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Gastroduodenal ulcer incidence in patients with venous thromboembolism.

The presence of peptic ulcer disease implies a high risk of bleeding in patients on heparin therapy. We reviewed our experience with 166 consecutive patients admitted because of venous thromboembolism. Of these 166 patients, 29 were referred for upper gastrointestinal endoscopy in order to detect the presence of any lesion that might contraindicate heparin therapy. A gastric ulcer was found in 10 patients, a duodenal ulcer in 11, and gastric erosions with signs of bleeding in 3 patients. Given the unexpectedly high frequency of ulcer in these patients, an upper gastrointestinal endoscopy was routinely performed early in the course of admission in 50 consecutive patients with venous thromboembolism. A gastric ulcer was found in 5 patients (10%), a duodenal ulcer in 7 (14%), and erosions in 2. Five of these patients had an unsuspected ulcer. A case can be made for prophylactic antiulcer therapy for all patients placed on anticoagulants for venous thromboembolism. Upper gastrointestinal endoscopy is indicated in patients with ulcer symptoms, in those with a previous history of peptic ulcer disease, and perhaps, in patients developing occult blood in the stools while on treatment with anticoagulants.

Adult↗

[Risk factors and clinical characteristics of thromboembolic venous disease in young patients: a prospective study].

BACKGROUND AND OBJECTIVE: We aimed to determine the risk factors of thromboembolic disease in young patients and to study the clinical characteristics according to the etiology. PATIENTS AND METHOD: A prospective study of 100 patients under 50 years who were not affected by neoplasias or chronic diseases and who required hospitalization due to thromboembolic disease. The morphological diagnosis was performed by eco-Doppler, flebography, lung gammagraphy or CT scan. Risk factors assessed were antithrombin, protein C and S deficiency, presence of factor V Leiden, prothrombin G20210A, hyperhomocisteinemia, increased PAI-I, increased factor VIII, and presence of antiphospholipid antibodies (APAs). Acquired factors were also evaluated. RESULTS: In 87% of patients, a venous thrombosis was observed in lower limbs. 37% of patients had congenital risk factors and 19% had APAs, whereas in the remaining patients only acquired factors were demonstrated. Most frequent congenital factors were factor V Leiden, pothrombin G20210A, and protein C and S deficiency. Most patients presented several risk factors. A family thrombotic history was significantly more frequent in the group with congenital risk factors. CONCLUSIONS: In 56% of young patients with thromboembolic disease, a congenital etiology or APAs are identified. In these patients the number of acquired factors needed to trigger thrombosis is fewer than in patients in whom a cause is not identified.

Adult↗

Treatment of venous thromboembolism.

The combination of heparin and oral anticoagulants has been the treatment of choice for most patients with venous thromboembolism in the last two decades. Heparin has been proven to be effective when administered by intravenous continuous infusion or by subcutaneous injection. Oral anticoagulants should be started at the same time and heparin should be discontinued when the levels of the International Normalized Ratio reach the therapeutic range, between 2.0 and 3.0. Low molecular weight heparin has potential advantages over heparin and can be administered in subcutaneous weight-adjusted fixed doses without need for monitoring. This has made home treatment of a large proportion of patients possible. Randomized clinical trials have demonstrated the efficacy and safety of this approach. The optimal duration of the secondary prophylaxis with oral anticoagulants is still a matter of debate. The rate of recurrence has been shown to be elevated, particularly in those patients with idiopathic venous thromboembolism. The presence of an active cancer or a thrombophilic state may require long-term anticoagulation, although not all the congenital hypercoagulable states seem to carry the same level of risk. A 3-month therapy is recommended when a transient risk factor is identified; lifelong treatment is recommended for patients with a second episode of venous thromboembolism. In all other cases, 6 months are currently recommended, but thereafter close monitoring of the patients is advisable. The use of different treatment strategies such as vena caval filter placement, thrombolysis, and surgical thrombectomy should be restricted to a limited number of situations.

Administration, Oral↗

Venous thromboembolism in the intensive care unit.

Venous thromboembolic disease has emerged as a significant cause of morbidity and mortality in hospitalized patients. This article reviews the salient features of venous thromboembolism as they pertain to the critically ill. Emphasis is placed on identifying risk factors, diagnostic strategies, prophylaxis, and treatment of this disorder. Deep venous thrombosis and pulmonary embolism, both being manifestations of the same disease processes, are considered together in this discussion of venous thromboembolism.

