The worcester venous thromboembolism study

BACKGROUND: While there have been marked advances in diagnostic and therapeutic strategies for venous thromboembolism, our understanding of its clinical epidemiology is based on studies conducted more than a decade ago. OBJECTIVE: The purpose of this observational study was to describe the incidence and attack rates of venous thromboembolism in residents of the Worcester Statistical Metropolitan Area in 1999. We also describe demographic and clinical characteristics, management strategies, and associated hospital and 30-day outcomes. DESIGN AND MEASUREMENTS: The medical records of all residents from Worcester, MA (2000 census=477,800), diagnosed with International Classification of Diseases, 9th revision (ICD-9) codes consistent with possible venous thromboembolism during 1999 were independently validated, classified, and reviewed by trained abstractors. RESULTS: A total of 587 subjects were enrolled with validated venous thromboembolism. The incidence and attack rates of venous thromboembolism were 104 and 128 per 100,000 population, respectively. Three quarters of patients developed their venous thromboembolism in the outpatient setting - a substantial proportion of these patients had undergone recent surgery or had a recent prior hospitalization. Less than half of the patients received anticoagulant prophylaxis during high-risk periods before their venous thromboembolism. Thirty-day rates of venous thromboembolism recurrence, major bleeding, and mortality were 4.8%, 7.7%, and 6.6%, respectively. CONCLUSION: These data provide insights into recent incidence and attack rates, changing patient profiles, management strategies, and subsequent outcomes in patients with venous thromboembolism. The underutilization of prophylaxis before venous thromboembolism, and relatively high 30-day recurrence rates, suggest a continued need for the improvement of venous thromboembolism prophylaxis and management in the community.     

A comparison of three rapid D-dimer methods for the diagnosis of venous thromboembolism

We compared three rapid D-dimer methods for the diagnosis of venous thromboembolism. Patients presenting to four teaching hospitals with the possible diagnosis of deep vein thrombosis or pulmonary embolism were investigated with a combination of clinical likelihood, D-dimer (SimpliRED) and initial non-invasive testing. Patients were assigned as being positive or negative for deep vein thrombosis or pulmonary embolism based on their three-month outcome and initial test results. The three D-dimer methods compared were: (a) Accuclot D-dimer (b) IL-Test D-dimer (c) SimpliRED D-dimer. Of 993 patients, 141 had objectively confirmed deep vein thrombosis or pulmonary embolism. The sensitivity of SimpliRED, Accuclot and IL-Test were 79, 90 and 87% respectively. All three D-dimer tests gave similar negative predictive values. The SimpliRED D-dimer was found to be less sensitive than the Accuclot or IL-Test. When combined with pre-test probability all three methods are probably acceptable for use in the diagnosis of venous thromboembolism.     

Recent air travel and venous thromboembolism resulting in hospital admission

OBJECTIVE: The objective of the study was to determine the proportion of patients admitted to hospital with a deep vein thrombosis (DVT) or pulmonary embolism (PE) in whom recent air travel was documented in the medical records. METHODS: A retrospective review of the medical records of patients with a primary or secondary discharge diagnosis of DVT or PE in four hospitals in New Zealand was undertaken. From the medical records information was collected on demographic details, documentation of the presence of risk factors and results of radiological investigations. Strict radiological criteria were applied to ensure that the diagnosis of DVT or PE was firmly established. RESULTS: In 60 of 576 (10.4%) patients with a confirmed venous thromboembolism there was documentation of recent air travel; in 31 of these 60 subjects no other risk factors were recorded. In those cases in whom details of the air travel had been recorded, it had been undertaken in the previous 1 week in 65.0%, and in 43.3% the air travel was of at least 10-h duration. CONCLUSION: Long distance air travel is an important risk factor for venous thromboembolism requiring hospital admission and represents a significant public health problem in New Zealand.     

Prolonged seated immobility at work is a common risk factor for venous thromboembolism leading to hospital admission

The role of seated immobility at work in the pathogenesis of venous thromboembolism (VTE) is uncertain. In this case series, 61 patients aged <65 years with a recent admission for deep venous thrombosis and/or pulmonary embolism completed an interviewer-administered questionnaire to obtain information regarding risk factors. Prolonged seated immobility at work in the 4 weeks before the VTE event was defined as being seated at least 8 h in a 24-h period and at least 3 h at a time without getting up, at least 10 h in a 24-h period and at least 2 h at a time without getting up or at least 12 h in a 24-h period and at least 1 h at a time without getting up. The most commonly identified risk factors were family history of VTE (21 of 61, 34%), seated immobility at work (21 of 61, 34%) and a thrombophilic state (19 of 61, 31%). We conclude that prolonged seated immobility at work may represent a common and important risk factor for VTE.     

