (absolute risk) of gestational VTE associated with thrombophilia and whether these risk factors are independent of a family history of VTE in first-degree relatives. We studied 243 women with first VTE during pregnancy and the puerperium, and 243 age-matched normal women. Baseline incidence of VTE of 1:483 pregnancies in women ≥35 years and 1:741 deliveries in women <35 years was assumed, according to a recent population-based study. In women ≥35 years [<35 years], the individual probability of gestational VTE was: 0.7% [0.5%] for heterozygous FVL; 3.4% [2.2%], for homozygous FVL; 0.6% [0.4%], for heterozygous prothrombin G20210A; 8.2% [5.5%] for compound heterozygotes for FVL and prothrombin G20210A; 9.0% [6.1%] for antithrombin deficiency; 1.1% [0.7%] for protein C deficiency; and 1.0% [0.7%] for protein S deficiency These results were independent of a positive family history of VTE. We provide evidence that unselected women with these thrombophilias have an increased risk of gestational VTE independent of a positive family history of VTE. In contrast to current guidelines, these data suggest that women with high-risk thrombophilia should be considered for antenatal thromboprophylaxis regardless of family history of VTE.
Creary, Susan; Heiny, Mark; Croop, James; Fallon, Robert; Vik, Terry; Hulbert, Monica; Knoderer, Holly; Kumar, Manjusha; Sharathkumar, Anjali
Postthrombotic syndrome (PTS) is a chronic morbidity of venous thromboembolism (VTE) in children. Information about the evolution of PTS is lacking in children. Present study was aimed to evaluate the time-course of extremity PTS in children who were serially followed in a hematology clinic. This retrospective cohort study included 69 consecutive children with documented VTEs that presented with symptoms of extremity VTE: 67 extremity VTEs with or without extension to vena cava, 2 inferior vena cava VTEs. Severity of PTS was assessed using modified Villalta scale. Median age of the cohort was 12.6 years (interquartile range 1.6-15 years) while median follow-up was 28.7 months (interquartile range 13.3-33.4 months. PTS prevalence was 46.8% [95% confidence interval (CI) 37.9-57.7%]. Lower extremity VTE was associated with development of PTS compared to upper extremity VTE regardless of catheter use (P = 0.002). The time-course of PTS fluctuated in 11 of 33 children (33%; 95% CI 20-47%) at a median interval of 12 months from diagnosis of VTE (range 4-14 months): three progressed from mild/moderate to severe, one improved from moderate to mild, seven fluctuated between mild and moderate. Recurrence and incomplete resolution of VTE were associated with variability in PTS severity (P < 0.05). In summary, this study suggested that almost 50% of study cohort developed PTS, and the time-course of PTS was not static in one third of children. Future research should focus on identifying the predictors contributing to the worsening of PTS and developing risk-stratified treatment interventions so as to improve the outcome of children with VTE.
Torres, Cláudia; Fonseca, Ana Mafalda; Leander, Magdalena; Matos, Rui; Morais, Sara; Campos, Manuel; Lima, Margarida
Background Circulating endothelial cells (CEC) may be a biomarker of vascular injury and pro-thrombotic tendency, while circulating endothelial progenitor cells (CEP) may be an indicator for angiogenesis and vascular remodelling. However, there is not a universally accepted standardized protocol to identify and quantify these cells and its clinical relevancy remains to be established. Objectives To quantify CEC and CEP in patients with venous thromboembolism (VTE) and with myeloproliferative neoplasms (MPN), to characterize the CEC for the expression of activation (CD54, CD62E) and procoagulant (CD142) markers and to investigate whether they correlate with other clinical and laboratory data. Patients and Methods Sixteen patients with VTE, 17 patients with MPN and 20 healthy individuals were studied. The CEC and CEP were quantified and characterized in the blood using flow cytometry, and the demographic, clinical and laboratory data were obtained from hospital records. Results We found the CEC counts were higher in both patient groups as compared to controls, whereas increased numbers of CEP were found only in patients with MPN. In addition, all disease groups had higher numbers of CD62E+ CEC as compared to controls, whereas only patients with VTE had increased numbers of CD142+ and CD54+ CEC. Moreover, the numbers of total and CD62+ CEC correlated positively with the white blood cells (WBC) counts in both groups of patients, while the numbers of CEP correlated positively with the WBC counts only in patients with MPN. In addition, in patients with VTE a positive correlation was found between the numbers of CD54+ CEC and the antithrombin levels, as well as between the CD142+ CEC counts and the number of thrombotic events. Conclusions Our study suggests that CEC counts may reveal endothelial injury in patients with VTE and MPN and that CEC may express different activation-related phenotypes depending on the disease status. PMID:24339944
Bullock, Mark J; DeCarbo, William T; Hofbauer, Mark H; Thun, Joshua D
Background Despite the low incidence of deep vein thrombosis (DVT) in foot and ankle surgery, some authors report a high incidence of symptomatic DVT following Achilles tendon rupture. The purpose of this study was to identify DVT risk factors inherent to Achilles tendon repair to determine which patients may benefit from prophylaxis. Methods One hundred and thirteen patient charts were reviewed following elective and nonelective Achilles tendon repair. For elective repair of insertional or noninsertional Achilles tendinopathy, parameters examined included lateral versus prone positioning and the presence versus absence of a flexor hallucis longus transfer. For nonelective repair, acute Achilles tendon ruptures were compared to chronic Achilles tendon ruptures. Results Of 113 Achilles tendon repairs, 3 venous thromboembolism (VTE) events (2.65%) occurred including 2 pulmonary emboli (1.77%). Seventeen of these repairs were chronic Achilles tendon ruptures, and all 3 VTE events (17.6%) occurred within this subgroup. Elevated body mass index was associated with VTE in patients with chronic Achilles ruptures although this did not reach significance (P = .064). No VTE events were reported after repair of 28 acute tendon ruptures or after 68 elective repairs of tendinopathy. Two patients with misdiagnosed partial Achilles tendon tears were excluded because they experienced a VTE event 3 weeks and 5 weeks after injury, prior to surgery. Conclusion In our retrospective review, chronic Achilles ruptures had a statistically significant higher incidence of VTE compared with acute Achilles ruptures (P = .048) or elective repair (P = .0069). Pharmaceutical anticoagulation may be considered for repair of chronic ruptures. Repair of acute ruptures and elective repair may not warrant routine prophylaxis due to a lower incidence of VTE.
Lutsey, Pamela L; Steffen, Lyn M; Virnig, Beth A; Folsom, Aaron R
Background Little is known about the role of diet in the development of venous thromboembolism (VTE). We explored the prospective relation of dietary patterns, food groups, and nutrients to incident VTE in older women. Methods In 1986, Iowa women aged 55–69 completed a mailed survey, including a 127-item food frequency questionnaire. These data were linked to Medicare data from 1986–2004, and International Classification of Disease discharge codes were used to identify hospitalized VTE cases. Cox regression analyses evaluated relations of 2 principal components-derived dietary patterns, 11 food groups, and 6 nutrients to VTE, adjusted for age, education, smoking status, physical activity, and energy intake. Results Over 19 years of follow-up 1,950 of the 37,393 women developed VTE. Women consuming alcohol daily were at 26% (95% CI: 11%–38%) lower risk of VTE, as compared to nonconsumers. All alcoholic beverages types were in the direction of lower risk, however only beer and liquor were statistically significant. After basic adjustments coffee was inversely related to VTE, and diet soda and fish positively related. However, these associations were confounded, and became nonsignificant after adjustment for body mass index and diabetes. No associations were observed with consumption of ‘Western’ or ‘Prudent’ dietary patterns, fruit, vegetables, dairy, meat, refined grains, whole grains, regular soda, vitamins E, B6, B12, folate, omega-3 fatty acids, or saturated fat. Conclusions In this cohort of older women, greater intake of alcohol was associated with a lower risk of incident VTE. No other independent associations were seen between diet and VTE. PMID:19464420
Pulanić, Dražen; Gverić-Krečak, Velka; Nemet-Lojan, Zlatka; Holik, Hrvoje; Coha, Božena; Babok-Flegarić, Renata; Komljenović, Mili; Knežević, Dijana; Petrovečki, Mladen; Zupančić Šalek, Silva; Labar, Boris; Nemet, Damir
Aim To analyze the incidence and characteristics of venous thromboembolism (VTE) in Croatia. Methods The Croatian Cooperative Group for Hematologic Diseases conducted an observational non-interventional study in 2011. Medical records of patients with newly diagnosed VTE hospitalized in general hospitals in 4 Croatian counties (Šibenik-Knin, Koprivnica-Križevci, Brod-Posavina, and Varaždin County) were reviewed. According to 2011 Census, the population of these counties comprises 13.1% of the Croatian population. Results There were 663 patients with VTE; 408 (61.54%) had deep vein thrombosis, 219 (33.03%) had pulmonary embolism, and 36 (5.43%) had both conditions. Median age was 71 years, 290 (43.7%) were men and 373 (56.3%) women. Secondary VTE was found in 57.3% of participants, idiopathic VTE in 42.7%, and recurrent VTE in 11.9%. There were no differences between patients with secondary VTE and patients with idiopathic VTE in disease recurrence and sex. The most frequent causes of secondary VTE were cancer (40.8%), and trauma, surgery, and immobilization (38.2%), while 42.9% patients with secondary VTE had ≥2 causes. There were 8.9% patients ≤45 years; 3.3% with idiopathic or recurrent VTE. Seventy patients (10.6%) died, more of whom had secondary (81.4%) than idiopathic (18.6%) VTE (P < 0.001), and in 50.0% VTE was the main cause of death. Estimated incidence of VTE in Croatia was 1.185 per 1000 people. Conclusion Characteristics of VTE in Croatia are similar to those reported in large international studies. Improved thromboprophylaxis during the presence of risk factors for secondary VTE might substantially lower the VTE burden. PMID:26718761
Zilio, Marialuisa; Mazzai, Linda; Sartori, Maria Teresa; Barbot, Mattia; Ceccato, Filippo; Daidone, Viviana; Casonato, Alessandra; Saggiorato, Graziella; Noventa, Franco; Trementino, Laura; Prandoni, Paolo; Boscaro, Marco; Arnaldi, Giorgio; Scaroni, Carla
Cushing's syndrome (CS) is associated with an incidence of venous thromboembolism (VTE) about ten times higher than in the normal population. The aim of our study was to develop a model for identifying CS patients at higher risk of VTE. We considered clinical, hormonal, and coagulation data from 176 active CS patients and used a forward stepwise logistic multivariate regression analysis to select the major independent risk factors for thrombosis. The risk of VTE was calculated as a 'CS-VTE score' from the sum of points of present risk factors. VTE developed in 20 patients (4 pulmonary embolism). The group of CS patients with VTE were older (p < 0.001) and had more cardiovascular events (p < 0.05), infections and reduced mobility (both p < 0.001), higher midnight plasma cortisol levels (p < 0.05), and shorter APTT (p < 0.01) than those without. We identified six major independent risk factors for VTE: age ≥69 years and reduced mobility were given two points each, whereas acute severe infections, previous cardiovascular events, midnight plasma cortisol level >3.15 times the normality and shortened APTT were given one point each. A CS-VTE score <2 anticipated no risk of VTE; a CS-VTE score of two mild risk (10 %); a CS-VTE score of three moderate risk (46 %); a CS-VTE score ≥4 high risk (85 %). Considering a score ≥3 as predictive of VTE, 94 % of the patients were correctly classified. A simple score helps stratify the VTE risk in CS patients and identify those who could benefit from thromboprophylaxis.
Cote, David J; Dubois, Heloise M; Karhade, Aditya V; Smith, Timothy R
Background Patients who undergo craniotomy for brain tumor have an increased risk of developing venous thromboembolism (VTE). Using the National Surgical Quality Improvement Program (NSQIP) registry, patients undergoing craniotomy for brain tumor from 2006 and 2014 were analyzed to identify risk factors for postoperative VTE. Methods The study population, identified by Current Procedural Terminology codes, included all NSQIP-reported patients who underwent a craniotomy for brain tumor resection. Results There were 629 instances of VTE among 19,409 craniotomies for brain tumor (3.2%) recorded in NSQIP. Occurrence of VTE was associated with other postoperative complications on univariate analysis, including pneumonia, respiratory failure, stroke, and sepsis (all p < 0.001). On multivariate analysis, independent predictors of VTE included age 46 to 57 years (odds ratio [OR], 1.432; p = 0.006), 57 to 66 years (OR, 1.550; p = 0.001), or over 66 years (OR, 2.493; p < 0.001), body mass index (BMI) over 32.1 kg/m(2) (OR, 1.835; p < 0.001), functional dependence (OR, 1.657; p < 0.001), ventilator dependence (OR, 2.516; p < 0.001), steroid use (OR, 1.661; p < 0.001), prior sepsis (OR, 1.845; p < 0.001), and total operative time 183 to 271 minutes (OR, 1.462; p = 0.032) and longer than 271 minutes (OR, 1.945; p < 0.001). Conclusions VTE occurs in approximately 3% of patients undergoing craniotomy for brain tumor resection. Independent predictors for developing VTE include older age, higher BMI, recent steroid use, and total operative time.
Wang, Yang; Liu, Jiannan; Yin, Xuelai; Hu, Jingzhou; Kalfarentzos, Evagelos; Zhang, Chenping
Background Venous thromboembolism (VTE) including deep vein thrombosis (DVT) and pulmonary embolism (PE) is a leading cause of death in cancer patients. The aim of this study was to explore the potential risk factor of VTE in oral and maxillofacial oncological surgery. Material and Methods The data of patients who received operation in our institution were gathered in this retrospective study. A diagnosis of VTE was screened and confirmed by computer tomography angiography (CTA) of pulmonary artery or ultrasonography examination of lower extremity. Medical history and all perioperative details were analyzed. Results 14 patients were diagnosed as VTE, including 6 cases of PE, 7 cases of DVT, 1case of DVT and PE. The mean age of these patients was 62.07 years. Reconstruction was performed in 12 patients of these cases, most of which were diagnosed as malignance. Mean length of surgery was 8.74 hours, and lower extremity deep venous cannula (DVC) was performed in all these patients. Conclusions We analyzed several characters of oral and maxillofacial surgery and suggested pay attention to lower extremity DVC which had a high correlation with DVT according to our data. Key words:Venous thromboembolism, pulmonary embolism, deep vein thrombosis, oral and maxillofacial surgery. PMID:27918738
Roy, Pierre-Marie; Rachas, Antoine; Meyer, Guy; Le Gal, Grégoire; Durieux, Pierre; El Kouri, Dominique; Honnart, Didier; Schmidt, Jeannot; Legall, Catherine; Hausfater, Pierre; Chrétien, Jean-Marie; Mottier, Dominique
Background Misuse of thromboprophylaxis may increase preventable complications for hospitalized medical patients. Objectives To assess the net clinical benefit of a multifaceted intervention in emergency wards (educational lectures, posters, pocket cards, computerized clinical decision support systems and, where feasible, electronic reminders) for the prevention of venous thromboembolism. Patients/Methods Prospective cluster-randomized trial in 27 hospitals. After a pre-intervention period, centers were randomized as either intervention (n = 13) or control (n = 14). All patients over 40 years old, admitted to the emergency room, and hospitalized in a medical ward were included, totaling 1,402 (712 intervention and 690 control) and 15,351 (8,359 intervention and 6,992 control) in the pre-intervention and intervention periods, respectively. Results Symptomatic venous thromboembolism or major bleeding (primary outcome) occurred at 3 months in 3.1% and 3.2% of patients in the intervention and control groups, respectively (adjusted odds ratio: 1.02 [95% confidence interval: 0.78–1.34]). The rates of thromboembolism (1.9% vs. 1.9%), major bleedings (1.2% vs. 1.3%), and mortality (11.3% vs. 11.1%) did not differ between the groups. Between the pre-intervention and intervention periods, the proportion of patients who received prophylactic anticoagulant treatment more steeply increased in the intervention group (from 35.0% to 48.2%: +13.2%) than the control (40.7% to 44.1%: +3.4%), while the rate of adequate thromboprophylaxis remained stable in both groups (52.4% to 50.9%: -1.5%; 49.1% to 48.8%: -0.3%). Conclusions Our intervention neither improved adequate prophylaxis nor reduced the rates of clinical events. New strategies are required to improve thromboembolism prevention for hospitalized medical patients. Trial Registration ClinicalTrials.gov NCT01212393 PMID:27227406
Li, Guowei; Cook, Deborah J.; Levine, Mitchell A.H.; Guyatt, Gordon; Crowther, Mark; Heels-Ansdell, Diane; Holbrook, Anne; Lamontagne, Francois; Walter, Stephen D.; Ferguson, Niall D.; Finfer, Simon; Arabi, Yaseen M.; Bellomo, Rinaldo; Cooper, D. Jamie; Thabane, Lehana
Abstract Failure to recognize the presence of competing risk or to account for it may result in misleading conclusions. We aimed to perform a competing risk analysis to assess the efficacy of the low molecular weight heparin dalteparin versus unfractionated heparin (UFH) in venous thromboembolism (VTE) in medical-surgical critically ill patients, taking death as a competing risk. This was a secondary analysis of a prospective randomized study of the Prophylaxis for Thromboembolism in Critical Care Trial (PROTECT) database. A total of 3746 medical-surgical critically ill patients from 67 intensive care units (ICUs) in 6 countries receiving either subcutaneous UFH 5000 IU twice daily (n = 1873) or dalteparin 5000 IU once daily plus once-daily placebo (n = 1873) were included for analysis. A total of 205 incident proximal leg deep vein thromboses (PLDVT) were reported during follow-up, among which 96 were in the dalteparin group and 109 were in the UFH group. No significant treatment effect of dalteparin on PLDVT compared with UFH was observed in either the competing risk analysis or standard survival analysis (also known as cause-specific analysis) using multivariable models adjusted for APACHE II score, history of VTE, need for vasopressors, and end-stage renal disease: sub-hazard ratio (SHR) = 0.92, 95% confidence interval (CI): 0.70–1.21, P-value = 0.56 for the competing risk analysis; hazard ratio (HR) = 0.92, 95% CI: 0.68–1.23, P-value = 0.57 for cause-specific analysis. Dalteparin was associated with a significant reduction in risk of pulmonary embolism (PE): SHR = 0.54, 95% CI: 0.31–0.94, P-value = 0.02 for the competing risk analysis; HR = 0.51, 95% CI: 0.30–0.88, P-value = 0.01 for the cause-specific analysis. Two additional sensitivity analyses using the treatment variable as a time-dependent covariate and using as-treated and per-protocol approaches demonstrated similar findings. This competing risk analysis
Li, Guowei; Cook, Deborah J; Levine, Mitchell A H; Guyatt, Gordon; Crowther, Mark; Heels-Ansdell, Diane; Holbrook, Anne; Lamontagne, Francois; Walter, Stephen D; Ferguson, Niall D; Finfer, Simon; Arabi, Yaseen M; Bellomo, Rinaldo; Cooper, D Jamie; Thabane, Lehana
Failure to recognize the presence of competing risk or to account for it may result in misleading conclusions. We aimed to perform a competing risk analysis to assess the efficacy of the low molecular weight heparin dalteparin versus unfractionated heparin (UFH) in venous thromboembolism (VTE) in medical-surgical critically ill patients, taking death as a competing risk.This was a secondary analysis of a prospective randomized study of the Prophylaxis for Thromboembolism in Critical Care Trial (PROTECT) database. A total of 3746 medical-surgical critically ill patients from 67 intensive care units (ICUs) in 6 countries receiving either subcutaneous UFH 5000 IU twice daily (n = 1873) or dalteparin 5000 IU once daily plus once-daily placebo (n = 1873) were included for analysis.A total of 205 incident proximal leg deep vein thromboses (PLDVT) were reported during follow-up, among which 96 were in the dalteparin group and 109 were in the UFH group. No significant treatment effect of dalteparin on PLDVT compared with UFH was observed in either the competing risk analysis or standard survival analysis (also known as cause-specific analysis) using multivariable models adjusted for APACHE II score, history of VTE, need for vasopressors, and end-stage renal disease: sub-hazard ratio (SHR) = 0.92, 95% confidence interval (CI): 0.70-1.21, P-value = 0.56 for the competing risk analysis; hazard ratio (HR) = 0.92, 95% CI: 0.68-1.23, P-value = 0.57 for cause-specific analysis. Dalteparin was associated with a significant reduction in risk of pulmonary embolism (PE): SHR = 0.54, 95% CI: 0.31-0.94, P-value = 0.02 for the competing risk analysis; HR = 0.51, 95% CI: 0.30-0.88, P-value = 0.01 for the cause-specific analysis. Two additional sensitivity analyses using the treatment variable as a time-dependent covariate and using as-treated and per-protocol approaches demonstrated similar findings.This competing risk analysis yields no
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) acquired during hospitalization is common, yet preventable by the proper implementation of thromboprophylaxis which remains to be underutilized worldwide. As a result of an initiative by the Saudi Ministry of Health to improve medical practices in the country, an expert panel led by the Saudi Association for Venous Thrombo Embolism (SAVTE; a subsidiary of the Saudi Thoracic Society) with the methodological guidance of the McMaster University Guideline working group, produced this clinical practice guideline to assist healthcare providers in VTE prevention. The expert part panel issued ten recommendations addressing 10 prioritized questions in the following areas: thromboprophylaxis in acutely ill medical patients (Recommendations 1-5), thromboprophylaxis in critically ill medical patients (Recommendations 6-9), and thromboprophylaxis in chronically ill patients (Recommendation 10). The corresponding recommendations were generated following the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) approach. PMID:27761572
Agnelli, Giancarlo; Bolis, Giorgio; Capussotti, Lorenzo; Scarpa, Roberto Mario; Tonelli, Francesco; Bonizzoni, Erminio; Moia, Marco; Parazzini, Fabio; Rossi, Romina; Sonaglia, Francesco; Valarani, Bettina; Bianchini, Carlo; Gussoni, Gualberto
Summary Background Data: The epidemiology of venous thromboembolism (VTE) after cancer surgery is based on clinical trials on VTE prophylaxis that used venography to screen deep vein thrombosis (DVT). However, the clinical relevance of asymptomatic venography-detected DVT is unclear, and the population of these clinical trials is not necessarily representative of the overall cancer surgery population. Objective: The aim of this study was to evaluate the incidence of clinically overt VTE in a wide spectrum of consecutive patients undergoing surgery for cancer and to identify risk factors for VTE. Methods: @RISTOS was a prospective observational study in patients undergoing general, urologic, or gynecologic surgery. Patients were assessed for clinically overt VTE occurring up to 30 ± 5 days after surgery or more if the hospital stay was longer than 35 days. All outcome events were evaluated by an independent Adjudication Committee. Results: A total of 2373 patients were included in the study: 1238 (52%) undergoing general, 685 (29%) urologic, and 450 (19%) gynecologic surgery. In-hospital prophylaxis was given in 81.6% and postdischarge prophylaxis in 30.7% of the patients. Fifty patients (2.1%) were adjudicated as affected by clinically overt VTE (DVT, 0.42%; nonfatal pulmonary embolism, 0.88%; death 0.80%). The incidence of VTE was 2.83% in general surgery, 2.0% in gynecologic surgery, and 0.87% in urologic surgery. Forty percent of the events occurred later than 21 days from surgery. The overall death rate was 1.72%; in 46.3% of the cases, death was caused by VTE. In a multivariable analysis, 5 risk factors were identified: age above 60 years (2.63, 95% confidence interval, 1.21–5.71), previous VTE (5.98, 2.13–16.80), advanced cancer (2.68, 1.37–5.24), anesthesia lasting more than 2 hours (4.50, 1.06–19.04), and bed rest longer than 3 days (4.37, 2.45–7.78). Conclusions: VTE remains a common complication of cancer surgery, with a remarkable proportion
Marks, Morgan A.; Engels, Eric A.
Background Few studies have evaluated cancer risk following venous thromboembolism (VTE). Both VTE and cancer disproportionately affect older adults. Methods Using linked Surveillance, Epidemiology, and End Results (SEER)-Medicare data, we evaluated 1.2 million cancer cases and 200,000 controls (66–99 years old, 1992–2005). VTEs occurring before selection were identified using Medicare claims. Logistic regression was used to estimate odds ratios (ORs). Results VTE was present in 2.5% of cases and 2.2% of controls. VTE was associated with risk of cancers of the lung (OR 1.18, 95%CI 1.12–1.23), stomach (1.19, 1.09–1.30), small intestine (1.42, 1.17–1.71), colon (1.25, 1.18–1.31), gallbladder (1.39, 1.16–1.67), pancreas (1.53, 1.43–1.64), soft tissue (1.43, 1.21–1.68), ovary (1.35, 1.22–1.50), and kidney/renal pelvis (1.34, 1.23–1.46), and melanoma (1.17, 1.08–1.27), non-Hodgkin lymphoma (1.27, 1.20–1.35), myeloma (1.48, 1.35–1.63), and acute myeloid leukemia (1.35, 1.19–1.54). Strongest risks were observed within 1 year of VTE diagnosis, but risk were elevated more than 6 years after VTE for colon cancer (OR 1.24, 95%CI 1.12–1.37), pancreatic cancer (1.33, 1.15–1.54), and myeloma (1.35, 1.10–1.66). Few differences in risk were observed by VTE subtype. Cancers of the lung, stomach, and pancreas were more likely to have distant metastases within one year after VTE. Conclusion Among elderly adults, cancer risk is elevated following VTE diagnosis. Impact Short-term associations with cancer are likely driven by enhanced screening following VTE and reverse causation. While obesity, other co-morbidities, and smoking cannot be excluded as explanations, longer-term elevations for select cancers suggest that some VTEs may be caused by cancer precursors. PMID:24608188
Barco, Stefano; Woersching, Alex L; Spyropoulos, Alex C; Piovella, Franco; Mahan, Charles E
Annual costs for venous thromboembolism (VTE) have been defined within the United States (US) demonstrating a large opportunity for cost savings. Costs for the European Union-28 (EU-28) have never been defined. A literature search was conducted to evaluate EU-28 cost sources. Median costs were defined for each cost input and costs were inflated to 2014 Euros (€) in the study country and adjusted for Purchasing Power Parity between EU countries. Adjusted costs were used to populate previously published cost-models based on adult incidence-based events. In the base model, annual expenditures for total, hospital-associated, preventable, and indirect costs were €1.5-2.2 billion, €1.0-1.5 billion, €0.5-1.1 billion and €0.2-0.3 billion, respectively (indirect costs: 12 % of expenditures). In the long-term attack rate model, total, hospital-associated, preventable, and indirect costs were €1.8-3.3 billion, €1.2-2.4 billion, €0.6-1.8 billion and €0.2-0.7 billion (indirect costs: 13 % of expenditures). In the multiway sensitivity analysis, annual expenditures for total, hospital-associated, preventable, and indirect costs were €3.0-8.5 billion, €2.2-6.2 billion, €1.1-4.6 billion and €0.5-1.4 billion (indirect costs: 22 % of expenditures). When the value of a premature life-lost increased slightly, aggregate costs rose considerably since these costs are higher than the direct medical costs. When evaluating the models aggregately for costs, the results suggests total, hospital-associated, preventable, and indirect costs ranging from €1.5-13.2 billion, €1.0-9.7 billion, €0.5-7.3 billion and €0.2-6.1 billion, respectively. Our study demonstrates that VTE costs have a large financial impact upon the EU-28's healthcare systems and that significant savings could be realised if better preventive measures are applied.