Adult↗

[Multicenter, prospective study comparing enoxaparin with unfractionated heparin in the treatment of submassive pulmonary thromboembolism].

OBJECTIVE: To compare the safety and efficacy of enoxaparin and unfractionated heparin in the treatment of submassive pulmonary thromboembolism (PTE). MATERIAL AND METHODS: Fifty-six patients with PTE who did not need fibrinolytic treatment were enrolled prospectively. The patients were randomly assigned to 2 treatment groups: Group A received enoxaparin (1 mg/kg every 12 hours) and Group B received adjusted doses of unfractionated heparin. The oral anticoagulant therapy was started on confirmation of the diagnosis and continued for 6 months. Incidences of recurrence of thromboembolism and of severe bleeding were assessed at the end of this period. RESULTS: Six patients were withdrawn from the study. Twenty-nine of the 50 remaining patients were in Group A (enoxaparin) and 21 in Group B (unfractionated heparin). A recurrence of thromboembolism was diagnosed in 3 patients from Group A (10.7%) and 2 patients from Group B (9.5%). There were no significant differences. Two patients died, one death being attributed to bleeding secondary to the oral anticoagulant treatment (Group A) and the other to a process unrelated to PTE. CONCLUSIONS: Enoxaparin seems to be as effective and safe as unfractionated heparin in the initial treatment of PTE.

Aged↗

Factor V Leiden, prothrombin 20210G --> A, methylenetetrahydrofolate reductase 677C --> T and plasminogen activator inhibitor 4G/5G polymorphism in women with pregnancy-related venous thromboembolism.

OBJECTIVE: To establish the prevalence of inherited and acquired risk factors for development of venous thromboembolism (VTE) in pregnancy and the puerperium. STUDY DESIGN: In a retrospective study, 30 women with a history of objectively confirmed venous thromboembolism during pregnancy or the puerperium were studied. Fifty-six women with normal pregnancies were included as controls. Antithrombin, protein C, protein S, lupus anticoagulants, homocysteine, factor V Leiden mutation, prothrombin 20210G-->A polymorphism, methylenetetrahydrofolate reductase (MTHFR) 677C-->T polymorphism and the -675 (4G/5G) polymorphism in plasminogen activator inhibitor 1 gene were analysed. RESULTS: At least one thrombophilic defect was observed in 16 (53.3%) cases and in 12 (21.4%) controls (P=0.003); factor V Leiden in 8 (26.7%) cases and 3 (5.7%) controls (P=0.009); prothrombin 20210G-->A polymorphism in 8 (26.7%) cases and 4 (7.5%) controls (P=0.021) and antithrombin deficiency in 4 (13.3%) cases and in 1 (1.8%) control (P=0.029). Other inherited and acquired risk factors were similarly distributed among cases and controls. CONCLUSION: Women with pregnancy-related venous thromboembolism have an increased prevalence of inheritable thrombophilic defects predisposing them to an increased risk of thrombosis.

Alleles↗

[Optimizing history taking for evaluating the risk of venous thromboembolism: the OPTIMEV study].