Duration of anticoagulant therapy for venous thromboembolism: balancing benefits and harms on the long term

Venous thromboembolism (VTE) is effectively treated with anticoagulant therapy. After an initial treatment phase, extended treatment is effective to prevent recurrence after a first event but this is at the expense of a continued risk of bleeding. Ideally, patients at a high risk of recurrence and low risk of bleeding continue anticoagulant therapy, and for those at low risk of recurrence the duration of treatment can be limited. Identifying these patients, however, is difficult. Duration of treatment after a first VTE provoked by a transient risk factor should be limited to 3 months. Although guidelines suggest extended treatment for all patients after unprovoked VTE unless bleeding risk is high, we emphasize that the long-term risks of recurrent VTE off anticoagulation are uncertain whereas the risk of bleeding associated with anticoagulant therapy increases with age. In the absence of evidence of replaced mortality or improved quality of life with extended anticoagulant treatment, we suggest a limited duration for most patients after a first VTE. Extended treatment can be considered, based mainly on patient preference.     

Management of venous thromboembolism – controversies and the future

Despite the availability of comprehensive evidence‐based guidelines there are difficult and controversial areas in the management of venous thromboembolism. Institutions and even countries disagree on the importance of calf vein thrombosis, with some rigorously detecting and treating it and others deliberately not looking for it. The need to treat proximal deep vein thrombosis and pulmonary embolism is accepted but which patients with an unprovoked first event should have long‐term anticoagulation has become a difficult clinical decision. We are uncertain how to reduce the incidence of post‐thrombotic syndrome seen in a substantial number of patients. How hard to look for an undiagnosed underlying cancer has become a contentious issue particularly in the United Kingdom following the recent publication of a guideline from the National Institute for Health and Clinical Excellence. Whilst we are wrestling with these dilemmas we are entering an era of new anticoagulants and have to solve the logistical problems of introducing them into clinical practice despite cost pressures. These issues will be explored in this review.     

Prevalence of factor V Leiden and prothrombin G20210A mutations in unselected patients with venous thromboembolism

We determined the prevalence of factor V Leiden and of prothrombin G20210A mutations in a cohort of unselected outpatients (n = 748) referred for suspected deep vein thrombosis (DVT) and/or pulmonary embolism (PE) and a pooled analysis of similar studies was also performed. Based on the clinical presentation, the prevalence of factor V Leiden was 15.7% in the 83 patients with DVT and 14.1% in the 99 patients with PE compared with 5.3% in patients without DVT and/or PE (control group). The prevalence of the prothrombin G20210A mutation did not differ among the three groups (3.9% for controls, 4. 8% for DVT and 3.9% for PE patients). We then divided the 99 patients with PE by separately analysing those with PE but without DVT (n = 57) and those with PE and DVT (n = 42). Compared with the control group, the prevalence of factor V Leiden was 10.5%, odds ratio (OR) 2.10 [95% confidence interval (95% CI) 0.68-5.45] in patients with primary PE and 19.1%, OR 4.20 (95% CI 1.54-10.30) in patients with DVT and PE. For the prothrombin G20210A mutation, no statistically significant differences were found between the control group and the three other groups. In conclusion, our data and the pooled analysis indicate that patients with primary PE are less often affected by the factor V Leiden mutation. No statistically significant differences were observed between patients and controls for the prothrombin G20210A mutation.     

Update on diagnosis and anticoagulant therapy for venous thromboembolism

Venous thromboembolism (VTE) continues to be a common medical problem requiring the need for rapid treatment with anticoagulant therapy. Until the recent availability of the direct oral anticoagulants for treatment of VTE, the option for oral anticoagulation was limited to warfarin therapy. The addition of these new medications has been welcomed, but has led to added complexities in deciding the most appropriate agent for each patient based on individual risk factors. Furthermore, there are several circumstances where optimal duration of therapy is not well established. This article will focus on the diagnosis of VTE, the choice of anticoagulant and treatment duration.     