Reitter, E-M; Ay, C; Kaider, A; Pirker, R; Zielinski, C; Zlabinger, G; Pabinger, I
Cytokines have been found to be elevated in cancer patients and have been associated with worse prognosis in single tumour entities. We investigated the association of eight different cytokines with venous thromboembolism (VTE) and prognosis in cancer patients. The Vienna Cancer and Thrombosis Study (CATS), a prospective study, includes patients with newly diagnosed tumour or disease progression. Patients with an overt infection are excluded. Study end-points are VTE, death, loss to follow-up or study completion. Interleukin (IL) serum levels were measured using the xMAP technology developed by Luminex. Among 726 included patients, no associations between IL levels and VTE were found, with the exception of a trend for IL-1β and IL-6 in pancreatic cancer. Elevated levels of IL-6 [as continuous variable per double increase hazard ratio (HR) = 1·07, 95% confidence interval (CI) = 1·027-1·114, P = 0·001, IL-8 (HR = 1·12, 95% CI = 1·062-1·170, P < 0·001) and IL-11 (HR = 1·37, 95% CI = 1·103-1·709, P = 0·005] were associated with worse survival. In subgroup analyses based on tumour type, colon carcinoma patients, who had higher IL-6 levels, showed a shorter survival (HR = 2·405, 95% CI = 1·252-4·618, P = 0·008). A significant association of elevated IL-10 levels with a decrease in survival (HR = 1·824, 95% CI = 1·098-3·031, P = 0·020) was seen among patients with lung cancer. No correlation between VTE and IL levels was found, but higher IL-6, IL-8 and IL-11 levels were associated with worse survival in cancer patients. Further, elevated IL-6 levels might be a prognostic marker in colorectal cancer and elevated IL-10 levels in lung cancer patients.
Yih, W Katherine; Greene, Sharon K; Zichittella, Lauren; Kulldorff, Martin; Baker, Meghan A; de Jong, Jill L O; Gil-Prieto, Ruth; Griffin, Marie R; Jin, Robert; Lin, Nancy D; McMahill-Walraven, Cheryl N; Reidy, Megan; Selvam, Nandini; Selvan, Mano S; Nguyen, Michael D
After the Food and Drug Administration (FDA) licensed quadrivalent human papillomavirus vaccine (HPV4) in 2006, reports suggesting a possible association with venous thromboembolism (VTE) emerged from the Vaccine Adverse Event Reporting System and the Vaccine Safety Datalink. Our objective was to determine whether HPV4 increased VTE risk. The subjects were 9-26-year-old female members of five data partners in the FDA's Mini-Sentinel pilot project receiving HPV4 during 2006-2013. The outcome was radiologically confirmed first-ever VTE among potential cases identified by diagnosis codes in administrative data during Days 1-77 after HPV4 vaccination. With a self-controlled risk interval design, we compared counts of first-ever VTE in risk intervals (Days 1-28 and Days 1-7 post-vaccination) and control intervals (Days 36-56 for Dose 1 and Days 36-63 for Doses 2 and 3). Combined hormonal contraceptive use was treated as a potential confounder. The main analyses were: (1) unadjusted for time-varying VTE risk from contraceptive use, (2) unadjusted but restricted to cases without such time-varying risk, and (3) adjusted by incorporating the modeled risk of VTE by week of contraceptive use in the analysis. Of 279 potential VTE cases identified following 1,423,399 HPV4 doses administered, 225 had obtainable charts, and 53 were confirmed first-ever VTE. All 30 with onsets in risk or control intervals had known risk factors for VTE. VTE risk was not elevated in the first 7 or 28 days following any dose of HPV in any analysis (e.g. relative risk estimate (95% CI) from both unrestricted analyses, for all-doses, 28-day risk interval: 0.7 (0.3-1.4)). Temporal scan statistics found no clustering of VTE onsets after any dose. Thus, we found no evidence of an increased risk of VTE associated with HPV4 among 9-26-year-old females. A particular strength of this evaluation was its control for both time-invariant and contraceptive-related time-varying potential confounding.
Alfonso, Ana; Redondo, Margarita; Rubio, Tomás; Del Olmo, Beatriz; Rodríguez-Wilhelmi, Pablo; García-Velloso, María J; Richter, José A; Páramo, José A; Lecumberri, Ramón
Extensive screening strategies to detect occult cancer in patients with unprovoked venous thromboembolism (VTE) are complex and no benefit in terms of survival has been reported. FDG-PET/CT (2-[F-18] fluoro-2-deoxy-D-glucose positron emission tomography combined with computed tomography), a noninvasive technique for the diagnosis and staging of malignancies, could be useful in this setting. Consecutive patients ≥ 50 years with a first unprovoked VTE episode were prospectively included. Screening with FDG-PET/CT was performed 3-4 weeks after the index event. If positive, appropriate diagnostic work-up was programmed. Clinical follow-up continued for 2 years. Blood samples were collected to assess coagulation biomarkers. FDG-PET/CT was negative in 68/99 patients (68.7%), while suspicious FDG uptake was detected in 31/99 patients (31.3%). Additional diagnostic work-up confirmed a malignancy in 7/31 patients (22.6%), with six of them at early stage. During follow-up, two patients with negative FDG-PET/CT were diagnosed with cancer. Sensitivity (S), positive (PPV) and negative predictive values (NPV) of FDG-PET/CT as single tool for the detection of occult malignancy were 77.8% (95% CI: 0.51-1), 22.6% (95% CI: 0.08-0.37) and 97.1% (95% CI: 0.93-1), respectively. Median tissue factor (TF) activity in patients with occult cancer was 5.38 pM vs. 2.40 pM in those without cancer (p = 0.03). Limitation of FDG-PET/CT screening to patients with TF activity > 2.8 pM would improve the PPV to 37.5% and reduce the costs of a single cancer diagnosis from 20,711€ to 11,670€. FDG-PET/CT is feasible for the screening of occult cancer in patients with unprovoked VTE, showing high S and NPV. The addition of TF activity determination may be useful for patient selection.
Skotland, Tore; Hustvedt, Svein Olaf; Oulie, Inger; Jacobsen, Petter Balke; Friisk, Grete Arneberg; Langøy, Ann Svendsen; Uran, Steinar; Sandosham, Jessie; Cuthbertson, Alan; Toft, Kim Gunnar
The 99mTc-complex of NC100668 [Acetyl-Asn-Gln-Glu-Gln-Val-Ser-Pro-Tyr(3-iodo)-Thr-Leu-Leu-Lys-Gly-NC100194] is being evaluated for nuclear medical imaging of venous thromboembolism. NC100668 is a 13-amino acid peptide with a Tc-binding chelator [NC100194; -NH-CH2-CH2-N(CH2-CH2-NH-C(CH3)2-C(CH3)=N-OH)2] linked to the C-terminal end. Following injection in rats of [Asn-U-14C]NC100668 (labeling of the N-terminal amino acid), approximately 70% of the radioactivity was recovered in urine within 3 days. Following injection of [Lys-U-14C]NC100668 (labeling close to the C-terminal amino acid), radioactivity was cleared more slowly, with only 8% recovered in urine and approximately 80% of the radioactivity present in the body after 3 days. The highest concentration of radioactivity in the body following injection of [Lys-U-14C]NC100668 was observed in the kidney inner cortex; this probably represents 14C-labeled Lys, which is reabsorbed in the kidney tubules and incorporated into protein metabolism. Metabolite profiling by high-performance liquid chromatography with radiochemical detection revealed that following injection of [Asn-U-14C]NC100668, there is a rapid appearance in blood of one peak containing radioactive metabolite(s) originating from the N-terminal part of the molecule. In urine samples, only this radioactive peak was observed with no intact NC100668 remaining; this very hydrophilic N-terminal metabolite was probably either the N-terminal amino acid or a very short peptide. Liquid chromatography-mass spectrometry analyses of rat urine samples obtained after injection of nonlabeled NC100668 confirmed the identity of two metabolites generated from the C-terminal end of the molecule; Gly-NC100194 was identified as the major of these metabolites and NC100194 as a minor metabolite present at approximately one-tenth the amount of Gly-NC100194. No other metabolites were identified.
Ashrani, Aneel A.; Silverstein, Marc D.; Rooke, Thom W.; Lahr, Brian D.; Petterson, Tanya M.; Bailey, Kent R.; Melton, L. Joseph; Heit, John A.
The role of venous stasis syndrome (VSS) mechanisms (i.e. venous outflow obstruction [VOO] and venous valvular incompetence [VVI]) on quality of life (QoL) and activities of daily living (ADL) is unknown. The objective of this study was to test the hypotheses that venous thromboembolism (VTE), VSS, VOO and VVI are associated with reduced QoL and ADL. This study is a follow-up of an incident VTE case–control study nested within a population-based inception cohort of incident residents from Olmsted County, MN, USA, between 1966 and 1990. The study comprised 232 Olmsted County residents with a first lifetime VTE and 133 residents without VTE. Methods included a questionnaire and physical examination for VSS; vascular laboratory testing for VOO and VVI; assessment of QoL by SF36 and of ADL by pertinent sections from the Older Americans Resources and Services (OARS) and Arthritis Impact Measurement Scales (AIMS2) questionnaires. Of the 365 study participants, 232 (64%), 161 (44%), 43 (12%) and 136 (37%) had VTE, VSS, VOO and VVI, respectively. Prior VTE was associated with reduced ADL and increased pain, VSS with reduced physical QoL and increased pain, and VOO with reduced physical QoL and ADL. VVI was not associated with QoL or ADL. In conclusion, VSS and VOO are associated with worse physical QoL and increased pain. VOO and VTE are associated with impaired ADL. We hypothesize that rapid clearance of venous outflow obstruction in individuals with acute VTE will improve their QoL and ADL. PMID:20926498
Freeman, Randall J; Li, Yuanzhang; Niebuhr, David W
The estimated incidence of idiopathic venous thromboembolism (IVTE) cases in the United States ranges from 24,000 to 282,000/year. This analysis explores the incidence and prevalence of IVTE in the military and if cases experience increased attrition. The Defense Medical Surveillance System was searched for incident IVTE cases from 1998 through 2007. Enlisted cases were each matched to 3 controls. Kaplan-Meier survival analysis and Cox proportional hazard modeling were performed. We matched 463 cases to 1,389 controls. Outpatient IVTE rates have increased markedly from 1998 through 2007. Cases of all-cause attrition risk (0.56 [95% CI = 0.44, 0.72]) and rates were significantly less than controls (p < 0.0001), and cases of medical attrition risk (1.64 [95% CI = 1.13, 2.37]) and rates were significantly higher (p < 0.01). Increasing rates with lower attrition suggests increasing case prevalence. Health care providers must maintain a high index of suspicion for venous thromboembolism to minimize adverse sequelae affecting health, unit readiness, and medical costs.
Wen, Siwan; Yang, Fan; Wang, Lemin; Duan, Qianglin; Gong, Zhu; Lv, Wei
In patients with pulmonary embolism (PE), forepart components of complements were activated. However there are interruption/decrease of cascade reaction and cytolytic effects in complement system. This study detected CRP, CH50, C3 and C4 levels in patients with venous thromboembolism (VTE) and compare with the imbalance of complement associated gene mRNA expression in PE patients. There was significant increase of CH50 in acute VTE patients. Even though CH50 increased significantly in acute VTE patients and had a relatively high sensitivity, cytolytic effects of complements might decrease, based on the genomics results of complement cascade reactions imbalance/interruption and increased total complements in VTE patients. PMID:25232435
Coupland, Carol; Hippisley-Cox, Julia
Objective To investigate the association between use of combined oral contraceptives and risk of venous thromboembolism, taking the type of progestogen into account. Design Two nested case-control studies. Setting General practices in the United Kingdom contributing to the Clinical Practice Research Datalink (CPRD; 618 practices) and QResearch primary care database (722 practices). Participants Women aged 15-49 years with a first diagnosis of venous thromboembolism in 2001-13, each matched with up to five controls by age, practice, and calendar year. Main outcome measures Odds ratios for incident venous thromboembolism and use of combined oral contraceptives in the previous year, adjusted for smoking status, alcohol consumption, ethnic group, body mass index, comorbidities, and other contraceptive drugs. Results were combined across the two datasets. Results 5062 cases of venous thromboembolism from CPRD and 5500 from QResearch were analysed. Current exposure to any combined oral contraceptive was associated with an increased risk of venous thromboembolism (adjusted odds ratio 2.97, 95% confidence interval 2.78 to 3.17) compared with no exposure in the previous year. Corresponding risks associated with current exposure to desogestrel (4.28, 3.66 to 5.01), gestodene (3.64, 3.00 to 4.43), drospirenone (4.12, 3.43 to 4.96), and cyproterone (4.27, 3.57 to 5.11) were significantly higher than those for second generation contraceptives levonorgestrel (2.38, 2.18 to 2.59) and norethisterone (2.56, 2.15 to 3.06), and for norgestimate (2.53, 2.17 to 2.96). The number of extra cases of venous thromboembolism per year per 10 000 treated women was lowest for levonorgestrel (6, 95% confidence interval 5 to 7) and norgestimate (6, 5 to 8), and highest for desogestrel (14, 11 to 17) and cyproterone (14, 11 to 17). Conclusions In these population based, case-control studies using two large primary care databases, risks of venous thromboembolism associated with combined oral
Trujillo-Santos, Javier; Casas, José Manuel; Casa, José Manuel; Casado, Ignacio; Samperiz, Angel Luis; Quintavalla, Roberto; Sahuquillo, Joan Carles; Monreal, Manuel
The influence of the site of cancer on outcome in cancer women with venous thromboembolism (VTE) is poorly understood. Reliable information on its influence might facilitate better use of prevention strategies. We assessed the 30-day outcome in all women with active cancer in the RIETE Registry, trying to identify if differences exist according to the tumor site. Up to May 2010, 2474 women with cancer and acute VTE had been enrolled. The most common sites were the breast (26%), colon (13%), uterus (9.3%), and haematologic (8.6%) cancers. During the 30-day study period, 329 (13%) patients died. Of them, 71 (2.9%) died of pulmonary embolism (PE), 22 (0.9%) died of bleeding. Fatal PE was more common in women with breast, colorectal, lung or pancreatic cancer (59% of the fatal PEs). Fatal bleeding was more frequent in women with colorectal, haematologic, ovarian cancer or carcinoma of unknown origin (55% of fatal bleedings).
Albornoz, Juan Pablo; Valenzuela, Andrés; Aizman, Andrés
The preferred dosification for low molecular weight heparins is in two doses for most patients with venous thromboembolic disease. A daily dose would make treatment simpler, less expensive and more comfortable while retaining a similar benefit and safety. Searching in Epistemonikos database, which is maintained by screening 30 databases, we identified two systematic reviews including five randomized trials. We combined the evidence using meta-analysis and generated a summary of findings table following the GRADE approach. We concluded it is not clear whether the risk of recurrence differs between the two alternatives because the certainty of the evidence is very low, and that administering low molecular weight heparin in two doses might be associated to little or no difference in the risk of major bleeding and mortality.
Moroz, L.A.; MacLean, L.D.; Langleben, D.
Fibrinolytic activities of whole blood and plasma were determined by /sup 125/I-fibrin radiometric assay in 16 normal subjects, and in 11 patients with systemic lupus erythematosus (SLE), 14 with progressive systemic sclerosis (PSS), 23 with venous thromboembolic disease, and 20 patients awaiting elective surgery. Mean whole blood and plasma activities for patients with PSS, and for those awaiting elective surgery, were similar to normal values, as was the mean plasma activity in patients with SLE. However, mean whole blood activity in SLE was significantly decreased compared with normals (p less than 0.05), with mean plasma activity accounting for 44% of mean whole blood activity (compared with 17% in normal subjects), representing a 67% decrease in mean calculated cellular phase activity in SLE, when compared with normals. Since the numbers of cells (neutrophils, monocytes) possibly involved in cellular activity were not decreased, the findings suggest a functional defect in fibrinolytic activity of one or more blood cell types in SLE. An additional finding was the participation of the cellular phase as well as the well-known plasma phase of blood in the fibrinolytic response to thromboembolism.
Mahajerin, Arash; Branchford, Brian R; Amankwah, Ernest K; Raffini, Leslie; Chalmers, Elizabeth; van Ommen, C Heleen; Goldenberg, Neil A
Hospital-associated venous thromboembolism, including deep vein thrombosis and pulmonary embolism, is increasing in pediatric centers. The objective of this work was to systematically review literature on pediatric hospital-acquired venous thromboembolism risk factors and risk-assessment models, to inform future prevention research. We conducted a literature search on pediatric venous thromboembolism risk via PubMed (1946-2014) and Embase (1980-2014). Data on risk factors and risk-assessment models were extracted from case-control studies, while prevalence data on clinical characteristics were obtained from registries, large (n>40) retrospective case series, and cohort studies. Meta-analyses were conducted for risk factors or clinical characteristics reported in at least three studies. Heterogeneity among studies was assessed with the Cochran Q test and quantified by the I(2) statistic. From 394 initial articles, 60 met the final inclusion criteria (20 case-control studies and 40 registries/large case series/cohort studies). Significant risk factors among case-control studies were: intensive care unit stay (OR: 2.14, 95% CI: 1.97-2.32); central venous catheter (OR: 2.12, 95% CI: 2.00-2.25); mechanical ventilation (OR: 1.56, 95%CI: 1.42-1.72); and length of stay in hospital (per each additional day, OR: 1.03, 95% CI: 1.03-1.03). Three studies developed/applied risk-assessment models from a combination of these risk factors. Fourteen significant clinical characteristics were identified through non-case-control studies. This meta-analysis confirms central venous catheter, intensive care unit stay, mechanical ventilation, and length of stay as risk factors. A few pediatric hospital-acquired venous thromboembolism risk scores have emerged employing these factors. Prospective validation is necessary to inform risk-stratified prevention trials.
Mahajerin, Arash; Branchford, Brian R.; Amankwah, Ernest K.; Raffini, Leslie; Chalmers, Elizabeth; van Ommen, C. Heleen; Goldenberg, Neil A.
Hospital-associated venous thromboembolism, including deep vein thrombosis and pulmonary embolism, is increasing in pediatric centers. The objective of this work was to systematically review literature on pediatric hospital-acquired venous thromboembolism risk factors and risk-assessment models, to inform future prevention research. We conducted a literature search on pediatric venous thromboembolism risk via PubMed (1946–2014) and Embase (1980–2014). Data on risk factors and risk-assessment models were extracted from case-control studies, while prevalence data on clinical characteristics were obtained from registries, large (n>40) retrospective case series, and cohort studies. Meta-analyses were conducted for risk factors or clinical characteristics reported in at least three studies. Heterogeneity among studies was assessed with the Cochran Q test and quantified by the I2 statistic. From 394 initial articles, 60 met the final inclusion criteria (20 case-control studies and 40 registries/large case series/cohort studies). Significant risk factors among case-control studies were: intensive care unit stay (OR: 2.14, 95% CI: 1.97–2.32); central venous catheter (OR: 2.12, 95% CI: 2.00–2.25); mechanical ventilation (OR: 1.56, 95%CI: 1.42–1.72); and length of stay in hospital (per each additional day, OR: 1.03, 95% CI: 1.03–1.03). Three studies developed/applied risk-assessment models from a combination of these risk factors. Fourteen significant clinical characteristics were identified through non-case-control studies. This meta-analysis confirms central venous catheter, intensive care unit stay, mechanical ventilation, and length of stay as risk factors. A few pediatric hospital-acquired venous thromboembolism risk scores have emerged employing these factors. Prospective validation is necessary to inform risk-stratified prevention trials. PMID:26001789
Hirokawa, Masayuki; Yamamoto, Takashi
Objective: Endovenous laser ablation (EVLA) and radiofrequency ablation (RFA) are safe and effective treatments for varicose veins caused by saphenous reflux. Deep venous thrombosis (DVT) and endovenous heat-induced thrombosis (EHIT) are known complications of these procedures. The purpose of this article is to investigate the incidence of postoperative DVT and EHIT in patients undergoing EVLA and RFA. Methods: The patients were assessed by clinical examination and venous duplex ultrasonography before operation and at 24–72 hours, 1 month, and 1 year follow-up after operation. Endovenous ablation (EVA) had been treated for 1026 limbs (835 patients) using an RFA; 1174 limbs (954 patients) using a 1470-nm wavelength diode laser with radial two-ring fiber (1470R); and 6118 limbs (5513 patients) using a 980-nm wavelength diode laser with bare-tip fiber (980B). Results: DVT was detected in 3 legs (0.3%) of RFA, 5 legs (0.4%) of 1470R, and 27 legs (0.4%) of 980B. One patient in three symptomatic DVT treated with 980B developed asymptomatic pulmonary embolus. In all, 31 of the 35 DVTs were confined to the calf veins. The incidence of EHIT classes 2 and 3 was 2.7% following RFA procedure, 6.7% after 1470R, and 7.5% after 980B. Conclusion: The incidence of EHIT following EVA was low, especially the RFA procedure. EHIT resolves within 2–4 weeks in most patients. DVT rates after EVA were compared with those published for saphenous vein stripping. (This is a translation of J Jpn Coll Angiol 2015; 55: 153–161.) PMID:28018495
Raskob, Gary E; Hirsh, Jack
Adjusted doses of oral warfarin sodium or fixed doses of subcutaneous low-molecular-weight heparin (LMWH) are the standard approaches for preventing venous thromboembolism following major orthopedic surgery of the legs. In recent years, new anticoagulants have been compared with either LMWH or warfarin. The optimal timing for the first dose of LMWH prophylaxis and of the new anticoagulants is controversial. Recent clinical trials of LMWH and of newer anticoagulants have provided new information on the relationship between the timing of the first anticoagulant dose and the efficacy and safety of thromboprophylaxis after major orthopedic surgery. These data on the optimal timing of initiating prophylaxis come from limited direct randomized comparisons of different timing with the same anticoagulant, subgroup analysis of large studies with a single anticoagulant, indirect comparisons across studies in systematic reviews, and single randomized trials comparing different anticoagulants. In the direct comparison of the same anticoagulant, preoperative initiation of the same regimen of LMWH (dalteparin) increased major bleeding, without improved antithrombotic efficacy compared to the early postoperative regimen. Fondaparinux, 2.5 mg, begun 6 h postoperatively is more effective and as safe as the currently approved regimens of enoxaparin begun either 12 h preoperatively, or 12 to 24 h postoperatively, in patients undergoing major orthopedic surgery. In a subgroup analysis of several large randomized trials, fondaparinux, 2.5 mg, begun < 6 h postoperatively was associated with increased major bleeding, without improved efficacy. The results of indirect comparisons also favor the use of a 6-h postoperative starting time for the first dose, while the single randomized trials comparing different anticoagulants performed to date are not helpful in establishing an optimal time for the first dose. The aggregate clinical research evidence supports the following general
Kerlin, Bryce A.; Stephens, Julie A.; Hogan, Mark J.; Smoyer, William E.; O'Brien, Sarah H.
Background Pediatric venous thromboembolism (VTE) is an increasingly common, difficult to diagnose problem. Clinical probability tools (CPT) for adults estimate VTE likelihood, but are not available for children. We hypothesized that a pediatric-specific CPT is feasible. Methods Radiology reports were utilized to identify children imaged for suspected VTE. Relevant signs, symptoms, and co-morbidity variables, identified from published literature, were extracted from corresponding medical records. Variables associated with pediatric VTE were incorporated into a multivariate logistic regression to create a pilot CPT which was confirmed on a separate cohort. Results 389 subjects meeting inclusion criteria were identified: 91 with VTE and 298 without. Univariate analysis revealed male gender (OR 2.96; p<0.001), asymmetric extremity (OR 1.76; p=0.033), central venous catheter utilization and/or dysfunction (OR 2.51; p<0.001), and cancer (OR 2.35; p=0.014) as VTE predictive variables. Documentation of an alternate diagnosis was inversely related to VTE (OR 0.42; p=0.004). Receiver operating characteristic analysis of the derived CPT demonstrated reasonable ability to discriminate VTE probability in the training cohort (AUC 0.73; p<0.001) and moderate discrimination in a separate validation cohort of 149 children (AUC 0.64; p=0.011). Conclusion A pediatric-specific VTE CPT is feasible, would facilitate early diagnosis, and could lead to improved outcomes. PMID:25518012
Königsbrügge, Oliver; Pabinger, Ingrid; Ay, Cihan
Venous thromboembolism (VTE) occurs frequently in patients with cancer and contributes to elevated morbidity and mortality. Risk factors for the occurrence of VTE events in patients with cancer have been investigated in numerous clinical studies. For now more than 10 years, the Vienna Cancer and Thrombosis Study (CATS) has focused on the identification of parameters predictive of future VTE occurrence. CATS has contributed to new findings, which may help identify patients at high risk of developing VTE, by means of biomarkers (such as D-dimer, prothrombin fragment 1+2, soluble P-selectin, platelet count, coagulation factor VIII activity, thrombin generation potential, etc.). The association of tissue factor bearing microparticles and the mean platelet volume with the risk of VTE was also elaborately investigated in the framework of CATS. More recently CATS has researched clinical and clinicopathologic parameters which contribute to identification of patients at risk of VTE. The type of cancer is one of the most important risk factor for VTE occurrence. Also the stage of cancer and the histological grade of a tumor have been found to be associated with the occurrence of cancer-related VTE. In further investigations, venous diseases including a history of previous VTE, a history of superficial thrombophlebitis and the presence of varicose veins, have been associated with the risk of VTE in CATS.