UNLABELLED: Venous thromboembolism (VTE) is a frequent disease and remains a major cause of mortality and morbidity among our patients. During the 20 past years, clinical description, diagnostic tools, and treatment have changed dramatically. Most published data describing risk factors for VTE no longer apply to the patients seen in daily practice. We present here the rationale, aims, and methodology of the OPTIMEV Study (OPTimisation de l'Interrogatoire pour la Maladie thromboEmbolique Veineuse). RATIONALE: Risk factors for VTE are numerous, complex and interactions between them and their clinical importance is difficult to measure (table I). For example, odds ratios for VTE recurrence vary greatly across longitudinal studies. We searched the National Library of Medecine (PubMed) and the Amedeo website using the following keywords: "venous thromboembolism", "pulmonary embolism", "deep vein thrombosis", "risk factors". We selected 84 relevant articles published between 1972 and 2005. Based on this literature analysis, we identified the following major risk factors: VTE recurrence, surgery, cancer, immobilization, age, biological factors. For these factors, data are lacking and some questions are proposed. OBJECTIVES: The broad objective of the study is to better evaluate clinical risk factors that fit today's practice against VTE. Specific aims are: 1) to determine whether risk factors are different between proximal and distal deep vein thrombosis (DVT); 2) to develop and prospectively validate a new prediction rule for outpatients. The primary hypothesis is that careful assessment of VTE recurrence, adequate surgical thromboprophylaxis, cancer staging, and varicose vein stratification according to the CEAP classification, is mandatory for accurate evaluation of thromboembolic disease risk. METHODS: We conducted a multicenter, prospective, cohort study of 10000 patients. Enrollees are inpatients and outpatients presenting with a clinical suspicion of VTE in Emergency Departments and outpatient clinics in France. 4173 patients have been enrolled at this time (Figure 2). All eligible patients are enrolled during a selected period of time through different seasons. Data are collected by physicians in charge of the patients using an electronic case recording form. Collected data include baseline characteristics, risk factors, results of diagnostic investigations. Outcome measures obtained through telephone interview at 3 and 12 months include cancer diagnosis, VTE recurrence, haemorrhagic events, treatments, death. Univariate and multivariate analysis will be performed using multilevel logistic regression. The study organization is performed by the Centre d'Investigation Clinique de Grenoble and is sponsored by the French Society of Vascular Medicine. First results, to be published in 2006, will allow development of new prediction rules for VTE diagnosis.

Age Factors↗

Preventive and therapeutic approach to venous thromboembolic disease and pulmonary embolism--can death from pulmonary embolism be prevented?

Venous thromboembolism produces chronic sequelae in the legs and occasional immediate mortality due to pulmonary embolism. Because it occurs in certain high risk situations (for example, after surgery) its prevention is a practical proposition. This has been attempted using many different approaches. Administration of low dose heparin with or without dihydroergotamine to enhance venous return has been one of the most widely tested regimens. There is little doubt that this can prevent, in many patient groups, postoperative deep venous thrombosis and fatal pulmonary embolism, with a low incidence of adverse reactions. Some particularly high risk postoperative patient groups (for example, those undergoing hip surgery) warrant more aggressive measures to prevent thrombosis. Surveys have shown that increasing use is being made of this approach, and it is hoped that all surgeons will adopt a policy that will reduce postoperative venous thrombosis and pulmonary embolism. A reduction in the incidence of venous thromboembolism in large acute myocardial infarction is achieved by low dose heparin, although early mobilization is important. In addition, many of the patients at risk merit full dose anticoagulation to prevent intracardiac thromboembolism. Established venous thrombosis is treated effectively by intravenous heparin, followed by warfarin to keep the prothrombin time at 1.2 to 1.5 times control, as assessed using rabbit thromboplastin; most patients need three months of treatment. Anticoagulation is warranted for pulmonary embolism, with fibrinolytic therapy reserved for patients with massive embolism and hemodynamic compromise. Embolectomy is a heroic measure, which may occasionally be lifesaving.

Dihydroergotamine↗

Left atrial appendage "stunning" after electrical cardioversion of atrial flutter: an attenuated response compared with atrial fibrillation as the mechanism for lower susceptibility to thromboembolic events.