Prevalence of APC resistance and its relationship to arterial and venous thromboembolism in a general population sample of elderly Swedish men: The Study of Men Born in 1913

BACKGROUND: Most studies of hereditary resistance to activated protein C (APC resistance) as a risk factor for venous thromboembolism are derived from case-control studies of hospitalized patients, whilst the importance of this condition in the general population has been only sparsely investigated. OBJECTIVE: To study the prevalence of APC resistance and its relationship to morbidity and mortality in a general population sample of elderly men. DESIGN: Cross-sectional and prospective follow-up study. SETTING: General community: The Study of Men Born in 1913. SUBJECTS: A random population sample of 404 men, all 75 years of age. MAIN OUTCOME MEASURES: Four hundred and four men participated in a screening examination in 1988. The APC ratio was analysed in 382 of them. All the men were followed up for 5 years. Medical records were reviewed for all the men with a history of deep vein thrombosis, pulmonary embolism, myocardial infarction or stroke. RESULTS: Twenty-five men (6.5%) were found to have APC resistance. The incidence of venous thromboembolism, myocardial infarction or stroke did not differ between men with or without APC resistance, either retrospectively or during follow-up. Only two men experienced a deep vein thrombosis before the age of 80 and there was no case of pulmonary embolism. Mortality during 5 years of follow-up did not differ between men with and without APC resistance. CONCLUSION: The prevalence of APC resistance was 6.5% in this study of Swedish men. Although the size of the population sample is somewhat small, the study shows that, amongst elderly men, the association between APC resistance and venous thromboembolic disease was weak and men with this hereditary condition did not have any increase in morbidity or mortality compared with men without APC resistance.     

By word of mouse: using animal models in venous thrombosis research

Abstract

Deep vein thrombosis (DVT) is a disease with high prevalence and morbidity. It can lead to pulmonary embolism with severe respiratory insufficiency and risk of death. Mechanisms behind all stages of DVT, such as thrombosis commencement, propagation, and resolution, remain incompletely understood. Animal models represent an invaluable tool to explore these problems and identify new targets for DVT prevention and treatment. In this review, we discuss existing models of venous thrombosis, their advantages and disadvantages, and applicability to studying different aspects of DVT pathophysiology. We also speculate about requirements for an “ideal model” that would best recapitulate features of human DVT and discuss readouts of various models.     

Serum homocysteine,thermolabile variant of methylene tetrahydrofolate reductase (MTHFR), and venous thromboembolism: Longitudinal Investigation of Thromboembolism Etiology (LITE)

We sought to examine prospectively the association of serum homocysteine and the methylene tetrahydrofolate reductase (MTHFR) C677T gene polymorphism with risk of venous thromboembolism (VTE). We studied these relationships in a nested case-control study of 303 VTE cases and 635 matched controls from a population-based cohort of 21,680 adults from six U.S. communities. The highest quintile of serum homocysteine carried a non-statistically significant adjusted odds ratio of 1.55 (95% CI, 0.93-2.58) compared to the lowest quintile in the overall cohort but a significant association among adults aged 45-64 years (OR = 2.05, 95% CI, 1.10-3.83) and an inverse association in those > or = 65 years of age. Carriers of the MTHFR C677T polymorphism were not at higher risk for VTE than those with normal genotype (OR = 0.74, 95% CI = 0.56-0.98). Our prospective data showed, at most, a weak relationship between homocysteine and VTE risk, with associations larger among younger participants. MTHFR C677T was not a risk factor for VTE.     

Venous thromboembolism and ethnicity

Venous thromboembolism (VTE) has long been considered a disease that affects predominantly white populations, a misconception resulting from a paucity of epidemiological data from non-Western countries, and the low incidence of hereditary thrombophilia in those of non-Caucasian background. Over the last decade, interest has grown in this area with the emergence of evidence that VTE is as prevalent, if not more so, in the black population and is also common in Asian groups. Much is still to be learned, as our current knowledge of hereditary thrombophilia and acquired risk factors do not fully explain the risk of VTE in non-Caucasian groups. This review summarises the current understanding of ethnic variation in VTE and highlights the need for further research in this area.     

Heterogeneity in reporting venous thromboembolic phenotypes in COVID-19: methodological issues and clinical implications

COVID-19 is associated with increased risk of venous thromboembolic events (VTE). However, there is significant heterogeneity in the thromboembolic phenotypes of COVID-19 patients (deep vein thrombosis, pulmonary embolism/thrombosis). The latter might be partly attributed to the variation in VTE risk factors in COVID-19 patients including: (i) patients’ characteristics; (ii) hospitalization conditions and interventions; and (iii) SARS-CoV-2-specific factors (coagulopathy, endothelial injury/microthrombosis). Furthermore, there is methodological heterogeneity in relation to the assessment of VTE (indications for screening, diagnostic methodology, etc). Physicians should be aware of the increased VTE risk, strongly consider VTE screening, and use thromboprophylaxis in all hospitalized patients.