De Souza, Andre Luiz; Saif, Muhammad Wasif
Venous thromboembolism (VTE) is a frequent event in the clinical course of patients with exocrine pancreatic cancer; studies have been designed to evaluate the role of prophylactic anticoagulation in this ominous disease. Searching for the molecular basis of thrombosis in cancer, Bozkurt et al. present in the Abstract #e22049 the result of their investigation on the frequency of inherited and carcinogenesis-acquired proteins in oncologic patients with and without venous thromboembolism. From the bedside, Muñoz Martin et al. present in the Abstract #e15187 their work on the incidence of venous thromboembolism in patients with exocrine pancreatic cancer and the role of the established Khorana score in predicting symptomatic and incidental venous thromboembolism. At last, Cella et al. in the Abstract #e20625 expand the predictor landscape from the Khorana score to other risk factors for venous thromboembolism, refining the selection of oncologic patients who can benefit from prophylactic anticoagulation.
Tilve-Gómez, A; Rodríguez-Fernández, P; Trillo-Fandiño, L; Plasencia-Martínez, J M
Early diagnosis is one of the most important factors affecting the prognosis of pulmonary embolism (PE); however, the clinical presentation of PE is often very unspecific and it can simulate other diseases. For these reasons, imaging tests, especially computed tomography angiography (CTA) of the pulmonary arteries, have become the keystone in the diagnostic workup of PE. The wide availability and high diagnostic performance of pulmonary CTA has led to an increase in the number of examinations done and a consequent increase in the population's exposure to radiation and iodinated contrast material. Thus, other techniques such as scintigraphy and venous ultrasonography of the lower limbs, although less accurate, continue to be used in certain circumstances, and optimized protocols have been developed for CTA to reduce the dose of radiation (by decreasing the kilovoltage) and the dose of contrast agents. We describe the technical characteristics and interpretation of the findings for each imaging technique used to diagnose PE and discuss their advantages and limitations; this knowledge will help the best technique to be chosen for each case. Finally, we comment on some data about the increased use of CTA, its clinical repercussions, its "overuse", and doubts about its cost-effectiveness.
Haider, Dominik G; Bucek, Robert A; Reiter, Markus; Minar, Erich; Hron, Gregor; Kyrle, Paul A; Mittermayer, Friedrich; Wolzt, Michael
Asymmetrical dimethylarginine (ADMA) is an endogenous inhibitor of endothelial nitric oxide synthase, causes vasoconstriction, impairs cardiac function, and may predict cardiovascular risk. The prognostic value of plasma ADMA concentrations in acute vascular situations may be confounded by concomitant factors such as clot formation. In an effort to address the effect of hemostatic system activation, the authors have measured plasma concentrations of ADMA, its stereoisomer symmetrical dimethylarginine (SDMA), and L-arginine in 74 patients with suspected deep vein thrombosis (DVT). DVT was confirmed by sonography or venography in 39 subjects. There was no difference of L-arginine, ADMA, or SDMA (all P > 0.05) between subjects with or without DVT. ADMA correlated with SDMA, L-arginine, and plasma creatinine (all P < 0.05) but not with age, body mass index, D-dimer, thrombus extension, or history of symptoms. Venous thrombembolism does not influence circulating ADMA concentrations. The lack of association between ADMA and DVT argues against a contribution of endogenous NO synthase inhibition in hemostatic systemic activation.
Gaspard, Dany; Vito, Karen; Schorr, Christa; Hunter, Krystal; Gerber, David
Background. Thromboembolic events are major causes of morbidity, and prevention is important. We aimed to compare chemical prophylaxis (CP) and mechanical prophylaxis (MP) as methods of prevention in nonsurgical patients on mechanical ventilation. Methods. We performed a retrospective study of adult patients admitted to the Cooper University Hospital ICU between 2002 and 2010. Patients on one modality of prophylaxis throughout their stay were included. The CP group comprised 329 patients and the MP group 419 patients. The primary outcome was incidence of thromboembolic events. Results. Acuity measured by APACHE II score was comparable between the two groups (p = 0.215). Univariate analysis showed 1 DVT/no PEs in the CP group and 12 DVTs/1 PE in the MP group (p = 0.005). Overall mortality was 34.3% and 50.6%, respectively. ICU LOS was similar. Hospital LOS was shorter in the MP group. Multivariate analysis showed a significantly higher incidence of events in the MP prophylaxis group (odds ratio 9.9). After excluding patients admitted for bleeding in both groups, repeat analysis showed again increased events in the MP group (odds ratio 2.9) but this result did not reach statistical significance. Conclusion. Chemical methods for DVT/PE prophylaxis seem superior to mechanical prophylaxis in nonsurgical patients on mechanical ventilation and should be used when possible. PMID:26682067
Grosse, Scott D.; Nelson, Richard E.; Nyarko, Kwame A.; Richardson, Lisa C.; Raskob, Gary E.
Venous thromboembolism (VTE), which includes deep vein thrombosis and pulmonary embolism, is an important cause of preventable mortality and morbidity. In this study, we summarize estimates of per-patient and aggregate medical costs or expenditures attributable to incident VTE in the United States. Per-patient estimates of incremental costs can be calculated as the difference in costs between patients with and without an event after controlling for differences in underlying health status. We identified estimates of the incremental per-patient costs of acute VTEs and VTE-related complications, including recurrent VTE, post-thrombotic syndrome, chronic thromboembolic pulmonary hypertension, and anticoagulation-related adverse drug events. Based on the studies identified, treatment of an acute VTE on average appears to be associated with incremental direct medical costs of $12,000 to $15,000 (2014 US dollars) among first-year survivors, controlling for risk factors. Subsequent complications are conservatively estimated to increase cumulative costs to $18,000–23,000 per incident case. Annual incident VTE events conservatively cost the US healthcare system $7–10 billion each year for 375,000 to 425,000 newly diagnosed, medically treated incident VTE cases. Future studies should track long-term costs for cohorts of people with incident VTE, control for comorbid conditions that have been shown to be associated with VTE, and estimate incremental medical costs for people with VTE who do not survive. The costs associated with treating VTE can be used to assess the potential economic benefit and cost-savings from prevention efforts, although costs will vary among different patient groups. PMID:26654719
Grosse, Scott D; Nelson, Richard E; Nyarko, Kwame A; Richardson, Lisa C; Raskob, Gary E
Venous thromboembolism (VTE), which includes deep vein thrombosis and pulmonary embolism, is an important cause of preventable mortality and morbidity. In this study, we summarize estimates of per-patient and aggregate medical costs or expenditures attributable to incident VTE in the United States. Per-patient estimates of incremental costs can be calculated as the difference in costs between patients with and without an event after controlling for differences in underlying health status. We identified estimates of the incremental per-patient costs of acute VTEs and VTE-related complications, including recurrent VTE, post-thrombotic syndrome, chronic thromboembolic pulmonary hypertension, and anticoagulation-related adverse drug events. Based on the studies identified, treatment of an acute VTE on average appears to be associated with incremental direct medical costs of $12,000 to $15,000 (2014 US dollars) among first-year survivors, controlling for risk factors. Subsequent complications are conservatively estimated to increase cumulative costs to $18,000-23,000 per incident case. Annual incident VTE events conservatively cost the US healthcare system $7-10 billion each year for 375,000 to 425,000 newly diagnosed, medically treated incident VTE cases. Future studies should track long-term costs for cohorts of people with incident VTE, control for comorbid conditions that have been shown to be associated with VTE, and estimate incremental medical costs for people with VTE who do not survive. The costs associated with treating VTE can be used to assess the potential economic benefit and cost-savings from prevention efforts, although costs will vary among different patient groups.
Deguchi, Hiroshi; Banerjee, Yajnavalka; Elias, Darlene J.
Aim: Cholesteryl ester transfer protein (CETP) is an important lipid transfer factor in plasma that enhances prothrombinase activity in purified systems. This study was conducted to test the association of plasma CETP activity with venous thrombosis (VTE) and to address the procoagulant mechanism of CETP activity in prothrombinase assays. Methods: We measured CETP lipid transfer activity in plasmas of 49 male VTE patients and in plasmas of matched controls. CETP procoagulant activity was tested in purified prothrombinase systems. Results: CETP lipid transfer activity levels were significantly higher in VTE patients than in controls (p = 0.0008). A subset of patients carrying the CETP mutations Ala373Pro and Arg451Gln, which were also linked to the VTE risk, showed significantly higher plasma CETP activity than the non-carriers. The plasma CETP activity negatively correlated with APTT, suggesting that the CETP activity is associated with plasma coagulability. Recombinant (r) CETP bound to both factor Xa (Kd = 15 nM) and Gla-domainless factor Xa (Kd = 59 nM), whereas rCETP enhanced prothrombin activation by factor Xa, but not by Gla-domainless factor Xa. rCETP also required factor Va for enhancement of prothrombinase activity. When we addressed the effects of mutations in CETP on prothrombinase activity, Gln451-rCETP was found to have five-fold higher thrombin generation activity than wt-rCETP or Pro373-rCETP. Conclusions: Elevated CETP lipid transfer activity in plasma was associated with the risk of VTE. Gln451-CETP, which is linked to VTE, has much higher procoagulant activity than wt-CETP. CETP might act as a physiologic procoagulant by mechanisms that involve its direct binding to factor Xa. PMID:27169917
Petersen, J F; Bergholt, T; Nielsen, A K; Paidas, M J; Løkkegaard, E C L
Estimating the risk of venous thromboembolism (VTE) associated with combined hormonal contraceptives following early terminated pregnancies or birth, a Danish nationwide retrospective cohort observing a one-year follow-up was defined using three unique registries. All Danish women with confirmed pregnancies aged 15-49 during the period of 1995-2009 were included. The main outcomes were relative and absolute risks of first time venous thromboembolism in users as well as non-users of combined hormonal contraceptives. In 985,569 person-years, 598 venous thromboembolisms were recorded. After early terminated pregnancies and births, respectively, 113 and 485 events occurred in 212,552 and 773,017 person-years. After early terminated pregnancies, the crude VTE incidence ratios were similar, and the numbers needed to harm were equal between groups that did or did not use combined hormonal contraceptives throughout the follow-up year. After childbirth, individuals that used combined hormonal contraceptives were more likely than non-users to experience VTE depicted by crude incidence ratios; however, the difference was only significant after 14 weeks. This implied that the numbers needed to harm were lower for those that used compared to those that did not use combined oral contraceptives in the initial 14 weeks postpartum. In conclusion, the use of combined hormonal contraceptives after early terminated pregnancies was not detrimental, but during the puerperal period, they should be used with caution.
Karimi, Ali; Abolhasani, Marziyeh; Hashemzadeh-Chaleshtori, Morteza; Pourgheysari, Batoul
Background & objectives: Inherited thrombophilia is known to be an important risk factor for developing venous thromboembolism. Whether such abnormalities may impact the development of deep vein thrombosis (DVT) and pulmonary embolism (PE) differently is not well defined. This preliminary study was undertaken to compare thrombophilic polymorphism in patients with DVT and PE. Methods: A total of 35 DVT, 23 DVT/PE, and 37 PE patients admitted to the Hajar Hospital, Shahrekord, Iran, between October 2009 and February 2011 were included in the study and 306 healthy volunteers matched by age and sex from the same geographical area with no history of venous or arterial diseases were included as control group. Factor V Leiden (FV 1691G/A, rs6025), prothrombin (FII 20210G/A), methylene tetrahydrofulate reductase (MTHFR 677C/T, rs1801133), and PLA2 polymorphisms of platelet glycoprotein IIb/IIIa (GpIIIa 1565T/C, rs5918) were investigated by polymerase chain reaction-restriction fragment length polymorphism. Results: The number of patients with the investigated polymorphisms and homozygous carriers was significantly different among the groups (P<0.05). No significant difference was observed in the presence of FV 1691G/A and FII 20210G/A between any of the patients groups and the control group. GpIIIa 1565T/C and homozygous MTHFR 677C/T polymorphisms were higher in DVT patients compared with the control group (OR=6.65, 95% CI=3.09-14.30 and OR=4.08, 95% CI=1.35-12.38, respectively). Interpretation & conclusions: As none of the investigated polymorphisms were associated with PE, other thrombophilia polymorphisms may have a role in the pathogenesis of PE in these patients and should be investigated. Because of different prognostic risk factors among different types of patients, the treatment approach could be different. PMID:26261166
Kline, Jeffrey A; Kahler, Zachary P; Beam, Daren M
Background Oral monotherapy anticoagulation has facilitated home treatment of venous thromboembolism (VTE) in outpatients. Objectives The aim of this study was to measure efficacy, safety, as well as patient and physician perceptions produced by a protocol that selected VTE patients as low-risk patients by the Hestia criteria, and initiated home anticoagulation with an oral factor Xa antagonist. Methods Patients were administered the Venous Insufficiency Epidemiological and Economic Study Quality of life/Symptoms questionnaire [VEINEs QoL/Sym] and the physical component summary [PCS] from the Rand 36-Item Short Form Health Survey [SF36]). The primary outcomes were VTE recurrence and hemorrhage at 30 days. Secondary outcomes compared psychometric test scores between patients with deep vein thrombosis (DVT) to those with pulmonary embolism (PE). Patient perceptions were abstracted from written comments and physician perceptions specific to PE outpatient treatment obtained from structured survey. Results From April 2013 to September 2015, 253 patients were treated, including 67 with PE. Within 30 days, 2/253 patients had recurrent DVT and 2/253 had major hemorrhage; all four had DVT at enrollment. The initial PCS scores did not differ between DVT and PE patients (37.2±13.9 and 38.0±12.1, respectively) and both DVT and PE patients had similar improvement over the treatment period (42.2±12.9 and 43.4±12.7, respectively), consistent with prior literature. The most common adverse event was menorrhagia, present in 15% of women. Themes from patient-written responses reflected satisfaction with increased autonomy. Physicians’ (N=116) before-to-after protocol comfort level with home treatment of PE increased 48% on visual analog scale. Conclusion Hestia-negative VTE patients treated with oral monotherapy at home had low rates of VTE recurrence and bleeding, as well as quality of life measurements similar to prior reports. PMID:27143861
Heit, John A.; Lahr, Brian D.; Ashrani, Aneel A.; Petterson, Tanya M.; Bailey, Kent R.
Background Predictors of venous thromboembolism (VTE) recurrence are uncertain. Objective To identify predictors of VTE recurrence, adjusted for treatments and interim exposures. Materials and Methods Using Rochester Epidemiology Project resources, all Olmsted County, MN residents with objectively-diagnosed incident VTE over the 13-year period, 1988–2000, who survived ≥1 day were followed for first objectively-diagnosed VTE recurrence. For all patients with recurrence, and a random sample of all surviving incident VTE patients (n=415), we collected demographic and baseline characteristics, treatments and interim exposures. In a case-cohort study design, demographic, baseline, treatment and interim exposure characteristics were tested as potential predictors of VTE recurrence using time-dependent Cox proportional hazards modeling. Results Among 1262 incident VTE patients, 306 developed recurrence over 6,440 person-years. Five-year recurrence rates, overall and for cancer-associated, idiopathic and non-cancer secondary VTE, were 24.5%, 43.4%, 27.3% and 18.1%, respectively. In multivariable analysis, interim hospitalization, active cancer, pregnancy, central venous catheter and respiratory infection were associated with increased hazards of recurrence, and warfarin and aspirin were associated with reduced hazards. Adjusting for treatments and these interim risk factors, male sex, baseline active cancer and failure to achieve a therapeutic aPTT in the first 24 hours were independently associated with increased hazards of VTE recurrence over the entire follow-up period, while the hazards of recurrence for patient age, chronic lung disease, leg paresis, prior superficial vein thrombosis and idiopathic VTE varied over the follow-up period. Conclusions Baseline and interim exposures can stratify VTE recurrence risk and may be useful for directing secondary prophylaxis. PMID:26143712
Xing, Lydia; Lim, Wendy; Crowther, Mark
Background. Hereditary antithrombin deficiency is a thrombogenic disorder associated with a 50–90% lifetime risk of venous thromboembolism (VTE), which is increased during pregnancy and the puerperium in these patients. We present a case of a woman with antithrombin (AT) deficiency who presented with a VTE despite therapeutic low molecular weight heparin (LMWH). Though the pregnancy was deemed unviable, further maternal complications were mitigated through the combined use of therapeutic anticoagulation and plasma-derived antithrombin concentrate infusions to normalize her functional antithrombin levels. Methods. A review of the literature was conducted for studies on prophylaxis and management of VTE in pregnant patients with hereditary AT deficiency. The search involved a number of electronic databases, using combinations of keywords as described in the text. Only English language studies between 1946 and 2015 were included. Conclusion. Antithrombin concentrate is indicated in pregnant women with hereditary AT deficiency who develop VTE despite being on therapeutic dose anticoagulation. Expert opinion suggests AT concentrate should be used concomitantly with therapeutic dose anticoagulation. However, further high-quality studies on the dose and duration of treatment in the postpartum period are required. Use of AT concentrate for prophylaxis is controversial and should be based on individual VTE risk stratification. PMID:28168066
Weingarz, Lea; Schwonberg, Jan; Schindewolf, Marc; Hecking, Carola; Wolf, Zsuzsanna; Erbe, Matthias; Weber, Adele; Lindhoff-Last, Edelgard; Linnemann, Birgit
Thrombophilia is a well-established risk factor for a venous thromboembolic event (VTE), and it has been proposed that hereditary thrombophilia may substantially contribute to the development of VTE in young patients. We aimed to analyse the prevalence of thrombophilia with special regard to the age of VTE manifestation. The study cohort consisted of 1490 patients (58% females) with a median age 43 years at the time of their first VTE. At least one thrombophilic disorder was identified in 50·1% of patients. The probability of detecting a hereditary thrombophilia declined significantly with advancing age (from 49·3% in patients aged 20 years and younger to 21·9% in patients over the age of 70 years; P < 0·001). This may be primarily attributed to the decreasing frequencies of the F5 R506Q (factor V Leiden) mutation and deficiencies of protein C or protein S with older age at the time of the initial VTE event. Moreover, thrombophilia was more prevalent in unprovoked compared with risk-associated VTE (57·7% vs. 47·7%; P = 0·001). The decline in the prevalence of hereditary thrombophilia with older ages supports the use of a selected thrombophilia screening strategy dependent on age and the presence or absence of additional VTE risk factors.
This meta-analysis was designed to compare the incidence of deep vein thrombosis (DVT) and venous thromboembolism (VTE) following total knee arthroplasty (TKA) in patients with rheumatoid arthritis (RA) and osteoarthritis (OA). All studies directly comparing the post-TKA incidence of DVT and/or VTE in patients with RA and OA were included. For all comparisons, odds ratios and 95% confidence intervals (CI) were calculated for binary outcomes. Six studies were included in the meta-analysis. The pooled data showed that the combined rates of asymptomatic and symptomatic DVT did not differ significantly in the RA and OA groups (1065/222,714 [0.5%] vs. 35,983/6,959,157 [0.5%]; OR 0.77, 95% CI: 0.57 to 1.02; P = 0.07). The combined rates of asymptomatic and symptomatic DVT and pulmonary embolism (PE) after TKA were significantly lower in the RA than in the OA group (1831/225,406 [0.8%] vs. 63,953/7,018,721 [0.9%]; OR 0.76, 95% CI: 0.62 to 0.93; P = 0.008). Conclusiviely, the DVT rates after primary TKA were similar in RA and OA patients. In contrast, the incidence of VTE (DVT plus PE) after primary TKA was lower in RA than in OA patients, despite patients with RA being at theoretically higher risk of thrombi due to chronic inflammation. PMID:27911916
Imberti, Davide; Benedetti, Raffaella; Ageno, Walter
Venous thromboembolism (VTE) is a common potentially life-threatening complication in acutely ill medical patients; over 70 % of the fatal episodes of pulmonary embolism during hospitalization occur in non-surgical patients. In the absence of thromboprophylaxis, the incidence of venographically detected deep vein thrombosis is about 15 % in medical patients. Several trials and meta-analyses have clearly demonstrated the prophylactic role of unfractionated heparin, low molecular weight heparin and fondaparinux. Although over the past few years the knowledge of epidemiology, clinical features and prophylaxis in medical patients has significantly improved, there remain a number of controversial areas that require further investigation. Newer VTE risk assessment models have been proposed to select high risk hospitalized medical patients, but they still require external validation; scarce data are available to stratify patients to identify their individual bleeding risk. The optimal duration of thromboprophylaxis in medical patients is still a matter of debate; currently, extended prophylaxis after discharge is not recommended, but it may be required for subgroup of patients with persistently high VTE risk and a negligible risk of bleeding. Based on the results of recent studies, the new oral anticoagulants appear to have a very limited role, if any. However, a better risk stratification of patients who have a persistently increased risk of VTE is warranted to improve the risk to benefit profile of any anticoagulant drug to be used in this setting.
Borris, Lars C
Extended thromboprophylaxis is vital in patients undergoing total hip arthroplasty (THA) because of the prolonged risk of venous thromboembolism (VTE). Despite evidence that extended prophylaxis can reduce the incidence of symptomatic VTE in this high-risk patient population and the evidence-based guideline recommendations, a large proportion of patients still do not receive an adequate duration of thromboprophylaxis. This is partly due to the limitations of conventional anticoagulants, such as the subcutaneous route of administration or the requirement for routine coagulation monitoring and dose adjustment. New oral anticoagulants (such as the direct thrombin inhibitor dabigatran etexilate and the Factor Xa inhibitor rivaroxaban) could address the current unmet need. Phase III clinical studies in VTE prevention in patients undergoing THA and total knee arthroplasty (TKA) showed that dabigatran etexilate was non-inferior to the EU regimen of enoxaparin, but did not achieve non-inferiority to the US regimen of enoxaparin. In contrast, rivaroxaban demonstrated superiority to both enoxaparin regimens for the prevention of VTE after THA and TKA, without a significant increase in major bleeding rates. Their convenient, once-daily, fixed dosing, with no need for routine coagulation monitoring, could facilitate adherence to evidence-based guideline recommendations of extended thromboprophylaxis after THA.
Ikejiri, Makoto; Wada, Hideo; Yamada, Norikazu; Nakamura, Maki; Fujimoto, Naoki; Nakatani, Kaname; Matsuda, Akimasa; Ogihara, Yosihito; Matsumoto, Takeshi; Kamimoto, Yuki; Ikeda, Tomoaki; Katayama, Naoyuki; Ito, Masaaki
Congenital thrombophilia which is characterized by deficiencies in proteins such as antithrombin (AT), protein C (PC) and protein S (PS), is a major cause of venous thromboembolism (VTE). A total of 130 patients with VTE were evaluated for congenital thrombophilia based on the activity of AT, PC, or PS. Fifteen VTE patients with congenital AT deficiency (11.5 %), 16 with congenital PC deficiency (12.3 %) and eight with congenital PS deficiency (6.2 %) were diagnosed using DNA analysis. The frequency of congenital AT deficiency was significantly higher in subjects with pregnancy-related and idiopathic VTE than in those with VTE due to other causes, and congenital PC and PS deficiency were frequently associated with idiopathic VTE. Among the groups examined, the plasma levels of AT were the lowest in subjects with pregnancy-related VTE. Although our findings may have been influenced by some unintentional bias, congenital thrombophilia is nevertheless a major cause of VTE in pregnant patients as well as in young or middle-aged patients without any underlying diseases.
Suchon, Pierre; Al Frouh, Fadi; Henneuse, Agathe; Ibrahim, Manal; Brunet, Dominique; Barthet, Marie-Christine; Aillaud, Marie-Françoise; Venton, Geoffroy; Alessi, Marie-Christine; Trégouët, David-Alexandre; Morange, Pierre-Emmanuel
Identifying women at risk of venous thromboembolism (VTE) is a major public health issue. The objective of this study was to identify environmental and genetic determinants of VTE risk in a large sample of women under combined oral contraceptives (COC). A total of 968 women who had had one event of VTE during COC use were compared to 874 women under COC but with no personal history of VTE. Clinical data were collected and a systematic thrombophilia screening was performed together with ABO blood group assessment. After adjusting for age, family history, and type and duration of COC use, main environmental determinants of VTE were smoking (odds ratio [OR] =1.65, 95% confidence interval [1.30-2.10]) and a body mass index higher than 35 kg.m⁻² (OR=3.46 [1.81-7.03]). In addition, severe inherited thrombophilia (OR=2.13 [1.32-3.51]) and non-O blood groups (OR=1.98 [1.57-2.49]) were strong genetic risk factors for VTE. Family history poorly predicted thrombophilia as its prevalence was similar in patients with or without first degree family history of VTE (29.3% vs 23.9%, p=0.09). In conclusion, this study confirms the influence of smoking and obesity and shows for the first time the impact of ABO blood group on the risk of VTE in women under COC. It also confirms the inaccuracy of the family history of VTE to detect inherited thrombophilia.