OBJECTIVES: This study sought to determine whether left atrial appendage stunning occurs in patients with atrial flutter and to compare left atrial appendage function in the pericardioversion period with that in patients with atrial fibrillation. BACKGROUND: Left atrial appendage stunning has recently been proposed as a key mechanistic phenomenon in the etiology of postcardioversion thromboembolic events in atrial fibrillation. Atrial flutter is thought to be associated with a negligible risk of thromboembolic events; therefore, anticoagulation is commonly withheld before and after cardioversion in these patients. METHODS: Sixty-three patients with atrial flutter (n = 19) or atrial fibrillation (n = 44) underwent transesophageal echocardiography immediately before and after electrical cardioversion. In addition to assessing the presence of thrombus and spontaneous echo contrast, we measured left atrial appendage emptying velocity and calculated shear rates by pulsed wave Doppler and two-dimensional echocardiography. RESULTS: Patients with atrial flutter exhibited greater left atrial appendage flow velocities before cardioversion than those with atrial fibrillation (42 +/- 19 vs. 28 +/- 15 cm/s [mean +/- SD], p < 0.001). Left atrial appendage shear rates were also higher in patients with atrial flutter (103 +/- 82 vs. 59 +/- 37 s-1, p < 0.001). After cardioversion, left atrial appendage flow velocities decreased compared with precardioversion values in patients with atrial fibrillation (28 +/- 15 before to 15 +/- 14 cm/s after cardioversion, p < 0.001) and atrial flutter (42 +/- 19 to 27 +/- 18 cm/s, respectively, p < 0.001). Shear rates decreased from 59 +/- 37 before cardioversion to 30 +/- 31 s-1 after cardioversion in atrial fibrillation (p < 0.001), and from 103 +/- 82 s to 65 +/- 52 s-1, respectively (p < 0.001), in atrial flutter. This decrease in flow velocity from before to after cardioversion occurred in 36 (82%) of 44 patients with atrial fibrillation and 14 (74%) of 19 with atrial flutter. The impaired left atrial appendage function after cardioversion was less pronounced in the group with atrial flutter (27 +/- 18 cm/s for atrial flutter vs. 15 +/- 14 cm/s for atrial fibrillation, p < 0.001). New or increased spontaneous echo contrast occurred in 22 (50%) of 44 patients with atrial fibrillation versus 4 (21%) of 19 with atrial flutter (p < 0.05). CONCLUSIONS: Left atrial appendage stunning also occurs in patients with atrial flutter, although to a lesser degree than in those with atrial fibrillation. These data suggest that patients with atrial flutter are at risk for thromboembolic events after cardioversion, although this risk is most likely lower than that in patients with atrial fibrillation because of better preserved left atrial appendage function.

Aged↗

Age-related changes in risk factor effects on the incidence of thromboembolic and hemorrhagic stroke.

We examined the changes in risk factor effects on the incidence of thromboembolic and hemorrhagic stroke as they may occur with age. Findings were based on repeated risk factor measurements at four examinations over a 26-year period in 7589 men in the Honolulu Heart Program. After each examination, 6 years of follow-up were available to assess risk factor effects on the incidence of stroke over a broad range of ages (45-93 years). As compared with normotensive men, the risk of thromboembolic stroke in the presence of hypertension declined from a 7-fold excess in men aged 45 to 54 years to a 1.4-fold excess in men aged > or =75 (P<.001). Adverse effects of diabetes and atrial fibrillation seemed to be equally important across all ages, whereas a protective effect of physical activity increased with age. Except for men with atrial fibrillation, the incidence of thromboembolic stroke increased significantly with age regardless of risk factor status, including men with normal blood pressure (P<.001). Although hemorrhagic events were less common, positive relations with cigarette smoking seemed to strengthen with age, whereas those with hypertension tended to decline. Our findings suggest that strategies for the prevention of stroke may need to account for changes in risk factor effects as they occur with age. Control of diabetes and the encouragement of active lifestyles in the elderly seem to be especially important.

Aged↗

Thrombophilia: disorders predisposing to venous thromboembolism.

Venous thromboembolism continues to present a challenge to clinicians. Over the years, a number of risk factors which predispose to venous thromboembolism have been identified, and these risk factors are taken into account in the formulation of recommendations for the prevention and treatment of these disorders. In more recent years, there have been major advances in our understanding of congenital or acquired defects that predispose to thrombosis leading to these so-called acquired or inherited forms of thrombophilia. The list of acquired forms of thrombophilia now includes anti-thrombin, protein C, protein S, activated protein C resistance, the prothrombin 20210A mutant, homocysteinemia and a number of rare defects which either enhance coagulation or interfere with fibrinolysis. In spite of these advances, there are numerous families with thrombophilia in whom none of the known defects can be demonstrated. The challenge for the future is to discover some of these as yet unknown factors and to determine the most appropriate methods for the prevention and treatment of venous thromboembolism in susceptible individuals with thrombophilia.

Activated Protein C Resistance↗

Fatal paradoxic embolism occurring during IVC filter insertion in a patient with chronic pulmonary thromboembolic disease.

A patient diagnosed with chronic thromboembolic disease experienced a fatal intraprocedural paradoxic embolism during inferior vena cava (IVC) filter insertion. The frequency of patent intra-atrial shunts in patients with chronic thromboembolic disease is surprisingly high, occurring in approximately 29.5% of patients with chronic thromboembolic disease. Prevention of embolic events during venous interventions in such cases requires that the operator recognize that central shunts may be present and strictly adhere to meticulous technique during IVC filter insertion.

Aged↗

Venous thromboembolism risk and management in women with cancer and thrombophilia.

BACKGROUND: Venous thromboembolism (VTE) and its complications result in a high rate of morbidity and mortality. OBJECTIVE: The aim of this study was to review the risk of VTE in women with cancer and other predisposing risk factors, as well as the management of these patients. METHODS: Data for this review were identified by searches of MEDLINE, Current Contents, and references from relevant articles using the search terms venous thrombosis, venous thromboembolism, pulmonary embolism, anticoagulation, risk factors, cancer, thrombophilia, heparin, and warfarin. Abstracts and reports from meetings were included only when they directly related to previously published work. Only papers published in English between 1960 and 2005 were included. RESULTS: VTE risk is increased in patients with cancer, with 15% of these patients developing VTE or disseminated intravascular coagulation. Understanding a patient's thromboembolic risk is essential because it affects the type and duration of antithrombotic therapy. The incidence of VTE is dependent on a number of factors, including tumor type, mode of treatment, surgical procedures, patient immobility, and thrombophilia. Progression and recurrence of VTE can be prevented by therapy with unfractionated or low-molecular-weight heparin (LMWH_ followed by warfarin for at least three months. In selected women with advanced cancer disease, a long-term course of LMWH in therapeutic doses is the treatment of choice. CONCLUSIONS: In women with cancer, the clinical course is often complicated by VTE episodes. The risk of VTE increases in association with either inherited or acquired thrombophilic conditions. Appropriate management of throemboembolism in women with cancer has the potential to reduce the negative clinical outcomes related to these complications.

Comorbidity↗

Haemostatic changes and thromboembolic risk during tamoxifen therapy in normal women.

Tamoxifen has been implicated as a risk factor for venous thrombosis in advanced breast cancer although the evidence for increased arterial or venous thrombosis with tamoxifen in early breast cancer is less clear. The effect of tamoxifen on haemostasis, and thereby possible thromboembolic risk, was investigated in normal women enrolled in a placebo controlled trial of tamoxifen as a chemopreventative agent for breast cancer. There was an initial reduction in fibrinogen levels in all women on tamoxifen over the first year of follow-up and a marginal reduction in antithrombin III and Protein S in postmenopausal women at 6 months. There were no changes in cross linked fibrinogen degradation products or Protein C for pre or post-menopausal women. There was no increase in the incidence of thromboembolic events on tamoxifen. This study demonstrates that tamoxifen has only marginal effects on factors involved in haemostasis reported to affect the incidence of arterial or venous thromboembolic disease. The follow-up time is relatively short (maximum 36 months) and careful long term follow-up is necessary to detect clinically significant morbidity.

Antithrombins↗

Venous thromboembolism after hip fracture surgery in a patient with haemophilia B and factor V Arg506Gln (factor V Leiden).

We describe a patient with mild haemophilia B who developed symptomatic venous thromboembolism after hip arthroplasty for a traumatic fracture. A deep vein thrombosis developed in the operated leg while he was receiving a high-purity factor IX concentrate. Subsequently, he was determined to be a heterozygous carrier for the factor V Arg506Gln (Leiden) mutation. This case illustrates the importance of providing thromboprophylaxis for all patients with haemophilia receiving coagulation factor replacement and who undergo surgical procedures known to be associated with a high risk of venous thromboembolism. In patients with haemophilia and a family history of venous thromboembolism, preoperative screening for the presence of the factor V Arg506Gln mutation and other thrombophilias may be useful.

Aged↗

High-flow perfusion of sheaths for prevention of thromboembolic complications during complex catheter ablation in the left atrium.