Kodama, Junichi; Seki, Noriko; Fukushima, Chikako; Kusumoto, Tomoyuki; Nakamura, Keiichiro; Hongo, Atsushi; Hiramatsu, Yuji
The purpose of the present study was to determine the incidence of increased levels of D-dimer and associated factors in preoperative patients with gynecological cancer. Furthermore, we determined the incidence and risk factors associated with preoperative venous thromboembolism (VTE). Overall, 456 patients with invasive gynecological cancer scheduled to undergo surgery were recruited. Preoperative plasma D-dimer levels were measured and patients whose plasma D-dimer concentration exceeded the pre-set cut-off value underwent computed tomography scanning. The incidence of elevated D-dimer and VTE was identified as significantly higher in patients with ovarian cancer. Multivariate analysis revealed that advanced age, low hemoglobin levels and elevated C-reactive protein (CRP) levels were independent factors for preoperative elevations in plasma D-dimer levels. Advanced age was an independent risk factor for preoperative VTE. Massive ascites and the presence of co-morbidities were independent risk factors for preoperative VTE in ovarian cancer. Advanced age and stage were independent risk factors for preoperative VTE in endometrial cancer. Advanced age was an independent risk factor for preoperative VTE in cervical cancer. Plasma D-dimer levels and the incidence of preoperative VTE were higher in patients with ovarian cancer compared with those with other gynecological cancers. Advanced age, low hemoglobin levels and elevated CRP levels were significant factors associated with elevated plasma D-dimer levels and age was an independent risk factor for preoperative VTE in gynecological cancer.
Alotaibi, Ghazi S; Wu, Cynthia; Senthilselvan, Ambikaipakan; McMurtry, M Sean
The purpose of this study was to evaluate the accuracy of using a combination of International Classification of Diseases (ICD) diagnostic codes and imaging procedure codes for identifying deep vein thrombosis (DVT) and pulmonary embolism (PE) within administrative databases. Information from the Alberta Health (AH) inpatients and ambulatory care administrative databases in Alberta, Canada was obtained for subjects with a documented imaging study result performed at a large teaching hospital in Alberta to exclude venous thromboembolism (VTE) between 2000 and 2010. In 1361 randomly-selected patients, the proportion of patients correctly classified by AH administrative data, using both ICD diagnostic codes and procedure codes, was determined for DVT and PE using diagnoses documented in patient charts as the gold standard. Of the 1361 patients, 712 had suspected PE and 649 had suspected DVT. The sensitivities for identifying patients with PE or DVT using administrative data were 74.83% (95% confidence interval [CI]: 67.01-81.62) and 75.24% (95% CI: 65.86-83.14), respectively. The specificities for PE or DVT were 91.86% (95% CI: 89.29-93.98) and 95.77% (95% CI: 93.72-97.30), respectively. In conclusion, when coupled with relevant imaging codes, VTE diagnostic codes obtained from administrative data provide a relatively sensitive and very specific method to ascertain acute VTE.
Crowson, Cynthia S.; Makol, Ashima; Ytterberg, Steven R.; Saitta, Antonino; Salvarani, Carlo; Matteson, Eric L.; Warrington, Kenneth J.
Objective To investigate the incidence of venous thromboembolism (VTE) and cerebrovascular events in a community-based incidence cohort of patients with giant cell arteritis (GCA) compared to the general population. Methods A population-based inception cohort of patients with incident GCA between January 1, 1950 and December 31, 2009 in Olmsted County, Minnesota and a cohort of non-GCA subjects from the same population were assembled and followed until December 31, 2013. Confirmed VTE and cerebrovascular events were identified through direct medical record review. Results The study population included 244 patients with GCA with a mean ± SD age at diagnosis of 76.2 ± 8.2 years (79% women) and an average length of follow-up of 10.2 ± 6.8 years. Compared to non-GCA subjects of similar age and sex, patients diagnosed with GCA had a higher incidence (%) of amaurosis fugax (cumulative incidence ± SE: 2.1 ± 0.9 versus 0, respectively; p = 0.014) but similar rates of stroke, transient ischemic attack (TIA), and VTE. Among patients with GCA, neither baseline characteristics nor laboratory parameters at diagnosis reliably predicted risk of VTE or cerebrovascular events. Conclusion In this population-based study, the incidence of VTE, stroke and TIA was similar in patients with GCA compared to non-GCA subjects. PMID:26901431
Ahmed, Zaheer; Hassan, Seemeen; Salzman, Gary A.
Warfarin was the only oral anticoagulant available for the treatment of venous thromboembolism for about half a century until the recent approval of novel oral agents dabigatran, rivoraxaban and apixaban. This presents new classes of medications less cumbersome to use. They do not require frequent laboratory monitoring or have nurmerous drug interactions. On the other hand it also poses a challenge to the physicians deciding which agent to use in specific patient populations, how to predict the bleeding risk compared to warfarin and between the different novel agents and how to manage bleeding with relatively recent discovery of few potential antidotes. This review summarizes the major trials that led to the approval of these agents and their exclusion criteria helping physicians understand which patient types might not benefit from these agents. It provides clinical pearls invaluable in everyday practice such as transitioning between traditional and novel anticoagulants, dose adjustments for high risk populations, drug interactions and cost analysis. Futhermore, the review provides direct comparisons with warfarin and indirect comparisons among the novel agents in terms of efficacy and bleeding risk narrating the numbers of patients with intracranial, gastrointestinal and fatal hemorrhages in each of the major trials. We hope that this review will help the physicians inform their patients about the benefits and risks of these agents and enable them to make an informed selection of the most appropriate anticoagulant. PMID:27594818
Schwingl, P J; Shelton, J
Consistent reports from several recent studies suggest that users of third generation oral contraceptives (OCs) containing gestodene and desogestrel may be at increased risk of venous thromboembolic disease (VTE). Paradoxically, other reports indicate that these users may be at decreased risk of acute myocardial infarction (MI) compared with users of second generation OCs. To determine whether the potentially increased risk of VTE would outweigh the potentially reduced risk of MI in users of third generation OCs, we conducted an analysis to quantify the trade-offs providers and users may be faced to make between these formulations. The baseline rates of VTE and MI among non-users were calculated using US data on incidence and mortality of these conditions and estimates of the proportion of women exposed to these formulations in the US. These were multiplied by relative risks published in recent studies on third generation progestins to produce age- and formulation-specific risks. Results indicate that there would be small differences in disease burden between users of second and third generation OCs under the model assumptions at younger ages. However, among women 35-44 years of age, modeling results indicate that the potentially decreased incidence of MI among users of third generation OCs more than offsets the potentially increased risk of VTE at this age.
Raza, Shahzad; Kale, Gautam; Kim, Daniel; Akbar, Syed A; Holm, Lisa; Naidzionak, Ulad; Hossain, Akm M; Dong, Xiang; Doll, Donald C; Freter, Carl E; Hopkins, Tamara
Total hip replacement (THR) and total knee arthroplasty (TKA) carry a high risk of postoperative venous thromboembolism (VTE); therefore, anticoagulation prophylaxis is recommended in these patients. Unfortunately, there are no guidelines about VTE prophylaxis in patients with hemophilia who underwent these high-risk surgeries. To determine whether these patients have high risk of VTE, we conducted a retrospective study on patients with hemophilia who underwent elective THR/TKA at our institute from 2004 to 2012. Postoperatively, we collected information on duration and method of factor VIII/IX infusion, VTE-prophylaxis, and complications. There were 23 patients with hemophilia, 18 (78%) with hemophilia A and 5 (22%) with hemophilia B, who underwent high-risk surgeries (39% THR and 61% TKA). The VTE prophylaxis included sequential compression device, 12 (52%), and prophylactic enoxaparin, 1 (4%). Ten (43%) patients did not receive VTE prophylaxis. At 1-year follow-up, we did not find any evidence of clinical VTE in our patients. Better risk stratification is needed to identify patients who would benefit from pharmacological prophylaxis.
Palareti, Gualtiero; Cosmi, Benilde; Legnani, Cristina; Antonucci, Emilia; De Micheli, Valeria; Ghirarduzzi, Angelo; Poli, Daniela; Testa, Sophie; Tosetto, Alberto; Pengo, Vittorio; Prandoni, Paolo
The optimal duration of anticoagulation in patients with venous thromboembolism (VTE) is uncertain. We investigated whether persistently negative D-dimers in patients with vein recanalization or stable thrombotic burden can identify subjects at low recurrence risk. Outpatients with a first VTE (unprovoked or associated with weak risk factors) were eligible after at least 3 months (12 in those with residual thrombosis) of anticoagulation. They received serial D-dimer measurements using commercial assays with predefined age/sex-specific cutoffs and were followed for up to 2 years. Of 1010 patients, anticoagulation was stopped in 528 (52.3%) with persistently negative D-dimer who subsequently experienced 25 recurrences (3.0% pt-y; 95% confidence interval [CI], 2.0-4.4%). Of the remaining 482 patients, 373 resumed anticoagulation and 109 refused it. Recurrent VTE developed in 15 patients (8.8% pt-y; 95% CI, 5.0-14.1) of the latter group and in 4 of the former (0.7% pt-y; 95% CI, 0.2-1.7; hazard ratio = 2.92; 95% CI, 1.87-9.72; P = .0006). Major bleeding occurred in 14 patients (2.3% pt-y; 95% CI, 1.3-3.9) who resumed anticoagulation. Serial D-dimer measurement is suitable in clinical practice for the identification of VTE patients in whom anticoagulation can be safely discontinued. This study was registered at clinicaltrials.gov as #NCT00954395.
Koutroumpi, S; Daidone, V; Sartori, M T; Cattini, M G; Albiger, N M; Occhi, G; Ferasin, S; Frigo, A; Mantero, F; Casonato, A; Scaroni, C
A high incidence of venous thromboembolic (VTE) complications has been reported in Cushing's syndrome (CS), mostly post-operatively and attributable to hypercoagulability. The prevalence of symptomatic VTE was investigated retrospectively in 58 consecutive CS patients in relation to acquired and genetic thrombotic risk factors. Eight CS patients (14 %) developed VTE (group A), 3 of them related and 5 unrelated to surgery. These patients had higher urinary free cortisol (p = 0.01) and VWF levels (p = 0.02) than the 50 patients without VTE (group B), as well an increase in the hemostatically more efficient, high-molecular-weight VWF multimers (p = 0.002). Factor V Leiden and the prothrombin gene 20210A variants (the most common inherited thrombophilic defects) were more represented in group A than in group B, as was the genotype GCAG/GCAG of the VWF gene promoter, known to hyperinduce VWF upregulation under cortisol excess. All but one of the patients with VTE unrelated to surgery had at least four acquired and at least one inherited risk factor. Severe hypercortisolism and VWF levels with increased haemostatic activity are strongly associated with VTE in CS. VTE episodes unrelated to surgery are attributable to the synergistic action of acquired and inherited thrombotic risk factors. Based on these observations, we believe that severely affected CS patients should be screened for coagulation disorders and receive antithrombotic prophylaxis whenever they have concomitant prothrombotic risk factors.
Dranitsaris, George; Shane, Lesley G; Crowther, Mark; Feugere, Guillaume; Woodruff, Seth
Background Patients with cancer are at increased risk of venous thromboembolism (VTE) and the risk is further elevated after a primary VTE. To reduce the risk of recurrent events, extended prophylaxis with vitamin K antagonists (VKA) is available for use. However, in a large randomized trial (Comparison of Low-Molecular-Weight Heparin versus Oral Anticoagulant Therapy for the Prevention of Recurrent Venous Thromboembolism in Patients with Cancer [CLOT]; Lee et al), extended duration dalteparin reduced the relative risk of recurrent VTE by 52% compared to VKA (p=0.002). A recent subgroup analysis of patients with moderate-to-severe renal impairment also revealed lower absolute VTE rates with dalteparin (3% vs. 17%; p=0.011). To measure the economic value of dalteparin as an alternative to VKA, a patient-level cost utility analysis was conducted from a Canadian perspective. Methods Resource use data captured during the CLOT trial were extracted and linked to 2015 Canadian unit cost estimates. Health state utilities were then measured using the Time-Trade-Off technique in 24 randomly selected members of the general Canadian public to estimate the gains in quality-adjusted life years (QALYs). Results For the entire CLOT trial population (n=676), the dalteparin group had significantly higher mean costs compared to the VKA group ($Can5,771 vs. $Can2,569; p<0.001). However, the utility assessment revealed that 21 of 24 respondents (88%) selected dalteparin over VKA, with an associated gain of 0.14 (95% confidence interval [CI]: 0.10–0.18) QALYs. When the incremental cost of dalteparin was combined with the QALY gain, dalteparin had a cost of $Can23,100 (95% CI: $Can19,200–$Can25,800) per QALY gained. The analysis in patients with renal impairment suggested even better economic value with the cost per QALY gained being <$14,000. Conclusion Extended duration dalteparin is a cost-effective alternative to VKA for the prevention of recurrent VTE in patients with cancer
Kekre, Natasha; Kim, Haesook T; Ho, Vincent T; Cutler, Corey; Armand, Philippe; Nikiforow, Sarah; Alyea, Edwin P; Soiffer, Robert J; Antin, Joseph H; Connors, Jean M; Koreth, John
Although venous thromboembolism rates and risk factors are well described in patients with cancer, there are limited data on the incidence, risk factors and outcomes of thrombosis after allogeneic stem cell transplantation, a curative therapy for patients with hematologic malignancies. We aimed to determine the incidence and risks associated with venous thrombosis in allogeneic stem cell transplant. We studied 2276 recipients of first transplant between 2002-2013 at our institution with a median follow-up of 50 months (range 4-146). Using pharmacy records and subsequent chart review, 190 patients who received systemic anticoagulation for venous thrombosis were identified. The 1 and 2-year cumulative incidence of all venous thrombotic events were 5.5% (95% CI 4.6-6.5%) and 7.1% (95% CI 6.1-8.2%) respectively. There was no difference in age, gender, body mass index, diagnosis, disease risk index, conditioning intensity, donor type or graft source between transplant recipients with and without subsequent thrombosis. In multivariable models, both acute and chronic graft-versus-host disease were independently associated with thrombosis occurrence (HR=2.05, 95% CI 1.52-2.76; HR=1.71, 95% CI 1.19-2.46 respectively). Upper extremity thrombosis differed from all other thrombosis in timing, risk factors and clinical impact, and was not associated with non-relapse mortality (HR=1.15; 95% CI 0.69-1.90), unlike all other thrombosis which did increase non-relapse mortality (HR=1.71; 95% CI 1.17-2.49). In subgroup analysis evaluating conventional thrombosis predictors by comparing patients with and without thrombosis, history of prior venous thrombosis was the only significant predictor. Venous thromboembolism has a high incidence after allogeneic stem cell transplant and is associated with graft-versus-host disease and non-relapse mortality.
Background Patients with cancer have an increased risk of VTE. We compared VTE rates and bleeding complications in 1) cancer patients receiving LMWH or UFH and 2) patients with or without cancer. Methods Acutely-ill, non-surgical patients ≥70 years with (n = 274) or without cancer (n = 2,965) received certoparin 3,000 UaXa o.d. or UFH 5,000 IU t.i.d. for 8-20 days. Results 1) Thromboembolic events in cancer patients (proximal DVT, symptomatic non-fatal PE and VTE-related death) occurred at 4.50% with certoparin and 6.03% with UFH (OR 0.73; 95% CI 0.23-2.39). Major bleeding was comparable and minor bleedings (0.75 vs. 5.67%) were nominally less frequent. 7.5% of certoparin and 12.8% of UFH treated patients experienced serious adverse events. 2) Thromboembolic event rates were comparable in patients with or without cancer (5.29 vs. 4.13%) as were bleeding complications. All cause death was increased in cancer (OR 2.68; 95%CI 1.22-5.86). 10.2% of patients with and 5.81% of those without cancer experienced serious adverse events (OR 1.85; 95% CI 1.21-2.81). Conclusions Certoparin 3,000 UaXa o.d. and 5,000 IU UFH t.i.d. were equally effective and safe with respect to bleeding complications in patients with cancer. There were no statistically significant differences in the risk of thromboembolic events in patients with or without cancer receiving adequate anticoagulation. Trial Registration clinicaltrials.gov, NCT00451412 PMID:21791091
Koster, T; Small, R A; Rosendaal, F R; Helmerhorst, F M
A meta-analysis of controlled studies between 1966 and 1993 was conducted by means of a Medline computer search. A total of 588 articles were reviewed for controlled studies. 1 randomized trial, 6 follow-up studies, and 8 case-control studies were included. Summary thrombosis risk for oral contraceptive users, number needed to discontinue oral contraceptives to prevent one (recurrent) thrombosis, comparison of additional unwanted pregnancies, and postpartum thrombosis between alternative birth-control methods were the main outcome measures. The studies proved highly heterogeneous with regard to size and direction of the risk estimate. The summary relative risk of first thrombosis during oral contraceptive use was 2.9 (95% CI 0.5-17). The reported risks were higher in case control (RR 4.2) than in follow-up studies (RR 2.1). Various hypothetical assumptions were advanced wherein women would continue to take oral contraceptives after a first episode of thrombosis, or switch to use of an IUD, condom, or the progestogen-only pill. The cost-benefit ratio of advising against the use of oral contraceptives after a first thrombosis varied tremendously. The outcome with regard to pregnancies and thrombosis in 5 hypothetical cohorts of 100,000 post-thrombotic women monitored for 1 year indicated that under all but the highest assumption for recurrence risk, among typical couples the number of unexpected pregnancies as well as thrombotic episodes would be highest among condom users. IUDs would result in a reduction of at least 30% in the number of venous thrombotic episodes and accidental pregnancies. The lowest expected failures rates would lead to a decrease in thrombosis for both IUD and condom use. These findings indicate that there is a lack of necessary data for recurrence risk of venous thrombosis during continuing use of oral contraceptives, or after switching to other modes of contraception.
Weitz, Jeffrey I; Bauersachs, Rupert; Beyer-Westendorf, Jan; Bounameaux, Henri; Brighton, Timothy A; Cohen, Alexander T; Davidson, Bruce L; Holberg, Gerlind; Kakkar, Ajay; Lensing, Anthonie W A; Prins, Martin; Haskell, Lloyd; van Bellen, Bonno; Verhamme, Peter; Wells, Philip S; Prandoni, Paolo
Patients with unprovoked venous thromboembolism (VTE) are at high risk for recurrence. Although rivaroxaban is effective for extended VTE treatment at a dose of 20 mg once daily, use of the 10 mg dose may further improve its benefit-to-risk ratio. Low-dose aspirin also reduces rates of recurrent VTE, but has not been compared with anticoagulant therapy. The EINSTEIN CHOICE study is a multicentre, randomised, double-blind, active-controlled, event-driven study comparing the efficacy and safety of two once daily doses of rivaroxaban (20 and 10 mg) with aspirin (100 mg daily) for the prevention of recurrent VTE in patients who completed 6-12 months of anticoagulant therapy for their index acute VTE event. All treatments will be given for 12 months. The primary efficacy objective is to determine whether both doses of rivaroxaban are superior to aspirin for the prevention of symptomatic recurrent VTE, while the principal safety outcome is the incidence of major bleeding. The trial is anticipated to enrol 2,850 patients from 230 sites in 31 countries over a period of 27 months. In conclusion, the EINSTEIN CHOICE study will provide new insights into the optimal antithrombotic strategy for extended VTE treatment by comparing two doses of rivaroxaban with aspirin (clinicaltrials.gov NCT02064439).
Yong, Yao Pey; Karangizi, Alvin; Banerjea, Ayan
Extended venous thromboembolism (VTE) prophylaxis has been shown to reduce the incidence of VTE in patients following cancer resections. However, ensuring patients are discharged with the prescription remains a challenge, with junior doctors frequently rotating throughout different specialties. We conducted an audit to assess the compliance rate in the colorectal and hepatobiliary (HPB) unit at the Queen's Medical Centre in Nottingham. Extended VTE prophylaxis was considered compliant to the guideline if it was prescribed on discharge. The baseline measurement demonstrated compliance rates of 79% and 48% in the colorectal and HPB units respectively. Following discussion with the stakeholders, several interventions that include education and visual reminders were implemented to increase awareness of the importance of extended VTE prophylaxis among junior doctors. Results of the re-audit have shown a remarkable improvement; compliance rates were increased to 93% and 72% in the colorectal and HPB units respectively. We conclude that visual reminder is a simple yet effective tool to improve awareness among junior doctors on the importance of extended VTE prophylaxis in cancer patients. Nevertheless, education remains crucial to ensure the sustainability of any intervention.
Yong, Yao Pey; Karangizi, Alvin; Banerjea, Ayan
Extended venous thromboembolism (VTE) prophylaxis has been shown to reduce the incidence of VTE in patients following cancer resections. However, ensuring patients are discharged with the prescription remains a challenge, with junior doctors frequently rotating throughout different specialties. We conducted an audit to assess the compliance rate in the colorectal and hepatobiliary (HPB) unit at the Queen's Medical Centre in Nottingham. Extended VTE prophylaxis was considered compliant to the guideline if it was prescribed on discharge. The baseline measurement demonstrated compliance rates of 79% and 48% in the colorectal and HPB units respectively. Following discussion with the stakeholders, several interventions that include education and visual reminders were implemented to increase awareness of the importance of extended VTE prophylaxis among junior doctors. Results of the re-audit have shown a remarkable improvement; compliance rates were increased to 93% and 72% in the colorectal and HPB units respectively. We conclude that visual reminder is a simple yet effective tool to improve awareness among junior doctors on the importance of extended VTE prophylaxis in cancer patients. Nevertheless, education remains crucial to ensure the sustainability of any intervention. PMID:26734263
Bauersachs, R; Schellong, S M; Haas, S; Tebbe, U; Gerlach, H-E; Abletshauser, C; Sieder, C; Melzer, N; Bramlage, P; Riess, H
Patients with severe renal insufficiency (sRI) have been suggested to be at an increased risk of bleeding with low-molecular-weight heparins (LMWH). We aimed at assessing the benefits and risks of certoparin in comparison to unfractionated heparin (UFH) in these patients. In this subgroup analysis of the CERTIFY trial, acutely ill, non-surgical patients ≥70 years received certoparin 3,000U aXa o.d. or UFH 5,000 IU t.i.d. One hundred eighty-nine patients had a glomerular filtration rate (GFR) ≤30 ml/min/1.73 m2, 3,050 patients served as controls. Patients with sRI had a mean age of 85.9 ± 6.6 years (controls 78.4 ± 6.0) and were treated for a mean of 9.3 ± 3.7 days (9.9 ± 4.3). Thromboembolic event rates were comparable (4.55 vs. 4.21%; OR1.08; 95%CI 0.5-2.37) but bleeding was increased in sRI (9.52 vs. 3.54%; OR2.87; 95%CI 1.70-4.83). The incidence of the combined end-point of proximal DVT, symptomatic non-fatal PE and VTE related death was 6.49% with certoparin and 2.60% with UFH (OR2.60; 95%CI 0.49-13.85). There was a decrease in total bleeding with certoparin (OR0.33; 95%CI 0.11-0.97), which was non-significant in patients with GFR >30 ml/min/1.73 m2. In two multivariable regression models certoparin and immobilisation <10 days were associated with less bleeding while a GFR ≤30 ml/min/1.73 m2 was associated with increased bleeding. A total of 11.3% of certoparin- and 18.5% of UFH-treated patients experienced serious adverse events (14.8 in patients with a GFR ≤30 vs. 5.6% vs. >30 ml/min/1.73 m2). In conclusion, certoparin 3,000U anti Xa o.d. was as efficacious as 5,000 IU UFH t.i.d. in patients with sRI but had a reduced risk of bleeding.
Wang, Yong; Liu, Zhi-Hong; Zhang, Hong-Liang; Luo, Qin; Zhao, Zhi-Hui; Zhao, Qing
D-dimer can be used to exclude acute pulmonary embolism (PE) for its high negative predictive value (NPV). Also, it is a predictor of recurrent venous thromboembolism (VTE) after anticoagulation withdrawal. The aim of the present study was to assess the predictive value of D-dimer for recurrent VTE when tested at hospital discharge. Plasma D-dimer levels were repeatedly measured at hospital discharge in 204 consecutive patients with the first episode of acute pulmonary embolism. Patients were categorized to two groups by D-dimer levels at hospital discharge and followed up at 3, 6, and 12 months and yearly thereafter. The primary end point was symptomatic, recurrent fatal or nonfatal VTE. D-dimer levels were persistently abnormal in 66 patients (32%). After 31±19 months follow-up, patients with persistently abnormal D-dimer level levels showed a higher rate of of recurrent VTE (14 patients, 21%) compared to those with D-dimer regression (8 patients, 6%) (P = 0.001). At the multivariate analysis, after adjustment for other relevant factors, persistently abnormal D-dimer level levels were an independent predictor of recurrent VTE in all subjects investigated, (hazard ratio, 4.10; 95% CI, 1.61-10.39; P = 0.003), especially in those with unprovoked PE (hazard ratio, 4.61; 95% CI, 1.85-11.49; P = 0.001). The negative predictive value of D-dimer was 94.2 and 92.9% in all subjects or those with unprovoked PE, respectively. Persistently abnormal D-dimer level levels at hospital discharge have a high negative predictive value for recurrence in patients with acute pulmonary embolism, especially in subjects with an unprovoked previous event.
Heit, John A.; Cunningham, Julie M.; Petterson, Tanya M.; Armasu, Sebastian M.; Rider, David N.; de Andrade, Mariza
Summary Background Venous thromboembolism (VTE) is highly heritable (estimated heritability [h2]=0.62) and likely a result of multigenic action. Objective To systematically test variation within genes encoding for important components of the anticoagulant, procoagulant, fibrinolytic and innate immunity pathways for an independent association with VTE. Methods Non-Hispanic adults of European ancestry with objectively-diagnosed VTE, and age-, sex-group frequency matched controls were genotyped for 13,031 single nucleotide polymorphisms (SNPs) within 764 genes. Analyses (n=12,296 SNPs) were performed with PLINK using an additive genetic model and adjusted for age, sex, state of residence, and myocardial infarction or stroke. Results Among 2927 individuals, one or more SNPs within ABO, F2, F5, F11, KLKB1, SELP and SCUBE1 were significantly associated with VTE, including Factor V Leiden, Prothrombin G20210A, ABO non-O blood type, and a novel association with ABO rs2519093 (OR=1.68, p-value=8.08×10−16) that was independent of blood type. In stratified analyses, SNPs in the following genes were significantly associated with VTE: F5 and ABO among both genders and LY86 among women; F2, ABO and KLKB1 among Factor V Leiden non-carriers; F5, F11, KLKB1 and GFRA1 in ABO non-O blood type; and ABO, F5, F11, KLKB1, SCUBE1 and SELP among Prothrombin G20210A non-carriers. The ABO rs2519093 population-attributable risk (PAR) exceeded that of Factor V Leiden and Prothrombin G20210A, and the joint PAR of Factor V Leiden, Prothrombin G20210A, ABO non-O and ABO rs2519093 was 0.40. Conclusions Anticoagulant, procoagulant, fibrinolytic and innate immunity pathway genetic variation accounts for a large proportion of VTE among non-Hispanic adults of European-ancestry. PMID:21463476
Di Nisio, Marcello; Porreca, Ettore
Venous thromboembolism (VTE) is a frequent complication among acutely ill medical patients hospitalized for congestive heart failure, acute respiratory insufficiency, rheumatologic disorders, and acute infectious and/or inflammatory diseases. Based on robust data from randomized controlled studies and meta-analyses showing a reduced incidence of VTE by 40% to about 60% with pharmacologic thromboprophylaxis, prevention of VTE with low molecular weight heparin (LMWH), unfractionated heparin (UFH), or fondaparinux is currently recommended in all at-risk hospitalized acutely ill medical patients. In patients who are bleeding or are at high risk for major bleeding, mechanical prophylaxis with graduated compression stockings or intermittent pneumatic compression may be suggested. Thromboprophylaxis is generally continued for 6 to 14 days or for the duration of hospitalization. Selected cases could benefit from extended thromboprophylaxis beyond this period, although the risk of major bleeding remains a concern, and additional studies are needed to identify patients who may benefit from prolonged prophylaxis. For hospitalized acutely ill medical patients with renal insufficiency, a low dose (1.5 mg once daily) of fondaparinux or prophylactic LMWH subcutaneously appears to have a safe profile, although proper evaluation in randomized studies is lacking. The evidence on the use of prophylaxis for VTE in this latter group of patients, as well as in those at higher risk of bleeding complications, such as patients with thrombocytopenia, remains scarce. For critically ill patients hospitalized in intensive care units with no contraindications, LMWH or UFH are recommended, with frequent and careful assessment of the risk of bleeding. In this review, we discuss the evidence for use of thromboprophylaxis for VTE in acutely ill hospitalized medical patients, with a focus on (low-dose) fondaparinux.
Ananthakrishnan, Ashwin N.; Cagan, Andrew; Gainer, Vivian S.; Cheng, Su-Chun; Cai, Tianxi; Scoville, Elizabeth; Konijeti, Gauree G; Szolovits, Peter; Shaw, Stanley Y; Churchill, Susanne; Karlson, Elizabeth W.; Murphy, Shawn N.; Kohane, Isaac; Liao, Katherine P.
Background & Aims Patients with inflammatory bowel diseases (IBD) have increased risk for venous thromboembolism (VTE); those who require hospitalization have particularly high risk. Few hospitalized patients with IBD receive thromboprophylaxis. We analyzed the frequency of VTE following IBD-related hospitalization, risk factors for post-hospitalization VTE, and the efficacy of prophylaxis in preventing post-hospitalization VTE. Methods In a retrospective study, we analyzed data from a multi-institutional cohort of patients with Crohn's disease or ulcerative colitis and at least 1 IBD-related hospitalization. Our primary outcome was a VTE event. All patients contributed person time from the date of the index hospitalization to development of VTE, subsequent hospitalization, or end of follow-up. Our main predictor variable was pharmacologic thromboprophylaxis. Cox proportional hazard models adjusting for potential confounders were used to estimate hazard ratios (HR) and 95% confidence intervals (CI). Results From a cohort of 2788 patients with at least 1 IBD-related hospitalization, 62 patients developed VTE following discharge (2%). Incidences of VTE at 30, 60, 90, and 180 days after the index hospitalization were 3.7/1000, 4.1/1000, 5.4/1000, and 9.4/1000 person-days respectively. Pharmacologic thromboprophylaxis during the index hospital stay was associated with a significantly lower risk of post-hospitalization VTE (HR, 0.46; 95% CI, 0.22–0.97). Increased numbers of co-morbidities (HR, 1.30; 95% CI, 1.16–1.47) and need for corticosteroids before hospitalization (HR 1.71, 95% CI 1.02 –2.87) were also independently associated with risk of VTE. Length of hospitalization or surgery during index hospitalization was not associated with post-hospitalization VTE. Conclusions Pharmacologic thromboprophylaxis during IBD-related hospitalization is associated with reduced risk of post-hospitalization VTE. PMID:24632349
Tzeng, Ching-Wei D; Katz, Matthew H G; Lee, Jeffrey E; Fleming, Jason B; Pisters, Peter W T; Vauthey, Jean-Nicolas; Aloia, Thomas A
Background The fear of an early post-pancreatectomy haemorrhage (PPH) may prevent surgeons from prescribing post-operative venous thromboembolism (VTE) chemoprophylaxis. The primary hypothesis of this study was that the national post-pancreatectomy early PPH rate was lower than the rate of VTE. The secondary hypothesis was that patients at high risk for post-discharge VTE could be identified, potentially facilitating the selective use of extended chemoprophylaxis. Patients and methods All elective pancreatectomies were identified in the 2005 to 2010 American College of Surgeons-National Surgical Quality Improvement Program (ACS-NSQIP) database. Factors associated with 30-day rates of (pre-versus post-discharge) VTE, early PPH (transfusions > 4 units within 72 h) and return to the operating room (ROR) with PPH were analysed. Results Pancreaticoduodenectomies (PD) and distal pancreatectomies (DP) numbered 9140 (66.4%) and 4631 (33.6%) out of 13 771 pancreatectomies, respectively. Event rates included: VTE (3.1%), PPH (1.1%) and ROR+PPH (0.7%). PD and DP had similar VTE rates (P > 0.05) with 31.9% of VTE occurring post-discharge. Independent risk factors for late VTE included obesity [odds ratio (OR), 1.5], age ≥ 75 years (OR, 1.8), DP (OR, 2.4) and organ space infection (OR, 2.1) (all P < 0.02). Conclusions Within current practice patterns, post-pancreatectomy VTE outnumber early haemorrhagic complications, which are rare. The fear of PPH should not prevent routine and timely post-pancreatectomy VTE chemoprophylaxis. Because one-third of VTE occur post-discharge, high-risk patients may benefit from post-discharge chemoprophylaxis. PMID:23869628
Walker, A J; West, J; Card, T R; Humes, D J; Grainge, M J
Background Patients with colorectal cancer are at high risk of developing venous thromboembolism (VTE), and recent international guidelines have advised extended prophylaxis for some of these patients following surgery or during chemotherapy. However, our understanding of which patients are at increased risk, and to what extent, is limited. Objectives To determine absolute and relative rates of VTE among patients with colorectal cancer according to Dukes stage, surgical intervention, and chemotherapy. Methods We analyzed data from four linked databases from 1997 to 2006: the Clinical Practice Research Datalink, linked to Hospital Episode Statistics, Cancer Registry data, and Office for National Statistics cause of death data, all from England. Rates were compared by the use of Cox regression. Results There were 10 309 patients with colorectal cancer, and 555 developed VTE (5.4%). The incidence varied by Dukes stage, being three-fold higher among Dukes D patients than among Dukes A patients (hazard ratio [HR] 3.08, 95% confidence interval [CI] 1.95–4.84), and 40% higher for those receiving chemotherapy than for those not receiving chemotherapy (HR 1.39, 95% CI 1.14–1.69). The risk following surgery varied by stage of disease and chemotherapy, with Dukes A patients having a low incidence of VTE (0.74%; 95% CI 0.28–1.95) at 6 months, with all events occurring within 28 days of surgery, as compared with Dukes B and Dukes C patients, whose risk at 6 months was ∼ 2%. Conclusion Twenty-eight days of prophylaxis following surgery for colorectal cancer is appropriate for Dukes A patients. However, Dukes B and Dukes C patients receiving postoperative chemotherapy have a longer duration of risk. PMID:24977288
Hofmann, Eveline; Faller, Nicolas; Limacher, Andreas; Méan, Marie; Tritschler, Tobias; Rodondi, Nicolas; Aujesky, Drahomir
Whether the level of education is associated with anticoagulation quality and clinical outcomes in patients with acute venous thromboembolism (VTE) is uncertain. We thus aimed to investigate the association between educational level and anticoagulation quality and clinical outcomes in elderly patients with acute VTE. We studied 817 patients aged ≥65 years with acute VTE from a Swiss prospective multicenter cohort study (09/2009-12/2013). We defined three educational levels: 1) less than high school, 2) high school, and 3) post-secondary degree. The primary outcome was the anticoagulation quality, expressed as the percentage of time spent in the therapeutic INR range (TTR). Secondary outcomes were the time to a first recurrent VTE and major bleeding. We adjusted for potential confounders and periods of anticoagulation. Overall, 56% of patients had less than high school, 25% a high school degree, and 18% a post-secondary degree. The mean percentage of TTR was similar across educational levels (less than high school, 61%; high school, 64%; and post-secondary, 63%; P = 0.36). Within three years of follow-up, patients with less than high school, high school, and a post-secondary degree had a cumulative incidence of recurrent VTE of 14.2%, 12.9%, and 16.4%, and a cumulative incidence of major bleeding of 13.3%, 15.1%, and 15.4%, respectively. After adjustment, educational level was neither associated with anticoagulation quality nor with recurrent VTE or major bleeding. In elderly patients with VTE, we did not find an association between educational level and anticoagulation quality or clinical outcomes. PMID:27606617
Hibbert, Peter D; Hannaford, Natalie A; Hooper, Tamara D; Hindmarsh, Diane M; Braithwaite, Jeffrey; Ramanathan, Shanthi A; Wickham, Nicholas; Runciman, William B
Objectives The prevention and management of venous thromboembolism (VTE) is often at variance with guidelines. The CareTrack Australia (CTA) study reported that appropriate care (in line with evidence-based or consensus-based guidelines) is being provided for VTE at just over half of eligible encounters. The aim of this paper is to present and discuss the detailed CTA findings for VTE as a baseline for compliance with guidelines at a population level. Setting The setting was 27 hospitals in 2 states of Australia. Participants A sample of participants designed to be representative of the Australian population was recruited. Participants who had been admitted overnight during 2009 and/or 2010 were eligible. Of the 1154 CTA participants, 481(42%) were admitted overnight to hospital at least once, comprising 751 admissions. There were 279 females (58%), and the mean age was 64 years. Primary and secondary outcome measures The primary measure was compliance with indicators of appropriate care for VTE. The indicators were extracted from Australian VTE clinical practice guidelines and ratified by experts. Participants’ medical records from 2009 to 2010 were analysed for compliance with 38 VTE indicators. Results Of the 35 145 CTA encounters, 1078 (3%) were eligible for scoring against VTE indicators. There were 2–84 eligible encounters per indicator at 27 hospitals. Overall compliance with indicators for VTE was 51%, and ranged from 34% to 64% for aggregated sets of indicators. Conclusions The prevention and management of VTE was appropriate for only half of the at-risk patients in our sample; this provides a baseline for tracking progress nationally. There is a need for national and, ideally, international agreement on clinical standards, indicators and tools to guide, document and monitor care for VTE, and for measures to increase their uptake, particularly where deficiencies have been identified. PMID:26962033
Pellino, Gianluca; Sciaudone, Guido; Caprio, Francesca; Candilio, Giuseppe; De Fatico, G Serena; Reginelli, Alfonso; Canonico, Silvestro; Selvaggi, Francesco
Recent studies showed an increased risk of venous thromboembolism (VTE) in patients receiving oral hormonal contraceptives. Inflammatory bowel diseases (IBD) often affect young patients and represent a pro-coagulant condition. This could result from active inflammation, but a potential role for genetic and molecular factors has been suggested. Hormonal contraceptives have also been associated with increased risk of VTE and the risk may be greater in IBD patients that already are in a pro-coagulant status, but no definitive data are available in this population. The purpose of our study was to seek for differences of the risk of VTE in IBD patients receiving hormonal contraceptives compared with controls. This is a retrospective study. We interrogated a prospectively maintained database of IBD patients observed at our outpatient clinic between 2000 and 2014. All female patients managed conservatively, with no active disease, who were taking oral hormone contraceptives in the study period, were included. Patients observed for other-than-IBD conditions at our Unit and at the Unit of Gynaecology and Obstetrics, receiving contraceptives, served as controls (ratio 1:2). Patients with cancer, those receiving hormonal therapy, and those with known genetic predisposition to VTE were excluded. We included 146 six IBD patients and 290 controls. One patient in each group developed VTE. Overall, the incidence of VTE associated with oral contraceptives was 0.5%. IBD was associated with increased risk of VTE (OR 1.9, 95% CI 0.12-32.12, p > 0.99). Active smokers since 10 years (17.2%) had higher risks of VTE (OR 8.6, 95% CI 1.16-19.25, p = 0.03). Our data show that patients with IBD in remission are not at higher risk of VTE due to oral oestrogen-containing contraceptives compared with non-IBD controls. Smokers are at increased risk, irrespective of the baseline disease.
Chai-Adisaksopha, Chatree; Linkins, Lori-Ann; ALKindi, Said Y; Cheah, Matthew; Crowther, Mark A; Iorio, Alfonso
Venous thromboembolism (VTE) is one of the most common complications in patients with brain tumours. There is limited data available in the literature on VTE treatment in these patients. We conducted a matched retrospective cohort study of patients with primary or metastatic brain cancer who were diagnosed with cancer-associated VTE. Patients were selected after a retrospective chart review of consecutive patients who were diagnosed with cancer-associated VTE between January 2010 and January 2014 at the Juravinski Thrombosis Clinic, Hamilton, Canada. Controls were age- and gender-matched patients with cancer-associated VTE from the same cohort, but without known brain tumours. A total of 364 patients with cancer-associated VTE were included (182 with primary or metastatic brain tumours and 182 controls). The median follow-up duration was 6.7 (interquartile range 2.5-15.8) months. The incidence rate of recurrent VTE was 11.0 per 100 patient-years (95 % CI; 6.7-17.9) in patients with brain tumours and 13.5 per 100 patient-years (95 % CI; 9.3-19.7) in non-brain tumour group. The incidence of major bleeding was 8.6 per 100 (95 % CI; 4.8-14.7) patient-years in patients with brain tumours versus 5.0 per 100 patient-years (95 % CI; 2.8-9.2) in controls. Rate of intracranial bleeding was higher in brain tumour patients (4.4 % vs 0 %, p-value=0.004). In summary, rates of recurrent VTE and major bleeding were not significantly different in patients with cancer-associated VTE in the setting of primary or metastatic brain tumours compared those without known brain tumours. However, greater numbers of intracranial bleeds were observed in patients with brain tumours.
Ruíz-Giménez, Nuria; Suárez, Carmen; González, Rocío; Nieto, José Antonio; Todolí, José Antonio; Samperiz, Angel Luis; Monreal, Manuel
A score that can accurately determine the risk of major bleeding during anticoagulant therapy may help to make decisions on anticoagulant use. RIETE is an ongoing registry of consecutive patients with acute venous thromboembolism (VTE). We composed a score to predict the risk for major bleeding within three months of anticoagulant therapy. Of 19,274 patients enrolled, 13,057 (67%) were randomly assigned to the derivation sample, 6,572 to the validation sample. In the derivation sample 314 (2.4%) patients bled (fatal bleeding, 105). On multivariate analysis, age >75 years, recent bleeding, cancer, creatinine levels >1.2 mg/dl, anemia, or pulmonary embolism at baseline were independently associated with an increased risk for major bleeding. A score was composed assigning 2 points to recent bleeding, 1.5 to abnormal creatinine levels or anemia, 1 point to the remaining variables. In the derivation sample 2,654 (20%) patients scored 0 points (low risk); 9,645 (74%) 1-4 points (intermediate); 758 (5.8%) >4 points (high risk). The incidences of major bleeding were: 0.3% (95% confidence interval [CI]: 0.1-0.6), 2.6% (95% CI: 2.3-2.9), and 7.3% (95% CI: 5.6-9.3), respectively. The likelihood ratio test was: 0.14 (95% CI: 0.07-0.27) for patients at low risk;2.96 (95% CI: 2.18-4.02) for those at high risk. In the validation sample the incidence of major bleeding was: 0.1%, 2.8%, and 6.2%, respectively. In conclusion, a risk score based on six variables documented at entry can identify VTE patients at low, intermediate, or high risk for major bleeding during the first three months of therapy.
Fuzinatto, Fernanda; de Waldemar, Fernando Starosta; Wajner, André; Elias, Cesar Al Alam; Fernandez, Juliana Fernándes; Hopf, João Luiz de Souza; Barreto, Sergio Saldanha Menna
OBJECTIVE: To determine the impact that implementing a combination of a computer-based clinical decision support system and a program of training seminars has on the use of appropriate prophylaxis for venous thromboembolism (VTE). METHODS: We conducted a cross-sectional study in two phases (prior to and after the implementation of the new VTE prophylaxis protocol) in order to evaluate the impact that the combined strategy had on the use of appropriate VTE prophylaxis. The study was conducted at Nossa Senhora da Conceição Hospital, a general hospital in the city of Porto Alegre, Brazil. We included clinical and surgical patients over 18 years of age who were hospitalized for ≥ 48 h. The pre-implementation and post-implementation phase samples comprised 262 and 261 patients, respectively. RESULTS: The baseline characteristics of the two samples were similar, including the distribution of patients by risk level. Comparing the pre-implementation and post-implementation periods, we found that the overall use of appropriate VTE prophylaxis increased from 46.2% to 57.9% (p = 0.01). Looking at specific patient populations, we observed that the use of appropriate VTE prophylaxis increased more dramatically among cancer patients (from 18.1% to 44.1%; p = 0.002) and among patients with three or more risk factors (from 25.0% to 42.9%; p = 0.008), two populations that benefit most from prophylaxis. CONCLUSIONS: It is possible to increase the use of appropriate VTE prophylaxis in economically constrained settings through the use of a computerized protocol adhered to by trained professionals. The underutilization of prophylaxis continues to be a major problem, indicative of the need for ongoing improvement in the quality of inpatient care. PMID:23670498
Trujillo-Santos, Javier; Di Micco, Pierpaolo; Iannuzzo, Mariateresa; Lecumberri, Ramón; Guijarro, Ricardo; Madridano, Olga; Monreal, Manuel
A significant association between elevated white blood cell (WBC) count and mortality in patients with cancer has been reported, but the predictive value of elevated WBC on mortality in cancer patients with acute venous thromboembolism (VTE) has not been explored. RIETE is an ongoing registry of consecutive patients with acute VTE. We compared the three-month outcome of cancer patients with acute VTE according to their WBC count at baseline. As of May 2007, 3805 patients with active cancer and acute VTE had been enrolled in RIETE. Of them, 215 (5.7%) had low- (<4,000 cells/microl), 2,403 (63%) normal- (4,000-11,000 cells/microl), 1,187 (31%) elevated (>11,000 cells/microl) WBC count. During the study period 190 patients (5.0%) had recurrent VTE, 156 (4.1%) major bleeding, 889 (23%) died (399 of disseminated cancer, 113 of PE, 46 of bleeding. Patients with elevated WBC count at baseline had an increased incidence of recurrent VTE (odds ratio [OR]: 1.6; 95% confidence interval [CI]: 1.2-2.2), major bleeding (OR: 1.5; 95% CI: 1.1-2.1) or death (OR: 2.7; 95% CI: 2.3-3.2). Most of the reported causes of death were significantly more frequent in patients with elevated WBC count. Multivariate analysis confirmed that elevated WBC count was independently associated with an increased incidence of all three complications. In conclusion, cancer patients with acute VTE and elevated WBC count had an increased incidence of VTE recurrences, major bleeding or death. This worse outcome was consistent among all subgroups and persisted after multivariate adjustment.
Haxaire, Claudie; Tromeur, Cécile; Couturaud, Francis; Leroyer, Christophe
Objective This study aimed to examine perception, knowledge and concerns developed by patients and their family as regards venous thromboembolism (VTE) risk. Methods We conducted a qualitative study. Participants were: (1) patients with unprovoked VTE with either factor V Leiden mutation or G20210A prothrombin gene mutation or not; and (2) their first-degree relatives. Interviews took place mostly at Brest University Hospital. Participants produced narratives of the patient’s illness, stressing their perception of the disorder, its mechanisms, etiology, circumstances and risk factors. Interviews were audiotaped and transcribed verbatim. On an ongoing basis, central themes were identified and data from narratives were categorized by these themes. Results A total of ten patients and 25 first-degree relatives were interviewed. Analyses of patient’s narratives suggested 4 main themes: (1) concerns about initial symptoms and suspicion of VTE. The longer the duration of the initial phase, the more likely anxiety took place and persisted after diagnosis; (2) underestimation of potential life-threatening episode once being managed in emergency; (3) possible biographical disruption with inability to cope with the event; and (4) secondary prevention attitudes motivated by remains of the episode and favoring general prevention attitudes. Analyses of the first-degree relatives narratives suggested 3 main themes: (1) common interpretation of the VTE episode shared within the family; (2) diverse and sometimes confusing interpretation of the genetic status; and, (3) interpretation of clinical signs linked to VTE transmission within the family. Conclusions Construction of the risk of VTE is based on patient’s initial experience and shared within the family. Collection of narratives illustrates the gap between these perceptions and current medical knowledge. These results support the need to collect the perceptions of the VTE episode and its consequences, as a prerequisite to
Ensor, Joie; Riley, Richard D; Moore, David; Bayliss, Susan; Fitzmaurice, David
Objectives To review studies developing or validating a prognostic model for individual venous thromboembolism (VTE) recurrence risk following cessation of therapy for a first unprovoked VTE. Prediction of recurrence risk is crucial to informing patient prognosis and treatment decisions. The review aims to determine whether reliable prognostic models exist and, if not, what further research is needed within the field. Design Bibliographic databases (including MEDLINE, EMBASE and the Cochrane Library) were searched using index terms relating to the clinical field and prognosis. Screening of titles, abstracts and subsequently full texts was conducted by 2 reviewers independently using predefined criteria. Quality assessment and critical appraisal of included full texts was based on an early version of the PROBAST (Prediction study Risk Of Bias Assessment Tool) for risk of bias and applicability in prognostic model studies. Setting Studies in any setting were included. Primary and secondary outcome measures The primary outcome for the review was the predictive accuracy of identified prognostic models in relation to VTE recurrence risk. Results 3 unique prognostic models were identified including the HERDOO2 score, Vienna prediction model and DASH score. Quality assessment highlighted the Vienna, and DASH models were developed with generally strong methodology, but the HERDOO2 model had many methodological concerns. Further, all models were considered at least at moderate risk of bias, primarily due to the need for further external validation before use in practice. Conclusions Although the Vienna model shows the most promise (based on strong development methodology, applicability and having some external validation), none of the models can be considered ready for use until further, external and robust validation is performed in new data. Any new models should consider the inclusion of predictors found to be consistently important in existing models (sex, site of index
Hooper, W Craig; Dowling, Nicole F; Wenger, Nanette K; Dilley, Anne; Ellingsen, Dorothy; Evatt, Bruce L
Genetic polymorphisms/mutations associated with venous thrombosis have largely been confined to the genes that encode for proteins in either the coagulant or the anticoagulant pathway. Although genetic alterations in the renin-angiotensin system have been reported to have a role in myocardial infarction and hypertension, there is recent evidence to suggest that there may also be an association with venous thrombosis. To extend our earlier observation of an association between the ACE DD genotype in African-American males and venous thrombosis, other genes in the renin-angiotensin pathway were investigated for possible disease association and were compared with African-Americans with myocardial infarction. African-American patients with a documented history of venous thrombosis or a history of myocardial infarction were eligible for participation as cases in the study. Control subjects were African-American outpatients attending a clinical laboratory for routine blood tests who had comparable age and gender distributions to the cases. Persons with a history of myocardial infarction, stroke, or thrombosis were excluded. Genes that were analyzed for known polymorphisms included angiotensinogen, angiotensin-converting enzyme (ACE), and the angiotensin II type I receptor. Our results showed that the ACE DD genotype was also associated with MI in African-American males but not in females. Racial/ethnic and sex differences were also found with respect to the genotype distribution of the ACE 4656(CT)(2/3) polymorphism. It was observed that the 2/2 genotype had a protective effective in males for myocardial infarction and venous thrombosis. The data also demonstrated that the allele frequencies of the A1166C variant of the angiotensin II type I receptor were different in African-Americans as compared to Caucasians.
... effectiveness and safety of pharmacologic and mechanical strategies to prevent VTE in patients having bariatric surgery? Question 7 What is the comparative effectiveness and safety of pharmacologic prophylaxis...