INTRODUCTION: Mechanisms for thromboembolic complications during complex ablation procedures in left atrium (LA) have not been defined. The aim of this study was to determine the effect of the perfusion rate of the transseptal sheath on the incidence of thromboembolic complications during catheter ablation for atrial fibrillation (AF) or LA macroreentrant tachycardia. METHODS AND RESULTS: We analyzed clinical and procedural data from 86 consecutive patients (153 procedures) referred for catheter ablation of AF (74 patients) or LA macroreentrant tachycardia (12 patients). The transseptal sheath was continuously perfused at a low flow rate (3 mL/hour) for the first 32 patients and at a high flow rate (180 mL/hour) for the subsequent 54 patients. Ablation was mainly performed using map-guided isolation of pulmonary veins for AF and three-dimensional electroanatomic mapping for LA macroreentrant tachycardia. Five patients (6% of patients and 3.5% of procedures) developed a cerebral thromboembolic complication, all during procedures using low-flow perfusion. Sheath perfusion rate and total procedure duration were the two variables significantly associated with the occurrence of stroke (P = 0.013 and 0.001, respectively). After adjustment in a multivariable analysis, sheath perfusion rate remained the only risk factor for stroke. The risk was 17 times higher using low-flow than high-flow perfusion (odds ratio 17.26, 95% confidence interval 1.14-260.81, P = 0.04). No other clinical or procedural parameters had any significant effect. CONCLUSION: Sheath perfusion rate is an important determinant of the risk factor for stroke during complex LA ablation procedures. Continuous high-flow perfusion appears to be effective in preventing this complication.

Adult↗

Venous thromboembolism in inflammatory bowel disease.

OBJECTIVES: Venous thromboembolism has been associated with inflammatory bowel disease (IBD). We sought to describe the clinical features, acquired and congenital risk factors, and outcomes of venous thromboembolism in IBD. METHODS: All patients with confirmed IBD and deep venous thrombosis (DVT) or pulmonary embolism (PE) at our institution between 1991 and 2000 were identified. Medical records were abstracted for clinical features, risk factors, treatment, and outcomes. RESULTS: Fifty-nine ulcerative colitis (UC) patients (68% males) and 39 Crohn's disease (CD) patients (41% males) were identified. UC extent was pancolonic in 76%, and CD extent was ileocolonic in 56%, colonic in 23%, and ileal in 21%. Eighty percent of CD patients and 79% of UC patients had active disease. Thrombophilia was present in 33% of the 40 patients tested. Most patients (87%) had other risk factors for DVT/PE. Long-term treatment included warfarin alone (62%), warfarin and IVC filter (18%), and IVC filter alone (7%). Five CD patients (13%) had recurrent DVT/PE. Among the 16 UC patients who underwent proctocolectomy following DVT/PE, there were two recurrences (13%), similar to the three recurrences (10%) seen among the 29 patients who had intact colons. Mortality rate was 22% after a median follow-up of 1.8 yr. CONCLUSIONS: Venous thromboembolism is a serious complication of IBD that may lead to death. Thrombophilia evaluations have a relatively high diagnostic yield overall, although specific genetic abnormalities are individually uncommon. Other DVT/PE risk factors are usually present. Proctocolectomy is not protective of recurrent DVT/PE.

Adolescent↗

Venous thromboembolism in young women; role of thrombophilic mutations and oral contraceptive use.

AIMS: The interaction between the R506Q mutation of factor V and the G20210A mutation of prothrombin with oral contraceptives on venous thromboembolism was evaluated. METHODS AND RESULTS: Three hundred and one women of reproductive age who had venous thromboembolism (140 while using oral contraceptives) and 650 healthy women (173 on oral contraceptives at presentation) were examined. Of the patients, 19.3% were carriers of R506Q (two homozygotes) and 9.6% were heterozygous carriers of G20210A; eight patients (2.7%) were heterozygous for both mutations. Among controls, 2.9% were carriers of R506Q, 3.1% of G20210A, while one case was a heterozygous carrier of both mutations. The relative risk (odds ratio) associated with carriership of R506Q or G20210A mutations was 10.3 and 4.7, respectively; it was 45.6 in carriers of both mutations. The odds ratio of using oral contraceptives in the absence of both mutations was 2.4. The odds ratios according to oral contraceptives use and the presence of R506Q or G20210A or both mutations were 41.0, 58.6 and 86.5, respectively. While the odds ratio for R506Q remains elevated (8.9) in non-oral contraceptive users, the odds ratio for G20210A was 2.0 and did not reach statistical significance. CONCLUSIONS: Our data showed a strong interaction between oral contraceptive use and the presence of either R506Q or G20210A mutations. In non-oral contraceptive users the risk of venous thromboembolism was significantly increased in carriers of R506Q but not in those with the G20210A mutation.

Adolescent↗