Kirkby, Brooke E; Wong, Sophia; Foong, Yi Chao; Ranjan, Nishant; Luttrell, James; Mathew, Ronnie; Chilvers, Charles M; Mauldon, Emily; Sharp, Colin; Hannan, Terry
Objectives This study was conducted to assess the incidence and risk factors for venous thromboembolism (VTE) in a cohort of medical patients both during the period of hospitalisation and following discharge. Design This was a prospective observational study to document the risk profile and incidence of VTE posthospitalisation among all medical patients admitted to our institution during the trial period. Settings Primary healthcare. Single tertiary referral centre, Tasmania, Australia. Participants A total of 986 patients admitted to the medical ward between January 2012 and September 2012 were included in the study with male to female ratio of 497:489. The mean age of patients was 68 years (range 17–112, SD 16). Results Overall, 54/986 patients (5.5%) had a VTE during the study period. Of these, 40/54 (74.1%) occurred during hospitalisation and 14/54 (25.9%) occurred following discharge. VTE risk factors revealed in multivariate analysis to be associated with a previous diagnosis of VTE (p<0.001, OR=6.63, 95% CI 3.3 to 13.36), the occurrence of surgery within the past 30 days (p<0.001, OR=2.52, 95% CI 1.33 to 4.79) and an admission diagnosis of pulmonary disease (p<0.01, OR 3.61, 95% CI 1.49 to 8.76). Mobility within 24 hours of admission was not associated with an increased risk. There was risk of VTE when the length of stay prolonged (p=0.046, OR=1.01, 95% CI 1.00 to 1.03), however it was not sustained with multivariate modelling. VTE-specific prophylaxis was used in 53% of the studied patients. Anticoagulation including antiplatelet agents were administered in 63% of patients who developed VTE. Conclusions This prospective observational study found that 5.5% of the studied patients developed VTE. Among those, 25.9% (14/54) of patients had a detected VTE posthospitalisation with this risk being increased if there was a history of VTE, recent surgery and pulmonary conditions. Thromboprophylaxis may be worth considering in these cohorts. Further study to
Zöller, Bengt; Li, Xinjun; Sundquist, Jan; Sundquist, Kristina
Inherited hypercoagulable states (i.e. thrombophilia) have been suggested to be involved in retinal vascular occlusion but results are divergent. Vascular micronutrition and ischemia have been hypothesised to be involved in the pathogenesis of glaucoma. This nationwide study determines the importance of family history of venous thromboembolism (VTE) as a risk factor for retinal vein occlusion (RVO), retinal artery occlusion (RAO), primary open angle glaucoma (POAG) and primary angle-closure glaucoma (PACG). A total of 6,007,042 Swedish individuals were studied. Data from the Swedish Multigeneration Register for subjects aged 0-78 years old for the period 1997-2010 were linked to the Swedish Hospital Discharge Register and the Hospital Outpatient Register. Main exposure measure was family history of VTE in first-degree relatives (parents and/or siblings). Main outcomes were hazard ratios (HRs) for RVO, RAO, POAG, and PACG. During follow-up 9036 individuals developed RVO, 2137 individuals developed RAO, 29,176 individuals developed POAG and 1498 individuals developed PACG. There was no association between family history of VTE and risk of RVO (HR = 1.04, 95 % CI 0.98-1.10), RAO (HR = 1.00, 95 % CI 0.89-1.13), POAG (HR = 0.96, 95 % CI 0.93-0.99), and PACG (HR = 0.92, 95 % CI 0.80-1.06) in the crude age and sex adjusted model. The results were similar in the fully adjusted model: RVO (HR = 1.04, 95 % CI 0.99-1.11), RAO (HR = 1.01, 95 % CI 0.89-1.13), POAG (HR = 0.97, 95 % CI 0.94-1.00), and PACG (HR = 0.91, 95 % CI 0.79-1.05). Family history of VTE is not a risk factor for RVO, RAO, POAG and PACG. Thus, it is unlikely that strong and common genetic variants associated with VTE are of importance for these disorders.
Jick, H; Jick, S S; Gurewich, V; Myers, M W; Vasilakis, C
Concern about the risks of cardiovascular illness in women using combined oral contraceptives (OC) containing the progestagens desogestrel and gestodene prompted two studies of data from the UK General Practice Research Database. We compared the risks of certain cardiovascular illnesses in otherwise healthy women exposed to one of three OCs containing < 35 micrograms oestrogen plus levonorgestrel, desogestrel, or gestodene. In the first study, based on some 470 general practices, there were 15 cases of unexpected idiopathic cardiovascular death among 303,470 women who were current users of one of the study OCs. The estimated incidence rates were 8/184,536 (4.3 per 100,000) woman-years at risk for users of combined OCs containing levonorgestrel, 2/135,567 (1.5 per 100,000) for desogestrel users, and 5/105,201 (4.8 per 100,000) for gestodene users. The relative risk (RR) estimates were 0.4 (95% CI 0.1-2.1) and 1.4 (CI 0.5-4.5) for desogestrel and gestodene, respectively, compared with levonorgestrel. In the second study, derived from some 370 general practices, there were 80 cases of nonfatal venous thromboembolism (VTE) in a cohort of 238,130 otherwise healthy women. The incidence rates of VTE per 100,000 woman-years at risk were 16.1 for levonorgestrel users, 29.3 for desogestrel, and 28.1 for gestodene. The adjusted RR estimates from the cohort analysis were 1.9 (1.1-3.2) and 1.8 (1.0-3.2) for desogestrel and gestodene users, respectively, compared with users of levonorgestrel. In a nested case-control analysis the adjusted matched RR estimates were 2.2 (1.1-4.4) and 2.1 (1.0-4.4) for desogestrel and gestodene users, respectively, compared with users of levonorgestrel. The excess risk for nonfatal VTE associated with the new generation of combined OCs containing low-dose oestrogen and the progestagens desogestrel or gestodene compared with levonorgestrel is estimated to be 16 per 100,000 woman-years.
Farmer, R D; Lawrenson, R A; Todd, J C; Williams, T J; MacRae, K
The results of three independent studies of venous thromboembolic disease (VTE) and oral contraceptives are reviewed together with two further cohort/case-control studies which we conducted using the MediPlus and General Practice Research Database (GPRD) databases. These latter studies jointly involved 395 cases and uniquely examined the association between VTE and individual combined oral contraceptive (COC) formulations. The two studies yielded very similar results. Crude incidence rates for idiopathic VTE of 4.6 and 3.8 were found per 10,000 exposed woman-years (EWY), in the MediPlus and GPRD studies respectively. Incidence rates increased markedly with age, and in both databases the rates amongst users of levonorgestrel products were lower than those amongst users of desogestrel and gestodene products. A case fatality rate of 3% and a mortality rate of 10 per million EWY were estimated. Odds ratios (OR) were calculated for confounding variables and different COC formulations. Both database studies indicated an excess of current smokers and women with high body mass indices amongst cases. There were significantly more cases with asthma in the GPRD study and cases who had been using their COC for less than a year. No statistically significant differences between COC formulations were found in the analyses where controls were matched to cases by practice and year of birth in both the MediPlus and GPRD studies. In the GPRD study we also ran a study where controls were matched by practice and within 5 year age bands. In this study the OR were consistently higher for the newer or 'third generation' products than when controls were matched by year of birth. However only the acne formulation/OC containing cyproterone acetate and 35 microg ethinyloestradiol yielded a significant OR of 2.3. It may be concluded that improvements in prescribing are paramount as the results strongly indicate that overweight women and those who smoke are at a greater risk of VTE. Further
Vinogradova, Yana; Coupland, Carol; Hippisley-Cox, Julia
Introduction Many studies have found an increased risk of venous thromboembolism (VTE) associated with the use of combined hormonal contraceptives, but various methodologies have been used in the study design relating to definition of VTE event and the selection of appropriate cases for analysis. This study will focus on common oral hormonal contraceptives, including compositions with cyproterone because of their contraceptive effect and will perform a number of sensitivity analyses to compare findings with previous studies. Methods and analysis 2 nested case–control studies will be based on the general population using records from UK general practices within the QResearch and Clinical Practice Research Datalink databases. Cases will be female patients aged 15–49 with primary VTE diagnosed between 2001 and 2013. Each case will be matched by age, year of birth and practice to five female controls, who are alive and registered with the practice at the time of diagnosis of the case (index date). Exposure to different hormonal contraceptives will be defined as at least one prescription for that contraceptive in the year before the index date. The effects of duration and the length of any gap since last use will also be investigated. Conditional logistic regression will be applied to calculate ORs adjusted for smoking, ethnicity, comorbidities and use of other medications. Possible indications for prescribing hormonal contraceptives, such as menstrual disorders, acne or hirsutism will be included in the analyses as confounding factors. A number of sensitivity analyses will be carried out. Ethics and dissemination The initial protocol has been reviewed and approved by ISAC (Independent Scientific Advisory Committee) for Medicine and Healthcare Products Regulatory Agency Database Research. The project has also been reviewed by QResearch and meets the requirements of the Trent Research Ethics Committee. The results will be published in a peer-reviewed journal. PMID
Mismetti, Patrick; Samama, Charles-Marc; Rosencher, Nadia; Vielpeau, Claude; Nguyen, Philippe; Deygas, Beatrice; Presles, Emilie; Laporte, Silvy
Despite the need for effective and safe thromboprophylactic drugs for patients with renal impairment, clinical trial data on anticoagulant agents are limited in this population. The study aim was to assess in the real-world setting the use of the once-daily 1.5 mg reduced dosage regimen of fondaparinux available for this context. In this prospective cohort study, patients with a creatinine clearance (CrCl) of 20-50 ml/minute, undergoing total hip (THR) or knee (TKR) replacement or hip fracture surgery (HFS) received fondaparinux thromboprophylaxis. Main clinical outcomes were bleeding (major/clinically relevant non-major), symptomatic venous thromboembolism (VTE) and death. Overall, 442 patients (353 women; median age: 82 years; 39.4% in ASA class ≥3; mean ± SD CrCl: 39.0 ± 8.0 ml/minute; 78% with additional risk factors for bleeding), undergoing THR (43.7%), TKR (27.6%), or HFS (28.7%) received fondaparinux 1.5 mg for a mean ± SD duration of 16.0 ± 12.5 days. At postoperative day 10, the rates (95% confidence interval) of major bleeding, clinically relevant bleeding and symptomatic VTE were 4.5% (2.8-6.9), 0.5% (0.1-1.6) and 0.5% (0.05-1.62), respectively; no fatal bleeding, bleeding into a critical organ, pulmonary embolism or proximal deep-vein thrombosis occurred. Corresponding rates at one month were 5.2%, 0.7% and 0.7%. One-month mortality was 2.3% (0.9-3.6). This large clinical prospective study provides for the first time, under conditions reflecting "real-world" routine clinical practice, data on the bleeding and VTE risks of thromboprophylaxis with fondaparinux 1.5 mg after major orthopaedic surgery in renally impaired patients. It shows that these patients constitute a very elderly and fragile population.
Burness, Celeste B; Perry, Caroline M
Rivaroxaban (Xarelto(®)), an oral direct factor Xa inhibitor, is approved for the initial treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE), as well as the prevention of recurrent DVT and PE. It is administered at a fixed oral dose and does not require routine coagulation monitoring. In the EINSTEIN-DVT and EINSTEIN-PE trials, in over 8,000 patients with DVT and/or PE, a single-drug approach with rivaroxaban was shown to be noninferior to standard therapy consisting of subcutaneous enoxaparin sodium overlapping with and followed by an oral dose-adjusted vitamin K antagonist (enoxaparin-VKA) with regard to the incidence of symptomatic recurrent venous thromboembolism (VTE) after 3, 6 or 12 months of treatment. Rivaroxaban was generally well tolerated in patients with DVT or PE, with no significant between-group differences in clinically relevant bleeding between the rivaroxaban and enoxaparin-VKA groups. Notably, rivaroxaban was associated with a significantly lower rate of major bleeding compared with enoxaparin-VKA when EINSTEIN-DVT and EINSTEIN-PE data were pooled. Pharmacoeconomic analyses indicated that rivaroxaban may be a cost-effective alternative to enoxaparin-VKA for the treatment of DVT or PE and prevention of recurrent VTE. Extended prophylaxis with rivaroxaban reduced the incidence of symptomatic recurrent VTE to a greater extent than placebo in the EINSTEIN-Extension trial, but was associated with a non-significant increase in the risk of clinically relevant bleeding compared with placebo. In conclusion, rivaroxaban is a reasonable alternative to standard therapy for the treatment of DVT and PE, and as extended thromboprophylaxis.
Verhamme, Peter; Gunn, Sophie; Sonesson, Elisabeth; Peerlinck, Kathelijne; Vanassche, Thomas; Vandenbriele, Christophe; Ageno, Walter; Glazer, Steven; Prins, Martin; Buller, Harry; Tangelder, Marco
TB-402 is a long-acting monoclonal antibody that partially inhibits factor VIII. A single administration of TB-402 was effective and well-tolerated for the prevention of venous thromboembolism (VTE) after total knee replacement. In this study, the efficacy and safety of a single administration of TB-402 for the extended prophylaxis of VTE after total hip replacement (THR) was investigated. This was a phase II, randomised, active-controlled, double-blind study that included patients undergoing elective THR surgery. Patients were randomised to TB-402 25 mg or TB-402 50 mg, administered as a single intravenous administration 2-4 hours postoperatively, or to rivaroxaban 10 mg once daily for 35 days. The primary efficacy outcome was total VTE defined as symptomatic VTE and asymptomatic deep-vein thrombosis (DVT) detected by bilateral venography at day 35. The principal safety outcome was the incidence of major bleeding and clinically relevant non-major bleeding until day 35. Total VTE was similar in all groups: 5.3% (95%CI 2.9-9.6), 5.2% (95%CI 2.8-9.3) and 4.7% (95%CI 2.5-8.7) for TB-402 25 mg, TB-402 50 mg and rivaroxaban, respectively. All were asymptomatic DVTs. Major or clinically relevant non-major bleedings were observed in 5.8% (95%CI 3.3-9.9), 7.2% (95%CI 4.4-11.6) and 1.4% (95%CI 0.5-4.2) for TB-402 25 mg, TB-402 50 mg and rivaroxaban, respectively. In conclusion, TB-402, administered as a single postoperative dose, had a similar efficacy compared to rivaroxaban for the prevention of VTE after THR. The incidence of major and clinically relevant non-major bleeding was higher in the TB-402 groups than in the rivaroxaban group.
Zhang, Shuai; Zhai, Zhenguo; Yang, Yuanhua; Zhu, Jianguo; Kuang, Tuguang; Xie, Wanmu; Yang, Suqiao; Liu, Fangfang; Gong, Juanni; Shen, Ying H; Wang, Chen
Venous thromboembolism (VTE) recurrence carries significant mortality and morbidity. Accurate risk assessment and effective treatment for patients with acute pulmonary embolism (PE) is important for VTE recurrence prevention. We examined the association of VTE recurrence with risk stratification and PE treatment. We enrolled 627 patients with a first episode of confirmed PE. Baseline clinical information was collected. PE severity was assessed by the European Society of Cardiology's (ESC) risk stratification, the simplified PE Severity Index (sPESI) and the Qanadli score of clot burden. Patients were followed for 1-5 years. The cumulative recurrent VTE and all-cause death were documented. The association between recurrent VTE and risk factors was analyzed. The cumulative incidences of recurrent VTE were 4.5%, 7.3%, and 13.9% at 1, 2, and 5 years of follow-up, respectively. The VTE recurrence was associated with higher (high- and intermediate-) risk stratification predicted by ESC model (HR 1.838, 95% CI 1.318-2.571, P<0.001), as well as with unprovoked PE (HR 2.809, 95% CI 1.650-4.781, P b 0.001) and varicose veins (HR 4.747, 95% CI 2.634-8.557, P<0.001). The recurrence was negatively associated with longer (≥6 months) anticoagulation (HR 0.473, 95% CI 0.285-0.787, P=0.004), especially in patients with higher risk (HR 0.394, 95% CI 0.211-0.736, P=0.003) and unprovoked PE (HR 0.248, 95% CI 0.122-0.504, P<0.001). ESC high-risk and intermediate-risk PE, unprovoked PE and varicose veins increase recurrence risk. Longer anticoagulation treatment reduces recurrence, especially in higher risk and unprovoked PE patients.
Prescott, Lauren S.; Kidin, Lisa M.; Downs, Rebecca L.; Cleveland, David J.; Wilson, Ginger L.; Munsell, Mark F.; DeJesus, Alma Y.; Cain, Katherine E.; Ramirez, Pedro T.; Kroll, Michael H.; Levenback, Charles F.; Schmeler, Kathleen M.
Objective National guidelines recommend prophylactic anticoagulation for all hospitalized patients with cancer to prevent hospital-acquired venous thromboembolism (VTE). However, adherence to these evidence-based recommended practice patterns remains low. We performed a quality improvement project to increase VTE pharmacologic prophylaxis rates among patients with gynecologic malignancies hospitalized for nonsurgical indications and evaluated the resulting effect on rates of development of VTE. Methods/materials In June 2011, departmental VTE practice guidelines were implemented for patients with gynecologic malignancies who were hospitalized for nonsurgical indications. A standardized VTE prophylaxis module was added to the admission electronic order sets. Outcome measures included: number of admissions receiving VTE pharmacologic prophylaxis within 24 hours of admission; and number of potentially preventable hospital-acquired VTEs diagnosed within 30 and 90 days of discharge. Outcomes were compared between a pre-guideline implementation cohort (N=99), a post-guideline implementation cohort (N=127), and a sustainability cohort assessed 2 years after implementation (N=109). Patients were excluded if upon admission they had a VTE, were considered low risk for VTE, or had a documented contraindication to pharmacologic prophylaxis. Results Administration of pharmacologic prophylaxis within 24 hours of admission increased from 20.8% to 88.2% immediately following the implementation of guidelines, but declined to 71.8% in our sustainability cohort (p<0.001). There was no difference in VTE incidence among the three cohorts (n=2 (4.2%) v. n=3 (3.9%) v. n=3 (4.2%), respectively; p=1.00). Conclusions Our quality improvement project improved pharmacologic VTE prophylaxis rates. A small decrease in prophylaxis over the subsequent 2 years suggests a need for continued surveillance to optimize quality improvement initiatives. Despite increased adherence to guidelines, VTE rates
Feuring, Martin; Schulman, Sam; Eriksson, Henry; Kakkar, Ajay J; Schellong, Sebastian; Hantel, Stefan; Schueler, Elke; Kreuzer, Jörg; Goldhaber, Samuel Z
The direct oral anticoagulants, e.g., dabigatran etexilate (DE), are effective and well tolerated treatments for venous thromboembolism (VTE). Net clinical benefit (NCB) is a useful concept in weighing potential benefits against potential harm of comparator drugs. The NCB of DE vs. warfarin in VTE treatment was compared. Post-hoc analyses were performed on pooled data from the 6-month RE-COVER® and RE-COVER™ II trials, and data from the RE-MEDY™ trial (up to 36 months), to compare the NCB of DE (150 mg twice daily) and warfarin [target international normalized ratio (INR) 2.0-3.0]. Patients (≥18 years old) had symptomatic proximal deep vein thrombosis and/or pulmonary embolism. NCB was the composite of cardiovascular endpoints (non-fatal events of recurrent VTE, myocardial infarction, stroke or systemic embolism), all-cause death, and bleeding outcomes, all weighted equally. A broad definition of NCB included major bleeding events (MBE) and clinically relevant non-major bleeding events as bleeding outcomes, while a narrow definition included just MBE. The pooled dataset totalled 5107 patients from RE-COVER/RE-COVER II and 2856 patients from RE-MEDY. When NCB was narrowly defined, NCB was similar between DE and warfarin. When broadly defined, NCB was superior with DE vs. warfarin [RE-COVER/RE-COVER II, hazard ratio (HR) 0.80; 95% confidence interval (CI), 0.68-0.95 and RE-MEDY, HR 0.73; 95% CI 0.59-0.91]. These findings were unaffected by warfarin time in therapeutic range. The NCB of DE was similar or superior to warfarin, depending on the NCB definition used, regardless of the quality of INR control.
Ye, Xiaobu; Kickler, Thomas S.; Desideri, Serena; Jani, Jayesh; Fisher, Joy; Grossman, Stuart A.
Venous thromboembolism (VTE) is a common complication in patients with high-grade gliomas. The purpose of this prospective multicenter study was to determine the hazard rate of first symptomatic VTE in newly-diagnosed glioma patients and identify clinical and laboratory risk factors. On enrollment, demographic and clinical information were recorded and a comprehensive coagulation evaluation was performed. Patients were followed until death. The study end point was objectively-documented symptomatic VTE. One hundred seven patients were enrolled with a median age of 57 years (range 29–85) between June 2005 and April 2008. Ninety-one (85 %) had glioblastoma multiforme (GBM). During an average survival of 17.7 months, 26 patients (24 %) (95 % CI 17–34 %) developed VTE (hazard rate 0.15 per person-year) and 94 patients (88 %) died. Median time to VTE was 14.2 weeks post-operation (range 3–126). Patients with an initial tumor biopsy were 3.0 fold more likely to suffer VTE (p = 0.02). Patients with an elevated factor VIII activity (>147 %) were 2.1-fold more likely to develop VTE. ABO blood group, D dimer and thrombin generation were not associated with VTE. No fatal VTE occurred. VTE is a common complication in patients with newly-diagnosed high grade gliomas, particularly in the first six months after diagnosis. Patients with an initial tumor biopsy and elevated factor VIII levels are at increased risk. However, VTE was not judged to be pri-marily responsible for any patient deaths. Therefore, out-patient primary VTE prophylaxis remains investigational until more effective primary prophylaxis strategies and therapies for glioma are identified. PMID:26100546
Rojas-Hernandez, Cristhiam M; Oo, Thein Hlaing; García-Perdomo, Herney Andrés
Intracranial hemorrhage (ICH) in cancer patients can result from tumor bleeding and from antitumor and anticoagulation therapy. The effect of anticoagulation on the incidence of ICH in cancer patients has not been quantified. Our objective was to determine the risk of intracranial hemorrhage associated with anticoagulation therapy for cancer-associated venous thromboembolism (VTE). Systematic review and meta-analysis of studies assessing the safety of anticoagulation therapy in patients with cancer-associated VTE. The primary endpoint of interest was the incidence of ICH and secondary outcomes included all major bleeding, and the time to ICH and major bleeding. After identifying 595 studies, five studies and 2089 patients were included in the analyses. We found that the relative risk (RR) for ICH was 0.494, 95 % CI (0.105-2.331) when low molecular weight heparin (LMWH) with vitamin K antagonist (VKA) anticoagulants were compared. No statistically significant differences in risk were measured. The risk of major bleeding using any type of anticoagulation therapy in patients with cancer-associated VTE was RR 0.853, 95 % CI (0.549, 1.327). After meta-analytic review of data published through August 2015, we conclude that therapeutic anticoagulation with LMWH given ≤6 months does not increase the risk of ICH in cancer patients compared to VKA. The risk of ICH in cancer patients is also similar to that of non-cancer patients. Available data were insufficient to determine if the ICH risk increase changes when the duration of anticoagulation is >6 months.
Sugie, Masayuki; Iizuka, Natsuko; Shimizu, Yuki; Ichikawa, Hiroo
We herein report a case presenting with cerebral venous sinus thrombosis (CVST) associated with primary antiphospholipid syndrome (APS). The patient developed recurrent CVST followed by a hemorrhagic ischemic stroke despite the use of warfarin during the appropriate therapeutic window. Thus, we substituted warfarin to rivaroxaban with prednisolone and obtained a good clinical course. In addition to the effect of prednisolone of inhibiting elevated lupus anticoagulants and the recurrence of arterial thrombosis, rivaroxaban may prevent CVST and inhibit hypercoagulability induced by corticosteroids. The combination of an anti-Xa inhibitor and corticosteroid may be an alternative treatment for CVST and arterial thrombus with warfarin-resistant APS.
Canonico, Marianne; Plu-Bureau, Geneviève; O’Sullivan, Mary Jo; Stefanick, Marcia L.; Cochrane, Barbara; Scarabin, Pierre-Yves; Manson, JoAnn E.
Objectives To investigate VTE risk in relation to age at menopause, age at menarche, parity, bilateral oophorectomy and time since menopause, as well as any interaction with randomized HT assignment among postmenopausal women. Methods Using pooled data from the Women’s Health Initiative HT clinical trials including 27,035 postmenopausal women ages 50 to 79 years with no history of VTE, we assessed the risk of VTE in relation to age at menopause, age at menarche, parity, bilateral oophorectomy and time since menopause by Cox proportional hazard models. Linear trends, quadratic relationships and interactions of reproductive life characteristics with HT on VTE risk were systematically tested. Results During the follow-up, 426 women reported a first VTE, including 294 nonprocedure-related events. No apparent interaction of reproductive life characteristics with HT assignment on VTE risk was detected and there was any significant association of VTE with age at menarche, age at menopause, parity, oophorectomy or time since menopause. However, analyses restricted to nonprocedure-related VTE showed a U-shaped relationship between age at menopause and thrombotic risk that persisted after multivariable analysis (p<0.01). Compared to women aged 40 to 49 years at menopause, those with early menopause (age<40 years) or with late menopause (age>55 years) had a significant increased VTE risk (HR=1.8;95%CI:1.2–2.7 and HR=1.5;95%CI:1.0–2.4, respectively). Conclusion Reproductive life characteristics have little association with VTE and do not seem to influence the effect of HT on thrombotic risk among postmenopausal women. Nevertheless, early and late onset of menopause might be newly identified risk factors for nonprocedure-related VTE. PMID:23760439
... you experience these signs or symptoms seek medical attention right away. How are DVTs and PEs diagnosed? The easiest and most reliable method for diagnosing deep vein thrombosis is an ultrasound ...
Park, Kyung-Hyun; Cheon, Sang-Ho; Lee, Ji-Ho
Purpose This study evaluated the incidence of a venous thromboembolism (VTE) after total knee arthroplasty (TKA) using multidetector row computed tomography-indirect venography (MDCT-indirect venography) and assessed the efficacy of anti-coagulation therapy. Materials and Methods We enrolled 118 patients with 126 cases of TKA. The average age of the patients was 68.4 years. We used 64 channel MDCT-indirect venography for the detection of VTE. We treated selectively proximal deep vein thrombosis (DVT) or pulmonary thromboembolism (PTE) cases according to the results of MDCT-indirect venography. We re-evaluated the change in VTE using follow-up MDCT-indirect venography after 3 months. Results We identified VTE in 35.7%. DVT only was identified in 22.2% including 8 cases of proximal DVT and 20 cases of distal DVT. PTE without DVT was identified in 4.8%, and combined DVT and PTE in 8.7%. All patients with PTE were asymptomatic, but 4 DVT patients had signs of leg swelling. After anti-coagulation therapy, 20 patients showed complete resolution in 16 cases, improvement in 3 cases and one case showed a new distal DVT. Conclusions The incidence of VTE after primary TKA was 35.7% in Korea. Furthermore, anti-coagulation therapy for proximal DVT and PTE patients may be a useful method for preventing the occurrence of a fatal PTE. PMID:22570848
Multicentre validation of the Geneva Risk Score for hospitalised medical patients at risk of venous thromboembolism. Explicit ASsessment of Thromboembolic RIsk and Prophylaxis for Medical PATients in SwitzErland (ESTIMATE).
Nendaz, M; Spirk, D; Kucher, N; Aujesky, D; Hayoz, D; Beer, J H; Husmann, M; Frauchiger, B; Korte, W; Wuillemin, W A; Jäger, K; Righini, M; Bounameaux, H
There is a need to validate risk assessment tools for hospitalised medical patients at risk of venous thromboembolism (VTE). We investigated whether a predefined cut-off of the Geneva Risk Score, as compared to the Padua Prediction Score, accurately distinguishes low-risk from high-risk patients regardless of the use of thromboprophylaxis. In the multicentre, prospective Explicit ASsessment of Thromboembolic RIsk and Prophylaxis for Medical PATients in SwitzErland (ESTIMATE) cohort study, 1,478 hospitalised medical patients were enrolled of whom 637 (43%) did not receive thromboprophylaxis. The primary endpoint was symptomatic VTE or VTE-related death at 90 days. The study is registered at ClinicalTrials.gov, number NCT01277536. According to the Geneva Risk Score, the cumulative rate of the primary endpoint was 3.2% (95% confidence interval [CI] 2.2-4.6%) in 962 high-risk vs 0.6% (95% CI 0.2-1.9%) in 516 low-risk patients (p=0.002); among patients without prophylaxis, this rate was 3.5% vs 0.8% (p=0.029), respectively. In comparison, the Padua Prediction Score yielded a cumulative rate of the primary endpoint of 3.5% (95% CI 2.3-5.3%) in 714 high-risk vs 1.1% (95% CI 0.6-2.3%) in 764 low-risk patients (p=0.002); among patients without prophylaxis, this rate was 3.2% vs 1.5% (p=0.130), respectively. Negative likelihood ratio was 0.28 (95% CI 0.10-0.83) for the Geneva Risk Score and 0.51 (95% CI 0.28-0.93) for the Padua Prediction Score. In conclusion, among hospitalised medical patients, the Geneva Risk Score predicted VTE and VTE-related mortality and compared favourably with the Padua Prediction Score, particularly for its accuracy to identify low-risk patients who do not require thromboprophylaxis.
Gómez-Outes, Antonio; Suárez-Gea, M Luisa; Lecumberri, Ramón; Terleira-Fernández, Ana Isabel; Vargas-Castrillón, Emilio
Pulmonary embolism (PE) is a relatively common cardiovascular emergency. PE and deep vein thrombosis (DVT) are considered expressions of the same disease, termed as venous thromboembolism (VTE). In the present review, we describe and meta-analyze the efficacy and safety data available with the direct oral anticoagulants (DOAC; dabigatran, rivaroxaban, apixaban, edoxaban) in clinical trials testing these new compounds in the acute/long-term and extended therapy of VTE, providing subgroup analyses in patients with index PE. We analyzed ten studies in 35,019 randomized patients. A total of 14,364 patients (41%) had index PE. In the acute/long-term treatment of VTE, the DOAC showed comparable efficacy in preventing recurrent VTE to standard treatment in patients with index PE (risk ratio [RR]: 0.88; 95% confidence interval [CI]: 0.70-1.11) and index DVT (RR: 0.93; 95% CI: 0.75-1.16) (P for subgroup differences =0.76). VTE recurrence depending on PE anatomical extension and presence/absence of right ventricular dysfunction was only reported in two trials, with results being consistent with those obtained in the overall study populations. In the single trial comparing extended therapy of VTE with DOAC versus warfarin, the point estimate for recurrent VTE tended to disfavor the DOAC in patients with index PE (RR: 2.05; 95% CI: 0.83-5.03) and in patients with index DVT (RR: 1.11; 95% CI: 0.49-2.50) (P for subgroup differences =0.32). In trials that compared DOAC versus placebo for extended therapy, the reduction in recurrent VTE was consistent in patients with PE (RR: 0.15; 95% CI: 0.01-1.82) and in patients with DVT (RR: 0.25; 95% CI: 0.10-0.61) (P for subgroup differences =0.71). The DOAC were associated with a consistently lower risk of clinically relevant bleeding (CRB) than standard treatment of acute VTE and higher risk of CRB than placebo for extended therapy of VTE regardless of index event. In summary, the DOAC were as effective as, and safer than, standard
Gómez-Outes, Antonio; Suárez-Gea, Mª Luisa; Lecumberri, Ramón; Terleira-Fernández, Ana Isabel; Vargas-Castrillón, Emilio
Pulmonary embolism (PE) is a relatively common cardiovascular emergency. PE and deep vein thrombosis (DVT) are considered expressions of the same disease, termed as venous thromboembolism (VTE). In the present review, we describe and meta-analyze the efficacy and safety data available with the direct oral anticoagulants (DOAC; dabigatran, rivaroxaban, apixaban, edoxaban) in clinical trials testing these new compounds in the acute/long-term and extended therapy of VTE, providing subgroup analyses in patients with index PE. We analyzed ten studies in 35,019 randomized patients. A total of 14,364 patients (41%) had index PE. In the acute/long-term treatment of VTE, the DOAC showed comparable efficacy in preventing recurrent VTE to standard treatment in patients with index PE (risk ratio [RR]: 0.88; 95% confidence interval [CI]: 0.70–1.11) and index DVT (RR: 0.93; 95% CI: 0.75–1.16) (P for subgroup differences =0.76). VTE recurrence depending on PE anatomical extension and presence/absence of right ventricular dysfunction was only reported in two trials, with results being consistent with those obtained in the overall study populations. In the single trial comparing extended therapy of VTE with DOAC versus warfarin, the point estimate for recurrent VTE tended to disfavor the DOAC in patients with index PE (RR: 2.05; 95% CI: 0.83–5.03) and in patients with index DVT (RR: 1.11; 95% CI: 0.49–2.50) (P for subgroup differences =0.32). In trials that compared DOAC versus placebo for extended therapy, the reduction in recurrent VTE was consistent in patients with PE (RR: 0.15; 95% CI: 0.01–1.82) and in patients with DVT (RR: 0.25; 95% CI: 0.10–0.61) (P for subgroup differences =0.71). The DOAC were associated with a consistently lower risk of clinically relevant bleeding (CRB) than standard treatment of acute VTE and higher risk of CRB than placebo for extended therapy of VTE regardless of index event. In summary, the DOAC were as effective as, and safer than
Larsen, Torben Bjerregaard; Nielsen, Peter Brønnum; Skjøth, Flemming; Rasmussen, Lars Hvilsted; Lip, Gregory Y. H.
Background This study sought to investigate the relative efficacy and safety of non-vitamin K oral anticoagulants (NOACs) for the treatment of venous thromboembolism (VTE) in cancer patients. Methods A systematic search of the PubMed, EMBASE, and ClinicalTrials.gov databases identified all multicentre, randomised phase III trials investigating the initial use of NOAC against a vitamin K antagonist (VKA) together with subcutaneous heparin or low molecular weight heparin (upstart) for treatment of VTE. Outcomes of interest were recurrent VTE (deep venous thrombosis or pulmonary embolism), and clinically relevant bleeding. Results Four randomised controlled phase III trials were included, comprising a total of 19,060 patients randomised to either NOAC or VKA. For patients with active cancer (N = 759), the analysis on the efficacy outcomes demonstrated a trend in favour of NOAC (OR 0.56, 95% CI 0.28–1.13). Similar, analyses on the safety outcomes comparing NOAC to VKA and enoxaparin demonstrated a trend in favour of NOAC (OR 0.88, 95% CI 0.57–1.35). Conclusion Point estimates of the effect size suggest an important estimated beneficial effect of NOAC in the treatment of VTE in cancer, in terms of efficacy and safety, but given the small numbers of patients with cancer in the randomised trials, statistical significance was not achieved. PMID:25479007
Sueta, Daisuke; Akahoshi, Rika; Okamura, Yoshinori; Kojima, Sunao; Ikemoto, Tomokazu; Yamamoto, Eiichiro; Izumiya, Yasuhiro; Tsujita, Kenichi; Kaikita, Koichi; Katabuchi, Hidetaka; Hokimoto, Seiji
A 40-year-old woman experiencing sudden dyspnea went to her personal doctor for advice. She was previously diagnosed with endometriosis and prescribed oral contraceptives for treatment. During earthquakes, she spent 7 nights sleeping in a vehicle. The patient had swelling and pain in her left leg and high D-dimer concentration levels. A contrast-enhanced computed tomography scan revealed a contrast deficit in the bilateral pulmonary artery and in the left lower extremity. She was diagnosed with pulmonary thromboembolism (PTE), and anticoagulation therapy was initiated. This present case is the first report of PTE attributed to the use of oral contraceptives after earthquakes.
Sueta, Daisuke; Akahoshi, Rika; Okamura, Yoshinori; Kojima, Sunao; Ikemoto, Tomokazu; Yamamoto, Eiichiro; Izumiya, Yasuhiro; Tsujita, Kenichi; Kaikita, Koichi; Katabuchi, Hidetaka; Hokimoto, Seiji
A 40-year-old woman experiencing sudden dyspnea went to her personal doctor for advice. She was previously diagnosed with endometriosis and prescribed oral contraceptives for treatment. During earthquakes, she spent 7 nights sleeping in a vehicle. The patient had swelling and pain in her left leg and high D-dimer concentration levels. A contrast-enhanced computed tomography scan revealed a contrast deficit in the bilateral pulmonary artery and in the left lower extremity. She was diagnosed with pulmonary thromboembolism (PTE), and anticoagulation therapy was initiated. This present case is the first report of PTE attributed to the use of oral contraceptives after earthquakes. PMID:28202862
Kleiner, Matthew T; Ahmed, Awad A; Huser, Aaron; Mooar, Pekka; Torg, Joseph
Anticoagulation bridges consisting of subcutaneous enoxaparin combined with oral-dosed warfarin are commonly used in orthopedic procedures as chemoprophylaxis against thromboembolic disease. For some patients, these bridges result in complications. One hundred twenty-one patients were evaluated after primary total hip arthroplasty (THA) between 2008 and 2009. Sixty-three patients were given bridged therapy after THA, and 58 were given warfarin only. The 2 groups were statistically matched on various comorbidities. Outcomes of interest were number of days to dry wound and length of hospital stay. Wounds of patients given anticoagulation bridges took longer to heal than wounds of patients given warfarin only (odds ratio, 2.39; P < .05). In addition, patients given anticoagulation bridges had longer hospital stays (odds ratio, 1.27; P < .05). Compared with warfarin-only therapy after THA, use of warfarin bridged with enoxaparin increased the risk for prolonged wound healing and subsequent infection. In addition, bridged therapy cost $2000 more per patient than warfarin-only therapy. Further studies should examine the risks and benefits of these bridges in reducing thromboembolic disease.
Yamanaka, Yasuhiro; Ito, Hiroshi
Background: Venous thoromboembolism (VTE) is one of the most significant complications after hip surgeries. Many studies have been reported about the incidence of VTE after THA, but a small number of reports were found concerning Periacetabular osteotomy, Revision THA and Surgery for hip fracture postoperatively. Furthermore, there exists no comparative study of the incidence of VTE among major hip surgeries at a single institution. We reported the incidence of VTE among hip surgeries performed at a single institution. Methods: A total of 820 Hip surgeries were performed at same institution. The procedures included 420 hips that underwent primary total hip arthroplasties (THA), 91 revision or removal of total hip arthroplasties (Revision THA), 144 periacetabular osteotomy (PAO) and 165 surgery for hip fracture (SHF) between 2006 and 2012. VTE was detected by Multidetector computed tomography (MDCT) that scanned 768 cases and by ultrasound that scanned 52cases postoperative 10-14 days. Results: The overall incidence of VTE was 12.2% (100 of 820). The incidence of VTE after THA was 13.1% (55 of 420), Revision THA was 13.2% (12 of 91), PAO was 2.1% (3 of 144) and SHF was 18.1% (30 of 165). The incidence of VTE was significantly higher in SHF than in PAO. Conclusion: This data indicates that the incidence of VTE after PAO is significantly lower than SHF and relatively lower than THA and Revision THA. A younger age and non-invasion of the bone marrow of the femur may have affected the result. Prophylaxis therapy was effective especially on SHF. PMID:27499823
Bern, Murray; Deshmukh, Rahul V; Nelson, Russell; Bierbaum, Benjamin; Sevier, Nancy; Howie, Noreen; Losina, Elena; Katz, Jeffrey N
Consecutive patients having elective total hip arthroplasty were prescribed 1 mg of warfarin for 7 days preceding surgery, variable doses while in hospital (target international normalized ratio, 1.5-2.0), and discharged to rehabilitation center or home taking 1 mg daily until 4-week to 6-week follow-up visit. Lower leg pneumatic compression was used postoperatively and elastic compression stockings after discharge. Hospital and clinic charts plus auxiliary sources were reviewed for evidence of thromboembolic diseases (TED). Of 1003 consecutive patients studied, 3 (0.3%, 95% CI 0.0-0.6%) had symptomatic TED, including 2 with deep venous thrombosis and 1 with nonfatal pulmonary embolus. Follow-up rate was 99.1%. Complications from warfarin were minimal. Very-low-dose warfarin coupled with lower leg compression is effective prophylaxis against TED after elective hip arthroplasty when prescribed as described.
Sun, Xuefeng; Feng, Jun; Wu, Wei; Peng, Min; Shi, Juhong
ABO blood types are putatively associated with the risk of venous thromboembolism (VTE), but it is not proved in Chinese people. A large population of Han Chinese patients discharged from Peking Union Medical College Hospital between January 2010 and June 2016 were retrospectively analyzed in a case-control study. A total of 1412 VTE patients were identified from 200,660 discharged Han Chinese patients, including 600 patients with deep vein thrombosis (DVT), 441 patients with pulmonary embolism, and 371 patients with both DVT and pulmonary embolism. The prevalence of non-O blood type was weakly but statistically higher in VTE patients compared with 199,248 non-VTE patients, with an odds ratio (OR) of 1.362 (95% confidence interval [CI], 1.205-1.540). Subgroup analysis showed that the OR for non-O blood type was still increased. It was greater in pre-hospital VTE (OR = 1.464) than that in hospital-acquired VTE (OR = 1.224), and greater in unprovoked VTE (OR = 1.859) than that in provoked VTE (OR = 1.227). The OR for non-O blood type decreased with age in subgroup analysis. These results suggest a weak but statistically significant correlation between non-O blood type and risk of VTE in Han Chinese people.
Background Patients with chronic obstructive pulmonary disease (COPD) have a modified clinical presentation of venous thromboembolism (VTE) but also a worse prognosis than non-COPD patients with VTE. As it may induce therapeutic modifications, we evaluated the influence of the initial VTE presentation on the 3-month outcomes in COPD patients. Methods COPD patients included in the on-going world-wide RIETE Registry were studied. The rate of pulmonary embolism (PE), major bleeding and death during the first 3 months in COPD patients were compared according to their initial clinical presentation (acute PE or deep vein thrombosis (DVT)). Results Of the 4036 COPD patients included, 2452 (61%; 95% CI: 59.2-62.3) initially presented with PE. PE as the first VTE recurrence occurred in 116 patients, major bleeding in 101 patients and mortality in 443 patients (Fatal PE: first cause of death). Multivariate analysis confirmed that presenting with PE was associated with higher risk of VTE recurrence as PE (OR, 2.04; 95% CI: 1.11-3.72) and higher risk of fatal PE (OR, 7.77; 95% CI: 2.92-15.7). Conclusions COPD patients presenting with PE have an increased risk for PE recurrences and fatal PE compared with those presenting with DVT alone. More efficient therapy is needed in this subtype of patients. PMID:23865769
Ramirez, Jesus I; Vassiliu, Pantelis; Gonzalez-Ruiz, Claudia; Vukasin, Petar; Ortega, Adrian; Kaiser, Andreas M; Beart, Robert W
The American Society of Colorectal Surgeons (ASCRS) recently endorsed low-molecular-weight heparin and low-dose heparin as primary prophylaxis for venous thromboembolism (VTE) in highest-risk patients. Our study evaluates the feasibility of sequential compression device (SCD) use for VTE prophylaxis in these patients. Computerized databases of discharge diagnoses from three hospitals were reviewed. All patients with colorectal cancer or inflammatory bowel disease during a 7-year period were identified. Those who underwent major abdominal surgery and received VTE prophylaxis exclusively with SCDs were selected for the study. Patients diagnosed with postoperative VTE were identified through review of the three databases and of patient records for 90 days after surgery. One thousand two hundred eighty-one patients classified as highest-risk under the published ASCRS parameters underwent major abdominal surgery and received SCDs perioperatively. The incidence of clinically detectable postoperative VTE was 0.78 per cent. There were trends toward lower incidence among patients with malignancy (0.53%) compared with inflammatory bowel disease (1.48%, P = 0.09), and those with abdominal compared to pelvic procedures (0.62% vs. 1.04%, P = 0.41). Prophylaxis for perioperative VTE solely with SCD is a viable option for patients classified as highest-risk under ASCRS parameters.
Leleu, Xavier; Rodon, Philippe; Hulin, Cyrille; Daley, Laurent; Dauriac, Charles; Hacini, Maya; Decaux, Olivier; Eisemann, Jean-Claude; Fitoussi, Olivier; Lioure, Bruno; Voillat, Laurent; Slama, Borhane; Al Jijakli, Ahmad; Benramdane, Riad; Chaleteix, Carinne; Costello, Régis; Thyss, Antoine; Mathiot, Claire; Boyle, Eileen; Maloisel, Frédéric; Stoppa, Anne-Marie; Kolb, Brigitte; Michallet, Mauricette; Lamblin, Anne; Natta, Patrick; Facon, Thierry; Elalamy, Ismail; Fermand, Jean-Paul; Moreau, Philippe
Immunomodulatory drugs (IMiDs) are associated with an increased risk of venous thromboembolism (VTE) in multiple myeloma (MM) patients. We designed MELISSE, a multicentre prospective observational study, to evaluate VTE incidence and identify risk factors in IMiDs-treated MM. Our objective was to determine the real-life practice of VTE prophylaxis strategy. A total of 524 MM patients were included, and we planned to collect information at baseline, at four and at 12 months, on MM therapy, on VTE risk factors and management. VTE incidence was 7% (n=31), including 2.5% pulmonary embolism (PE) (n=11), similar at four or 12 months. VTE was observed at all risk assessment levels, although the increased risk assessment level correlated to a lower rate of VTE, maybe due to the implemented thromboprophylaxis strategy. VTE occurred in 7% on aspirin vs 3% on low-molecular-weight heparin (LMWH) prophylaxis, and none on vitamin K antagonists (VKA). New risk factors for VTE in IMiDs-treated MM were identified. In conclusion, VTE prophylaxis is compulsory in IMiDs-treated MM, based on individualised VTE risk assessment. Anticoagulation prophylaxis with LMWH should clearly be prioritised in MM patients with high VTE risk, along with VKA. Further prospective studies will identify most relevant VTE risk factors in IMiDs-treated MM to select accurately which MM patients should receive LMWH prophylaxis and for which duration to optimise VTE risk reduction.
Andro, Marion; Delluc, Aurélien; Moineau, Marie-Pierre; Tromeur, Cécile; Gouillou, Maelenn; Lacut, Karine; Carré, Jean-Luc; Gentric, Armelle; Le Gal, Grégoire
The prevalence of both vitamin D deficiency and venous thromboembolism (VTE) is important in the elderly. Previous studies have provided evidence for a possible association between vitamin D status and the risk of VTE. Thus, we aimed to investigate the association between vitamin D levels and VTE in the population aged 75 and over included in the EDITH case-control study. The association between vitamin D status and VTE was analysed. We also analysed the monthly and seasonal variations of VTE and vitamin D. Between May 2000 and December 2009, 340 elderly patients (mean age 81.5 years, 32% men) with unprovoked VTE and their controls were included. The univariate and multivariate analysis found no significant association between serum levels of vitamin D and the risk of unprovoked VTE. In the unadjusted analysis, a higher BMI was statistically associated with an increased risk of VTE (OR 1.09; 95% CI 1.05-1.13) whereas a better walking capacity and living at home were associated with a decreased rate of VTE: OR 0.57; 95% CI 0.36-0.90 and 0.40; 95% CI 0.25-0.66, respectively. Although not significant, more VTE events occurred during winter (p=0.09). No seasonal variations of vitamin D levels were found (p=0.11). In conclusion, in contrast with previous reports our findings suggest that vitamin D is not associated with VTE in the elderly population.
Jang, Moon Ju; Jeon, Young Joo; Choi, Won-Il; Choi, Yi Seul; Kim, Su Yeoun; Chong, So Young; Oh, Doyeun; Kim, Nam Keun
The frequency of methylenetetrahydrofolate reductase (MTHFR) mutations varies between racial and ethnic groups, and there are also conflicting data regarding MTHFR gene mutations in Asian patients with venous thromboembolism (VTE). The aim of this study was to examine the association between common MTHFR gene mutations (677C>T and 1298A>C) and risk of VTE in Koreans. This study was a retrospective case-control study. We enrolled 203 patients with VTE and 403 controls. For the 677C>T polymorphism, there was no difference in the frequency of the CT genotype and TT genotype between the patients with VTE and the controls. However, in the recessive analysis (CC + CT vs TT), the frequency of the TT genotype was significantly higher in VTE than in controls (odds ratio = 1.700; 95% confidence interval = 1.108-2.607, P = .015). In conclusion, the TT genotype of MTHFR 677C>T increases the risk of VTE in Koreans. This finding was supported by meta-analysis of previous Asian studies.
Meza-Reyes, G E; Cymet-Ramírez, J; Esquivel-Gómez, R; del Campo-Sánchez, Martínez A; Martínez-Guzmán, M A E; Espinosa-Larrañaga, F; Majluf-Cruz, A; Torres-González, R; De la Fuente-Zuno, J C; Villalobos-Garduño, E; Méndez-Huerta, J V; Ibarra-Hirales, E; Valles-Figueroa, J F; Aguilera-Zepeda, J M; Díaz-Borjón, E
Venous thromboembolic disease (VTED) is a public health problem worldwide. In the United States it causes 2 million annual cases. Its annual incidence is 1-2 cases per 1,000 individuals in the general population. It is a disease frequently associated with life threatening complications and its mortality rate is 1-5% of cases. Due to its high complication rate, its slow recovery, and the need for prolonged disability, it is considered as a high-cost disease. VTED may occur in both surgical and medical patients; the known associated risk factors include prolonged rest, active cancer, congestive heart failure, atrial fibrillation, and stroke, among the major medical conditions. Orthopedic surgery represents the main surgical risk factor for VTED, including mainly hip and knee replacements, as well as polytraumatized patients with severe spinal lesions, and major fractures. VTED may be prevented with the appropriate use of antithrombotics. The participants in this consensus defined thromboprophylaxis as the strategy and actions undertaken to reduce the risk of VTED in patients undergoing high risk orthopedic surgery. The position of the Mexican College of Orthopedics and Traumatology regarding the prevention of VTED in orthopedic surgery is described herein.
Sun, Xuefeng; Feng, Jun; Wu, Wei; Peng, Min; Shi, Juhong
ABO blood types are putatively associated with the risk of venous thromboembolism (VTE), but it is not proved in Chinese people. A large population of Han Chinese patients discharged from Peking Union Medical College Hospital between January 2010 and June 2016 were retrospectively analyzed in a case-control study. A total of 1412 VTE patients were identified from 200,660 discharged Han Chinese patients, including 600 patients with deep vein thrombosis (DVT), 441 patients with pulmonary embolism, and 371 patients with both DVT and pulmonary embolism. The prevalence of non-O blood type was weakly but statistically higher in VTE patients compared with 199,248 non-VTE patients, with an odds ratio (OR) of 1.362 (95% confidence interval [CI], 1.205–1.540). Subgroup analysis showed that the OR for non-O blood type was still increased. It was greater in pre-hospital VTE (OR = 1.464) than that in hospital-acquired VTE (OR = 1.224), and greater in unprovoked VTE (OR = 1.859) than that in provoked VTE (OR = 1.227). The OR for non-O blood type decreased with age in subgroup analysis. These results suggest a weak but statistically significant correlation between non-O blood type and risk of VTE in Han Chinese people. PMID:28262729
Abdel-Razeq, Hikmat; Ismael, Yousef
Purpose: Thrombocytopenia is not uncommonly encountered following active anticoagulation of thromboembolism with unfractionated or even low-molecular-weight heparins. In this report, and utilizing a case study, we will address issues related to the diagnosis and treatment of heparin-induced thrombocytopenia (HIT) in a community-based clinical practice. Methods: The case of a 73-year-old female patient who was recently diagnosed with gastroesophageal junction cancer and who developed left lower extremity deep vein thrombosis (DVT) while on active chemotherapy is presented. Following the initiation of anticoagulation, a significant drop in platelet counts was noted and a clinical diagnosis of HIT was made. Articles published in English addressing issues related to anticoagulation and thrombocytopenia were accessed from PubMed and are discussed. Results: HIT is not uncommon, but its diagnosis can occasionally be difficult to confirm. Alternative anticoagulants might not be available for immediate use and many require special expertise for appropriate use. Fondaparinux, a synthetic pentasaccharide, is approved for active anticoagulation of DVT and pulmonary embolism and can be given once daily subcutaneously at a fixed dose with no need for monitoring. Many recent reports described the successful use of this agent in the treatment of HIT. Conclusion: HIT can be difficult to diagnose; diagnostic tests are generally not available in most hospitals and the available ones lack the sensitivity and specificity needed to confirm such diagnosis. Additionally, the alternative anticoagulants are not widely available. In such circumstances, fondaparinux can be used as an alternative anticoagulant. PMID:21753883
Humphries, Angela; Peden, Carol; Jordan, Lesley; Crowe, Josephine; Peden, Carol
A significant incidence of post-procedural deep vein thrombosis (DVT) and pulmonary embolus (PE) was identified in patients undergoing surgery at our hospital. Investigation showed an unreliable peri-operative process leading to patients receiving incorrect or missed venous thromboembolism (VTE) prophylaxis. The Trust had previously participated in a project funded by the Health Foundation using the “Safer Clinical Systems” methodology to assess, diagnose, appraise options, and implement interventions to improve a high risk medication pathway. We applied the methodology from that study to this cohort of patients demonstrating that the same approach could be applied in a different context. Interventions were linked to the greatest hazards and risks identified during the diagnostic phase. This showed that many surgical elective patients had no VTE risk assessment completed pre-operatively, leading to missed or delayed doses of VTE prophylaxis post-operatively. Collaborative work with stakeholders led to the development of a new process to ensure completion of the VTE risk assessment prior to surgery, which was implemented using the Model for Improvement methodology. The process was supported by the inclusion of a VTE check in the Sign Out element of the WHO Surgical Safety Checklist at the end of surgery, which also ensured that appropriate prophylaxis was prescribed. A standardised operation note including the post-operative VTE plan will be implemented in the near future. At the end of the project VTE risk assessments were completed for 100% of elective surgical patients on admission, compared with 40% in the baseline data. Baseline data also revealed that processes for chemical and mechanical prophylaxis were not reliable. Hospital wide interventions included standardisation of mechanical prophylaxis devices and anti-thromboembolic stockings (resulting in a cost saving of £52,000), and a Trust wide awareness and education programme. The education included
Dennis, J; Truong, V; Aïssi, D; Medina-Rivera, A; Blankenberg, S; Germain, M; Lemire, M; Antounians, L; Civelek, M; Schnabel, R; Wells, P; Wilson, M D; Morange, P-E; Trégouët, D-A; Gagnon, F
Essentials Tissue factor pathway inhibitor (TFPI) regulates the blood coagulation cascade. We replicated previously reported linkage of TFPI plasma levels to the chromosome 2q region. The putative causal locus, rs62187992, was associated with TFPI plasma levels and thrombosis. rs62187992 was marginally associated with TFPI expression in human aortic endothelial cells. Click to hear Ann Gil's presentation on new insights into thrombin activatable fibrinolysis inhibitor SUMMARY: Background Tissue factor pathway inhibitor (TFPI) regulates fibrin clot formation, and low TFPI plasma levels increase the risk of arterial thromboembolism and venous thromboembolism (VTE). TFPI plasma levels are also heritable, and a previous linkage scan implicated the chromosome 2q region, but no specific genes. Objectives To replicate the finding of the linkage region in an independent sample, and to identify the causal locus. Methods We first performed a linkage analysis of microsatellite markers and TFPI plasma levels in 251 individuals from the F5L Family Study, and replicated the finding of the linkage peak on chromosome 2q (LOD = 3.06). We next defined a follow-up region that included 112 603 single nucleotide polymorphisms (SNPs) under the linkage peak, and meta-analyzed associations between these SNPs and TFPI plasma levels across the F5L Family Study and the Marseille Thrombosis Association (MARTHA) Study, a study of 1033 unrelated VTE patients. SNPs with false discovery rate q-values of < 0.10 were tested for association with TFPI plasma levels in 892 patients with coronary artery disease in the AtheroGene Study. Results and Conclusions One SNP, rs62187992, was associated with TFPI plasma levels in all three samples (β = + 0.14 and P = 4.23 × 10(-6) combined; β = + 0.16 and P = 0.02 in the F5L Family Study; β = + 0.13 and P = 6.3 × 10(-4) in the MARTHA Study; β = + 0.17 and P = 0.03 in the AtheroGene Study), and contributed to the linkage peak in the F5L Family Study. rs
Testing for inherited thrombophilia and consequences for antithrombotic prophylaxis in patients with venous thromboembolism and their relatives. A review of the Guidelines from Scientific Societies and Working Groups.
De Stefano, Valerio; Rossi, Elena
The clinical penetrance of venous thromboembolism (VTE) susceptibility genes is variable, being lower in heterozygous carriers of factor V Leiden and prothrombin 20210A (mild thrombophilia), and higher in the rare carriers of deficiencies of antithrombin, protein C or S, and those with multiple or homozygous abnormalities (high-risk thrombophilia). The absolute risk of VTE is low, and the utility of laboratory investigation for inherited thrombophilia in patients with VTE and their asymptomatic relatives has been largely debated, leading to the production of several Guidelines from Scientific Societies and Working Groups. The risk for VTE largely depends on the family history of VTE. Therefore, indiscriminate search for carriers is of no utility, and targeted screening is potentially more fruitful. In patients with VTE inherited thrombophilia is not scored as a determinant of recurrence, playing a minor role in the decision of prolonging anticoagulation; indeed, a few guidelines consider testing worthwhile to identify carriers of high-risk thrombophilia, particularly those with a family history of VTE. The identification of the asymptomatic carrier relatives of the probands with VTE and thrombophilia could reduce cases of provoked VTE, offering them primary antithrombotic prophylaxis during risk situations. In most guidelines, this is considered justified only for relatives of probands with a deficiency of natural anticoagulants or multiple abnormalities. Counselling the asymptomatic female relatives of individuals with VTE and/or thrombophilia before pregnancy or the prescription of hormonal treatments should be administered with consideration of the risk driven by the type of thrombophilia and the family history of VTE.
Heit, John A.; Armasu, Sebastian M.; Asmann, Yan W.; Cunningham, Julie M.; Matsumoto, Martha E.; Petterson, Tanya M.; de Andrade, Mariza
Summary Objectives To identify venous thromboembolism (VTE) disease-susceptibility genes. Patients/Methods We performed in silico genome wide association (GWAS) analyses using genotype data imputed to ~2.5 million single nucleotide polymorphisms (SNPs) from adults with objectively-diagnosed VTE (n=1503), and controls frequency-matched on age and sex (n=1459; discovery population). SNPs exceeding genome-wide significance were replicated in a separate population (VTE cases, n=1407; controls, n=1418). Genes associated with VTE were resequenced. Results Seven SNPs exceeded genome-wide significance (P < 5 × 10-8); four on chromosome 1q24.2 (F5 rs6025 [Factor V Leiden], BLZF1 rs7538157, NME7 rs16861990 and SLC19A2 rs2038024) and three on chromosome 9q34.2 (ABO rs2519093 [ABO intron 1], rs495828, rs8176719 [ABO blood type O allele]). The replication study confirmed a significant association of F5, NME7, and ABO with VTE. However, F5 was the main signal on 1q24.2 as only ABO SNPs remained significantly associated with VTE after adjusting for F5 rs6025. This 1q24.2 region was shown to be inherited as a haplotype block. ABO resequencing identified 15 novel single nucleotide variations (SNV) in ABO intron 6 and the ABO 3’ UTR that were strongly associated with VTE (P < 10-4) and belonged to three distinct linkage disequilibrium (LD) blocks; none were in LD with ABO rs8176719 or rs2519093. Our sample size provided 80% power to detect odds ratios=2.0 and 1.51 for minor allele frequencies=0.05 and 0.5, respectively (α=1 × 10-8; 1% VTE prevalence). Conclusions Aside from F5 rs6025, ABO rs8176719 and rs2519093, and F2 rs1799963, additional common and high VTE-risk SNPs among whites are unlikely. PMID:22672568
Tsai, James; Abe, Karon; Boulet, Sheree L.; Beckman, Michele G.; Hooper, W. Craig; Grant, Althea M.
Background Venous thromboembolism (VTE), comprising deep vein thrombosis (DVT) and pulmonary embolism (PE), is a significant source of mortality and morbidity worldwide. By analyzing data of the 2010 Nationwide Inpatient Sample from the Agency for Healthcare Research and Quality (AHRQ), we evaluated the predictive accuracy of the AHRQ’s 29-comorbidity index with in-hospital death among US adult hospitalizations with a diagnosis of VTE. Methods We assessed the case-fatality and prevalence of comorbidities among a sample of 153,518 adult hospitalizations with a diagnosis of VTE that comprised 87,605 DVTs and 65,913 PEs (with and without DVT). We estimated adjusted odds ratios and 95% confidence intervals with multivariable logistic regression models by using comorbidities as predictors and status of in-hospital death as an outcome variable. We assessed the c-statistics for the predictive accuracy of the logistic regression models. Results In 2010, approximately 41,944 in-hospital deaths (20,212 with DVT and 21,732 with PE) occurred among 770,137 hospitalizations with a diagnosis of VTE. When compared separately to hospitalizations with VTE, DVT, or PE that had no corresponding comorbidities, congestive heart failure, chronic pulmonary disease, coagulopathy, liver disease, lymphoma, fluid and electrolyte disorders, metastatic cancer, other neurological disorders, peripheral vascular disorders, pulmonary circulation disorders, renal failure, solid tumor without metastasis, and weight loss were positively and independently associated with 10%−125% increased likelihoods of in-hospital death. The c-statistic values ranged from 0.776 to 0.802. Conclusion The results of this study indicated that comorbidity was associated independently with risk of death among hospitalizations with VTE and among hospitalizations with DVT or PE. The AHRQ 29-comorbidity index provides acceptable to excellent predictive accuracy for in-hospital deaths among adult hospitalizations with VTE
Nelson, Richard E.; Grosse, Scott D.; Waitzman, Norman J.; Lin, Junji; DuVall, Scott L.; Patterson, Olga; Tsai, James; Reyes, Nimia
Background There are limitations to using administrative data to identify postoperative venous thromboembolism (VTE). We used a novel approach to quantify postoperative VTE events among Department of Veterans Affairs (VA) surgical patients during 2005–2010. Methods We used VA administrative data to exclude patients with VTE during 12 months prior to surgery. We identified probable postoperative VTE events within 30 and 90 days post-surgery in three settings: 1) pre-discharge inpatient, using a VTE diagnosis code and a pharmacy record for anticoagulation; 2) post-discharge inpatient, using a VTE diagnosis code followed by a pharmacy record for anticoagulation within 7 days; and 3) outpatient, using a VTE diagnosis code and either anticoagulation or a therapeutic procedure code with natural language processing (NLP) to confirm acute VTE in clinical notes. Results Among 468,515 surgeries without prior VTE, probable VTEs were documented within 30 and 90 days in 3,931 (0.8%) and 5,904 (1.3%), respectively. Of probable VTEs within 30 or 90 days post-surgery, 47.8% and 62.9%, respectively, were diagnosed post-discharge. Among post-discharge VTE diagnoses, 86% resulted in a VA hospital readmission. Fewer than 25% of outpatient records with both VTE diagnoses and anticoagulation prescriptions were confirmed by NLP as acute VTE events. Conclusion More than half of postoperative VTE events were diagnosed post-discharge; analyses of surgical discharge records are inadequate to identify postoperative VTE. The NLP results demonstrate that the combination of VTE diagnoses and anticoagulation prescriptions in outpatient administrative records cannot be used to validly identify postoperative VTE events. PMID:25666908
Huang, W.; Goldberg, R.J.; Cohen, A.T.; Anderson, F.A.; Kiefe, C.I.; Gore, J.M.; Spencer, F.A.
Introduction Contemporary trends in health-care delivery are shifting the management of venous thromboembolism (VTE) events (deep vein thrombosis [DVT] and/or pulmonary embolism [PE]) from the hospital to the community, which may have implications for its prevention, treatment, and outcomes. Materials and Methods Population-based surveillance study monitoring trends in clinical epidemiology among residents of the Worcester, Massachusetts, metropolitan statistical area (WMSA) diagnosed with an acute VTE in all 12 WMSA hospitals. Patients were followed for up to 3 years after their index event. Total of 2334 WMSA residents diagnosed with first-time community-presenting VTE (occurring in an ambulatory setting or diagnosed within 24 hours of hospitalization) from 1999 through 2009. Results While PE patients were consistently admitted to the hospital for treatment over time, the proportion diagnosed with DVT-alone admitted to the hospital decreased from 67% in 1999 to 37% in 2009 (p value for trend <0.001). Among hospitalized patients, the mean length of stay decreased from 5.6 to 4.8 days (p value for trend <0.001). Between 1999 and 2009, treatment of VTE shifted from warfarin and unfractionated heparin towards use of low-molecular-weight heparins and newer anticoagulants; also, 3-year cumulative event rates decreased for all-cause mortality (41–26%), major bleeding (12–6%), and recurrent VTE (17–9%). Conclusions A decade of change in VTE management was accompanied by improved long-term outcomes. However, rates of adverse events remained fairly high in our population-based surveillance study, implying that new risk-assessment tools to identify individuals at increased risk for developing major adverse outcomes over the long-term are needed. PMID:25921936
Olson, Nels C.; Cushman, Mary; Judd, Suzanne E.; McClure, Leslie A.; Lakoski, Susan G.; Folsom, Aaron R.; Safford, Monika M.; Zakai, Neil A.
Background The American Heart Association's Life's Simple 7 metric is being used to track the population's cardiovascular health (CVH) toward a 2020 goal for improvement. The metric includes body mass index (BMI), blood pressure, cholesterol, glucose, physical activity (PA), cigarette smoking, and diet. We hypothesized a lower risk of venous thromboembolism (VTE) with favorable Life's Simple 7 scores. Methods and Results REGARDS recruited 30 239 black and white participants ≥45 years of age across the United States in 2003–2007. A 14‐point summary score for Life's Simple 7 classified participants into inadequate (0 to 4 points), average (5 to 9 points), and optimal (10 to 14 points) categories. Hazard ratios (HRs) of incident VTE were calculated for these categories, adjusting for age, sex, race, income, education, and region of residence. For comparison, HRs of VTE were calculated using the Framingham 10‐year coronary risk score. There were 263 incident VTE cases over 5.0 years of follow‐up; incidence rates per 1000 person‐years declined from 2.9 (95% confidence interval [CI], 2.3 to 3.7) among those in the inadequate category to 1.8 (95% CI, 1.4 to 2.4) in the optimal category. Compared to the inadequate category, participants in the average category had a 38% lower VTE risk (95% CI, 11 to 57) and participants in the optimal category had a 44% lower risk (95% CI, 18 to 62). The individual score components related to lower VTE risk were ideal PA and BMI. There was no association of Framingham Score with VTE. Conclusions Life's Simple 7, a CVH metric, was associated with reduced VTE risk. Findings suggest that efforts to improve the population's CVH may reduce VTE incidence. PMID:25725088
Sharma, Manuj; Cornelius, Victoria R; Patel, Jignesh P; Davies, J Graham; Molokhia, Mariam
Background Evidence regarding use of direct oral anticoagulants (DOACs) in the elderly, particularly bleeding risks, is unclear despite the presence of greater comorbidities, polypharmacy and altered pharmacokinetics in this age group. Methods and Results We performed a systematic review and meta-analysis of randomised trials of DOACs (dabigatran, apixaban, rivaroxaban, edoxaban) for efficacy and bleeding outcomes compared to VKA (vitamin k antagonists) in elderly participants (aged ≥75 years) treated for acute venous thromboembolism or stroke prevention in atrial fibrillation. Nineteen studies were eligible for inclusion but only 11 reported data specifically for elderly participants. Efficacy in managing thrombotic risks for each DOAC was similar or superior to VKA in the elderly. A non-significantly, higher risk of major bleeding than VKA was observed with dabigatran 150mg (Odds Ratio 1.18, 95% confidence interval 0.97-1.44) but not with the 110mg dose. Significantly higher gastrointestinal bleeding risks with dabigatran 150mg (1.78, 1.35-2.35) and 110mg (1.40, 1.04-1.90) and lower intracranial bleeding risks than VKA for dabigatran 150mg (0.43, 0.26-0.72) and dabigatran 110mg (0.36, 0.22-0.61) were also observed. A significantly lower major bleeding risk compared to VKA was observed for apixaban (0.63, 0.51-0.77), edoxaban 60mg (0.81, 0.67-0.98) and 30mg (0.46, 0.38-0.57) while rivaroxaban showed similar risk. Conclusion DOACs demonstrated at least equal efficacy to VKA in managing thrombotic risks in the elderly however bleeding patterns were distinct. In particular, dabigatran was associated with a higher risk of gastrointestinal bleeding than VKA. Insufficient published data for apixaban, edoxaban and rivaroxaban indicates further work is needed to clarify their bleeding risks in the elderly. PMID:25995317
De Ruyter, Bernadette; Semprini, Alex; Ebmeier, Stefan; Kiddle, Grant; Willis, Nigel; Carter, John; Weatherall, Mark; Beasley, Richard
Objectives To determine the likely enrolment rate of eligible participants into a randomised controlled trial (RCT) in which a within-cast intermittent pneumatic compression device using Jet Impulse Technology (IPC/JIT) is 1 of 3 possible interventions in a RCT for the prevention of venous thromboembolism (VTE) in the clinical setting of isolated lower limb cast immobilisation. Design A prospective, open-label feasibility study of the IPC/JIT device placed within a lower limb cast. Setting Wellington Regional Hospital Fracture Clinic. Participants Individuals aged 18–70 who presented with a lower limb injury requiring a minimum of 4 weeks below-knee cast immobilisation. Intervention Placement of an IPC/JIT device within lower limb cast. Outcome measures The main outcome measure was the proportion of eligible participants who participated in the feasibility study. Secondary outcome measures included adherence to device usage throughout the study, ease of application of the device and adverse events potentially associated with its use. Results The proportion of potentially eligible participants for the IPC/JIT device was only 7/142 (5%), 95% CI 2 to 9.9. Devices were used for a mean (range) of 4.1 (1.9 to 10.2) hours per day and none of 7 participants had adequate adherence to the device. 3 of the 7 participants suffered an adverse event, including 1 deep vein thrombosis, 2 dorsal foot ulcer and 1 skin maceration. Conclusions A within-cast IPC/JIT device is unlikely to be a feasible randomisation arm for a RCT assessing possible interventions for the reduction of VTE risk in the clinical setting of lower limb injury requiring below knee cast immobilisation for a minimum of 4 weeks. Trial registration number ANZCTR 12615000192583. PMID:27707834
Hennessy, S; Berlin, J A; Kinman, J L; Margolis, D J; Marcus, S M; Strom, B L
Controversy exists regarding whether oral contraceptives (OCs) containing desogestrel and gestodene are associated with an increased risk of venous thromboembolism (VTE) versus OCs containing levonorgestrel. We were interested in synthesizing the available data, exploring explanations for mixed results, and characterizing the degree of uncontrolled confounding that could have produced a spurious association. We performed a meta-analysis and formal sensitivity analysis of studies that examined the relative risk of VTE for desogestrel and gestodene versus levonorgestrel. Twelve studies, all observational, were included. The summary relative risk (95% CI) was 1.7 (1.3-2.1; heterogeneity p = 0.09). If real, the incremental risk of VTE would be about 11 per 100,000 women per year. An association was present when accounting for duration of use and when restricted to the first year of use in new users. However, in the sensitivity analysis, the association abated in many, but not all, scenarios in which an unmeasured confounding factor increased the risk of VTE three to fivefold and in nearly all examined scenarios in which the factor increased the risk 10-fold. The summary relative risk of 1.7 does not appear to be caused by depletion of susceptibles, but is sensitive to a modest degree of unmeasured confounding. Whether such confounding occurred is unknown. However, given this sensitivity, this issue probably cannot be settled unequivocally with observational data. In the absence of a definitive answer, this apparent increased risk, together with its uncertainty and small magnitude and its important consequences, should be considered when selecting an OC for a given woman.
Germain, Marine; Chasman, Daniel I.; de Haan, Hugoline; Tang, Weihong; Lindström, Sara; Weng, Lu-Chen; de Andrade, Mariza; de Visser, Marieke C.H.; Wiggins, Kerri L.; Suchon, Pierre; Saut, Noémie; Smadja, David M.; Le Gal, Grégoire; van Hylckama Vlieg, Astrid; Di Narzo, Antonio; Hao, Ke; Nelson, Christopher P.; Rocanin-Arjo, Ares; Folkersen, Lasse; Monajemi, Ramin; Rose, Lynda M.; Brody, Jennifer A.; Slagboom, Eline; Aïssi, Dylan; Gagnon, France; Deleuze, Jean-Francois; Deloukas, Panos; Tzourio, Christophe; Dartigues, Jean-Francois; Berr, Claudine; Taylor, Kent D.; Civelek, Mete; Eriksson, Per; Psaty, Bruce M.; Houwing-Duitermaat, Jeanine; Goodall, Alison H.; Cambien, François; Kraft, Peter; Amouyel, Philippe; Samani, Nilesh J.; Basu, Saonli; Ridker, Paul M.; Rosendaal, Frits R.; Kabrhel, Christopher; Folsom, Aaron R.; Heit, John; Reitsma, Pieter H.; Trégouët, David-Alexandre; Smith, Nicholas L.; Morange, Pierre-Emmanuel
Venous thromboembolism (VTE), the third leading cause of cardiovascular mortality, is a complex thrombotic disorder with environmental and genetic determinants. Although several genetic variants have been found associated with VTE, they explain a minor proportion of VTE risk in cases. We undertook a meta-analysis of genome-wide association studies (GWASs) to identify additional VTE susceptibility genes. Twelve GWASs totaling 7,507 VTE case subjects and 52,632 control subjects formed our discovery stage where 6,751,884 SNPs were tested for association with VTE. Nine loci reached the genome-wide significance level of 5 × 10−8 including six already known to associate with VTE (ABO, F2, F5, F11, FGG, and PROCR) and three unsuspected loci. SNPs mapping to these latter were selected for replication in three independent case-control studies totaling 3,009 VTE-affected individuals and 2,586 control subjects. This strategy led to the identification and replication of two VTE-associated loci, TSPAN15 and SLC44A2, with lead risk alleles associated with odds ratio for disease of 1.31 (p = 1.67 × 10−16) and 1.21 (p = 2.75 × 10−15), respectively. The lead SNP at the TSPAN15 locus is the intronic rs78707713 and the lead SLC44A2 SNP is the non-synonymous rs2288904 previously shown to associate with transfusion-related acute lung injury. We further showed that these two variants did not associate with known hemostatic plasma markers. TSPAN15 and SLC44A2 do not belong to conventional pathways for thrombosis and have not been associated to other cardiovascular diseases nor related quantitative biomarkers. Our findings uncovered unexpected actors of VTE etiology and pave the way for novel mechanistic concepts of VTE pathophysiology. PMID:25772935
Rationale and design of three observational, prospective cohort studies including biobanking to evaluate and improve diagnostics, management strategies and risk stratification in venous thromboembolism: the VTEval Project
Frank, Bernd; Ariza, Liana; Lamparter, Heidrun; Grossmann, Vera; Prochaska, Jürgen H; Ullmann, Alexander; Kindler, Florentina; Weisser, Gerhard; Walter, Ulrich; Lackner, Karl J; Espinola-Klein, Christine; Münzel, Thomas; Konstantinides, Stavros V; Wild, Philipp S
Introduction Venous thromboembolism (VTE) with its two manifestations deep vein thrombosis (DVT) and pulmonary embolism (PE) is a major public health problem. The VTEval Project aims to investigate numerous research questions on diagnosis, clinical management, treatment and prognosis of VTE, which have remained uncertain to date. Methods and analysis The VTEval Project consists of three observational, prospective cohort studies on VTE comprising cohorts of individuals with a clinical suspicion of acute PE (with or without DVT), with a clinical suspicion of acute DVT (without symptomatic PE) and with an incidental diagnosis of VTE (PE or DVT). The VTEval Project expects to enrol a total of approximately 2000 individuals with subsequent active and passive follow-up investigations over a time period of 5 years per participant. Time points for active follow-up investigations are at months 3, 6, 12, 24 and 36 after diagnosis (depending on the disease cohort); passive follow-up investigations via registry offices and the cancer registry are performed 48 and 60 months after diagnosis for all participants. Primary short-term outcome is defined by overall mortality (PE-related death and all other causes of death), primary long-term outcome by symptomatic VTE (PE-related death, recurrence of non-fatal PE or DVT). The VTEval Project includes three ‘all-comer’ studies and involves the standardised acquisition of high-quality data, covering the systematic assessment of VTE including symptoms, risk profile, psychosocial, environmental and lifestyle factors as well as clinical and subclinical disease, and it builds up a large state-of-the-art biorepository containing various materials from serial blood samplings. Ethics and dissemination The VTEval Project has been approved by the local data safety commissioner and the responsible ethics committee (reference no. 837.320.12 (8421-F)). Trial results will be published in peer-reviewed journals and presented at national and
Di Nisio, Marcello; Vedovati, Maria C; Riera-Mestre, Antoni; Prins, Martin H; Mueller, Katharina; Cohen, Alexander T; Wells, Philip S; Beyer-Westendorf, Jan; Prandoni, Paolo; Bounameaux, Henri; Kubitza, Dagmar; Schneider, Jonas; Pisters, Ron; Fedacko, Jan; Fontes-Carvalho, Ricardo; Lensing, Anthonie W A
The pharmacokinetics of oral rivaroxaban are highly predictable and only affected to a limited extent by bodyweight; therefore, dose adjustments for bodyweight are not required. However, this raises concerns among physicians for potential under- or overdosing. This substudy of the randomised EINSTEIN DVT and EINSTEIN PE trials, which compared rivaroxaban with enoxaparin/vitamin K antagonist (VKA) therapy, aimed to determine the incidence of major bleeding in patients with a low bodyweight and recurrent venous thromboembolism (VTE) in patients with a high bodyweight during rivaroxaban or enoxaparin/VKA therapy. More than 8,000 patients with objectively diagnosed deep-vein thrombosis or pulmonary embolism were included. Adjusted hazard ratios for recurrent VTE and bleeding were calculated using the Cox pro